Use of aloπic Acid Derivative Compounds f-or Increasing Crop Yield

Brief Summary of the Invention Technical Field

This invention relates to the use of malonic acid derivative compounds for increasing crop yield. This invention further relates to novel malonic acid derivative compounds and processes for the preparation thereof.

Background of the Invention

Certain malonic acid derivative compounds have been known for some time in the art. See, for example, U.S. Patent 2,504,896 and U.S. Patent 3,254,108. Some malonic acid derivative compounds have been described in the art as capable of providing certain plant growth regulating responses such as prevention of fruit drop, rooting of cuttings and formation of parthenogenetic fruit.

U.S. Patent 3,072,473 describes N-arylmalonamic acids and their esters and salts, N, N'-diarylmalonamides, N-alkyl-N-arylmalonamic acids and their esters and salts, and N, N'-dialkyl-N, N'-diarylmalonamides which may be useful as plant growth reguiants and herbicides. Japanese Patent 84 39,803 (1984) describes malonic acid anilide derivative compounds which may be useful as plant growth regulators. The plant growth regulating properties of substituted malonyl onoanilides are described by Shindo, N. and Kato, M. Meiji Oaigaku Noogaku-bu Kenkyu Hokoku, Vol. 63, pp. 41-58 (1984).

However, certain malonic acid derivative compounds and the use of malonic acid derivative

compounds for increasing crop yield as described herein have not been disclosed in the art.

Accordingly, it is an object of this invention to provide a method for the use of malonic acid derivative compounds to increase crop yield. It is another object of this invention to provide novel malonic acid derivative compounds and processes for the preparation thereof. These and other objects will readily become apparent to those skilled in the art in light of the teachings herein set forth.

Disclosure of the Invention

This invention relates to a method for increasing crop yield which comprises applying to the crop an effective amount, sufficient to increase crop yield, of a compound ha-ving-the formula:

^γ 3 ^γ 4 \ /

R-, - Y-, - C C C - Y ₂ - R ₂ 1

II II

^Y 5 ^γ 6 wherein R. , R_, Y. , Y_, Y_, Y., Y_ and 1 2 1 3 4 5

Y. are as defined hereinafter, o

■ This invention also relates to novel malbn1c-sacId derivative compounds and to processes for the prepartion of said compounds.

Detailed Description As indicated above, this invention relates to a method of increasing crop yield by use of certain malonic add derivative compounds. More

particularly, this invention involves a method for increasing crop yield which comprises applying to the crop an effective amount, sufficient to increase crop yield, of a compound having the formula:

^γ 5 ^γ 6 wherei n :

R ₁ and R- are independently a substituted or unsubstituted, carbocyclic or heterocyclic ring system selected from a monocyclic aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system, and a bridged ring system which may be saturated or unsaturated in which the permissible substituents (Z) are the same or different and are one or more hydrogen, halogen, alkylcarbonyl , alkylcarbonylalkyl, formyl, alkoxycarbonylalkyl , alkoxycarbonylalkylthio, polyhaloalkenylthio, thiocyano, propargylthlo, hydroxyi ino, alkoxyimino, trialkylsilyloxy, aryldialkylsi yloxy, triarylsilyloxy, formamidino, alkylsulfamido, dlalkylsulfamido, alkoxysulfonyl, polyhalβalkoxysulfonyl , hydroxy, amino, azido, azo, aminocarbonyl, alkylaminocarbonyl, hydrazino, dialkyla inocarbonyl , amlnothiocarbonyl ,

•m alkylamlnothiocarbonyl , dialkylaminothiocarbonyl, nitro, cyano, hydroxycarbonyl and derivative salts, formamido, alkyl, alkoxy, polyhaloalkyl, polyhaloalkoxy, alkoxycarbonyl, substituted amino in

which the permissible substituents are the same or different and are one or two propargyl, alkoxyalkyl, alkylthioal yl , alkyl, alkenyl, haloalkenyl or polyhaloalkenyl ; alkylthio, polyhaloalkylthio, alkylsulfinyl, polyhaloalkylsulfinyl, alkylsulfonyl, polyhaloal ylsulfonyl , alkylsulfonylamino, alkylcarbony!amino, polyhaloalkylsulfonylamino, polyhaloal ylcarbonylamino, trialkylsilyl , aryldialkylsilyl , triarylsilyl , sulfonic acid and derivative salts, phosphonic acid and derivative salts, alkoxycarbonylamino, alkylaminocarbonyloxy, di lkyla inocarbonyloxy, alkenyl, polyhaloalkenyl, alkenyloxy, alkynyl, alkynyloxy, polyhaloalkenyloxy, polyhaloalkynyl , polyhaloalkynyloxy, polyfluoroalkanol , cyanoalkylamino, semicarbazonomethyl , alkoxycarbonylhydrazonomethyl , alkoxyiminomethyl , unsubstituted or substituted aryloxyiminomethyl , hydrazonomethyl , unsubstituted or substituted arylhydrazonomethyl, a hydroxy group condensed with a mono-, di- or polysaccharide, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, aryloxy, aralkoxy, arylthio, aralkylthio, alkylthioalkyl, arylthioalkyl, arylsulfinyl, arylsulfonyl , haloalkylsulfinyl , haloalkylsulfonyl , haloalkenyloxy, haloalkynyloxy, haloalkynylthio, haloalkenylsulfonyl , polyhaloalkenylsulfonyl , isocyano, aryloxysulfonyl, propargyloxy, aroyl, haloacyl, polyhaloacyl, aryloxycarboπyl, aminosulfonyl , alkylamlnosulfonyl , dialkylaminosulfonyl , aryla lnosulfony , carboxyalkoxy, carboxyalkylthio, alkoxycarbonylalkoxy, acyloxy, haloacyloxy,

polyhaloacyloxy, aroyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, arylsulfonyloxy, haloalkylsulfonyloxy, polyhaloalkylsulfonyloxy, aroylamino, haloacyla ino, alkoxycarbonyloxy, arylsulfonylamino, aminocarbonyloxy, cyanato, isocyanato, isothiocyano, cycloalkylamino, trialkylammonium, arylamino, aryl(alkyl)amino, aralkylamino, alkoxyalkylphosphinyl , alkoxyalkylphosphinothioyl , alkylhydroxyphosphinyl , dialkoxyphosphino, hydroxyamino, alkoxyamino, aryloxyamino, aryloxyimino, oxo, thiono, diazo, alkylidene, alkylimino, hydrazono, se icarbazono, dialkylsulfoniurn, dialkylsulfuranylidene, dialkyloxosulfuranylidene, -X, = X, -X = R_, = X-R„,

