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Title:
SYNERGISTIC PLANT GROWTH REGULATOR COMPOSITIONS
Document Type and Number:
WIPO Patent Application WO/1987/005781
Kind Code:
A2
Abstract:
Synergistic plant growth regulator compositions containing (i) an ethylene response or ethylene-type response inducing agent and (ii) a malonic acid derivative compound. This invention also relates to the use of said compositions for inducing synergistic plant growth regulating responses or ethylene responses or ethylene-type responses.

Inventors:
See
Raymond
Michael, Fritz
Charles
David, Manning
David
Treadway, Wheeler
Thomas
Neil, Cooke
Anson
Richard
Application Number:
PCT/US1987/000648
Publication Date:
October 08, 1987
Filing Date:
March 30, 1987
Export Citation:
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Assignee:
Rhone-poulenc, Nederlands B.
, V.
International Classes:
C07C69/38; A01N37/30; A01N37/34; A01N41/04; A01N41/06; A01N41/12; A01N43/08; A01N43/10; A01N43/40; A01N43/58; A01N43/60; A01N43/64; A01N53/00; A01N53/10; A01N57/04; A01N57/06; A01N57/08; A01N57/18; A01N57/20; A01N57/22; A01N57/24; C07C67/00; C07C231/00; C07C233/00; C07C233/06; C07C233/07; C07C233/15; C07C233/25; C07C233/33; C07C233/43; C07C233/54; C07C233/58; C07C233/59; C07C233/60; C07C233/61; C07C233/62; C07C233/63; C07C235/00; C07C235/40; C07C235/72; C07C235/82; C07C237/24; C07C313/00; C07C317/44; C07C323/60; C07C325/00; C07C327/22; C07D213/00; C07D213/64; C07D213/70; C07D213/75; C07D237/20; C07D237/22; C07D241/20; C07D251/44; C07D295/08; C07D307/66; C07D317/32; C07D333/36; C07D339/06; C07D521/00; C07F9/40; (IPC1-7): A01N57/24; A01N57/22; A01N57/20; A01N57/08; A01N57/06; A01N57/04; A01N53/00; A01N41/04; A01N37/30; C07C103/36; C07C103/38
Foreign References:
US3879188A1975-04-22
US4240819A1980-12-23
US4352869A1982-10-05
US4374661A1983-02-22
US4401454A1983-08-30
US3885951A1975-05-27
US3927062A1975-12-16
US4332612A1982-06-01
US4359334A1982-11-16
US3072473A1963-01-08
JPS5939803A1984-03-05
Other References:
RICHTER, G. H.: "Textbook of Organic Chemistry", JOHN WILEY AND SONS, pages: 486
PARLHAR, N.S., HORMONAL CONTROL OF PLANT GROWTH, 1964, pages 69 - 79
SHINDO, N.; KATO, M., MEIJI DALGAKU NOOGAKU-BU KENKYU HOKOKU, vol. 63, 1984, pages 41 - 58
Download PDF:
Description:
Synergistic Plant Srowth Regulator Compositions

Brief Summary of the Invention

Technical Field

This Invention relates to synergistic plant growth regulator compositions and to the use of said compositions for Inducing plant growth regulating responses or ethylene responses or ethylene-type responses.

Background of the Invention

Plant growth regulating responses Involving the Inducement of an ethylene response or ethylene-type response have been known for some time 1n the art and Include, for example, Increasing yields, abscission of foliage and fruit, Increasing flowering and fruiting, prevention of lodging, disease resistance and other responses.

Ethylene response or ethylene-type response Inducing agents which have been used to achieve certain of these plant growth regulating responses Include, for example, the following: certain phosphonlc add compounds as described 1n U.S. Patents 3,879,188, 4,240,819, 4,352,869, 4,374,661 and 4,401,454; certain 2-haloethanesulph1n1c add compounds as described 1n U.S. Patent 3,885,951; certain beta-chloro- and beta-bromoethanesulf1n1c adds and esters as described 1n U.S. Patent 3,927,062; mixtures of a N-heterocycl1c amide and a haloalkyl sllane as described 1n U.S. Patent 4,332,612; mixtures of a N-heterocycl1c amide and a . 2-haloethylsulf1nate as described 1n U.S. Patent

4,359,334; and gaseous ethylene as described by Parlhar, N.S., Hormonal Control of Plant Growth, pp. 69-79 (1964).

Certain malonlc add derivative compounds have been described 1n the art as capable of providing plant growth regulating responses. U.S. Patent 3,072,473 describes N-arylmalonam1c adds and their esters and salts, N, N'-d1arylmalonam1des, N-alkyl-N-arylmalonam1c adds and their esters and salts, and N, N'-d1alkyl-N, N'-dlarylmalonam des which may be useful as plant growth regulants and herbicides. Japanese Patent 84 39,803 (1984) describes malonlc add anlHde derivative compounds which may be useful as plant growth regulators. The plant growth regulating properties of substituted malonyl monoanllldes are described by Shlndo, N. and ato, M., Me1j1 Dalgaku Noogaku-bu Kenkyu Hokoku, Vol. 63, pp. 41-58 (1984).

However, plant growth regulating compositions containing (1) an ethylene response or ethylene-type response nducing agent and (2) a malonlc add derivative compound, which compositions provide synergistic plant growth regulating responses as described herein, have not been disclosed 1n the art.

Accordingly, 1t 1s an object of th s Invention to provide novel synergistic plant growth regulating compositions. It 1s another object of this Invention to provide a method for the use of the novel plant growth regulating compositions to achieve synergistic plant growth regulating responses. These and other objects will readily

become apparent to those skilled 1n the art 1n light of the teachings herein set forth.

Disclosure of the Invention

This Invention relates to synergistic plant growth regulator compositions and to the Inducement of a synergistic plant growth regulating response or an ethylene response or an ethylene-type response through the application of a synergistic plant growth regulator composition at the plant site.

In particular, this Invention relates to synergistic plant growth regulator compositions containing (1) an ethylene response or ethylene-type response Inducing agent and (11) a malonlc add derivative compound having the formula:

*

Rl Yi C - C - R.

Y5 Yδ wherein R. , R 2 , Y. , Y 2 , Yg, Y 4 , Y g and Y, are as defined hereinafter, and 1n which the amount of compound (11) used with agent (1) results 1n a mixture having a greater plant growth regulating effect than the sum total plant growth regulating effect of agent (1) and compound (11) used alone.

This Invention further relates to a method for regulating plant growth by applying to the plant a synergistic plant growth regulator composition containing (1) an ethylene response or ethylene-type

response Inducing agent and (11) a malonlc add derivative compound having the formula:

Y3 * \ /

R-l - Y-j - C - C - C - Y - R ?

II II

wherein R- , R.,, Y. , Y.,, Yg, Y 4 , Y 5 and

Y, are as defined hereinafter, and 1n which the 0 amount of compound (11) used with agent (1) results 1n a mixture having a greater plant growth regulating effect than the sum total plant growth regulating effect of agent (1) and compound (11) used alone.

Detailed Description As Indicated above, th s Invention relates to synergistic plant growth regulator compositions and to a method for Inducing synergistic plant growth regulating responses by applying a synergistic plant growth regulator composition at the plant site. More particularly, this Invention relates to plant growth regulator compositions comprising (1) an ethylene response or ethylene-type response Inducing agent and (11) a malonlc add derivative compound having the formula:

R-| - Y-| - C - C - C - Y - 2 J

II II

wherei n :

R- and R- are Independently a substituted or unsubst tuted, carbocycllc or heterocycllc ring system selected from a monocycllc aromatic or nonaromatlc ring system, a b1cycl1c aromatic or nonaromatlc ring system, a polycycllc aromatic or nonaromatlc ring system, and a bridged ring system which may be saturated or unsaturated 1n which the permissible substltuents (Z) are the same or different and are one or more hydrogen, halogen, alkylcarbonyl, alkylcarbonylalkyl, for yl, alkoxycarbonylalkyl, alkoxycarbonylalkylthlo, polyhaloalkenylthlo, thlocyano, propargylthlo, hydroxy1m1no, alkoxy1m1no, tr1alkyls1lyloxy, aryldlalkylsllyloxy, tr1aryls1lyloxy, formam1d1no, alkylsulfamldo, dlalkylsulfa ldo, alkoxysulfonyl, polyhaloalkoxysulfonyl, hydroxy, amino, azldo, azo, amlnocarbonyl, alkylamlnocarbonyl, hydraz no, d1alkylam1nocarbonyl , am1noth1ocarbonyl , alkylam1noth1ocarbonyl , d1alkylam1noth1ocarbonyl, nltro, cyano, hydroxycarbonyl and derivative salts, fαrmamldo, alkyl, alkoxy, polyhaloalkyl, polyhaloalkoxy, alkoxycarbonyl, substituted amino 1n which the permissible substltuents are the same or different and are one or two propargyl, alkoxyalkyl, alkylthloalkyl, alkyl, alkenyl, haloalkenyl or polyhaloalkenyl ; alkylthlo, polyhaloalkylth o, alkylsulflnyl, polyhaloalkylsulflnyl , alkylsulfonyl, polyhaloalkylsulfonyl, alkylsulfonylamino, alkylcarbonylamino, polyhaloalkylsulfonylamlno, polyhaloalkylcarbonylamlno, trialkylsllyl, aryldlalkylsllyl, tr1aryls1lyl, sulfonlc add and

derivative salts, phosphon c add and derivative salts, alkoxycarbonylamlno, alkylamlnocarbonyloxy, dlalkyla lnocarbonyloxy, alkenyl, polyhaloalkenyl, alkenyloxy, alkynyl, alkynyloxy, polyhaloalkenyloxy, polyhaloalkynyl, polyhaloalkynyloxy, polyfluoroalkanol , cyanoalkylamlno, semlcarbazonomethyl , alkoxycarbonylhydrazonomethyl, alkoxy1m1nomethyl, unsubstltuted or substituted aryloxy1m1nomethyl, hydrazonomethyl, unsubstltuted or substituted arylhydrazonomethyl, a hydroxy group condensed with a mono-, d1- or polysaccharlde, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, aryloxy, aralkoxy, arylthlo, aralkylthlo, alkylthloalkyl, arylthloalkyl, arylsulflnyl, arylsulfonyl, haloalkylsulflnyl, haloalkylsulfonyl, haloalkenyloxy, haloalkynyloxy, haloalkynylthlo, haloalkenylsulfonyl , polyhaloalkenylsulfonyl, Isocyano, aryloxysulfonyl, propargyloxy, aroyl, haloacyl, polyhaloacyl, aryloxycarbonyl, amlnosulfonyl, alkylamlnosulfonyl, dlalkyl- amlnosulfonyl, arylamlnosulfonyl, carboxyalkoxy, carboxyalkylth o, alkoxycarbonylalkoxy, acyloxy, haloacyloxy, polyhaloacyloxy, aroyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, arylsulfonyloxy, haloalkylsulfonyloxy, polyhaloalkylsulfonyloxy, aroylamlno, haloacylamlno, alkoxycarbonyloxy, .arylsulfonylamino, amlnocarbonyloxy, cyanato, Isocyanato, Isothlocyano, cycloalkyla lno, tr1alkylammonium, arylamlno, aryl(alkyl)am1no, aralkylamlno, alkoxyalkylphosphlnyl , alkoxyalkylphosph1noth1αyl , alkylhydroxyphosphlnyl ,

dlalkoxyphosphlno, hydroxyamlno, alkoxyam no, aryloxyamlno, aryloxylmlno, oxo, thlono, dlazo, alkylldene, alkyl1m1no, hydrazono, semlcarbazono, d1alkylsulfon1um, d1alkyloxosulfon1um,

-X - R 3 - P - 8 R4 -Yio p - Y 8 R 4

Y9R5 Y9R5 or

R, and R_ are Independently hydrogen or derivative salts, or a substituted heteroatom or substituted carbon atom, or a substituted or unsubstltuted, branched or straight chain containing two or more carbon atoms or heteroatoms 1n any combination 1n which the permissible substltuents are Z as hereinbefore defined.

Y 1 and Y« are Independently a substi¬ tuted or unsubstltuted heteroatom 1n which the per¬ missible substltuents are Z as hereinbefore defined.

Y, and Y4. are Independently hydrogen, or a substituted or unsubstltuted heteroatom or substituted carbon atom, or a substituted or unsubstltuted, branched or straight chain containing two or more carbon atoms or heteroatoms 1n any combination, or halogen, alkylcarbonyl, formyl, alkylcarbonylalkyl, alkoxycarbonylalkyl ,

- 7a-

alkoxycarbonylalkylthlo, polyhaloalkenylthlo, thlocyano, propargylthlo, tr1alkyls1lyloxy, aryld1alkyls1lyloxy, tr1aryls1lyloxy, formam1d1πo, alkylsulfamldo, d1alkylsulfam1do, alkoxysulfonyl, polyhaloalkoxysulfonyl, hydroxy, amino, hydrazlno, azo, a lnocarbonyl, alkylamlnocarbonyl,' azldo, d1alkylam1nocarbonyl, am1noth1ocarbonyl, alkylam1noth1ocarbonyl, d1alkylam.1noth1ocarbonyl, nltro, cyano, hydroxycarbonyl and derivative salts, formamldo, alkyl, alkoxy, polyhaloalkyl, polyhaloalkoxy, alkoxycarbonyl, substituted amino 1n which the permissible substltuents are the same or different and are one or two propargyl, alkoxyalkyl, alkylthloalkyl, alkyl, alkenyl, haloalkenyl or polyhaloalkenyl; alkylthlo, polyhaloalkylthlo, alkylsulflnyl, polyhaloalkylsulflnyl, alkylsulfonyl, pol , yhaloalkylsulfonyl, alkylsulfonylam no, alkylcarbonylamlno, polyhaloalkylsulfonylamlno, polyhaloalkylcarbonyla lno, tr1alkyls1lyl, aryld1alkyls1lyl, tr1aryls1lyl, sulfonlc add and derivative salts, phosphon c add and derivative

salts, alkoxycarbonylamlno, alkylamlnocarbonyloxy, dlalkylamlnocarbonyloxy, alkenyl, polyhaloalkenyl, alkenyloxy, alkynyl, alkynyloxy, polyhaloalkenyloxy, polyhaloalkynyl , polyhaloalkynyloxy, polyfluoroalkanol , cyanoalkylamlno, semlcarbazonomethyl , alkoxycarbonylhydrazonomethyl , alkoxy1m1nomethyl, unsubstltuted or substituted aryloxy1m1nomethyl , hydrazonomethyl, unsubstltuted or substituted arylhydrazonomethyl, a hydroxy group condensed with a mono-, d1- or polysaccharlde, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, aryloxy, aralkoxy, arylthlo, aralkylthlo, alkylthloalkyl, arylthloalkyl, arylsulflnyl, arylsulfonyl, haloalkylsulflnyl, haloalkylsulfonyl, haloalkenyloxy, haloalkynyloxy, haloalkynylthlo, haloalkenylsulfonyl, polyhaloalkenylsulfonyl, Isocyano, aryloxysulfonyl, propargyloxy, aroyl, haloacyl, polyhaloacyl, aryloxycarbonyl, ami osulfonyl, al y1aminosulfonyl, dialkylamlnosulfonyl, arylaminosulfonyl, carboxyalkoxy, carboxyalkylthlo, alkoxycarbonylalkoxy, acyloxy, haloacyloxy, polyhaloacyloxy, aroyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, arylsulfonyloxy, haloalkylsulfonyloxy, polyhaloalkylsulfonyloxy, aroylamlno, haloacylamlno, alkoxycarbonyloxy, arylsulfonylamlno, amlnocarbonyloxy, cyanato, Isocyanato, Isothlocyano, cycloalkylamlno, tr1alkylammon1um, arylamlno, aryl(alkyl)am1no, aralkylamlno, alkoxyalkylphosph nyl , alkoxyalkylphosphlnothloyl , alkylhydroxyphosphlnyl ,

dlalkoxyphosphlno, hydroxyamlno, alkoxyamlno, aryloxyamlno,

-X, -X - R3,

-X _ R3 , _ p Y 8 4 , _γ 10 _ p - YgR 4

Y 9 R 5 Y 9 R 5 or

.Y 8 R Y9R5

1n which the permissible substltuents are Z as here- before defined,

or Y- and Y. taken together are oxo, thlono, d azo, = X or = X - R-, or substituted or unsubstltuted alkylldene, alkyl1m1no, hydrazono, dlalkylsulfonlum, d1al yloxosulfon1um, semlcarbazono, hydroxylm no, alkoxy1m1no or aryloxy1m1no 1n which the permissible substltuents are Z as hereinbefore defined, or Y„ and Y, may

3 4 be linked together to form a substituted or unsubstltuted, carbocycllc or heterocycllc ring system selected from a monocycllc aromatic or nonaromatlc ring system, a blcycllc aromatic or nonaromatlc ring system, a polycycllc aromatic or nonaromatlc ring system, and a bridged ring system which may be saturated or unsaturated 1n which the permissible substltuents are Z as hereinbefore de¬ fined,and Y g and Y, are Independently oxygen or sulfur; wherein:

X 1s a covalent single bond or double bond, a substituted or unsubstltuted heteroatom or substi¬ tuted carbon atom, or a substituted or unsubstltuted, branched or straight chain containing two or more carbon atoms or heteroatoms 1n any combination 1n which the permissible substltuents are Z as herein¬ before defined.