^Y 7

or

R and R are independently hydrogen or derivative salts, or a substituted heteroatom or substituted carbon atom, or a substituted or unsubstituted, branched or straight chain containing two or more carbon atoms or heteroatoms in any combination in which the permissible substituents are Z as hereinbefore defined;

Y ₁ and Y„ are independently a substituted or unsubstituted heteroatom in which the

permissible substituents are Z as hereinbefore defined;

Y- and Y. are independently hydrogen, or a substituted or unsubstituted heteroatom or substituted carbon atom, or a substituted or unsubstituted, branched or straight chain containing two or more carbon atoms or heteroatoms in any combination, or halogen, alkylcarbonyl , formyl, alkylcarboπylalkyl, alkoxycarbonylalkyl, alkoxycarbonylalkyIthio, polyhaloalkenylthio, thiocyano, propargylthio, trialkylsilyloxy, aryldialkylsilyloxy, triarylsilyloxy, forma idino, alkylsulfa ido, dialkylsulfamido, alkoxysulfonyl, polyhaloalkoxysulfonyl, hydroxy, amino, hydrazino, azo, aminocarbonyl , alkylaminocarbonyl , azido, dialkylarninocarbonyl, aminothiocarbonyl , alkylaminothiocarbonyl, dialkylaminothiocarbonyl , nitro, cyano, hydroxycarbonyl and derivative salts, formamido, alkyl, alkoxy, polyhaloalkyl, polyhaloalkoxy, alkoxycarbonyl, substituted amino in which the permissible substituents are the same or different and are one or two propargyl, alkoxyalkyl, alkylthioalkyl, alkyl, alkenyl, haloalkenyl or polyhaloalkenyl; alkylthlo, polyhaloalkylthio, alkylsulfinyl, polyhaloalkylsulfinyl, alkylsulfonyl, polyhaloalkylsulfonyl , alkylsulfonylamino, alkylcarbonylamlno, polyhaloalkylsulfonyTamino, polyhaloalkylcarbonyla ino, trialkylsilyl, aryldialkylsHyl, triarylsilyl, sulfonic acid and derivative salts, phosphonic acid and derivative salts, alkoxycarbonylamino, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkenyl, polyhaloalkenyl,

alkenyloxy, alkynyl, alkynyloxy, polyhaloalkenyloxy, polyhaloalkynyl , polyhaloalkynyloxy, poly luoroalkanol , cyanoalkylamino, semicarbazonomethyl , alkoxycarbonylhydrazono ethyl , alkoxyi inomethyl , unsubstituted or substituted aryloxyiminomethyl, hydrazono ethyl, unsubstituted or substituted arylhydrazonomethyl, a hydroxy group condensed with a mono-, di- or polysaccharide, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, aryloxy, aralkoxy, arylthio, aralkylthio, alkylthioalkyl , arylthioalkyl , arylsulfinyl , arylsulfonyl , haloalkylsulfinyl , haloalkylsulfonyl , haloalkenyloxy, haloalkynyloxy, haloalkynylthio, haloal enylsulfonyl , polyhaloalkenylsulfonyl , isocyano, aryloxysulfonyl , propargyloxy, aroyl, haloacyl, polyhaloacyl , aryloxycarbonyl , a inosulfonyl , alkylaminosulfonyl , dialkylaminosulfon l , arylaminosulfonyl , carboxyalkoxy, carboxyalkylthio, alkoxycarbonylalkoxy, acyloxy, haloacylOxy, polyhaloacyloxy, aroyloxy, alkylsulfonyloxy, alkenylsulfonyloxy, arylsulfonyloxy, haloalkylsulfonyloxy, polyhaloalkylsulfonyloxy, aroylamino, haloacyla ino, alkoxycarbonyloxy, arylsulfonylamino, a inocarbonyloxy, cyanato, isocyanato, isothiocyano, cycloalkylamino, trialkylam onium, arylamino, aryl(alkyl)amino, aralkylamino, alkoxyalkylphosphinyl ,

__•* alkoxyalkylphosphinothioyl , alkylhydroxyphosphinyl , dialkoxyphosphino, hydroxyamino, alkoxyamino, aryloxyamino,

-X, -X = R ₃ ,

^Y 7 Y ₇

-X - R-. P - Y ₈ R4 -Yio Y 8pR ^« 4

\

Y ₉ R ₅ Y _g R ₅ or

in which the permissible substituents are Z as hereinbefore defined; or

Y- and Y. taken together are oxo, 3 4 thiono, diazo, = X or =• X - R , or substituted or unsubstituted alkylidene, alkyli ino, hydrazono, dialkylsulfoniurn, dialkyloxosulfuranylidene, semicarbazσno, hydroxyimino, alkoxyimino or aryloxyimino in which the permissible substituents are Z as hereinbefore defined; Y_ and Y, may be

3 4 linked together to form a substituted or unsubstituted, carbocyclic or heterocyclic ring system selected from a monocyclic aromatic or ^" nonaromatic ring system, a blcyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system, and a bridged ring system which may be saturated or unsaturated in which the permissible substituents are Z as hereinbefore defined;

- Y_ and Y- are independently oxygen or 0 sulfur; wherein:

X is a covalent single bond or double bond, a substituted or unsubstituted heteroatom or

substituted carbon atom, or a substituted or unsubstituted, branched or straight chain containing two or more carbon atoms or heteroatoms in any combination in which the permissible substituents are Z as hereinbefore defined; R. 1s a substituted or unsubstituted, carbocyclic or heterocyclic ring system selected from a monocyclic aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system, and a bridged ring system which may be saturated or unsaturated 1n which the permissible substituents are Z as hereinbefore defined;

R- 1s a substituted heteroatom or substituted carbon atom, or a substituted or unsubstituted, branched or straight chain containing two or more carbon atoms or heteroatoms in any combination in which the permissible substituents are Z as hereinbefore defined;

Y and Y are independently oxygen or sulfur;

Y • and Y are independently oxygen,

8 9 sulfur, amino or a covalent single bond; and

R. and R_ are independently hydrogen or 4 5 substituted or unsubstituted alkyl, alkenyl, alkynyl? polyhaloalkyl, phenyl or benzyl 1n which the permissible substituents are Z as hereinbefore defined.

The alkyl-containlng moieties in formula _ 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 polysaccharide moiety may contain up to about 50 carbon atoms. It is appreciated that all compounds encompassed within formula _ are compounds having no unfilled bonding positions. In regard to the malonic acid derivative compounds used in this invention, it is preferred that R, and R ₂ are independently other than hhyyddrrtogen, 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 substituents which may be substituted therefore. Illustrative derivative salt substituents include, for example, ammonium, alkylammonium, polyalkylammonium, hydroxyalkylammonium, poly(hydroxyalkyl)ammonium, alkali metals, alkaline earth metals and the like including mixtures thereof.

Honocyclic ring systems encompassed by R , R and R in formula _ 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 ring-forming heteroatoms alone.

HσnocycUc ring systems encompassed by Y- and Y, linked together in formula 1 may include 4 ~ any monocycHc ring system of R , R and<- ₃ appropriately, positioned 1n formula 1.

R1rig-form1ng heteroatoms may in some cases bear oxygen atoms as in aromatic N-ox1des and ring systems,containing the su.f.nyl ^' sulfonyl, selenoxlde and phosphlne oxide moieties.

Selected carbon atoms contained 1n cycles formed by B. and A. containing at least 3 ring-forming atoms may bear carbonyl, thlocarbonyl , substituted or unsubstituted 1mino groups or substituted or unsubstituted methylidene groups.

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

Bicycllc ring systems encompassed by R-j , R2 and R3 in 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 ring-forming chains of atoms described below and

Z represents one or more substituents selected independently from among the group of substituents defined for Z herein. Combinations of A and A may contain in combination with B or B _Λ from 0

2 3 to 5 double bonds. A and A , independent of

B„ and B . may contain entirely from 1 to 11 2 3 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

__ _* ring-forming heteroatoms alone.

Ring-forming heteroatoms may in some cases bear oxygen atoms, as in aromatic N-ox1des and ring systems containing the sulfinyl, sulfonyl,

selenoxide and phosphine oxide groups. Selected carbon atoms contained in A and A may bear carbonyl, thiocarbonyl, substituted or unsubstituted imino groups or substituted or unsubstituted methylidene groups.

Bicyclic ring systems encompassed by Y and Y linked together in formula 1 may include any bicyclic ring system of R. , R and R appropriately positioned in formula _.

In regard to structures encompassed within formulae _ and 4, it is noted as follows:

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

(b) When B- but not B„ is nitrogen, either of A„ or A„ should contain at least three

2 3 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 contains a carbon atom bearing a carbonyl, thiocarbonyl, imino or methylidene group, it should together with 8 and B form a cycle having at least four members;

^" ϊ (e) When a annular double bond is exocyclic to either of the two rings represented in structures 3 and 4, it should be contained in a ring

«_* containing at least five members and be exocyclic to a ring containing at least five members; and

(f) When a group A _? or A_ 1s joined to the bridgehead atoms B and B by 2 double

bonds, the group A or A is understood to

< ^■ _. contain one double bond and the bridgehead atoms are considered to be unsaturated.

It is recognized that bicyclic ring systems defined for R, , R ₂ , R ₃ and Y ₃ and Y. linked together may be spirocyclic ring systems and are not limited to the fused bicyclic structures of formulae _ and 4. Spirocyclic ring systems may be saturated or unsaturated carbocyclic or heterocyclic and may be independently substituted by one or more substituents Z as defined herein.

Polycyclic ring systems, i.e., greater than 2 rings, encompassed by R. , R_ and R in formula 1 may be represented by generalized formulae _x _, 1 and 8_ as follows:

wherein B., B„, B, and B_, may be

4 5 6 7 independently a saturated or unsaturated carbon atom or a saturated nitrogen atom, and A., A_, A.

4 _ o 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 substituents selected independently from among the group of substituents defined for Z herein.

The ring-forming elements of A , A ,

A, and A_, independent of B . B . B„ and 6 7 4 5 6

B 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 N, 0, S, P or other heteroatoms, or may contain from 1-3 heteroatoms alone. Ring-forming heteroatoms may in some cases bear oxygen atoms as in aromatic N-oxides and ring systems containing the sulfinyl, sulfonyl, selenoxide and phosphine oxide groups. The group A _c may at times be defined as a o bond. Selected carbon atoms contained in A.,

4

A , A and A_ may bear one or more carbonyl,

D O 7 thiocarbonyl or substituted or unsubstituted imino groups.