R- 1s a substituted or unsubstl¬ tuted, carbocycllc or heterocycllc ring system se¬ lected from a monocycllc aromatic or nonaromatlc ring system, a blcycllc aromatic or nonaromatlc ring system, a polycycllc aromatic or nonaromatlc ring system, and a bridged ring system which may be saturated or unsaturated 1n which the permissible substltuents are Z as hereinbefore defined, or R_ 1s a substituted heteroatom or substituted carbon atom, or a substituted or unsubstltuted, branched or

- n -

straight chain containing two or more carbon atoms or heteroatoms 1n any combination 1n which the permissible substltuents are Z as hereinbefore defined,

Y 7 and Y n are Independently oxygen or sulfur;

Y„ and Y are Independently oxygen, sulfur, amino or a covalent single bond; and

R. and R ς are Independently hydrogen or substituted or unsubstltuted alkyl, alkenyl, alkynyl, polyhaloalkyl, phenyl or benzyl 1n which the permissible substltuents are Z as hereinbefore defined, 1n which the amount of compound (11) used with agent (1) results 1n a mixture having a greater plant growth regulating effect than the sum total plant growth regulating effect of agent (1) and compound (11) used alone.

The alkyl-conta1n1ng moieties 1n formula 1 may contain from about 1 to about 100 carbon atoms or greater, preferably from about 1 to about 30 carbon atoms, and more preferably from about 1 to about 20 carbon atoms. The polysaccharlde dety may contain up to about 50 carbon atoms. It 1s appreciated that all compounds encompassed within formula 1 are compounds having no unfilled bonding positions. In regard to the malonlc add derivative compounds used 1n the synergistic plant growth regulator compositions of this Invention, 1t 1s preferred that R η and R 2 are Independently other than hydrogen, alkyl or aryl when both Y, and Y» are -NH-.

As used herein, hydrogen or derivative salts refer to hydrogen or any appropriate derivative salt substltuents which may be substituted therefor. Illustrative derivative salt substltuents Include, for example, ammonium,

-

alkylammonium, polyalkyla mon um, hydroxyalkyl- ammonlum, poly(hydroxyalkyl)ammon1um, alkali metals, alkaline earth metals and the like Including mixtures thereof.

Monocycllc ring systems encompassed by R-, , R 2 and R„ 1n formula 1 may be represented by generalized formula 2. as follows:

wherein B. represents a saturated or unsaturated carbon atom and A. represents a ring-forming chain of atoms which together with B. forms a cyclic system containing from 0 to 3 double bonds or from 0 to 2 triple bonds. A. may contain entirely from 2 to 12 carbon atoms, may contain a combination of from 1 to 11 carbon atoms and from 1 to 4 heteroatoms which may be selected Independently from N, 0, S, P or other heteroatoms, or may contain 4 r1ng-form1ng heteroatoms alone.

Monocycllc ring systems encompassed by Y_ and Y. linked together 1n formula 1 may Include any monocycllc ring system of R.. , R 2 and R„ appropriately positioned 1n formula 1.

R1ng-form1ng heteroatoms may 1n some cases bear oxygen atoms as 1n aromatic N-ox1des and ring systems containing the sulflnyl, sulfonyl, selenoxlde and phosphine oxide moieties.

Selected carbon atoms contained 1n cycles formed by B, and A, containing at least 3 ring-form ng atoms may bear carbonyl, thlocarbonyl, substituted or unsubstltuted 1m1no groups or substituted or unsubstltuted methylldene groups.

- -

The group designated as Z represents one or more substltuents selected Independently from among the group of substltuents defined for Z herein.

Blcycllc ring systems encompassed by R. , R 2 and R. 1n formula 1 may be represented by generalized formulae 3. and i as follows:

wherein B ? and B» may be Independently a saturated or unsaturated carbon atom or a saturated nitrogen atom, A ? and A_ Independently represent the r1ng-form1ng chains of atoms described below and Z represents one or more substltuents selected Independently from among the group of substltuents defined for Z herein. Combinations of A„ and A_ may contain 1n combination with B 2 or B-, from 0 to 5 double bonds. A_ and A , Independent of B 2 and B 3 , may contain entirely from 1 to 11 carbon atoms, may contain a combination of 1 to 3 heteroatoms which may be selected Independently from among N, 0, S, P or other heteroatoms together with from 1 to 10 carbon atoms or may contain from 1-3 r1ng-form1ng heteroatoms alone.

R1ng-form1ng heteroatoms may 1n some cases bear oxygen atoms, as 1n aromatic N-ox1des and ring systems containing the sulflnyl, sulfonyl, selenoxlde and phosphine oxide groups. Selected carbon atoms contained 1n A ? and A. may bear carbonyl, thlocarbonyl, substituted or unsubstltuted 1m1no groups or substituted or unsubstltuted methylldene groups.

Blcycllc ring systems encompassed by Y 3 and Y. linked together 1n formula 1 may Include any blcycllc ring system of R.. , R_ and R„ appropriately positioned 1n formula 1-

In regard to structures encompassed within formulae 3 and 4, 1t 1s noted as follows:

(a) When B 2 and B 3 are both nitrogen, the groups A_ and A- should each contain no fewer than three ring atoms;

(b) When B 2 but not B 3 1s nitrogen, either of A ? or A^ should contain at least three ring atoms and the other at least two ring atoms;

(c) When either of groups A or A_ contains fewer than three ring atoms, the other should contain at least three ring atoms and the bridgehead atoms should be saturated;

(d) When the group A- or A 3 contains a carbon atom bearing a carbonyl, thlocarbonyl, 1m1no or methylldene group, 1t should together with B ? and B 3 form a cycle having at least four members;

(e) When a annular double bond 1s exocycllc to either of the two rings represented 1n structures 3. and i, 1t should be contained 1n a ring containing at least five members and be exocycllc to a ring containing at least five members; and

(f) When a group A 2 or A 3 1s joined to the bridgehead atoms B ? and B 3 by 2 double bonds, the group A. or A 3 1s understood to

1 5 -

contain one double bond and the bridgehead atoms are considered to be unsaturated.

It 1s recognized that blcycllc ring systems defined for R. , R., R_ and Y_ and Y. 1 2 3 3 4 linked together may be sp1rocycl1c ring systems and are not limited to the fused blcycllc structures of formulae 2 and 4. Sp1rocycl1c ring sy.stems may be saturated or unsaturated carbocycllc or heterocycllc and may bB Independently substituted by one or more substltuents Z as defined herein ' .

Polycycllc ring systems, I.e., greater than 2 rings, encompassed by R, , R 2 and 3 1n formula 1 may be represented by generalized formulae £, 6., 1 and £ as follows:

wherein B., B_, B, and B_. may be 4 b b / ndependently a saturated or unsaturated carbon atom or a saturated nitrogen atom, and A., A c , A,

4 3 0 and A., Independently represent ring forming chains of atoms which may contain together with one or the other (but not both) of their two associated bridgehead atoms, from 0-2 double bonds. The groups

Z represent one or more substltuents selected

Independently from among the group of substltuents defined for Z herein.

The r1ng-form1ng elements of A., A g ,

A, and A-, Independent of B., B 5 , B 6 and

B 7 may contain from 1-11 carbon atoms, may contain a combination of from 1-10 carbon atoms and from 1-3 heteroatoms which may be selected Independently from among H, 0, S, P or other heteroatoms, or may contain from 1-3 heteroatoms alone. R1ng-form1ng heteroatoms may 1n some cases bear oxygen atoms as

1n aromatic N-ox1des and ring systems containing the sulflnyl, sulfonyl, selenoxlde and phosphine oxide groups. The group A, may at times be defined as a o bond. Selected carbon atoms contained 1n A., A ζ , A, and A_ may bear one or more carbonyl, thlocarbonyl or substituted or unsubstltuted 1m1no groups.

On structure 8 the groups B g , B g and B, Q represent Independently a saturated or unsaturated carbon atom or a saturated nitrogen atom. The group B 11 may represent a saturated or unsaturated carbon atom or a nitrogen or phosphorous atom. The groups A_, A g and A 1Q represent r1ng-form1ng chains of atoms which may contain together with 1 of the groups B„, B g , B, Q and B,, from 0-2 double bonds.

The r1ng-form1ng elements of groups A_, A- and A 1Q Independent of groups B_, B g ,

- 17

B, Q and B,, may contain from 2-10 carbon atoms, may contain from 1-10 carbon atoms 1n combination with 1-3 heteroatoms which may be selected Independently from among N, Q, S, P or other heteroatoms, or may contain from 2-3 heteroatoms alone. Ring-form ng heteroatoms may 1n some cases bear oxygen atoms as 1n aromatic N-ox1des and 1n ring systems containing the sulflnyl, sulfonyl, selenoxlde and phosphine oxide groups. Selected carbon atoms contained 1n groups A», A g and A- 0 may bear one or more carbonyl, thlocarbonyl or substituted or unsubstltuted 1m1no groups.

It 1s recognized that polycycllc ring systems defined for R. , R 2 , R 3 and Y-. and Y, linked together may be splrocycllc ring systems and are not limited to the fused polycycllc structures of formulae ϋ, 6., 1 and 8. Splrocycllc ring systems may be saturated or unsaturated, carbocycllc or heterocycllc and may be Independently substituted by one or more substltuents Z as defined herein.

Polycycllc ring systems encompassed by Y 3 and Y. linked together 1n formula 1 may Include any polycycllc ring system of R, , R 2 and 3 appropriately positioned 1n formula 1.

Bridged blcycllc structures encompassed by R 1 , R 2 and R 3 1n formula 1 may be represented by generalized formulae 9, 1_0, and H as follows:

- -

wherein B- 2 and B- 3 may be Independently a saturated carbon atom optionally substituted by Z or a nitrogen atom, and the groups A...., A. ? and A- 3 Independently represent r1ng-form1ng chains of atoms which may contain, Independently of B... and B, 3 , from 0-2 double bonds. The groups Z represent one or more substltuents selected Independently from among the groups of substltuents defined for Z herein.

The r1ng-form1ng elements of A,,, A- 2 and A.., Independent of B, 2 and B- 3 , may contain entirely from 1-11 carbon atoms, may contain a combination of from 1-10 carbon atoms and from 1-3 heteroatoms which may be selected Independently from among N, 0, S, P or other heteroatoms, or may contain from 1-3 heteroatoms alone with the proviso that when one of the groups A...., A- 2 and A 13 1s a single heteroatom, the other two groups should contain two or more ring-forming atoms. A second proviso 1s that when one or both of the groups B._ and B 13 1s nitrogen, the groups A.., A- 2 and A- 3 should contain at least two saturated r1ng-form1ng atoms.

R1ng-form1ng heteroatoms may 1n some cases bear oxygen atoms as 1n the sulflnyl, sulfonyl, selenoxlde and phosphine oxide moieties. Selected carbon atoms contained 1n A..., A 12 and A- 3 may bear one or more carbonyl, thlocarbonyl or substituted or unsubstltuted 1m1no groups.

Bridged blcycllc structures encompassed by Y 3 and Y. linked together 1n formula 1 may Include any blcycllc bridged system of R- , R 2 and R 3 appropriately positioned 1n formula 1.

It 1s readily apparent that formula 1 encompasses a wide variety of malonlc add derivative compounds. Illustrative malonlc add

- 19 -

derivative compounds within the scope of formula 1 which may be used 1n the synergistic plant growth regulator compositions of this Invention are Included 1n Tables 1 through 11 below.

- 20 -

TABU . Heprt. . n Uvt r lonk Ad Dtrlvt . Compounds

l' m " 7 -F-5-C1 0C Z H S -F-S-Cl 0CH 3 -F-S-Cl °"

3-F-4-8. OH 3-F-4-B. OCH,

3-F-4-B. °-"- C 3 H ϊ

2-F-4-C1-S-βr OCH.

21 -

1A81E 1 (Cont.) R.or...ntitlv. r loπlC Acid D«r1v_tlv. Cowpoundt

o o . . ^ zτ.,

R r C-CH r C-NH-

\_=/

8 7

2-F-4-8.-5-C1 OH

- 22 -

1A8U 1 (Cont.l Repre.tπt-tlve Kilonlc Add 0«rlv«tlv« Com p ounds

R Γ C-CH 2 -C-NH-^_^>

} _!

2-C1-4-CF-0 OCH j

2-CF 3 0-4-Br M^

2-CH 3 -4-C 3 C 2 0- 0-π-C j H.

2-CH 3 -4-l °CH 3

2-F-4-1 OC 2 H 5

23 -

TABU 2 R-pr.sentitlvt H<Ionic Acid 0»r1v«tlv« Compounds

25 -

1ABU 2 (Cont.l Repre.en tlve . lonlc Acid Per Ivatlve Compounds

.oc Λ

SCH CH 9T- 3-Br-5-Cl

\ C 2 H s 0

0CH ? CH 2 SCH 2 H 2 0H 3-βr- S-C ,

OCHjCH SO.CHjCHjOH 3-F-4 •8r

0CH 2 C.« 4-1

OCH CH iH 2.4-C '.

0-C(CH 3 . 2 C.* 4-C1

OCH CH OCH 3-F-5 Cl

0CH 2 C0 2 C 2 Hj 3-F-4 Cl

OCHjCH j rt i 2-F-4 .S-Cl,

0CH(CH CH SC H 2-F-4-C1-5-B.

OCH COCH 2-F-4-Br-ϊ-Cl

OCH C.JI 2-F-4.S-8.

0-H. (CH 3 )-CO 2 C 2 H. 2.4-Cl 2 -5-F

0-CH ? S0 2 HH 2 2-CI-4-8.-5-F

0-CH SO MHCH 2.4-βr 2 -5-F

0-CH ? S0 2 «(C 2 H.) 2 2-Br-4-Cl-5-F

S-CH 2 CH ? SCH 3 2-CH 3 -4-Cl-5-F

S-CH 2 0 2 C j H 7 2-CH 3 -4-Br---F

26

t-mr 2 (Cont._

Represent* tlve π«ιo

O 0

II II / — \/ τ *

"l r-c-cH 2 - -C-NHH (J

R ' 8. z '-

- 27 -

TABU 3 Representative K. Ionic Ac id Derivative Compounds

10

- 28 -

TABU 3 (Cont.t Representative H.lonlc Add Oerlv.tlve Compounds

Y, γ 's z' ιo

H-

H 4-C1 OC 2 H 5

>

CH 3 2-CF.-4-C1 OH >

H0- H0- 2-CH 3 -4-8r OC-H.

29 -

30

TABLE 3 (Cont.l Representative Halonlc Add Derivative Compounds

CH 3 C0NH- H 2-CH -4-8r SC.H.

HC0NH- H 2-F-4-8r SC - H .

HCTH-N- H 2-C 2 H--4-Cl 0CH 3

-0-CH 2 -0- 2-CH 3 -4-Br SCHj HjOCH j

-S- Hji CHjS- 2-CH_-4-8r OC.H.

CH 3 0 H 3,5-Cl 2 0C 2 H 5

CH 3 0 H 3.5-8r 2 OC.H.

CH 3 0 H 3-Br-5-Cl 0- n -C 3 H-

CH 3 0 H 3-8r-5-F 0-t-C.H. C-H.0C0 4-C1 0CH 3

CH 3

CH S 3.S-C1. OC 2 H 5

CH 3

CHjSO 2-F-4-βr 0-n-C.H.

CH 3

CH 3 S0 2 H 2-CH -4-Br OC.H.

CH 3 S0 2 3,5-Clj 0C 2 H 5

CH 3

CN- H 2-CH -4-Br OC.H-

CH 3 S H 2-CHj-4-8r 0 2 H 5

- 31

X X z z x z

Representative Halonlc Add Compounds

r

»'. 10 » * * to v n 1

33

α u i t

«J u u *■»

o u αx uα xα ou αz o ac o w o o o o

X <_> i-i

TAB . (Cont.l Representative Malonlc Ad. Derivative Compounds

C

Y*

»'ll T 12 »*.3 14 1'

M 16 «',, Z 'l2

1

H H H H H H ONa 2-CH 3 0-4.S-Cl 2

H H H H H H OH 2-CH.Q-3.S-CI.