^" On structure 8 the groups B , B and

8 9

B _Q represent independently a saturated or unsaturated carbon atom or a saturated nitrogen atom. The group B.. may represent a saturated or unsaturated carbon atom or a nitrogen or phosphorous atom. The groups A_, A. and A _1Q represent r1ng-form1ng chains of atoms which may contain

together with 1 of the groups B , B , B and

B from 0-2 double bonds.

The ring-forming elements of groups A ,

8 A and A independent of groups B , B ,

B _ and B may contain from 2-10 carbon atoms, may contain from 1-10 carbon atoms in combination with 1-3 heteroatoms which may be selected independently from among N, 0, S, P or other heteroatoms, or may contain from 2-3 heteroatoms alone. Ring-forming heteroatoms may in some cases bear oxygen atoms as in aromatic N-oxides and in ring systems containing the sulfinyl, sulfonyl, selenoxide and phosphine oxide groups. Selected carf'n atoms contained in groups A , A and y y

A may bear one or more carbonyl, thiocarbonyl or substituted or unsubstituted imino groups.

It is recognized that polycyclic ring systems defined for R , R , R and Y and

I £ ■_.

Y. linked together may be spirocyclic ring systems 4 and are not limited to the fused polycyclic structures of formulae 5_, 6, 1_ and 8. Spirocyclic ring systems may be saturated or unsaturated, carbocyclic or heterocyclic and may be independently substituted by one or more substituents Z as defined herein.

- Polycyclic ring systems encompassed by Y and Y, linked together in formula 1 may include any p appropriately positioned in formula ]_.

Bridged bicyclic structures encompassed by R. , R ₂ and R ₃ in formula 1 may be represented by generalized formulae 9, J_0, and X\_ as follows:

II

wherein B and B may be independently a saturated carbon atom optionally substituted by Z or a nitrogen atom, and the groups A..., A., and A independently represent ring-forming chains of atoms which may contain, Independently of B and B- _« . ^ro 0-2 double bonds. The groups Z represent one or more substituents.selected Independently from among the groups of substituents defined for Z herein.

The ring-forming elements of A-., A. and A , independent of B and B , 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

1s a single heteroatom, the other two groups should contain two or more ring-forming atoms. A second proviso is that when one or both of the groups B. 12 and B is nitrogen, the groups A , A and

A,„ should contain at least two saturated 13

ring-forming atoms.

Ring-forming heteroatoms may in some cases bear oxygen atoms as in the sulfinyl, sulfonyl, selenoxide and phosphine oxide moieties. Selected carbon atoms contained in A-., A _1? and A- ₃ may bear one or more carbonyl, thiocarbonyl or substituted or unsubstituted imino groups.

Bridged bicyclic structures encompassed by Y ₃ and Y. linked together in formula 1 may include any bicyclic bridged system of R , R and R appropriately positioned in formula 1-

0

It is readily apparent that formula 1 encompasses a wide variety of malonic acid derivative compounds. Illustrative malonic acid derivative compounds within the scope of formula 1 which may be used for increasing crop yield are included in Tables 1 through 11 b'elow.

- 18aa -

It is appreciated that the particular compounds ^' listed in Tables 1 through 11 hereinabove are illustrative of malonic add derivative compounds which can be used for increasing crop yield according to this invention. This invention 1s not to be construed as being limited only to the use of these compounds; but rather, this invention includes the use of those malonic add derivative compounds encompassed within formula 1 hereinabove.

The novel malonic acid derivative compounds of this invention can be depicted.by the following formulae:

wherein:

I ABU I IConl.l Heprt-.n tlut Malonic Acid O.rlvatlve Compound.

V. «',

-1-4 βr-S-Cl OH

-18c-

.1

31 rs.e s.

2! O Z U X a α α α o α z

et -I

-18d-

I ABU 3 Bepreien tlve Malonic A d Derivative Compound}

-181-

X X

TABLE 3 (Cont.) • R.Pr.ien tlvt l lonlc Add Oerlvtlve Cowpoundt . - '

_* ''. ^r 4 ^T '- ^Z 'lO

CH.CONH- H 2-Cil -4.Br SC.H.

HCQNH. H 2- -Br ^SC 6 ^H 5

(fCl'H _j N- ^* • * H 2-C ₂ H--4-Cl OCH ₃

' -0-CH _j . 0- 2-CH ₃ -4.βr SCII ₂ CH ₂ 0CHj

-S-CH _j CH _j S- 2-CH ₃ -4-βr QC ₂ H.

CH ₃ 0 H 3.5-Cl ₂ oc ₂ .ι ₅

CM ₃ 0 H 3.5-βr ₂ OC.H.

:n ₃ α H 3-Br-S-Cl 0-n-Cjll _j

CH _j O H 3-βr-5-. ^' O---C ₄ H,

C _j 'H _j OCO CH, 4-C1 OCII _j

CH _j $' 3.5-Cl ₂ OC ₂ H ₅

. ^CH 3 cH _j Sα CH, 2-F-4-βr O-n-C.H.

CH ₃ SO ₂ v H 2-CH -4-βr OC.H.

CH.50. , CH, 3.S-,CI ₂ . oc ₂ .. _s C..N- H ^' 2-CH.-4-ar 0C ₂ H.

^' CH _j S H 2-CH ₃ -4-Br oc ₂ .i _s

X X

- 18m -

» ^J

w* Z w w w

X X X X Z X X X X w

I ABIC 4 (Cont.l Repreten tlve HJ Ionic Add Derlv_llve Cowpoundt

ϊ*

II 12 13 14 ^" *'. 16 II I?

H H H H H ON. ■ M O-1,1 Cl

H H H II H H OH CII O 3.4 C I

H H H H H II OCH Cl 4 Br

3 Cl

H H H II II H OK Cl 0 4 il C ₂ H. 4 I

H H H II H H O

IADU fc

BepretentJllve H. onic Add Per lv_tlve Cowpoundt

-'. »'. I" «'.