- 35

X X <__» w

36 -

o i _.« u

lAβie i

Representative Halonlc Add Derivative Compounds

TABLE I (Cont.l Representative Halonlc Add Derivative Compounds

oo

-CH ? CH 2 CH 2 CH 2 - s oc Λ 2.4 Cl 2 -CH 2 CH 2 CH 2 CH 2 - 0 NH 2-βr-4-CN

-CH CH CH CH - 0 OC 2 H- 4-C.H s 0

- H 2 CH 2 CH 2 CH 2 - S OH 3.5-Cl 2

-CH 2 CH 2 CH 2 CH 2 - 0 NHCH CH OCH 4-Cl 2 2 3

-CH 2 CH 2 - 0 3.4-Br 2

SC . H 5

-CH 2 CH 2 CH ? - 0 SCH CH OH 3-βr-5-CI

-CH CH CH - 0 SCH 2-Cf -4-βr

2 2 2 -CH 2 H 2 - s OCH, .5-(C 3 ) 2

TABLE 1 Representative Halonlc Add Derivative Compounds (Cont.l

- 40 -

TABLE 10 (Cont.l Representative Halonlc Add Derivative Compounds

____. 34 32 16 17

- 42

- 43 -

TABLE II (Cont.l

Representative Halonlc Add Derivative Compounds

i- 31 35 18 II

NH OCH.

N-N

Cl

NH OC.H.

Cl CN

CH H NH 0-n-C 3 H_

Cl

44 a-

- 45 -

It 1s appreciated that the particular compounds listed 1n Tables 1 through 10 herelnabove are Illustrative of malonlc add derivative compounds which can be used 1n the synergistic plant growth regulator compositions of this Invention. The synergistic plant growth regulator compositions of this Invention are not to be construed as being limited only to these particular compounds; but rather, the compositions of this Invention nclude those malonlc add derivative compounds encompassed within formula 1 herelnabove.

The malonlc add derivative compounds encompassed within formula 1 and ntermediate compounds used 1n the preparation thereof can be prepared by reacting appropriate starting Ingredients 1n accordance with conventional methods known 1n the art, and many may be available from various suppliers. Novel malonlc add derivative compounds encompassed within formula 1 which can be used 1n the synergistic plant growth regulator compositions of this Invention are described 1n copend ng U.S. Patent Application Serial No. (D-15299), filed on an even date herewith, and also U.S. Patent Application Serial No. (D-15328), filed on an even date herewith, both of which are Incorporated herein by reference. These novel malonlc add derivative compounds can be prepared by reacting appropriate starting Ingredients 1n accordance with conventional methods known 1n the art.

Illustrative procedures which can be. employed 1n preparing malonlc add derivative '

- 46 -

compounds encompassed within formula 1 and Intermediate compounds used 1n the preparation thereof are described, for example, 1n the following: Rlchter, G.H., Textbook of Organic Chemistry, Third Edition, John Wiley and Sons, New York, p. 486; Breslow, D.S. et al., Jour. Amer. Chem. Soc. 66, 1286-1288 (1944); Svendsen, A. and Boll, P.M., Jour. Org. Chem. 40, 1927-1932 (1975); Sen, A.K. and Sengupta, P., J. Ind. Chem. Soc. 46, (9), 857-859 (1969); Thlers, R. and Van Dormael, A., Bull. Soc. Ch1m. Belg. 6J_, 245-252 (1952); Brown, R.F.C., Austral. Jour, of Chem. 8, 121-124 (1955); U.S. Patent 3,951,996; United Kingdom Patent 1,374,900; Ch1r1ac, C.I., Revue Romalne de Chlm e 21, (3), 403-405 (1980); Welner, N., Org. Syn. Coll., Vol. II, 279-282 (1950), Sixth Printing, John WHey & Sons, New York; Block, Jr., Paul, Org. Syn. Coll. Vol. V, 381-383 (1973), John Wiley and Sons, New York; Rellquet, F. et al., Phos. and Sulfur 24, 279-289 (1985); Palmer, C.S. and McWherter, P.W., Org. Syn. Coll. Vol. I, 245-246 (1951), Second Edition, John Wiley and Sons, New York; Staudlnger, H. and Becker, H., Ber chte 50, 1016-1024 (1917); Purrlngton, S.T. and Jones, W.A., J. Org. Chem. 4_8, 761-762 (1983); K tazume, T. et al., Chem. Letters (1984) 1811-1814; Wolff, I.A. et al., Synthesis (1984), 732-734; Zamblto, A.J. and Howe, E.E.., Org. Syn. Coll. Vol. V, 373-375 (1973), John Wiley and Sons, New York; and Hartung, W.H. et al., Org. Syn. Coll. Vol. V, 376-378, John WHey and Sons, New York.

- 47

Still other Illustrative procedures which can be employed 1n preparing malonlc add derivative compounds encompassed within formula 1 and Intermediate compounds used 1n the preparation thereof are described, for example, 1n the following: Rathke, M.W. and Cowan, P.J., J. Org. Chem. 5J3, 2622-2624 (1985); Fones, W.S., Org. Syn. Coll. Vol. IV, 293 (1963), John Wiley and Sons, New York; Gompper, R. and Topfl, W., Chem. Ber. £5, 2861-2870 (1962); Gompper, R. and Kunz, R., Chem. Ber. 99., 2900-2904 (1966); Ono, N. et al., J. Org. Chem. 50, 2807-2809 (1985); U.S. Patent 4,154,952; Blankenshlp, C. and Paquette, 1.A., Synth. Comm. 14. (11), 983-987 (1984); Baldwin, J.E. et al., Tet. Lett. 2ji, (4), 481-484 (1985); Kawabata, N. et al., Bull. Chem. Soc. Jpn. .55, (8). 2687-2688 (1982); Bodanszky, M. and du V gnaud, V., J. Am. Chem. Soc. 81, 5688-5691 (1959); Neelakantan, S. et al., Tetrahedron 21, 3531-3536 (1965); U.S. Patent 4,020,099; Japan Patent Application 148,726 (1979); Fuson, R.C., Advanced Organic Chemistry, p. 202 (1950), John Wiley and Sons, New York; Duty, R.C., Anal. Chem. 49., (6). 743-746 (1977); Korner, G. f Contradl, Attl acad. L1nce1 22, I, 823-836 (CA. 8, 73 (1914)); Sch1melpfen1g, C.W., J. Chem. Soc. Perk. Trans. I, 1977 (10), 1129-1131; K1m, Y.S. et al., Taehan Hwahak Hoechl 1_8, (4), 278-288 (1974); German Patent 2,449,285; U.S. Patent 3,962,336; and U.S. Patent 3,992,189.

A variety of ethylene response or ethylene-type response Inducing agents can be used 1n the synergistic plant growth regulator

-de ¬

compositions of this Invention. Illustrative of an ethylene response or ethylene-type response Inducing agent 1s a compound having the formula:

R 18 " p " R 19

12 0 R 20 wherein:

R 1 1s haloethyl; and

R. Q and R_ Q are selected from:

1. A chlorine atom and a hydroxy group; 2. The group -0 2 ι an d the group

-Q-CH-R... where each R 21 1s one member of the group of unsubstltuted aryl, substituted aryl and a heterocycllc group;

3. The group -OR-, and tne 9 r0U P -Q-CH-R... where each R 21 1s a different member of the group of hydrogen, unsubstltuted alkyl, substituted alkyl, unsubstltuted cycloalkyl, substituted cycloalkyl, unsubstltuted aryl, substituted aryl, a heterocycllc group, alkene and alkyne, provided that when one R„. 1s selected from unsubstltuted alkyl, substituted alkyl, alkene and alkyne, the other R 2 - 1s selected from unsubstltuted aryl, substituted aryl and a heterocycllc group;

4. Together R.. g and 2Q represent the group

( 2 and R ? „ are each connected to the phosphorous atom by a separate single bond) where one of R and R 1s -0- and the other 1s selected from the group of -0-;

-0CH ; -CO-O- and CONH; and R_24, represents a cyclic group selected from benzene, substituted benzene, a heterocycllc ring and a substituted heterocycllc ring;

5. One of R-- and R 2Q 1s -0R 25 and the other 1s

0

II

- 0 - P - R 18

I

0R 25

wherein each R ?l .1s the same or different and 1s selected from hydrogen, unsubstltuted alkyl, substituted alkyl, unsubstltuted aryl, substituted aryl and a heterocycllc group, and wherein R. β 1s as defined hereinbefore; 1n which the permissible substltuents are as defined for Z herelnabove.

U.S. Patents 3,879,188, 4,240,819, 4,352,869, 4,374,661 and 4,401,454 describe the phosphonlc add derivative compounds of formula ]_2 and the plant growth regulating properties thereof. These patents are Incorporated herein by reference.

- 50 -

With reference to formula 1_2 compounds utilized 1n the synergistic plant growth regulator compositions of this Invention, preferred groups for substltuent R_ Q are haloethyl, for example,

Io

2-chloroethyl, 2-bromoethyl and 2-1odoethyl. Preferred half-esters of the phosphonlc add moiety Include the 2-chloroethyl mono-ester and the o-hydroxyphenyl mono-ester. Preferred dlesters nclude the dlphenyl and the b1s(2-oxo-l-pyrro!1d1nyl-methyl) esters and as mixed esters, the 2-hydroxyphenyl ester with an alkyl or alkenyl or aryl radical, for example, ethyl, Isopropyl, propynyl, butyl, octyl, hexadecyl or phenyl radicals. Aryl groups are preferably monocycllc, and b1- or polycycllc aryl groups may be used provided a group to render them soluble (e.g., a sulphonate group), 1s present thereon.

Preferred cyclic esters Include those formed with pyrocatechol or mono- or polyhalopyrocatechol derivatives, for example, 4-chloropyrocatechol or tetrachloropyrocatechol; with saHcycllc add, with sallgen; and with 2,3-pyr1d1ned1ol. Another preferred derivative 1s the add chloride.

The preferred phosphonlc add derivative to be used 1n the synergistic plant growth regulator compositions of this invention 1s 2-chloroethyl- phosphonlc acid (ethephon) or Its immediate derivatives.

As previously stated, the phosphonlc acid compounds of formula 1_2 usable in the synergistic

- 51 -

plant growth regulator compositions of this Invention fall within the general formula:

wherein R , R and R. Q are as defined herelnabove.

Specific phosphonlc add derivative compounds usable 1n the synergistic compositions for regulating plant growth include:

1. The b1s(acid chloride) of 2-chloroethylphosphon1c acid.

2. The pyrocatechol cyclic ester of 2-chloroethylphosphonic add.

3. The 4-chloropyrocatechol cyclic ester of 2-chloroethylphosphon1c add.

4. The mixed ethyl and 2-hydroxyphenyl dlester of 2-chloroethyl¬ phosphonic acid.

5. The mixed butyl and 2-hydroxyphenyl dlester of 2-chloroethyl¬ phosphonic acid.

6. The mixed propynyl and 2-hydroxyphenyl dlester of 2-chloroethyl¬ phosphonic acid.

7. The 2-chloroethyl monoester of 2-chloroethylphosphon1c acid.

8. 2-bromoethylphosphon1c add.

9. The b1s(phenyl)ester of 2-chloroethylphosphonic acid.

- 52 -

10. The tetrachloropyrocatechol cyclic ester of 2-chloroethylphosphonic acid.

11. 2-1odoethylphosphon1c acid.

12. The sallgen cyclic ester of 2-chloroethylphosphonic acid.

13. SaHcyclic add cyclic ester of 2-chloroethylphosphonic acid.

14. The ethyl monoester of 2-bromo- ethylphosphonic add.

15. The butyl monoester of 2-1odo- ethylphosphonic acid.

16. The 3-hydroxyphenyl monoester of 2-chloroethylphosphonic add (which exists in polymeric form).

17. The b1s(2-oxo-pyrrol1dinylmethyl) ester of 2-chloroethylphosphonic acid.

18. The o-hydroxyphenyl monoester of 2-chloroethylphosphonic acid.

19. The mixed isopropyl and 2-hydroxyphenyl dlester of 2-chloroethylphosphonic add.

20. 2-fluoroethylphosphonic add. * 21. The mixed octyl and

2-hydroxyphenyl dlester of 2-chloroethylphosphonic acid.

22. The mixed hexadecyl and 2-hydroxyphenyl dlester of 2-chloroethylphosphonic add.

23. The mixed tridecyl and 2-hydroxyphenyl dlester of 2-chloroethylphosphonic add.

53

24. The anhydride of 2-chloroethylphosphonic add.

25. 2-chloroethylphosphonic acid.

26. The mixed butyl and 2-hydroxyphenyl dlester of 2-chloroethylphosphonic add.

27. The 2-bromoethyl monoester of 2-bromoethylphosphonic add.

Other useful phosphonlc add derivative compounds within formula 1_2 are sallcyclic acid cyclic ester of phosphonamldic add, the mixed phenyl and 2-hydroxyphenyl dlester of 2-chloroethylphosphonic acid, 2-chloroethyld1chlorophosph1ne, the bis (pentachlorophenyl) ester of 2-chloroethylphosphonic acid; 2-chloropropylphosphonlc acid, 2-phenylthioethylphosphonic add, the 2,3-pyr1d1nedio cyclic ester of 2-chloroethylphosphonic add,

2-chloroethylth1ophosphon1c acid, (2-bromo, 2-fluoro and 2-1odo) and 2-chloroethyl-2,3-dibromo- 4-hydroxy-2-butenyl ester polymer. Salts of the phosphonlc derivatives of this Invention may be used. Examples of such salts include the sodium, aluminum, zinc, potassium and lithium salts.

Other illustrative ethylene response or ethylene-type response Inducing agents which can be used in the synergistic plant growth regulator compositions of this Invention Include, for example, the following: certain 2-haloethanesulph1nic acid compounds described in U.S. Patent 3,885,951 and French Patent 2,128,660; certain beta-chloro- and

0

- -

beta-bromoethanesulflnic adds and esters as described in U.S. Patents 3,927,062 and 3,876,678; mixtures of a N-heterocyclic amide and a haloalkyl sllane as described in U.S. Patent 4,332,612; mixtures of a N-heterocycl1c amide and a 2-haloethylsulf1nate as described in U.S. Patent 4,359,334. These agents can be prepared by conventional methods known 1n the art and many may be available from various suppliers.

Still other illustrative ethylene response or ethylene-type response Inducing agents include gaseous ethylene and 1-amino-l-cyclopropane- carboxylic acid (ACC) which is capable of breaking down into ethylene in plant tissue.

The synergistic plant growth regulator compositions of this invention can display a wide variety of plant growth regulating properties or ethylene responses or ethylene-type responses, depending upon the concentration used, the formulation employed and the type of plant species treated. While the compositions may be regarded as achieving an ethylene response or an ethylene-type response, the present Invention 1s not necessarily limited thereto since it 1s recognized that certain growth regulating responses achieved through the practice of the present Invention may not be regarded as being technically traditional or known or to be discovered ethylene responses or even ethylene-type responses. Hence, it 1s preferred to regard the results achieved 1n the practice of the present invention as growth regulating responses.

- -

In view of the foregoing, it can be seen that the term "method for regulating plant growth" or the term "growth regulation process" or the use of the words "growth regulation" or "plant growth regulator" or other terms using the word "regulate" as used in the specification and in the claims mean a variety of plant responses which attempt to Improve some characteristic of the plant as distinguished from herblcidal action, the Intention of which 1s to destroy a plant. For this reason, the synergistic plant growth regulator compositions of this Invention are used 1n amounts which are non-phytotox1c with respect to the plant being treated.

Nevertheless, the synergistic plant growth regulator compositions of this invention can sometimes be used 1n a herbiddal context, for Instance, to stimulate the growth of dormant rhizomes 1n order to make such rhizomes more susceptible to a herbicide. However, even here the compositions are not themselves in any practical sense herbicides since they promote the growth of the unwanted plant or otherwise make it very susceptible to a true herbicide. Thus, the present invention can be carried out in conjunction with or 1n the presence of other compounds or mixtures which are herbicides.

By virtue of the practice of the present invention, a wide variety of plant growth responses, generally ethylene responses or ethylene-type responses can be achieved, Including the following: 1. Increasing yields;

- -

2. Auxin activity;

3. Inhibition of terminal growth, control of apical dominance, Increase 1n branching and Increase in tillering;

4. Changing biochemical compositions of plant;

5. Abscission of foliage, flowers and fruit or stimulation of separation of abscission zone;

6. Hastening ripening and color promotion 1n fruit and leaves;

7. Increasing flowering and fruiting and causing flower Induction;

8. Abortion or inhibition of flowering and seed development;

9. Prevention of lodging;

10. Stimulation of seed germination and breaking of dormancy;

11. Resistance to freeze injury;

12. Hormone or eplnasty effects;

13. Interactions with other growth regulators;

14. Interactions with herbicides; and

15. Disease resistance.

It 1s Intended that as used 1n the appended claims the term "method for regulating plant growth" or "method for Inducing an ethylene response" or "method of inducing an ethylene-type response" means the achievement of any of the aforementioned fifteen categories of response as well as any other modification of plant, seed, fruit, vegetable (whether the fruit or vegetable 1s unharvested or

have been harvested) so long as the net result is to increase growth or benefit any property of the plant, seed, fruit or vegetable as distinguished from herbicidal action (unless the present invention is practiced 1n conjunction with or 1n the presence of a herbicide). The term "fruit" as used herein and 1n the appended claims 1s to be understood as meaning anything of economic value that 1s produced by the plant.

Certain preliminary details connected with the foregoing fifteen categories should make for a better appreciation of the Invention.

1. Increasing Yields:

The synergistic plant growth regulator compositions are capable of Increasing yields of many plants, including, but not limited to small grains, particularly oats (Avena sativa.. wheat (Trlticum aestivum) . and barley (Hordeum SPP.) : and of Increasing yields of other types of plants, such as beans and of cotton (Gossypium hlrsutum) ;

2. Auxin Activity:

When applied, for Instance, as a lanolin paste, to one side of a decapitated sunflower hypocotyl, the synergistic plant growth regulator compositions are capable of inducing bending of the hypocotyl away from the side of the application; they are also capable of inducing sprouting of underground rhizomes of monocotyledonous and dicotyledonous plants; of causing cell proliferation; and of inducing rooting, as illustrated by the production of large numbers of

- -

root primordia over the entire stem length of tomato plants (Lvcopersicon esculentum. after these have been sprayed with an aqueous solution thereof — this type of response makes 1t possible to root cuttings either when taken from treated plants or after treatment of their cut ends.

3. Inhibition of Terminal Growth, Control of Apical Dominance, Increase in Branching, and Increase 1n Tillering:

These types of plant growth response can be produced on a variety of plant species when they are treated with the synergistic plant growth regulator compositions including privet (Ligustrum ovaHfoHum) . blueberry (Vacdnum corvmbosum). azalea (Rhododendron obtusum). soybeans (Glvdne max.). snapbeans (Phaseolus vulgarisl. tomatoes (Lvcopersicon esculentum). alligator weed (Alternanthua phlloxeroides) and monoctyledons such as rice (Orvza satlva). johnsongrass (Sorghum halepense) and wild oats (Avena fatua) . This type of response can also be of value 1n the control of roadside grasses. It has been suggested that the removal of the lead bud (e.g., by pinching) should allow growth of axillary buds; but 1t is generally found that on removal of the lead bud, one of the axillary buds takes over the activity and dominance of the lead bud. The use of the synergistic plant growth regulator compositions, however, usually retards the activity of the lead bud for a while but then later restores the lead bud to normal growth, with production of normal flowers and normal fruit; and thus one avoids the permanent loss of buds

- 59 -

inevitably associated with pinching. However, some plant species may respond differently when treated with the synergistic plant growth regulator compositions for control of apical dominance — growth Inhibition may extend to Include not only the lead bud but also lateral buds along the stem. Examples of such plants are tobacco (Nicotlana tabacum) and chrysanthemum (Chrysanthemum sp.) -- this type of response 1s useful for preventing sucker growth from lateral buds on tobacco.

4. Changing Biochemical Composition of Plant:

The synergistic plant growth regulator compositions are capable of measurably increasing the leaf area relative to the stem area in many plants, and the Increased ratio of leaves to stem results in an Increase in total protein on a per plant basis, and modification of the protein, carbohydrate, fat, nicotine and sugar within the treated plant. The synergistic plant growth regulator compositions are also capable of Increasing latex flow in rubber trees to give a yield increase in dry rubber content.

5. Abscission of Foliage, Flowers and Fruit or Stimulation of Separation of Abscission Zone:

The synergistic plant growth regulator compositions may accelerate abscission of mature foliage on both perennial and annual plant species. They can be, for Instance, quite active as defoliants on cotton and inhibit regrowth, and

- 60 -

defoliation properties may also be observed in other plant species, such as roses, apples, dtrus, and nursery stock, once the leaves have attained a mature state. Abscission of flowers and/or fruit following application of the synergistic plant growth regulator compositions may be observed on a variety of plant species, including apples (Halus domestlca). pears (Pyrus communis). cherries (Prunus avjum). pecans (Carva 1llinoens1s). grapes (V1t1s ylnjfera). olives (Plea europaea) . coffee (Coffea arabica). and snapbeans (Phaseolus vulgaris) — these abscission responses can be used to regulate flower production and as an aid in harvesting fruit. Stimulation of separation of abscission zone may be observed, for example, 1n boll opening of cotton or in shuck split of nuts such as walnuts, pecans and the like.

6. Hastening Ripening and Color Promotion in Fruit and Leaves:

The synergistic plant growth regulator compositions are capable of hastening the ripening of fruit (picked or unpicked) from a number of plant species, such as apples (Halus domestlca) . pears (Pyrus communis). cherries (Prunus avium). tomatoes (Lvcopersicon esculentum). bananas and pineapples (Ananas comosus): and of removing the green color from harvestable leaves such as tobacco (Nicotlana tabacum) and regreened citrus such as oranges (Citrus sinensls) and lemons (Citrus limon).

61 -

7. Increasing Flowering and Fruiting and Causing Flower Induction:

Suitably applied, the syneristic plant growth regulator compositions are be capable of increasing flowering and fruiting and causing flower Induction in a number of economic crops, such as soybeans (Glvcine max.). snapbeans (Phaseolus vulgaris) . kidney beans (Phaseolus vulgaris). zinnias (Zinnia elegans) . pineapples and mangos.

8. Abortion or Inhibition of Flowering and Seed Development:

Suitably applied, the synergistic plant growth regulator compositions may Inhibit flowering and/or abort seed development, for example, in johnsongrass (Sorghum halepense).

9. Prevention of Lodging: Application of the synergistic plant growth regulator compositions may Induce rigor resulting in firmer and stronger plants capable of resisting natural tendencies towards lodging. This effect may be observed on a number of plant species, such as, for example, wheat (Trlticum aestlvum). barley (Hordeum vulgare). and pea (Pisum satlvum).

10. Stimulation of Seed Germination and Breaking of Dormancy:

The synergistic plant growth regulator compositions may stimulate the germination of, for instance, lettuce seed and to terminate the dormancy of tubers, such as seed potatoes.

- -

11. Resistance to Freeze Injury:

The synergistic plant growth regulator compositions may increase the hardiness of various plant species, such as, for example, lima beans (Phaseolus limensis) .

12. Hormone or Epinasty Effects:

The synergistic plant growth regulator compositions may produce hormone or epinasty effects upon various plants, Including, notably tomatoes (Lvcopersicon esculentum) .

13. Interactions with other Growth Regulators:

The synergistic plant growth regulator compositions may, of course, be used 1n conjunction with other plant growth regulators, such as malelc hydrazide, N-d1methylam1nosucc1namic add, gibberellic acid and naphthaleneacetlc add, and Interact therewith producing synergistic or antagonistic responses 1n various plants.

14. Interactions with Herbicides: While the synergistic plant growth regulator compositions have essentially no phytotoxic activity of their own, they may be used in their capacity as plant growth regulators 1n conjunction with herbicides, for instance, with aminotrlazole 1n the herbicidal control of Johnson grass (Sorghum halepense).

15. Disease Resistance:

Disease resistance makes tissue resistant to Invasion by plant pathogens by influencing the

- 63 -

enzyme and plant processes which regulate growth and natural disease immunity.

The proportional amount of the ethylene response or ethylene-type response inducing agent, I.e., agent (1), and the malonlc add derivative compound, i.e., compound (11), in the synergistic plant growth regulator compositions of this Invention 1s such that the amount of compound (11) used with agent (1) results in a mixture having a greater plant growth regulating effect than the sum total plant growth regulating effect of agent (1) and compound (11) used alone. The amount of agent (1) and compound (11) can vary over a wide range depending on the particular agent and compound employed, the particular crop to be treated, the particular plant growth regulating effect desired, environmental and climatic conditions, and the like. The weight proportion of agent (1) to compound (11) can be, for example, from about 0.1:1000 to about 1000:0.1 respectively. Preferably, the weight proportion of agent (1) to compound (11) can be from about 1:500 to about 500:1. The amount of synergistic plant growth regulator composition should preferably be non-phytotox1c with respect to the plant being treated.

The synergistic plant growth regulator compositions of this Invention can be prepared by conventional mixing methods and may be employed according to a variety of conventional methods known to those skilled 1n the art. Either combination (mix) or sequential application methods can be used

- -

according to this invention. However, in sequential application methods, compound (11) 1s generally appled prior to agent (1) to achieve a synergistic plant growth regulating response. Compositions containing agent (1) and compound (11) as the active Ingredient will usually comprise a carrier and/or diluent, either liquid or solid. As used herein, the active Ingredient refers to the combination of agent (1) and compound (11).

Suitable liquid diluents or carriers include water, petroleum distillates, or other liquid carriers with o: * without surface active agents. Liquid concentrates can be prepared by dissolving one of these compounds with a nonphytotoxlc solvent such as acetone, xylene, nitrobenzene, cyclohexanone or dimethyl formamide and dispersing the active Ingredients in water with the aid of suitable surface active emulsifying and dispersing agents.

The choice of dispersing and emulsifying agents and the amount employed are dictated by the nature of the composition and the ability of the agent to facilitate the dispersion of the active Ingredient. Generally, it 1s desirable to use as little of the agent as is possible, consistent with the desired dispersion of the active Ingredient in the spray so that rain does not re-emulsify the active Ingredient after 1t 1s applied to the plant and wash it off the plant. Nonlonic, anlonic, or catlonic dispersing and emulsifying agents may be employed, for example, the condensation products of alkylene oxides with phenol and organic acids, alkyl

-

aryl sulfonates, complex ether alcohols, quaternary ammonium compounds, and the like.

In the preparation of wettable powder or dust compositions, the active Ingredient 1s dispersed 1n and on an appropriately divided solid carrier such as clay, talc, bentonlte, diato aceous earth, fuller's earth, and the like. In the formulation of the wettable powders, the aforementioned dispersing agents as well as Hgnosulfonates can be included.

The required amount of the active Ingredient contemplated herein can be applied per acre treated 1n from 1 to 200 gallons or more of liquid carrier and/or diluent or in from about 5 to 500 pounds of Inert solid carrier and/or diluent. The concentration 1n the liquid concentrate will usually vary from about 5 to 95 percent by weight and in the solid formulations from about 0.5 to about 90 percent by weight. Satisfactory sprays or dusts for general use contain from about 0.001 to about 100 pounds of active Ingredient per acre, preferably from about 0.01 to about 15 pounds of active ingredient per acre, and more preferably from about 0.1 to about 5 pounds of active Ingredient per acre.

Formulations useful 1n the conduct of this Invention can also contain other optional ingredients such as stabilizers or other biologically active compounds, Insofar as they do not impair or reduce the activity of the active Ingredient and do not harm the plant being treated. Other biologically active compounds Include, for

example, one or more insectlcidal , herbicidal, funglcidal, nematlcidal, mlticidal, plant growth regulators or other known compounds. Such combinations may be used for the known or other purpose of each Ingredient and may provide a synergistic effect.

Although the preferred method of application of the synergistic plant growth regulator compositions is directed to the foliage and stems of plants, such compositions may be applied to the soil 1n which the plants are growing, and that such compositions may be root-absorbed to ? sufficient extent so as to result 1n plant growth regulator responses in accordance with the teachings of this Invention.

The synergistic plant growth regulator compositions of this Invention are preferably applied to growing plants as set forth in many of the examples 1n this specification. However, under certain circumstances, the compositions used may be active in seed treatment, for Instance, lettuce seeds and oat seeds, or root dipping.

The synergistic plant growth regulator compositions are preferably applied to plants and crops under average or normal growing conditions. The synergistic plant growth regulator compositions of this invention can be applied during the plant vegetation growth phase or the plant reproductive growth phase to obtain the desired plant growth regulating effects.

As used herein, plants refer in general to any agronomic or horticultural crops, ornamentals

and turfgrasses. Illustrative of plants which can be treated by the synergistic plant growth regulator compositions of this Invention Include, for example, corn, cotton, sweet potatoes, white potatoes, alfalfa, wheat, rye, rice, barley, oats, sorghum, dry beans, soybeans, sugar beets, sunflowers, tobacco, tomatoes, canola, deciduous fruit, citrus fruit, tea, coffee, olives, pineapple, cocoa, banana, sugar cane, oil palm, herbaceous bedding plants, woody shrubs, turfgrasses, ornamental plants, evergreens, trees, flowers, and the like. As used herein, crops refer 1n reneral to any of the Illustrative agronomic or horticultural crops above.

The synergistic plant growth regulator compositions contemplated herein are effective for inducing a variety of plant growth regulating responses. Such compositions have a high margin of safety 1n that when used in sufficient amount to provide a plant growth regulating effect, they do not burn or injure the plant, and they resist weathering which includes wash-off caused by rain, decomposition by ultraviolet light, oxidation, or hydrolysis 1n the presence of moisture or, at least, such decomposition, oxidation, and hydrolysis as would materially decrease the desirable plant growth regulating characteristic of the active ingredient or impart undesirable characteristics, for Instance, phytotoxidty, to the active ingredients. Mixtures of the active composition can be employed 1f desired as well as combinations of the active composition with other biologically active compounds or ingredients as indicated above.

- -

The following examples are Illustrative of the present invention.

Example I Preparation of ethyl 3-C(4-fluorophenvDaminol- 3-oxopropa " noate Into a nitrogen-purged, air-stirred reaction flask was charged 4.44 grams (0.04 mole) of 4-fluoroan1l1ne, 4.05 grams (0.04 mole) of trlethylamine and 200 milllllters of tetrahydrofuran solvent. A 6.02 gram (0.04 mole) portion of ethyl malonyl chloride was then added rapidly by a dropping funnel to the mixture with good stirring at room temperature followed by a few milllllters of tetrahydrofuran as a rinse. The temperature of the stirred mixture rose to 42°C and a white precipitate of trlethylamine hydrochlorlde separated therefrom. The mixture was then stirred at ambient temperature for about 2 hours and the trlethylamine hydro- chloride filtered off, washed with solvent and dried to give 5.2 grams (0.04 mole). The filtrate was freed of solvent on a rotary evaporator and the resulting purple solid dissolved in methylene chloride, which solution was washed 1n succession with 2N HC1 (3 x 75 mmiHters), and water (2 x 75 milllllters), and then dried over magnesium sulfate and solvent vacuum stripped to give a crude solid product. RecrystalHzatlon from ethyl acetate- cyclohexane followed by flash column chromatography gave 3.47 grams (0.015 mole) of ethyl 3-[(4-fluoro- phenyl)am1no]-3-oxopropanoate having a melting point of 68°C-71°C.

- -

Example II In a manner similar to that employed 1n Example I, other compounds were prepared. The structures and analytical data for Compounds 2 through 76 are set forth 1n Table A below.

- 0-

lAβLE A (Cont.l Representative Halonlc A id Derivative Compounds -

Substltuents Elemental Analysis HeIting

Compound *'l *'l Calculated " found Point

Ho. c

1) «-CH 3 NH NMR (COCI ): J' 1.11-1.39 (1.3.H), 2.33 (s. 3H). 80-63

C 2 H 5 3.45 (S.2H). 4.01-4.42 (q.2H). 6.99-1.5? ( ,4H). β.9-9.3 (br S. H) ppr».

Iβ 2,.-(CH 3 ) 2 NH HHR (C0C1 3 ):J- 1.15-1.41 (t.3H). 2.23 (s.-H), 9.-100

C 2 H 5

2.50 (1 ;.2H). 4.01- 4.50 (q.2H). 1.10 (S.3H).