19 20 v 21 II 13 12

H H H H II 2 ^* CH 4 Hr OCH.CH OCH, 2 2 3 OCII-CH._H

H H H H H 2 CHj 4 Hr

H H H H H 4 Cl 0CH ₂ CH _? SO ₂ CH ₃

H H H H 2-CI-4-B- OCH ₂ COCH

H

H H H H 2 l-4-Br OCH(CH »C .N

H

Represent atlve Malonic Add Derivative Compoundt

1

V ϊ' .' R*

21 22 23 "•24 24 2b ^r ,4 13

H H H H II H 2 III 4 Br OCH CH OCH

2 2 3

H H H H H H . 2 UI 4 Br OCH CH SO H CH OH

2 2 7 2 2

H H II H II H 2.4 Bi OCH CH OCH CH OH

H H II H II H 3.4 Cl . SCH _{2 2} C ₂ H.

CH. II H II H 7 1 4 Ui - 0 N .CIICII

C",

_- Cl "l3.

CH ₃ Cllj 7 LHj 4 Cl o-H c; SCIlj

Cl Cl II H II H 2 a. 4 βr OCH CONH, 2 2

H H Cl Cl II H 4 Cl OCH C.H

H H II H Cl Cl 4 Hr SCH ₂ P(OC ₂ H _i ) ₂ 0

CH ₃ H 3 I 4 LI OCH CH NHCO C H

2 2 2 2 V.

Cl 7.1 Cl ₍ OCH COCH

^CH 3 2 3 H II 7 LI 4 Cl 0 OCH CH CONH 3 3 2 2 2

H It 2 I. II 4 I OCH Cll OH

7 -J 7 2

H H 7 llr 4 LI SCH CH OCH

IABU B

Hepretentatlve Malonic Add Dei Ivatlve Conjoundt

»' R*

2B 21 14 14

IABU B (Cont.l Repretentatlve Malonic Acid Derivative Cowpoundt (Cont.l

»\ 2'

21 14 14

-CM CH CH CH - S OC ₂ H _s -.« ci ₂

-CH,CH CH,CH„- 0 NH, 2-Br-4 CN

2 2 7 2 2

-CH CH CH CH - 0 oc _Λ 4 C _fc .I.O

-CH CH CH CH - S OH 3.4 Cl

2 7 2 7 •» 2

-CH CH CH CH,- 0 NIICH CH OCH 4 Cl

2 2 2 2 2 2 3

-CH CH ¬ 0 ^SC 3.4 Br ₂

.CH CH CH - 0 SCH CH OH 3 Br-4 Cl

-CH CH CH,- 0 SCH 2 Cl. 4-Br 2 7 2

-CH CH - 4 OCH ₃ 3,4-(CI ₃ J ₂

im- i

Repretentatlve Malonic Add Derivative Cowpoundt

-•„ R*

29 14 lb

ll 0

IABU 10

Representative H_ Ionic Acid DtjJ a t \ vt Compoundt

R' I'

' 33 34 32 16 U

-18v-

w a «_>

Pa n n n pa n pa pa Pa Pa Pa Pa

X X X X Z X x x a a. v. a vi

- L8

I a n PI X Z Jx I * "

X X . u u> A

- #

lABU II

Repretenta^ve Malonic Acid Oerlvatlve Cowpoundt

V »' R'

36 31 34 IB II

NH "Λ JU

19

Z is independently substituted or unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, nitro, cyano, dialkoxyphosphinyl, acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl , acylamino, sulfonylamino, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n is a value of from 0 to 5;

Y is 0, S or NR wherein R is hydrogen or alkyl;

Y ₁₂ is 0, S, NH or N (alkyl); and

R is ammonium, alkylammonium, 6 polyalkylammonium, hydroxyalkylammonium, po1y(hydroxyalkyl)ammonium, an alkali metal or alkaline earth metal or substituted or unsubstituted hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyla inoalkyl, dlalkylaminoalkyl , aryl, mercaptoalkyl, alkylthloalkyl, arylthioalkyl, aryloxyalkyl, alkylsulfonylalkyl, alkylsulflnylalkyl, acylalkyl, aroylalkyl, dialkoxyphosphinylalkyl , diaryloxyphosphinylalkyl , hydroxyalkylthioalkyl , hydroxyalkylsulfonylalkyl , alkoxyal ** _* kylthloalkyl, alkoxyalkylsulfonylalkyl, poly(oxyalkylene)alkyl, cyanoalkyl, nitroalkyl, alkylidenea ino, carbamoylalkyl, alkylcaebamoylalkyl, dialkylcarba oylalkyl, aminoalkyl, acylaminoalkyl, acyloxyalkyl, alkoxycarbonyla inoalkyl, cyanoa inoalkyl, carbamoyloxyalkyl , alkylcarbamoyloxyalkyl, dialkylcarba oyloxyalkyl , alkoxycarbonyloxyalkyl ,

20

alkoxycarbonylthioalkyl, aminosulfonylalkyl , alkylaminosulfonylalkyl or dialkylaminosulfonylalkyl;

wherei n :

1- is independently substituted or unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio. arylsulfonyl, nitro, cyano, dialkoxyphosphinyl , acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl, acylamino, sulfonylamino, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n 1s a value of from 0 to 5;

Y ₃ is 0, S or NR _g wherein R. is hydrogen or alkyl ;

Y ₁₄ is 0, S, NH or N (alkyl);

Y._ and Y are Independently hydrogen, 15 16 alkyl, halogen, alkoxy, alkylthio, alkenyl, alkynyl, hydroxy, cyano, nitro, formyl, amino, alkylcarbonyl , dialkoxyalkyl , alkylcarbonylamino, formylamino, hydroxy*lkyl, haloalkyl or polyhaloalkyl provided that when Y.- is alkyl then 1. is not halogen or polyhaloalkyl at the para- position, and further provide that at least one of Y _1C and Y. _c is

It) ID other than hydrogen;

Y,_ and Y _1C may be linked together to

I - ID form a substituted or unsubstituted heterocyclic

21

ring system selected from a monocyclic aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system and a bridged ring system which may be saturated or unsaturated; and

R _Q is hydrogen or R ; o o

wherein:

Z is independently substituted or unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, nitro, cyano, dialkoxyphosphinyl , acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl, acyla ino, sulfonylamino, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n is a value of from 0 to 5;

Y- ₇ is 0, S or NR^ wherein R^ is hydrogen or alkyl;

Y-- is 0 or S;

Y and Y are independently hydrogen, alkyl, alkoxy, alkylthio, halogen, haloalkyl or polyhaloalkyl; or

Y _lg and Y _ may be linked together to form a substituted or unsubstituted, carbocyclic or

22

heterocyclic ring system selected from a monocyclic aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system and a bridged ring system which may be saturated or unsaturated; and

R-g is hydrogen or R,; and

^γ 3 Y

^R ι - ^γ ι - c c c Y ₂ - R ₂ (iv)

^Y S

wherein:

R. and R. are independently a substituted or unsubstituted, carbocyclic or heterocyclic ring system selected from a monocyclic aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system, and a bridged ring system which may be saturated or unsaturated; or

R and R are independently hydrogen or derivative salts, or a substituted heteroatom or substituted carbon atom, or a substituted or unsubstituted, branched or straight chain containing two or more carbon atoms or heteroatoms in any combination;

- Y. and Y are Independently a substituted or unsubstituted heteroatom;

Y and Y are linked together to form a substituted or unsubstituted, carbocyclic or heterocyclic ring system selected from a monocyclic

23

aromatic or nonaromatic ring system, a bicyclic aromatic or nonaromatic ring system, a polycyclic aromatic or nonaromatic ring system, and a bridged ring system which may be saturated or unsaturated; and

Y- and Y, are independently oxygen or

_ 0 sulfur; in which the permissible substituents for formulae

(i) through (iv) above are Z, as hereinbefore defined.

Novel malonic acid derivative compounds within the scope of formula (iv) above can be depicted by the following formulae:

wherein :

Z. is Independently substituted or unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, nitro, cyano, dialkoxyphosphinyl, acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl, acyla ino, sulfonylamlno, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n Is a value of from 0 to 5;

Y 1s 0, S or NR. wherein R. is hydrogen or alkyl;

Y ₂₂ 1s 0, S, NH or N (alkyl);

Y„„. Y„_. Y„_. and Y _c are 23 2 25 26

24

independently hydrogen, alkyl or halogen; and ₁₂ 1s hydrogen or R, or

wherein:

Z_ is Independently substituted or 5 unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, nitro, cyano, dialkoxyphosphinyl, acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl, acylamino, sulfonylamino, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n is a value of from 0 to 5;

Y ₂₇ is 0, S or NR ₁₅ wherein R- ₅ is hydrogen or alkyl;

Y ₂₈ is 0 S, NH or N (alkyl);

^Y -2 _Λ 9. Y3-Λ0. ^γ -3ι1. ^γ -3-2» ^γ -33- ^{and Y} 3-4a are independently hydrogen, alkyl or halogen; and hydrogen or

' ^R ! ^{1 S} V

^(vU)

25

wherein:

1. is independently substituted or unsubstituted halogen, haloalkyl, polyhaloalkyl, polyhaloalkoxy, alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfinyl, aryl, aryloxy, arylthio, arylsulfonyl, nitro, cyano, dialkoxyphosphinyl, acyl, aroyl, alkoxycarbonyl, alkoxycarbonylalkyl, acylamino, sulfonylamino, alkylsulfonylamino, acyloxy, alkenyl or -CH=CHCH=CH-; n 1s a value of from 0 to 5;

Y- _g Is 0, S or NR« ₇ wherein R,- is hydrogen or alkyl ;

R Is hydrogen or R , in which the

10 0 permissible substituents for formulae (v) through (v11) are as described for Z above for formulae (i) through (iv).

The malonic acid derivative compounds encompassed within formula 1 and the intermediate compounds used in the preparation thereof can be prepared by conventional methods known in the art and many may be available from various suppliers. The novel malonic acid derivative compounds of formulae (1) through (vii) above which may used in the method of this invention may be prepared by reacting appropriate starting ingredients in accordance with conventional procedures described in the art as illustrated below.

The novel malonic acid derivative compounds of formula (1) can be prepared by the following general reaction scheme:

26

Scheme I

wherein Z , n, Y , Y and R are as defined hereinabove. Reactions of this general type for preparing malonic acid derivative compounds of formula (1) including process conditions are described for example by Richter, G.H., Textbook of Organic Chemistry, Third Edition, John Wiley and Sons, New York, p. 486. In the Schotten-Baumann procedure described therein, cold aqueous sodium hydroxide is illustrated as the acid acceptor.

The novel malonic acid derivative compounds of formula (11) can be prepared by the following general reaction scheme:

27

Scheme II

wherein !_ , n, Y^, Y^, Y^, Y^ and R _Q are as defined hereinabove. Reactions of this general type for preparing malonic acid derivative compounds of formula (11) including process conditions are described for example by Richter,

G.H., supra, according to the known Schotten-Baumann procedure.

The novel malonic add derivative compounds of formula (111) can be prepared by the following general . reaction scheme:

28

Scheme III

wherein Z,_, n, Y , Y , Y , Y _2Q and

R are as defined hereinabove. Reactions of this general type for preparing malonic acid derivative compounds of formula (111) including process conditions are described for example by Richter,

G.H., supra, according to the known Schotten-Baumann procedure.