It -Cl NH 46.54 3.58 4.52 46.68 3.11 4.41 58.5-61

20 HH 41.05 4.02 5.01 41.84 4.05 5.0? 72-75

21 NH 41.85 4.02 5.0? 41.98 3.99 4.93 66-68

22 NH 36.19 3.04 3.84 36.59 3.11 3.?1 95-97

23 -C1 NH 56.3) 5.52 5.48 56.16 5.12 5.26 96-98

24 I 3 HH 42.54 3.25 4.51 42.95 3.16 4.28 111 113

25 -Cl NH 56.31 5.52 5.48 56.00 5.6? 5.21 103 104

26 NH 41.85 4.02 5.01 41.91 4.05 4.79 Jβ 19

21 NH 56.89 5.91 5.53 56.15 5.90 5.48 73-/5

- 72 -

X

f π σ* ιrt iΛ β* rt -M --- » o M m .— o ^ «r < __s w_

2 © σ» w

X X X X

1A8LE A (Cont.l Representative Malonlc Add βerlvatlve Compounds

Substltuents EInnerital Analysis Melting

Compound *'l *'. »'l Calculated found Point

No. C H N C H N c

43 2-CH 3 0-4.5-Cl 2 HH 47.08 4.28 4.58 47.31 4.64 4.59 95-98 '

C 2 M 5

44 c Λ 2-CH 3 -3.4-Cl 2 NH -49.6) 4.52 4.83 49.86 4.62 4.69 90-93

45 c Λ 2-E-4-CI NH 50.88 4.2? 5.39 50.90 4.56 5.21 66-69

46 3-βr-5-CI NH 41.21 3.46 4.3? 41.26 3.67 4.14 78-80

C 2 H 5

4? 2-CH 3 -4-βr NH 51.23 5.53 4.2? 51.59 5.41 4.17 91-93

B C 4 H »

4β 2-C0 H-4-βr NH NHR (DHSO d fc ): J 1 .16 -1.43 (t. 3H), , 3.48 - 151-154

C 2 M 5

(s. 2H) . 4.06-4.1 (». 4H). 7.5-8.7 («. 3H) pom-

4 * 9

50

51

52

53

54

55

56

lA β LE A (Cont. l Representat ive Halonlc Add Derivative Compounds

Substltuents Elemental Analysis Netting

Compound *'l 7 " l Calculated found Point

No. I H N . H N c

5? 2-CH 3 0- 3.5-CI 2 NH 41 08 4.28 4.58 47 .10 4.22 4.61 90-92

C 2 H 5

51 2-CH 3 -4 -βr-5-Cl NH - 43 07 3.92 4.19 . 41 85 4.31 3.12 132-135 C 2 H 5

59 4-(4-ClC H 0) NH 61 Iβ 4.83 4.20 .61 2? 4.94 4.14 86-87 °2 H 5

60 C 2 H- 3- .23 3.29 Oil

61 NH 71 .3? 6.56 96 70.97 6.66 3. 72 98- 100

C 2 H 5 [OX] 3.

lA β LE A (Cont - 1 Representative Halonlc Acid Derivative Compounds

O O 7'

R,O-C-CH 2 -C-Y | -^ )

SMbttltM'fts Elemental Analysis Melting

Compound *'l Calculated found Point

No. C H N c H N •c

62 3-C H.0- NH 68.22 5.73 4.68 68.15 5.84 4.69 Oil

C 2 H 5

63 2.5-Cl 2 -3-C0 2 CH 3 NH 46.73 3.92 4.19 46.85 3.91 4.12 Oil

C 2 M 5

64 2.3 (CH-CHCH.CH) HH 70.02 5.88 5.44 70.30 6.00 5.51 78-80

C 2 H 5

65 H NH 63.76 6.32 6.76 63.44 6.54 7.03 Oil

C 2 H 5

66 3.4-Cl, NH 47.85 4.02 5.07 47.76 4.09 5.36 80-83

C 2 H 5

61 4-Cf NH 52.37 4.39 5.09 52.17 4.56 5.17 78-79.5

C 2 H 5

6β 4 NO NH 52.38 4.80 11.11 52.20 4.2? 11.14 98-101

C 2 M 5

69 C Λ 4 Br NH 46.17 4.23 4.90 46.33 4.16 4.91 96-98

70 CH 2 CH 2 OCH. 2-CH -4-βr NH 41.29 4.88 - 47.56 5.02 - 93-95

71 2-CO CH -4-βr NH 45.37 4.10 4.07 45.61 4.0? 4.29 99-100 C 2»5

72 2-βr 4 CH. NH 48.02 4.70 4.67 48.35 4.88 4.56 91-94

C 2 H 5

?3 N-C.M- 4 -C.I NH 64.60 6.20 10.76 64.13 6.29 10.94 50-53

74 C H 3.5 S 45.06 3.44 - 44.81 3.68 - Oil 2 5 2

75 2-CH 4 βr NH 48.02 4.70 4.67 48.10 4.85 4.71 114 116

£ 2 H 5

76 c ". 2-CH CH 0 NH 62.14 6.-3 5.57 61.4? 6.?θ 5.30 109 110 3

Example III Preparation of ethyl l-(Σ-methyl^.S-dichloro- phenylamlnocarbonvDcyclopropanecarboxylate Into a nitrogen-purged round bottom flask was charged 5.53 grams (0.03 mole) of 2-methyl- 4,5-dichloroaniline, 3.18 grams (0.03 mole) of trlethylamine and 190 mmiliters of tetrahydrofuran solvent. With vigorous stirring, a 5.55 gram (0.03 mole) portion of ethyl 1-chlorocarbonylcyclopropane- carboxylate prepared in Example XVIII was added in one portion, after which the mixture was stirred at ambient temperature for a six-hour period. A precipitate of trlethylamine hydrochloride was then filtered off and the filtrate vacuum stripped to give a light yellow solid. The solid was taken up in ether and the solution water-washed, dried over magnesium sulfate, and solvent evaporated to give a yellow powder. Recrystallization from ethyl acetate-hexane gave 4.51 grams (0.01 mole) of ethyl 1-(2-methy1- ,5-d1chloropheny1aminocarbon 1)eye1o- propanecarboxylate Compound 77 having a melting point of 105°C-107°C.

Example IV In a manner similar to that employed in Example III, other compounds were prepared. The structures and analytical data for Compounds 78 through 96 are set forth in Table B below.

o —

3 — α» — w

LL '

lABll β (Cont.l Representative Halonlc Acid Derivative Compounds

GO

Substltuents Elemental Analysis HeIting

Compound R' 2 **2 Ca culated found Point • No. c H N c H N •c

C 2 H_ 2-f-4-Br 47.29 3.97 4.24 16'.8; 4.0? 4.02 102-103

H 66.83 6.47 6.00 66.54 6.48 5.80 85 89

£ 2 H 5

3.5 C1 2 51.6? 4.34 4.64 51.52 4.52 4.36 64-6?

C 2 H 5 4-C.N 65.10 5.46 10.85 65.02 5.51 10.67 129-132

C 2 H 5 C 2 H. 2-CH -4-βr 51.55 4.94 4.29 51.12 4.14 4.31 89-91

79 -

Example V Preparation of 3-1 " (4-bromo-2-methylphenyl)- am1nol-3-oxopropanoic acid A 6.0 gram (0.02 mole) portion of ethyl 3-[(4-bromo-2-methylphenyl)amino]-3-oxopropanoate prepared 1n Example I (Compound No. 75) was dissolved in approximately 80 miliniters of ethanol and 1.2 grams (0.03 mole) of sodium hydroxide pellets were added to the resulting mixture. The mixture was stirred for four hours and then allowed to stand overnight. The mixture was then evaporated to dryness and water added to give a yellow cloudy solution. This solution was extracted with methylene chloride and then acidified with 10 hydrochloric acid causing a white precipitate to form. The white precipitate was worked up to give 1.8 grams (0.01 mole) of 3-[(4-bromo-2-methylphenyl)- am1no]-3-oxopropanoic add, Compound 97, as a white solid having a melting point of 163°C-165 β C.

Example VI In a manner similar to that employed 1n Example V, other compounds were prepared. Compound 108 was obtained from Research Services, P.O. Box 11212, Santa Ana, California 92711.

Compound 109 was obtained from Or. A.K. Hittal, 32/17 E. Patel Nagar, New Delhi 110 008, India. The structures and analytical data for Compounds 98 through 109 are set forth in Table C below.

1ABIE C

Representative Malonlc Add Derivative Compounds

Substltuents Elemental Analysls Melting

Co pound »'3 ϊ"3 Calculated round Point No. c H N c H N c CD

O

98 H 4 Cl 50.60 3.77 6.56 50.67 3.80 6.37 140-141 1

99 H 2-CH 3 -4-βr-5-CI 39.18 2.96 4.57 • 39.36 3.14 4.44 181-182

100 H 3.5-βr 2 32.08 2.09 4.16 32.34 2.33 4.04 164-165.5

101 H 2-f-4-βr 39.15 2.56 5.07 39.24 2.42 4.94 161-162

102 H 2.4.5-CI 3 38.26 2.14 4.96 38.51 2.12 4.84 114-174.5

103 H 2-βr-4-CH 3 H R(C0Cl-,rOHSO-d ): 2.21(S, ,3H) . 3.4(s,2H), 154-151

6.95 -a .01 (m.4H). 9.5-9.7 (br s. H)PP«.

104 H 2-βr-4-C * l 36.95 2.41 4.79 37.18 2.J7 4.11 159-161

105 H 2-CI-4-βr 36.95 2.41 4.19 31.10 2.60 4.76 165.5-161

106 H 2.4-Br 2 32.08 2.09 4.16 32.2? 2.23 4.13 157-159

107 H 3.4 8r 2 32.08 2.09 4.16 31.96 2.22 4.08 14. 4 lOβ H 2.4-Cl NHR(C0CI /OMSO-d ): J 2.49-2.64 (brs.H). 3.52 (S.2H). 7.17-8.24 (m.3H), 9.86-10.05 (br s,H)ppm.

109 3-CI-4 CH, NHR(C0Cl 3 /DMSO-d.): J 2.30 (s.3H). 2.45-2.63 (b H), 3.34 (S.2H), 7.05-7.86 ( . 3H). 10.04 10.23 (br s.H)ppm.

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Example VII Preparation of l-(2-methyl-4.5-dichloro- phenylaminocarbonvDcyclopropanecarboxylie add A solution containing 0.34 gram (0.006 mole) of potassium hydroxide and 0.109 gram (0.006 mole) of water 1n 80 milllllters of ethanol was prepared in a 250 m1liπiter round bottom flask. With cooling to a temperature of 0°C 1n an 1ce/NaCl bath and stirring, a solution of ethyl l-(2-methyl-4,5-d1chlorophenylaminocarbonyl)cyclo- propanecarboxylate prepared in Example III in a small volume of ethanol was added and the mixture allowed to stir with warming to room temperature over a 72 hour period. The mixture was vacuum evaporated to give a white solid residue which was dissolved in water and extracted twice with ether. The ether extracts were discarded. The water solution was acidified to a pH of 2 with 25% HC1 solution causing separation of a solid which was taken up into ether, and the acidified aqueous phase was extracted four times. The combined ether extracts were dried over magnesium sulfate and vacuum evaporated to give a white solid. This white solid was water-washed and dried 1n a vacuum oven to give 1.85 grams (0.006 mole) of l-(2-methyl-4,5- d1chlorophenylam1nocarbonyl)cyclopropanecarboxylic add, Compound 110, having a melting point of 248°C-251°C.

" D

- 82 -

This compound 1s referred to hereinafter as Compound 110.

Example VIII In a manner similar to that employed 1n Example VII, other compounds were prepared. The structures and analytical data for Compounds 111 through 128 are set forth in Table D below.

TABLE D Representative Halonlc Acid Derivative Compounds

SuDStUuent Elemental Analysis Melting

Compd. 2' Calculated Found Point No. C h k C H •£ 1 D

Ill 2-CH--4-Br 46.34 4.06 .4.10 48.20 4.06 4.66 204.5-206

112 2.4.5-C1- 42.B2 2.61 4.54 43.11 3.14 4.42 250 '

113 2,S-C1 2 48.20 3.31 -5.11 48.33 3.26 4.96 223.5-226

1)4 2.4-Cl 2 48.20 3.31 5.11 45.26 3.40 5.03 169-190

115 2-F-4-C1 51.27 3.52 5.44 i 51.IB 3.70 5.22 202-204

116 4-Cl 55.12 4.21 5.84 54.69 4.35 5.59 217-219

117 4-Br 46.50 3.55 4.93 46.36 3.45 4.86 220-222

118 3.4-Br 2 36.39 2.50 3.86 37.13 2.70 3.83 224-226.5

119 3.5-Br 2 36.39 2.50 3.86 36.99 2.60 3.82 211-212

120 2.4-Br 2 36.39 2.50 3.86, 36.61 2.95 4.04 222-225

121 2-Cl-4-Br 41.47 2.85 4.40 39.74 3.90 3.95 166-168(dec.)

122 2-Br-4-Cl 41.47 2.85 4.40 41.67 3.28 3.91 210-211

123 ' 3-Cl-4-Br 41.41 2.85 4.40 41.70 3.23 4.11 211-214

124 2-CH -4-βr-5-Cl 43.33 3.33 4.21 45.47 4.0B 3.91 231-234

125 2-f-4-8r 43.73 3.00 4.64 43.97 3.05 4.30 203.5-207

126 52.75 3.69 5.13 52.73 3.90 5.04 195-196.5

4"Cf 3

121 3.5-C1- NHR (CDC1-: |: 1.52 (S.4H). 7.02-7.74 (n.4H), 10.08 196-202

(S. H) PPm-

128 3. -Cl, 48.20 3.31 5.11 48.19 3.80 5.26 220-222.5

Preparation of ethyl l-(4-bromo-2-methylphenyl- amlnocarbonyl)eyelobutanecarboxylate

Into a nitrogen-purged reaction flask was charged 2.74 grams (0.01 mole) of 4-bromo-2-methyl- aniline and 1.49 grams (Q.01 mole) of trlethylamine dissolved 1n 200 mllimters of tetrahydrofuran. With vigorous stirring, 2.80 grams (0.01 mole) of ethyl 1-chlorocarbony1eyelobutanecarboxylate prepared 1n Example XIX were added and the resulting mixture stirred at ambient temperature for 6 hours. A precipitate of trlethylamine hydrochlorlde was removed by filtration. The filtrate was vacuum stripped and the residue taken up in methylene chloride. This solution was washed successively with 2N HCl (2 x 75 mllimters) and water, and then dried over magnesium sulfate. Rotary evaporation gave a crude product which was flash ehromatographed on silica using 7:3 hexane-ethyl acetate to give 3.68 grams (0.01 mole) of ethyl l-(4-bromo-2-methyl- phenylaminocarbonyljcyclobutanecarboxylate as a white solid. A small sample which was recrystalHzed from hexane had a melting point of 61°C-64°C. Elemental analysis of the product indicated the following:

Analysis: C 15 H ιa BrN0 3

Calculated: C, 52.92; H, 5.33; N, 4.12

Found: C, 52.99; H, 5.44; N, 4.05 This compound 1s referred to hereinafter as Compound 129.

Example X

In a manner similar to that employed in Example IX, other compounds were prepared. The structures and analytical data for Compounds 130 through 134 are set forth in Table E below.

1ABIE E Representative Malonlc Add Derivative Compounds

Substltuents Elemerital Analysis Melting *

Corned. R'4 Z'5 Calculated Found Point

No. C H N C H H c

- 00

130 C 2 H 5 3.5-C1- 53.18 4.78 4.43 52.84 4.87 4.23 76.5-80 1

131 2.4.5-Cl 3 47.95 4.02 4.00 47.25 3.70 3.94 47-49

C 2 H 5 132 C-H- 2.4-Cl 2 53.18 4.78 4.43 52.84. 4.67 5.11 011

133 3.4-Cl 2 53.18 4.78 4.43 53.14 4.71 5.92 011

C 2 H 5 134 (a) C 2 H 5 4-Cl 59.68 5.73 59.89 5.70 85.5-87

( a ) ?repared by the mi xed anhydride proceαure _f Exampl e XXXI I I .

Example XI

Preparation of l-(3.5-dichlorophenyl- am1nocarbonyl)cyclobutanecarboxyl1c add

A 2.0 gram (0.006 mole) portion of ethyl l-(3,5-diehlorophenylaminocarbonyl)eyelobutanecarboxy- late prepared in Example X (Compound 130) was hydrolyzed in the presence of water (0.114 gram, 0.006 mole) and ethanollc potassium hydroxide (0.355 gram, 0.006 mole). The potassium salt of the acid was then acidified with 25% HCl solution and worked up in a manner similar to that described in Example VII to give 0.92 gram (0.003 mole) of l-(3,5-d1- chlαrophenylaminocarbonyl)eyelobutanecarboxy11c acid as a beige-colored solid having a melting point of 159°C-160°C. Elemental analysis of the product indicated the following:

Analysis: C-^C^NO-.

Calculated: C, 50.02; H, 3.85; N, 4.86

Found: C, 50.20; H, 3.83; N, 4.84 This compound 1s referred to hereinafter as Compound 135.

Example XII Preparation of ethyl l-(4-bromo-2-methylphenyl- aminocarbonyl)eyelopentanecarboxylate Ethyl 1-chlorocarbonylcyclopentane- carboxylate (3.10 grams, 0.02 mole) prepared in Example XX, 4-bromo-2-methylan1line (2.82 grams, 0.02 mole) and trlethylamine (1.53 grams, 0.02 mole) were reacted 1n tetrahydrofuran (200 milllllters) under conditions similar to that described 1n Example I to give 2.40 grams (0.007 mole) of ethyl 1-(4-bromo-2-methylphenylaminocarbonyl)eyelo- pentanecarboxylate, Compound 140, which, after recrystalHzatlon from hexane, had a melting point of 64°C-67°C.