The novel malonic acid derivative compounds of formula (iv) can be prepared by the following general reaction scheme:

^Y l ^Y 4 ³ \ / ⁴

K - ^X -Y«— C—C—C—Cl HY ₂ —R ₂

Scheme IV

wherein R , R , Y , Y . Y , Y Y_ and _ I _ 1 2 3 4 _

Y are as defined hereinabove. Reactions of this

6 general type for preparing malonic acid derivative compounds of formula (1v) Including process conditions are described for example by Richter,

29

G.H., supra, according to the known Schotten-Baumann procedure.

The novel malonic acid derivative compounds of formula (v) can be prepared by the following general reaction scheme:

Scheme V

wherein Z^, n, Y,,., Y^, Y^, Y^, Y^,

Y and R are as defined hereinabove.

Reactions of this general type for preparing malonic acid derivative compounds of formula (v) including process ^" .conditions are described for example by

Richter G.H., supra, according to the known

Schotten-Baumann procedure.

_ The novel malonic acid derivative compounds of formula (vi) can be prepared by the following general reaction scheme:

30

Scheme VI

wherein Z,., n, Y _2? , Y ₂₈ , Y ₂₉ , Y _3Q , Y ₃₁ , V ^Y 34 ^{and R} 14 ^{arβ 3S def1ned} hereinabove. Reactions of this general type for preparing malonic acid derivative compounds of formula (vi) Including process conditions are described for example by Richter, G.H., supra, according to the known Schotten-Baumann procedure.

The novel malonic acid derivative compounds of formula (v11) can be prepared by the following general eaction scheme:

31

Scheme VI I

wherein Z,, n, Y„_, Y_. and R,, are as 6 35 36 16 defined hereinabove. Reactions of this general type for preparing malonic acid derivative compounds of formula (v11) including process conditions are described for example by Richter, G.H., supra, according to the known Schotten-Baumann procedure.

In addition to the above, other Illustrative procedures which can be employed in preparing malonic add derivative compounds encompassed within formula 1 and intermediate compounds used in the preparation thereof are described, for example, in the following: Breslow, O.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.

32

Belg. 61, 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; Chiriac, C.I., Revue Ro aine de Chimie 25., (3), 403-405 (1980); Weiner, N., Org. Syn. Coll., Vol. II, 279-282 (1950), Sixth Printing, John Wiley & Sons, New York; Block, Jr., Paul, Org. Syn. Coll. Vol. V, 381-383 (1973), John Wiley and Sons, New York; Reliquet, 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; Staudinger, H. and Becker, H., Berichte 50, 1016-1024 (1917); Purrington, S.T. and Jones, W.A., J. Org. Chem. 48, 761-762 (1983); Kitazume, T. et al., Chem. Letters (1984) 1811-1814; Wolff, I.A. et al., Synthesis (1984), 732-734; Za blto, 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.

Still other illustrative procedures which can be employed in preparing malonic acid derivative compounds encompassed within formula and intermediate compounds used in the preparation thereof are described, for example, in the following: Rathke.'-M.W. and Cowan, P.J., J. Org. Chem. 5J0, 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. 95, 2861-2870 (1962); Gompper, R. and Kunz, R., Chem. Ber. 9£, 2900-2904 (1966); Ono, N. et al., J. Org. Chem. 50, 2807-2809 (1985); U.S. Patent 4,154,952;

33

Blankenship, C. and Paquette, I.A., Synth. Comm. 14, (11), 983-987 (1984); Baldwin, J.E. et al., Tet. Lett. 26, (4), 481-484 (1985); Kawabata, N. et al., Bull. Chem. Soc. Jpn. 55, (8), 2687-2688 (1982); Bodanszky, M. and du Vignaud, 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); Fusoπ, 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., Contradi, Atti acad. Llncei 22., I, 823-836 (CA. 8, 73 (1914)); Schimelpfenig, C.W., J. Chem. Soc. Perk. Trans. I, 1977 (10), 1129-1131; Kim, Y.S. et al . , Taehan Hwahak Hoechi l_, (4), 278-288 (1974); German Patent 2,449,285; U.S. Patent 3,962,336; and U.S. Patent 3,992,189.

Copending U.S. Patent Application Serial No. (D-15328), filed on an even date herewith, describes the use of malonic acid derivative compounds of formula 1 for retarding plant growth. Copending U.S. Patent Application Serial No. (D-15298), filed on an even date herewith, describes synergistic plant growth regulator compositions containing (1) an ethylene response or an ethylene-type response Inducing agent and (11) a malonic acid derivative compound of formula 1. Both of these applications are incorporated herein by reference.

The malonic acid derivative compounds of formula 1 have been found to significantly increase crop yield in comparison with untreated crops at

34

similar conditions. In addition, the malonic acid derivative compounds used in this invention are substantially non-phytotoxic to growing plants.

As used herein, an effective amount of a malonic acid derivative compound for increasing crop yield refers to a yield enhancing effective amount of the compound sufficient to increase crop yield. The effective amount of compound can vary over a wide range depending on the particular compound employed, the particular crop to be treated, environmental and climatic conditions, and the like. The amount of compound used preferably does not cause substantial phytotoxicity, e.g., foliar burn, chlorosis or necrosis, to the crop. In general, the compound can preferably be applied to plants and crops at a concentration of from about 0.01 to 15 pounds of compound per acre as more fully described below.

The malonic acid derivative compounds contemplated by formula 1 can be employed according to a variety of conventional methods known to those skilled in the art. Compositions containing the compounds as the active ingredient will usually comprise a carrier and/or diluent, either liquid or solid.