Example XIII Preparation of ethyl 2-(4-bromo-2- methylphenylaminocarbonvDbutanoate

Ethyl 2-(chlorocarbonyl)butanoate (5.8 grams, 0.03 mole), 4-bromo-2-methylan1l1ne (5.0 grams, 0.03 mole) and trlethylamine (3.27 grams, 0.03 mole) were reacted under conditions similar to that described for Example I to give 7.4 grams (0.02 mole) of ethyl 2-(4-bromo-2-methylphenylam1no- carbonyl)butanoate, Compound 141, as a white solid having a melting point of 98°C-100°C.

Example XIV In a manner similar to that employed in Example XIV, other compounds were prepared. The structures and analytical data for Compounds 142 through 152 are set forth in Table G below.

Representative Halonlc Acid Derivative Compounds

- 90 -

Example XV

Preparation of N-butyl 3-r(4-bromo-2- methylphenyl)aminol-3-oxopropanamide

A mixture of 4.90 grams (0.02 mole) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-3- oxopropanoate prepared 1n Example I (Compound No. 75), 358 grams (4.9 moles) of n-butylamine , 150 mmmters of ethanol and 5 drops of water was stirred at room temperature for about 16 hours. After this period, rotary evaporation gave a crude product as a white solid. The white solid was recrystalHzed from ethyl acetate-hexane to give 3.08 grams (0.009 mole) of N-butyl 3-[(4-bromo-2-methylphenyl)am1no]-3- oxopropanamide having a melting point of 123°C-125°C, Compound 154.

Example XVI Preparation of ethyl 1-chlorocarbonyl- cvclopropanecarboxylate Into a stirred solution containing 15.1 grams (0.27 mole) of potassium hydroxide in 240 mllimters of ethanol and 4.83 grams (0.27 mole) of water was added dropwise, with cooling at a temperature of 0 β C, 50.0 grams (0.27 mole) of diethyl 1 ,1-cyclopropanedicarboxylate. The mixture was stirred for about 16 hours at room temperature. Solvent was removed under reduced pressure to give a white residue which was dissolved 1n water and extracted with ether. The water solution was acidified to a pH of 2 with 25% aqueous hydrochloric acid and the organic acid was extracted from the aqueous suspension with ethyl ether (4 x 400 millHHers). The ether extract was dried over magnesium sulfate and vacuum stripped to give the monocarboxyllc acid as a clear liquid. The clear liquid was dissolved in 300 mllimters of methylene

chloride after which 74 grams (0.62 mole) of thionyl chloride were added, and the resulting mixture was then heated under reflux for approximately 16 hours. Volatiles were removed under reduced pressure to give 45.7 grams (0.25 mole) of ethyl 1-chlorocarbonyleyelopropanecarboxylate, Compound 155. NHR analysis of the product indicated the following:

NHR (CDClg):^ 1.22-1.50 (t, 3H) , 1.75

(s, 4H), ' 4.1-4.52 (q, 2H) ppm. .

Example XVII Preparation of ethyl 1-chlorocarbonyl- cvclopentanecarboxylate In a manner similar to the procedure described 1n Example XVIII, with the exception that refluxlng with thionyl chloride 1n methylene chloride was conducted for only a 2 hour period, a 10 gram (0.05 mole) portion of dlethyl 1,1-cyclo- pentanedlcarboxylate was converted into 5.67 grams (0.03 mole) of ethyl 1-chlorocarbonylcyclopentane- carboxylate, Compound 157. NHR analysis of the product indicated the following:

NHR (CDC1 3 ): £ 1.10-1.49 (t, 3H) , 1.56-2.48 (m, 8H), 4.0-4.5 (q, 2H) ppm.

Example XVIII Preparation of ethyl 2-bromo-2-ch1oro- carbonylprooanoate In a manner similar to the procedure described in Example XVIII, except that refluxlng with thionyl chloride 1n methylene chloride solution was conducted only for a 6 hour period followed by standing at room temperature for about 16 hours, a

25.0 gram (0.10 mole) portion of dlethyl 2-bromo-2-methylmalonate was converted into 12.94 grams (0.05 mole) of ethyl 2-bromo-2-chloro- carbonylpropanoate, Compound 158. This compound was employed in the preparation of Compound Nos. 144-148 and 152 in Example XV. NHR analysis of the product Indicated the following:

NHR (CDC1 3 ):<5 1.10-1.47 (t, 3H) ,

2.05-2.17 (s pair, 3H), 4.05-4.55 (q pair,

2H) ppm.

')

Example XIX Preparation of ethyl 2-chlorocarbonyl-3- methyl-2-butenoate Diethyl isopropylldenemalonate (30 grams, 0.15 mole) was saponified with 10.0 grams (0.15 mole) of potassium hydroxide 1n 200 militers of ethanol solution and worked up to give the monocarboxyllc add which was then reacted with thionyl chloride (10 mmiliters, 0.1 mole) in methylene chloride solution 1n a manner similar to the procedure described 1n Example XVIII. Removal of solvent gave 9.6 grams (0.05 mole) of ethyl 2-chlorocarbonyl-3- methyl-2-butencate. NHR analysis of the residue product 1n CDC1, solution Indicated complete conversion of the carboxylic add to the acid chloride as evidenced by absence of a downfleld carboxylic acid proton. This compound is referred to hereinafter as Compound 174.

Example XX Preparation of ethyl 2-f(4-bromo-2-methylphenyl)- aminocarbonyn-3-methyl-2-butenoate In a manner similar to the procedure described in Example I, ethyl 2-chlorocarbonyl-3- methyl-2-butenoate (9.6 grams, 0.05 mole) prepared 1n Example XXV, 4-bromo-2-methylanil1ne (5.3 grams, 0.03 mole) and trlethylamine (4.0 milllllters, 0.03 mole) were reacted to give 2.9 grams (0.009 mole) of ethyl 2-[(4-bromo- 2-methylphenyl)aminocarbonyl ]-3- methyl-2-butenoate, Compound 175, as a white solid having a melting point of 116 0 C-119°C.

- 94 -

Example XXI

Preparation of l-.4-bromo-2-methylphenylam1πo- carbony1)eyelobutanecarboxylie add

A 3.0 gram (0.009 mole) portion of ethyl l-(4-bromo-2-methylphenylaminocarbonyl)cyclobutane- carboxylate prepared in Example IX (Compound 129) was hydrolyzed 1n a manner similar to that described in Example XI to give 2.19 grams (0.007 mole) of 1-(4-bromo-2-methylphenylaminocarbonyl)eyelobutane- carboxyllc acid, Compound 181, having a melting point of 154°C-155°C.

Example XXII

Preparation of ethyl (chlorocarbonvPmethoxyacetate

Part A. Preparation of diethyl methoxymalonate

A mixture of 50.4 grams (0.3 mole) of dimethyl methoxymalonate, para-toluenesulfonic acid (2.76 grams) and 300 mmiliters of ethanol was heated under reflux for a period of about 24 hours. Volatile materials were then removed under reduced pressure, employing a water bath at about 25°C. A second 300 minil1ter-port1on of ethanol was added and the mixture then refluxed for about 5 hours after which it was stirred at room temperature for an approximate 64-hour period. Removal of ethanol from the mixture under reduced pressure gave 61.0 grams (0.3 mole) of dlethyl methoxymalonate, employed in the subsequent steps without purification.

Part B. Preparation of mono-ethyl methoxymalonate

A mixture of 30.0 grams (0.2 mole) of diethyl methoxymalonate (Part A, above), 8.85 grams (0.2 mole) of potassium hydroxide, 2.84 grams (0.2 mole) of water and 300 mmiliters of ethanol was stirred at room temperature for about 72 hours and volatiles then removed under reduced pressure. The residue was dissolved in water and the pH of the solution adjusted to 10 by addition of potassium hydroxide. The solution was saturated with potassium chloride and extracted with methylene chloride (3x100 milllllters) to remove unsaponlfled dlester. Acidification to pH=l and continuous extraction with methylene chloride afforded 9.45 grams (0.06 mole) of mono-ethyl methoxymalonate as a liquid.

Part C. Preparation of ethyl (chlorocarbonyl) methoxyacetate

A mixture of 5.88 grams (0.04 mole) of mono-ethyl methoxymalonate from Part B, above, 8.63 grams (0.07 mole) of thionyl chloride and 150 mmiliters of methylene chloride was stirred for about 17 hours and then evaporated free of volatile materials. As NHR examination indicated the reaction to be Incomplete, the above thionyl chloride treatment in methylene chloride was repeated for a period of about 65 hours. A third treatment with 8.63 grams of thionyl chloride in 150

mmiliters of methylene chloride was finally given, refluxlng for a period of approximately 7 hours. Removal of volatiles under reduced pressure gave 6.0 grams (0.03 mole) of ethyl (chlorocarbonyl) methoxyacetate. Compound 211. NHR analysis of the product Indicated the following:

Η NHR (CDC1 ) 6 1.16-1.53(t, 3H, CH..), 3.58(s, 3H, CH 3 0), 4.13-4.56 (q, 2H, CH-,) 4.62 (s, H, CH) ppm.

Example XXIII

Preparation of ethyl 3-173.5-dichlorophenyl)am1nol-

-2-methoxy-3-oxopropanoate

3,5-D1chloroanil1ne (2.69 grams, 0.02 mole) and ethyl (chlorocarbonyl)methoxyacetate (3.0 grams, 0.02 mole), prepared in Example LIII (Compound 211), were reacted 1n the presence of trlethylamine (1.68 grams, 0.02 mole) in 200 milllllters of methylene chloride 1n a manner similar to that described 1n Example I to give 1.34 grams (0.004 mole) of ethyl 3-[(3,5-d1chlorophenyl)amino]-2-methoxy-3-oxopropano- ate, Compound 213, having a melting point of 89.5°C-92.5°C.

Example XXIV Preparation of mono-methyl methoxymalonate

Dimethyl methoxymalonate (50.0 grams, 0.3 mole) was saponified with potassium hydroxide (17.3 grams, 0.3 mole) in a mixture of 500 mmiliters of methanol and 5.55 grams (0.3 mole) of water

according to the general procedure of Example VII but employing a reaction period of approximately 16 hours. The reaction mixture was evaporated free of solvents and the residue dissolved in water and extracted twice with ether to remove any unreacted dlester. The aqueous layer was then saturated with potassium chloride, acidified with 2H HCl and extracted twice with ethyl ether. As this procedure enabled recovery of only a minor amount of product the aqueous phase was then subjected to three 16-hour periods of continuous liquid-liquid extraction with methylene chloride, adjusting the pH from 4 to 1 at the beginning of the second extraction period. Workup of the combined extracts gave 29.24 grams (0.2 mole) of mono-methyl methoxymalonate, Compound 214. NHR analysis of the product Indicated the following:

Η NHR (CDCl-,)<5 3.54(s, 3H, alpha CH 0), 3.86(s, 3H, ester CH 0) , 4.51 (s, H, CH), 9.36(s, H, C0 2 H) ppm.

Example XXV

Preparation of methyl 3-f.4-bromo-2-fluoro- phenyl)am1nol-2-methoxy-3-oxopropanoate

To a stirred mixture of 2.78 grams (0.02 mole) of mono-methyl methoxymalonate prepared in Example LVI (Compound 214) and 3.56 grams (0.02 mole) of 4-bromo-2-fluoroan1line in approximately 100 milllllters of dry tetrahydrofuran was fed

dropwise a solution of 3.87 grams (0.02 mole) of 1,3-dicyclohexylcarbodiimlde 1n about 30 mmiliters of dry tetrahydrofuran, while cooling the reaction mixture in an ice-water bath. The reaction mixture was allowed to warm slowly to room temperature and stirring continued for an approximate 65-hour period. The precipitated 1 ,3-dicyclohexylurea by-product (3.15 grams) was removed by filtration and the filtrate vacuum evaporated and the residue dissolved in methylene chloride. The latter solution was extracted with dilute HCl and then water, then dried (HgSO.) and solvent vacuum evaporated to give a colorless liquid. Flash column chromatography of the latter on silica, eluting with hexane-ethyl acetate (7:3) gave, after workup, a liquid which crystallized on standing. RecrystalHzation from hexane containing a small amount of ethyl acetate gave 2.3 grams (0.01 mole) of methyl 3-[(4-bromo-2-fluorophenyl)amino]- -2-methαxy-3-oxopropanaote, Compound 215, having a melting point of 51°C-53°C.

Example XXVI

In a manner similar to that employed in Example XXXIII, other compounds were prepared. The structures and andlytical data for Compounds 216 through 219 are set forth 1n Table I below.

TABLE I

Representative Halonlc Add Derivative Compounds

Elemental Analysis Helt

Compound SubstUuent Calculated found Poi

No. I_«

216 3.4-Cl 2 45.23 3.45 4.80 45.21 3.91 4.20 78-8

217 4-CF 3 49.49 4.15 4.81 49.88 4.29 4.91 101-

218 4-Br 43.73 4.00 43.73 4.04 55-5

219 3.4.5-C13 40.46 3.09 40.44 3.22 117-

- -

Example XXVII

Preparation of t-butyl 3-r(3.5-d1chlorophenyl)aminol

-2-methoxy-3-oxopropanoate

Part A Preparation of t-butyl methyl methoxymalonate

To a stirred solution of 9.26 grams (0.06 mole) of methyl (chlorocarbonyl)methoxyacetate in 25 minniters of carbon tetrachloride was added a mixture of 4.94 grams (0.07 mole) of anhydrous t-butyl alcohol, 4.50 mllimters (0.06 mole) of pyridine and 25 milllllters of carbon tetrachloride over an approximate 20-minute period, with cooling to 0°C-5°C by an ice bath. On completing the addition, the cooling bath was removed and the mixture allowed to stir for a 4-hour period at ambient temperature after which pyridine hydrochloride was removed from the mixture by filtration. The filtrate was diluted with 100 mmiliters of methylene chloride and partitioned with 100 mllimters of saturated aqueous sodium bicarbonate following which the organic phase was extracted with cold 10% hydrochloric add (3 x 100 milllllters), then with cold water (3 x 100 mmiliters) after which it was dried (HgS0 4 ) and solvents then flash evaporated. The residue was vacuum distilled to give 7.57 grams (0.04 mole) of t-butyl methyl methoxymalonate having a boiling point of 93.5°C-95°C at 4.0 mm Hg.

Part B Preparation of mono-t-butyl methoxymalonate

t-Butyl methyl methoxymalonate (7.57 grams, 0.04 mole), prepared 1n Part A, was saponified with potassium hydroxide (2.45 g, 0.04 mole) in a mixture of 25 mmiliters of methanol and 668 m crolUers (0.04 mole) of water according to the general procedure of Example VII but employing a reaction period of 20 hours. Workup according to the general method of Example VII gave 5.42 grams (0.03 mole) of mono-t-butyl methoxymalonate. NHR analysis of the product indicated the following:

•H NHR (C0C1 ) 6 1.45(s, 9H, t-butyl), 3.58(s, 3H, CH 3 0), 4.45(S, H, CH) , 10.51(s, H, C0-H) ppm.

Part C Preparation of t-butyl 3-r(3.5-dichloro- phenyl)am1no1-2-methoχy-3-oxopropanoate

Hono-t-butyl methoxymalonate (5.42 grams, 0.03 mole), prepared in Part B, 3,5-d1chloroanil1ne (4.62 grams, 0.03 mole) and 1 ,3-dicyclohexyl- carbodHmide (5.88 grams, 0.03 mole) were reacted in a manner similar to that described in Example VII to give 2.92 grams (0.009 mole) of t-butyl 3-[(3,5-dichlorophenyl)am1no]-2-methoxy-3-oxopro- panoate having a melting point of 129.5°C-131.5°C.

Example XXVIII

Preparation of methyl 3-r(3.5-d1chlorophenyl)am1nol-

-2-methoxy-3-th1oxoρropanoate

A mixture of 3.50 grams (0.01 mole) of methyl 3-[(3,5-d1chlorophenyl)am1no]-2-methoxy- 3-oxopropanoate (Compound 233, Example LXX) , 2.42 grams (0.006 mole) of 2,4-bis(4-methoxyphenyl)-l ,3- d1th1a-2,4-d1phosphetane-2,4-d1sulfide and 35 milllllters of anhydrous 1 ,1-dimethoxyethane was stirred at room tempereture for a period of about 20 hours after which stirring was continued with testing at 55°C for a 168-hour interval. Solvent was removed from the reaction mixture under reduced pressure and the residue worked up by flash column chromatography to give 2.31 grams (0.007 mole) of methyl 3-[(3,5-d1chloro-phenyl)amino]-2-methoxy- 3-thioxopropanoate, Compound 238, having a melting point of 144°C-147°C.

Example XXIX Preparation of 2-cyclopropenyl-l-carboethoxy-l-rN-

(2-methyl-4-bromophenyl)lcarboxamlde

Part A. Preparation of diethyl bis(2.3-tr1methyl- s1lyl)cyclopropene-l .1-dicarboxylate

A 50 m liπiter round-bottom flask was equipped with a magnetic stirring bar and a reflux condenser with N_ Inlet. The flask was charged with 183.0 grams (1.07 mole) of bls(trimethylsilyl) acetylene and 0.40 gram (0.0015 mole) of cupric ace- tylacetαnate. Using an oil bath the temperature of

the stirred mixture was raised to 145°C. Using a syringe pump 39.3 grams (0.21 mole) of dlethyl dlazomalonate were added over 36 hours. Heating at 145°C was continued for an additional 12 hours after all of the dlazomalonate had been added. The excess b1s(tr1methylsilyl)acetylene was removed by vacuum distillation. The residue product was purified by flash chromatography eluting with 80:20 hexane-ethyl acetate to give 17.0 grams (0.05 mole) of dlethyl b1s(2,3-tr1methylsilyl)cyclopropene- 1 ,1-dicarboxylate as a yellow liquid. NHR analysis of the product indicated the following:

Η NHR (CDC1 3 ):<6 0.23(s,18H), 1.20 (t, 6H),4.17(q, 4H) ppm.

Part B. Preparation of dlethyl cvclopropene-1.1- dicarboxylate

A 500 mil11liter round-bottom flask was equipped with a magnetic stirrer and N inlet. The flask was charged with 21.0 grams (0.07 mole) of dlethyl bis (2,3-tr1methylsilyl)cyclopropene-l ,1- dicarboxylate, 125 milliters of acetonitrile, 12.2 grams (0.21 mole) of anhydrous KF, and 6.50 grams (0.02 mole) of dicyclohexano-18-crown-6 ether. The mixture was stirred 6 hours at room temperature. The mixture was filtered and the filtrate concentrated under reduced pressure to a deep red oil. This oil was taken up in 100 milllllters of methanol and stirred 24 hours at room temperature. The methanol was removed under vacuum and the residue purified by flash column chromatography to give 6.25 grams (0.02 mole) of dlethyl cyclo-

propene-1 ,1-dicarboxylate as a yellow oil. NHR analysis of the product indicated the following: H NHR (CDC1 3 ):6 1.25 (t, 6H) , 4.23 (q, 4H) ; 7.08 (S, 2H).

Part C. Preparation of mono-ethyl cycloprooene-1 ,1- dicarboxylate A 250 mmmter round-bottom flask was equipped with a magnetic stirring bar and an addition funnel with N inlet. The flask was charged with 6.15 grams (0.03 mole) of dlethyl- cyclopropene-1 ,1-dicarboxylate and 50 mllimters of ethanol. The stirred mixture was cooled in an

1ce bath and a solution of 1.33 grams (0.03 mole) of

NaOH In 5.0 mllimters of water was added dropwlse. The mixture was allowed to come to room temperature and stirred for 3 days. The reaction mixture was concentrated to 1/4 of the original volume under reduced pressure, diluted with 1ce water, and extracted twice with ether. The basic aqueous phase was acidified with 1ce cold 10% HCl, and extracted three times with ethyl acetate. The ethyl acetate was dried (HgSO.) and the solvent removed under reduced pressure to leave an orange colored solid. This was recrystalHzed from hexane- ethyl acetate to give 3.65 grams (0.02 mole) of mono- ethyl cyclopropene-1 ,1-dicarboxylate as a light yellow solid having a melting point of 76.0 °C to

-77.5°C.

NHR analysis of the product indicated the following:

Η NHR (COCl ) δ 1.20 (t, 3H) , 4.25 (q, 2H), 6.80 (s, 2H), 11.5 (br s, 1H) ppm.

Part D. Preparation of l-carboethoχy-1-ethoχy- carbonyloχycarbony1-2-cyclopropene

A 250 mmHiter round-bottom flask was equipped with a magnetic stirrer and an addition funnel with « Inlet. The flask was charged with 1.30 grams (0.008 mole) of mono-ethyl cyclopropene- 1,1-dicarboxylate, 50 mmiliters of dry THF, 2.3 grams (0.02 mole) of potassium carbonate (anhydrous), and 450 milligrams of dlcyclohexano-18- crown-6 ether. The stirred reaction mixture was cooled to 0°C, and 0.90 gram (0.008 mole) of ethyl chloroformate in 10 milllllters of THF was added dropwise. The mixture was stirred for 2 1/2 hours at 0°C. At this time an aliquot from the reaction mixture showed a very strong anhydride carbonyl stretch at 1820 cm- 1n the infrared Indicating the formation of the mixed anhydride 1-carbo- ethoxy-1-ethoxycarbonyloxycarbony1-2-cyclo¬ propene. The balance of the reaction mixture containing the mixed anhydride was carried on to Part E.

Part E. Preparation of 2-cvcloρropenyl-l-carbo- ethoχy-l-rN-(2-methy1-4-bromophenyl)l carboxamide

A solution of 1.40 grams (0.0075 mole) of 2-methyl-4-bromoan1line 1n 10 milllllters of tetrahydrofuran was added dropwise to the reaction mixture from part 0 at 0°C. The mixture was allowed to come to room temperature and stirred for 2 hours. The reaction mixture was filtered and the

filtrate concentrated under reduced pressure to give an orange colored solid. This solid was washed with ether and recrystalHzed from hexane-ethyl acetate to give 1.5 grams (0.004 mole) of 2-cyclopropenyl-l- carboethoxy-l-[N-(2-methyl-4-bromophenyl) ]carboxamide, Compound 256, as a white crystalline solid having a melting point of 151°C-153°C.

Example XXX Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants Solutions of the test compounds and compositions identified in Table J below were prepared by dissolving the compounds in acetone/water (50:50 volume/volume) containing 0.1 percent volume/volume of Triton X-100 surfactant commercially available from Rhom and Haas Company, Philadelphia, Pennsylvania. As detailed below, these solutions of the test compounds and compositions were applied to snapbean plants at a concentration of 0.25 pounds of each active Ingredient per acre or 0.50 pounds of each active ingredient per acre. The compositions were applied to the snapbean plants as a mixture. Ethephon is commercially available from Union Carbide Agricultural Products Company, Inc., Research Triangle Park, North Carolina.

Into 13.5 centimeter diameter plastic pots containing a potting soil mix, I.e., one-third sandy loam soil, one-third peat moss and one-third perlite by volume, were sown three snapbean seeds (Phaseolus vulgaris var. Cranberry). Five to seven days after planting, the plants were thinned to one plant per pot. Ten to fourteen days after planting at the time of full expansion of the primary leaves, each concentration of the test compounds and compositions Identified 1n Table J (each pot sprayed with a volume equivalent to 180 gallons per acre) was applied to three snapbean plants as a foliar spray by use of an aspirated spray apparatus set at 10

- 108 -

psig air pressure. As a control, a water-acetone solution containing no test compound or composition was also sprayed on three snapbean plants. When dry, all of the plants were placed in a greenhouse at a temperature of 80°F + 5°F and humidity of 50 percent ± 5 percent: At 96 hours after treatment, percent defoliation of the snapbean plants was determined by visual observation. The values obtained for the control and each test compound and composition were averaged to obtain the results in Table J.

TABLE J

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 0.25 0

0.50 21

Compound 75 0.25 0

0.50 0

Ethephon * Compound 0.25 i- 0.25 52

75 0.50 + 0.50 70

Compound 5 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 23

5 0.50 + 0.50 27

Compound 111 0.25 0

0.50 0

Ethephon + Compound 0.25 4- 0.25 93

111 0.50 4- 0.50 97

Compound 25 0.25 0

0.50 0

Ethephon & Compound 0.25 0.25 24

25 0.50 + 0.50 40

Compound 50 0.25 0

0.50 0

Ethephon + Compound 0.25 - 0.25 52

50 0.50 i- 0.50 37

Compound 96 0.25 0

0.50 0

- 110 -

TABLE J ( Cont.

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Ethephon i- Compound 0.25 + 0.25 17

96 0.50 + 0.50 37

Compound 126 0.25 0 0.50 0

Ethephon + Compound 0.25 + 0.25 82

126 0.50 ♦ 0.50 100

Compound 128 0.25 0 0.50 0

Ethephon + Compound 0.25 + 0.25 47

128 0.50 * 0.50 50

Compound 112 0.25 0 0.50 0

Ethephon I- Compound 0.25 + 0.25 77

112 0.50 + 0.50 40

Compound 80 0.25 0 0.50 0

Ethephon + Compound 0.25 4- 0.25 47

80 0.50 + 0.50 27

Compound 113 0.25 0 0.50 0

Ethephon + Compound 0.25 + 0.25 -

113 0.50 + 0.50 23

Compound 114 0.25 0 0.50 0

TABLE J f Cont. -

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Ethephon + Compound 0.25 + 0.25 -

114 0.50 i- 0.50 97

Compound 82 0.25 0

0.50 0

Ethephon + Compound 0.25 4- 0.25 -

82 0.50 4- 0.50 60

Compound 115 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 -

115 0.50 + 0.50 93

Compound 46 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 -

46 0.50 + 0.50 27

Compound 116 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 -

116 0.50 + 0.50 87

Compound 117 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 -

117 0.50 + 0.50 97

Compound 97 0.25 0

0.50 0

- 112 -

TABLE J fCont.l

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Ethephon 4- Compound 0.25 + 0.25 -

97 0.50 + 0.50 30

Compound 149 0.25 0

0.50 0

Ethephon 4- Compound 0.25 4- 0.25 -

149 0.50 4- 0.50 40

Compound 129 0.25 0

0.50 0

Ethephon + Compound 0.25 + 0.25 -

129 0.50 + 0.50 73

Compound 37 0.25 0

0.50 0

Ethephon + Compound 0.25 4- 0.25 -

37 0.50 + 0.50 67

Compound 88 0.25 0

0.50 0

Ethephon - Compound 0.25 + 0.25- -

88 0.50 + 0.50 40

Compound 90 0.25 0

0.50 0

Ethephon * Compound 0.25 + 0.25 -

90 0.50 + 0.50 30

Compound 120 0.25 0

0.50 0

- -

TABLE J ( Cont . )

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Ethephon + ' Compound 0.25 + 0.25 -

120 0.50 0.50 30

Compound 121 0.25 0

0.50 0

Ethephon + Compound 0.25 - 0.25 -

121 0.50 4- 0.50 60

Compound 122 0.25 0

0.50 0

Ethephon 4- Compound 0.25 4- 0.25 -

122 0.50 + 0.50 37

Compound 123 0.25 0

0.50 0

Ethephon 4- Compound 0.25 * 0.25 -

123 0.50 4- 0.50 86

Compound 96 0.25 0

0.50 0

Ethephon + Compound 0.25 4- 0.25 74

96 0.50 - 0.50 83

Compound 97 0.25 0

0.50 0

Ethephon - Compound 0.25 4- 0.25 -

97 0.50 4- 0.50 63

The results 1n Table J demonstrate that compositions containing ethephon and a malonlc add derivative compound provide a synergistic effect on defoliation of snapbean plants.

11 5

Example XXXI Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants In a manner similar to the procedure described 1n Example XXVIII, the defoliation effect on snapbean plants was determined for representative synergistic compositions at various rates of application except that percent defoliation of the snapbean plants was determined at 72 hours after treatment. The results of these tests are set forth in Table K below.

- 1 1 6 -

TABLE

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control — 0

Ethephon 0.25 0

Compound 96 0.25 0

Ethephon - Compound 0.25 4- 0.25 80

96

Ethephon 0.50 0

Compound 96 0.50 0

Ethephon - Compound 0.50 - 0.50 90

96

Ethephon 0.25 0

Compound 96 0.50 0

Ethephon 4- Compound 0.25 4- 0.50 83

96

Ethephon 0.50 0

Compound 96 0.25 0

Ethephon + Compound 0.50 4- 0.25 90

96

Ethephon 0.75 13

Compound 75 1.0 0

Ethephon +• Compound 0.75 - 1.0 83

75

- -

The results in Table K demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on defoliation of snapbean plants.

- 118 -

Example XXXII Effect of Combinatlon/Seguential Applications of Representative Synergistic Compositions on Defoliation of Snapbean Plants In a manner similar to the procedure described in Example XXVIII, the defoliation effect on snapbean plants was determined for representative synergistic compositions using both combination (tank mix) and sequential application methods. In the sequential application method, the second compound was applied 78 hours after the first compound. The results of these tests -ire set forth in Table L below.

TABLE L

Effect of Combination/Sequential Applications of Representative Synergistic Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 0.5 0

Compound 96 0.5 0

*Ethephon + Compound 0.5 + 0.5 87

96

**Ethephon - Compound 0.5 - 0.5 10

96

**Compound 96 - 0.5 - 0.5 86

Ethephon

Combination application method (tank mix). **Sequent1al application method.

The results 1n Table L demonstrate a synergistic defoliation effect for the combination application method (tank mix) of ethephon and a malonlc add derivative compound. In regard to the sequential application method, a synergistic defoliation effect is demonstrated by applying the malonlc add derivative compound prior to ethephon.

- 1 2 -

Example XXXIII

Effect of Representative Synergistic Compositions on Defoliation and Boll Opening of Cotton

Solutions of the test compounds and compositions identified in Table H were prepared by dissolving the compounds in acetone/water (50:50 volume/volume) containing 0.1 percent volume/volume of Surfel® spray adjuvant commercially available from Union Carbide Corporation, Danbury, Connecticut. As detailed below, these solutions of test compounds and compositions were applied to cotton plants at a concentration of 0.5 pounds of each active ingredient per acre or 2.0 pounds of active ingredient per acre. The compositions were applied to cotton as mixtures.

The above solutions were applied to cotton plants growing under field conditions at a spray volume equivalent to 100 gallons per acre by use of a carbon dioxide backpack sprayer set at about 30 psig air pressure. The application timing coincided with a cotton maturity phase equivalent to about 40 percent open bolls. As a control, a water-acetone solution containing no test compound or composition was also sprayed on the cotton plants. At four days after treatment, percent defoliation of the cotton plants was determined by visual observation. At 14 days after treatment, percent boll opening was determined by visual observation of the number of open bolls/total number of bolls. The percent defoliation and percent boll opening values obtained for the control and each of the test compounds and compositions are reported in Table H as the average of three replications.

- 122 -

TABLE H

Effect of Representative Synergistic Compositions on Defoliation and Boll Opening of Cotton

Compound/ Rate Percent Percent

Composition (Pounds Defolia¬ Boll

Identification per Acre)- tion Opening

Control - 0 41

Ethephon 2.0 5 64 Compound 96 2.0 0 * Ethephon - Compound 0.5 4- 0.5 91 70 96

Compound 111 2.0 0 * Ethephon - Compound 0.5 - 0.5 96 95 111

Compound 75 2.0 0 * Ethephon 4- Compound 0.5 4- 0.5 95 60 75

*Percent boll opening essentially the same as the control as determined by visual observation.

The results in Table H demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on defoliation and boll opening of cotton.

- 124 -

Example XXXIV Effect of Representative Synergistic Compositions on Defoliation of Cotton (Rank Growth) In a manner similar to the procedure described 1n Example XXXII, the defoliation effect on rank growth cotton was determined for representative synergistic compositions at various rates of application. The results of these tests are set forth in Table N below. Rank growth cotton refers to cotton which exhibits excessive vegetative growth.

TABLE N

Effect of Representative Synergistic Compositions on Defoliation of Cotton (Rank Growth)

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 2.0 12

Compound 96 2.0 0

Ethephon 4- Compound 1.0 + 0.25 85

96

Compound 96 2.0 0

Ethephon +• Compound 1.0 4- 0.50 96

96

Compound 111 2.0 0

Ethephon 4- Compound 1.0 - 0.25 97

Compound 111 2.0 0

Ethephon - Compound 1.0 - 0.50 99

111

Compound 75 2.0 0

Ethephon - Compound 1.0 - 0.25 40

75

- -

TABLE N ( Cont . l

Effect of Representative Synergistic Compositions on Defoliation of Cotton (Rank Growth)

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Compound 75 2.0 0

Ethephon - Compound 1.0 4- 0.50 70 75

Compound 75 2.0 0

Ethephon - Compound 1.0 4- 1.0 82

The results in Table N demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on defoliation of rank growth cotton.

Example XXXV Effect of Sequential Applications of Representative Synergistic Compositions on Defoliation of Cotton In a manner similar to the procedure described in Example XXXII, the defoliation effect on cotton was determined for representative synergistic compositions using sequential application. Ethephon applications were made 7 days after application of the particular malonlc add derivative compound. The results of these tests are set forth 1n Table 0 below.

- -

TABLE 0

Effect of Sequential Applications of

Representative Synergistic Compositions on

Defoliation of Cotton

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 0.25 3

Compound 96 0.5 0

1.0 0

Compound 111 0.5 0

1.0 0

Compound 75 1.0 0

Compound 96 + 0.5 - 0.25 93

Ethephon

Compound 96 + 1.0 - 0.25 90

Ethephon

Compound 111 4- 0.5 - 0.25 87

Ethephon

Compound 111 4- 1.0 - 0.25 93

Ethephon

Compound 75 + 1.0 + 0.25 79

Ethephon

- 129 -

The results 1n Table 0 demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on defoliation of cotton by sequential application.

- -

Example XXXVI

Effect of Representative Synergistic

Compositions on Defoliation of Cotton

In a manner similar to the procedure described in Example XXXII, the defoliation effect on cotton was determined for representative synergistic compositions at various rates of application. The results of these tests are set forth in Table P below.

TABLE P

Effect of Representative Synergistic Compositions on Defoliation of Cotton

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 0.5 13

Compound 96 0.5 0

Compound 96 + 0.5 - 0.5 99

Ethephon

Compound 96 0.5 0

Compound 96 + 0.5 - 0.25 99

Ethephon

Compound 97 0.5 0

Compound 97 4- 0.5 4- 0.5 75

Ethephon

Compound 65 0.5 0

Compound 65 + 0.5 4- 0.5 90

Ethephon

Compound 66 0.5 0

Compound 66 - 0.5 + 0.5 60

Ethephon

Compound 69 0.5 0

Compound 69 4- 0.5 4- 0.5 73

Ethephon

TABLE P ( Cont . l

Effect of Representative Synergistic Compositions on Defoliation of Cotton

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Compound 5 0.5 0

Compound 5 4- 0.5 - 0.5 78

Ethephon

Compound 26 0.5 0

Compound 26 4- 0.5 4- 0.5 97

Ethephon

Compound 35 0.5 0

Compound 35 4- 0.5 4- 0.5 67

Ethephon

Compound 102 0.5 0

Compound 102 4- 0.5 - 0.5 63

Ethephon

Compound 77 0.5 0

Compound 77 4- 0.5 - 0.5 97

Ethephon

Compound 110 0.5 0

Compound 110 +• 0.5 4- 0.5 83

Ethephon

- 133 -

The results 1n Table P demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on defoliation of cotton.

- 134 -

Example XXXVII Effect of Representative Synergistic Compositions on Defoliation of Cotton In a manner similar to the procedure described 1n Example XXXII, the defoliation effect on cotton was determined for representative synergistic compositions at various rates of application. The results of these tests are set forth 1n Table Q below.

TABLE 0 Effect of Representative Synergistic Compositions on Defoliation of Cotton

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control - 0

Ethephon 0.5 5

Compound 0.5 0

Compound 111 - 0.5 + 0.5 99

Ethephon

Compound 0.5 0

Compound - 0.5 4- 0.25 99

Ethephon

Compound in 0.25 0

Compound 111 4- 0.25 - 0.5 93

Ethephon

Compound 0.25 0

Compound 4- 0.25 - 0.5 96

Ethephon

The results 1n Table Q demonstrate that compositions containing ethephon and a malonlc add derivative compound provide a synergistic effect on defoliation of cotton.

Example XXXVIII

Effect of Representative Synergistic

Compositions on Regrowth of Cotton following Defoliation

In a manner similar to the procedure described in Example XXXII, the effect of cotton regrowth after defoliation was determined for representative synergistic compositions at various rates of application. The percent regrowth inhibition and stimulation in Table R below were determined by visual observation based on the percent of a cotton plant having regrowth using a DEF treated cotton plant as the standard. DEF is commercially available from Hobay Chemical Corporation, Kansas City, Hlssouri. The average regrowth of a cotton plant treated with DEF was 43 percent. As used in Table R, percent regrowth Inhibition resulted from a cotton plant having a regrowth percentage less than 43 percent (DEF standard), and percent regrowth stimulation resulted from a cotton plant having a regrowth percentage greater than 43 percent. The percent regrowth inhibition and stimulation were determined 30 days after treatment. The results of these tests are set forth 1n Table R.

- 138 -

TABLE R

Effect of Representative Synergistic Compositions on Regrowth of Cotton following Defoliation

Compound/ Rate Percent Percent

Composition (Pounds Stimula¬ Inhibi¬

Identification per Acre) tion tion

Control (DEF) - 0 0

Ethephon 0.5 16 0

1.0 70 0

2.0 62 0

Compound 96 0.5 0 0

Ethephon 4- Compound 0.5 + 0.5 0 53

96

Compound 96 0.5 0 0

Ethephon - Compound 0.5 4- 1.0 0 63

96

Compound 96 0.5 0 0

Ethephon - Compound 1.0 4- 0.5 0 46

96

Compound 96 0.5 0 0

Ethephon -t- Compound 1.0 + 1.0 0 72

96

TABLE R (Cont.) Effect of Representative Synergistic Compositions on Regrowth of Cotton following Defoliation

Compound/ Rate Percent Percent

Composition (Pounds Stimula¬ Inhibi¬

Identification per Acre) tion tion

Compound 111 0.5 0 0

Ethephon . Compound 0.5 4- 0.5 0 65

111

Compound 111 0.5 0 0

Ethephon - Compound 0.5 4- 1.0 0 53

111

Compound 111 0.5 0 0

Ethephon - Compound 1.0 4- 0.5 0 44

111

Compound 111 0.5 0 0

Ethephon 4- Compound 1.0 4- 1.0 0 51

111

Compound 75 0.5 0 0

Ethephon + Compound 0.5 4- 0.5 0 53

75

Compound 75 0.5 0 0

Ethephon 4- Compound 1.0 4- 1.0 0 16

75

The results in Table R demonstrate that compositions containing ethephon and a malonlc acid derivative compound provide a synergistic effect on regrowth Inhibition of cotton following defoliation.

Example XXXIX

Effect of Representative Synergistic Compositions on Leaf Ripening of Tobacco

In a manner similar to the procedure described in Example XXVIII except that mature tobacco plants were used in place of snapbean plants, the leaf ripening effect of tobacco was determined for representative synergistic compositions at various rates of application. About 14 days prior to treatment, the mature tobacco plants were topped and treated with 4.0 pounds per acre of HH-30 to retard axillary bud development. HH-30 is commercially available from Uniroyal Chemical Company, Bethany, Connecticut. Percent tobacco leaf ripening (chlorosis) was determined by visual observation of the upper three leaves of the tobacco plant at 7 days after treatment. The

* results of these tests are set forth 1n Table S below.

- -

TABLE S

Effect of Repi-esentative Svnergistic

Compositions on Leaf Rioenlnq of Tobacco

Compound/ Rate Percent

Composition (Pounds Ripening

Identification per Acre) (Chlorosis)

Control - 10

Ethephon 1 .0 10

Compound 96 1.0 10

Compound 96 4- 1.0 4- .25 25

Ethephon

Compound 96 1.0 10

Compound 96 4- 1.0 - 0.5 30

Ethephon

Compound 96 1.0 10

Compound 96 4- 1.0 - 1.0 60

Ethephon

The results 1n Table S demonstrate that compositions containing ethephon and a malonic acid derivative compound provide a synergistic effect on leaf ripening of tobacco.

- -

Example XL

Effect of Representative Synergistic Compositions on Defoliation of Snapbean Plants

In a manner similar to the procedure described in Example XXVIII, the defoliation effect on snapbean plants was determined for representative synergistic compositions at various rates of application using various ethylene releasing agents Identified 1n Table T below. The ethylene releasing agents used in Table S are known materials which can be prepared by conventional methods. The results of these tests are set forth 1n Table T.

TABLE T

Effect of Representative Synergistic

Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Control

Compound 111 0.125 0

0.25 0

0.50 0

2-Chloroethanesulfon1c 0.125 0 acid 0.25 0

0.50 0

Compound 111 4- 0.125 4- 0.125 30

2-Chloroethanesulfonic 0.125 + .25 20 acid 0.50 0.50 50

2-Chloroethylthiono- 0.125 0 phosphonic add 0.25 0

0.50 0

- -

TABLE T ( Cont . )

Effect of Representative Synergistic

Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Compound 111 -»- 0.125 - 0.125 60

2-Chloroethylth1ono- 0.125 - 0.25 50 phosphonic acid 0.50 - 0.50 100

Ethephon 0.125 0

0.25 0

0.50 0

Compound 111 - Ethephon 0.125 + 0.125 53

0.125 4- 0.25 67

0.50 4- 0.50 89

2-Chl oroethyl ester of 0.125 0

2-chloroethylphosphonic 0.25 0 add 0.50 0

Compound 111 4- 0.125 40 2-Chloroethyl ester of 0.125 4- 0.25 40 2-chloroethylphosphonic 0.50 -i- 0.50 87 add

2-Bromoethylphosphonic 0.125 0 acid 0.25 0

0.50 0

TABLE T ( Cont . )

Effect of Representative Synergistic

Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Compound 111 -» 0.125 4- 0.125 33

2-Bromoethylphosphonlc 0.125 4- 0.25 30 acid 0.50 4- 0.50 73

2-Chloroethylphosphonlc 0.125 0 diamide 0.25 0

0.50 0

Compound 111 -»• 0.125 - 0.125 33

2-Chloroethylphosphonlc 0.125 4- 0.25 27 diamide 0.50 4- 0.50 100

Tris-(2-methoxyethoxy)-2- 0.125 0 chloroethylsilane 0.25 0

0.50 0

Compound 111 4- 0.125 4- 0.125 37

TMs-(2-raethoxyethoxy)-2- 0.125 - 0.25 17 chloroethylsilane 0.50 4- 0.50 43

1-Amino-l-cyclopropane- 0.125 0 carboxylic add (ACC) 0.25 0

0.50 0

- -

TABLE T ( Cont. )

Effect of Representative Synergistic

Compositions on Defoliation of Snapbean Plants

Compound/ Rate

Composition (Pounds Percent

Identification per Acre) Defoliation

Compound 111 + 0.125 -»- 0.125 33

1-Amino—1-cyclopropane- 0.125 4- 0.25 73 carboxylic acid (ACC) 0.50 4- 0.50 83

The results In Table T demonstrate that compositions containing an ethylene releasing agent and a malonlc acid derivative compound provide a synergistic effect on defoliation of snapbean plants.

Example XLI Effect of Ethylene Gas and a Halonlc Acid

Derivative Compound on Abscission of Snapbean Plant Leaves

Solutions of test compounds identified in Table U below were prepared by dissolving the compounds in acetone/water (60:40 volume/volume) containing 0.1 percent volume/volume of Triton X-100 surfactant commercially available from Rohm and Haas Company, Philadelphia, Pennsylvania.

In a manner similar to the procedure described in Example XXVIII, the solutions of test compounds were applied as a foliar spray to snapbean plants at a concentration of 125 parts per million of active ingredient or 250 parts per million of active Ingredient. Prior to treatment, the snapbean plants with an expanded trlfoliolate leaf were topped leaving two fully expanded primary leaves. After a period of 24 hours following treatment, the snapbean plants were placed in 10.3 liter desiccators and exposed to ethylene gas at a concentration of 0.1 part per million (ppm). A carbon dioxide trap (2 milllllters of 40 percent potassium hydroxide) was included in each desiccator. The sealed desiccators were then placed in a dark environment. After a period of 48 hours and 96 hours 1n which the treated snapbean plants were exposed to ethylene gas, percent abscission was determined by visual observation of abscised leaves. The plants were also rated at 96 hours (48 hours after termination of ethylene gas exposure). The percent abscission values are reported 1n Table U as the average of three replications.

TABLE U

Effect of Ethylene Gas and a Halonlc Acid

Derivative Compound on Abscission of

Snapbean Plant Leaves

Compound/

Composition Concentration Percent

Identification (oom) Absdssion 48 96

Hours Hours

Control - 0 0

Ethylene Gas 0.1 0 0

Compound 111 125 0 17

Compound 111 - Ethylene 112255 4-- 00..11 33 100

Gas

Compound 111 250 33 50

Compound 111 +• Ethylene 250 4- 0.1 83 100

Gas

The results 1n Table U demonstrate that a combination of ethylene gas and a malonlc acid derivative compound provide a synergistic effect on abscission of snapbean plant leaves.

Example XLII

Effect of Representative Synergistic Compositions on Leaf Ripening of Snapbeans

Stock solutions containing 2 minigrams/m1liniter of the test compounds Identified 1n Table U below were prepared by dissolving appropriate amounts of ethephon in water and appropriate amounts of Compound 75 1n acetone/water (50:50 volume/volume). The test solutions Identified in Table U were made by dilution with water.

Into 7.6 centimeter diameter paper pots containing a potting soil (one-third perlite, one-third peat-lite and one-third sandy loam farm soil (volume:volume:volume)) were sown three snapbean seeds (Phaseolus vulgaris var. Cranberry). Five to seven days after planting, the plants were thinned to one plant per pot. Twelve days following treatment, 10 disks (9 millimeter diameter) were punched from the primary leaves of each bean plant. Each set of 10 disks was placed 1n a petri dish containing 20 mmiliters of the appropriate test solutions prepared above. As a control, a water-acetone solution containing no test compound was also used. Each petri dish was then placed in a dark environment for a period of 48 hours at a temperature of 28°C. Upon removal from the dark environment, each set of disks was visually rated for ripening activity. Visual Indications of leaf ripening were observed and recorded employing a system of numerical ratings.

-

Numerical ratings from "0" to "10" were used to designate the degree of leaf ripening observed in comparison with the untreated control. A "0" rating indicates no visible response and a "10" rating Indicates a maximum response, i.e., bright yellow. The results are reported in Table V and are the average of 3 repetitions.

TABLE V

Effect of Representative Synergistic

Compositions on Leaf Ripening of Snapbeans

Compound Concentration Ripening

No. (oom) Rating Control 0 0

Ethephon 50 1

100 4.7

Compound 75 100 0

200 0

500 1

Ethephon - Compound 75 50 4- 100 2.3

50 4- 200 3

100 4- 500 10

- -

The results in Table V demonstrate that compositions containing an ethylene releasing agent and a malonic add derivative compound provide a synergistic effect on ripening of snapbeans.

The results in Table V demonstrate that compositions containing an ethylene releasing agent and a malonic acid derivative compound provide a synergistic effect on ripening of snapbeans.

Example XLIII

Effect of Representative Synergistic Compositions on Plant Chlorophyll Content-Ripening

A stock solution of ethephon containing 2 minigrams/milliliter was prepared by dissolving an appropriate amount in water. A stock solution of Compound 75 was prepared by mixing 150 milligrams of Compound 75 with 0.5 miliπiters of Triton X-100 surfactant, 1 miliniter of gamma-butyrolactone and 500 mmiliters of water. The test solutions identified in Table V below were made by dilution with water. Triton X-100 surfactant is commercially available from Rohm and Haas Ccmpany, Philadelphia, Pennsylvania.

Into 7.6 centimeter diameter paper pots containing a potting soil (one-third perlite, one-third peat-lite and one-third sandy loam farm soil (volume:volume:volume)) were sown three snapbean seeds (Phaseolus vulgaris var. Cranberry).

Five to seven days after planting, the plants were thinned to one plant per pot. Twelve days following treatment, 10 disks (12 millimeter diameter) were punched from the primary leaves of each bean plant.

Each set of 10 disks was placed 1n a petri dish containing 20 miliniters of the appropriate test solutions prepared above. As a control, a water-acetone solution containing no test compound was also used. Each petri dish was then placed in a dark environment for a period of 48 hours at a o temperature of 28 C. Upon removal from the dark environment, each set of disks was blotted dry and placed in a test tube on ice.

Each set of disks were then homogenized in a Waring blender with 20 mlllHiters of a solution containing 80 percent acetone/20 percent water

(volume/volume). The resulting suspensions were centrifuged at a temperature of 0 C-2 C at

-2 12,000 X g (g = 980 cm sec )for a period of 5 minutes. The supernatant containing the chlorophyll was saved and the absorbance of light of the solutions at 645 nanometers (nm) and 663 nanometers

(nm) was determined by spectrophotometric analysis.

Total chlorophyll (milligrams chlorophyll/grams leaf tissue) was calculated according to the following equation:

milligrams (20.2)(absorbance at 645 nm) 4- of chlorophyll = (8.02)(absorbance at 663 nm) grams of leaf weight of leaf disks (grams) tissue

Each value for the control and test solutions Identified in Table W is the average of two repetitions.

TABLE W

Effect of Representative Synergistic Compositions on Plant Chlorophyll Content - Ripening

Chlorophyll

Content

(milligrams chlorophyll/ Chlorophyll

Compound Concentration grams leaf (X of

No. (pom) tissue) Control)

Control 41.40 100

Ethephon 75 33.54 81.0

Compound 75 150 36.90 89.1

Ethephon 75 - 150 26.77 64.7 -r Compound 75

The results in Table W demonstrate that compositions containing an ethylene releasing agent and a malonlc acid derivative compound provide a synergistic effect on ripening of snapbeans.