- Suitable liquid diluents or carriers include water, petroleum distillates, or other liquid carriers with or without surface active agents. Liquid concentrates can be prepared by dissolving one of these compounds with a nonphytotoxic solvent such as acetone, xylene, nitrobenzene, cyclohexanone or dimethyl formamide

35

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 is 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 it is applied to the plant and wash it off the plant. Nonionic, anionic, or cationic 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 is dispersed in and on an appropriately divided solid carrier such as clay, talc, bentonite, diatomaceous earth, fuller's earth, and the like. In the formulation of the wettable powders, the aforementioned dispersing agents as well as lignosuifonates can be included.

The required amount of the active ingredient contemplated herein can be applied per acre treated in 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 in the liquid concentrate will

36

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 in the conduct of this invention can also contain other optional ingredients such as stabilizers or other biologically active compounds, insofar as they do not i.-pair 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 insectiddal, herbicidal, fungicidal, nematicidal, miticidal, 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.

The malonic acid derivative compounds of formula 1 are preferably applied to plants and crops under average or normal growing conditions. The malonic.^acid derivative compounds used in this invention can be applied during the plant vegetative growth phase or the plant reproductive growth phase to obtain increased crop yield. It may be desirable for some crops to apply the malonic acid derivative compounds at the reproductive growth phase including, for example, the early flower stage,

37

fruit set stage or full flower bloom stage. In other crops, it may be desirable to apply the malonic acid derivative compounds at the vegetative growth phase. The application timing will in general depend upon the particular crop to be treated.

Such compounds are useful in agriculture, horticulture and related fields for increasing crop yield. An increase in crop yield can be attributable, for example, to various plant growth effects such as increased branching (increased reproductive sites), early pod (fruit) set, increased blossom set and inhibition of blossom (flower and fruit) abscission during early stages of plant reproductive development. As used herein, increased crop yield refers to an increase in the raw agricultural commodity in terms of harvestable yield, e.g., bushels of seeds, bales of cotton and the like. It may be possible to have an increased harvestable yield for a treated crop in comparison with an untreated crop, yet the total crop biomass may be less for the treated crop. However, harvestable yield as used herein may be inclusive of total crop biomass, e.g., bushels of corn per acre and the like. Treatment of certain crops such as alfalfa.-with the malonic acid derivative compounds of formula 1 may also increase the crop nutritional value, e.g., total digestable nutrients (TDN).

As used herein, plants and crops refer in general to any agronomic or horticultural crops, ornamentals and turfgrasses. Illustrative of plants and crops which can be treated by the malonic acid

38

derivative compounds of formula 1 according to the method 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.

The malonic acid derivative compounds contemplated herein are effective for increasing crop yields. Such compounds have a high margin of safety in that when used in sufficient amount to provide a yield enhancing effect, they do not burn or injure the crop or plant, and they resist weathering which indudes-wash-off caused by rain, decomposition by ultraviolet light, oxidation, or hydrolysis in the presence of moisture or, at least, such decomposition, oxidation, and hydrolysis as would materially decrease the desirable yield enhancing characteristic of the active ingredient or impart undesirable characteristics, for instance, phytotoxicity, to the active ingredients. Mixtures of the active compounds can be employed if desired as wel as combinations of the active compounds with other biologically active compounds or ingredients as indicated above.

This invention is illustrated by the following examples.

39

Example I Preparation of ethyl 3-.(4-f1uoropheπyl)amiπol- 3-oxopropanoate Into a nitrogen-purged, air-stirred reaction flask was charged 4.44 grams (0.04 mole) of 4-fluoroaniline, 4.05 grams (0.04 mole) of triethylamine and 200 mmiliters of tetrahydrofuran solvent. A 6.02 gram (0.04 mole) portion of ethyl malonyl chloride was added rapidly with stirring at room temperature followed by a few milliliters of tetrahydrofuran. The temperature rose to 42°C and triethylamine hydrochloride separated therefrom. The mixture was then stirred at ambient temperature and the triethylamine hydrochloride filtered off, washed with solvent and dried to give 5.2 grams (0.04 mole). The filtrate was freed of solvent and the resulting purple solid dissolved in methylene.- chlorlde, washed with 2N HCl (3 x 75 milliliters), and water (2 x 75 mmmters), and then dried and stripped to give a crude solid product. Recrystal- lization from ethyl acetate- cyclohexane followed by flash column chromatography gave 3.47 grams (0.015 mole) of ethyl 3-[(4-fluoro- phenyl)amino] -3-oxopropanoate (Compound 1) having a melting point of 68°C-71°C.

Example II In a similar manner Compounds 2-76 were prepared and identified in Table A.

«__

« _* X w tr ₀

• _* 1 α O D f* y «_» jo • e —

- - e * _* m I

0.

Repretenlatlve Halonlc A d Derivative Cowpoundt

Subttltutntt Elemental Anal

Coapwnd *'l *'l ϊ'l Calculated

__L

11 C-H _$ 4-CH ₃ NH NHR (COCI.): J 1.11-1.39 (t.3 3.44 (i.2H); 4.01-4.42 (q.2H).

• 1.9-9.3 (br s. H) pp«.

IR C.H. 2.6-(CH _j ) ₂ NH NHR (COCI-):./ ^* 1.14-1.46 (t,3H 2.40 (I.2H). 4.01-4.40 (q.2H). 1.31-1. B (br s.H) ppM.

It 46.44 3.41 4.42

^C 2 ^H 4 2-cr ₃ -4-ci NH

20 2.3-C1- NH 41.14 4.02 4.01

^C 2 ^H J

21 2.5-C1. NH 41.14 4.02 !>.0t

^C 2 ^M 4 2 3.4-8r. NH 36.19 3.04 3.B4

^C 2 ^H $ . 1 2-CH -S-CI NH 46.31 4.42 4.48

^C 2 ^H 4 4 3.4.5-CI ₃ NH 42.44 3.24 4.41

^C 2 ^H i 4 2-CH -4-CI NH 46.31 4.42 4.48

^C 2 ^H 4 6 ?,4 Cl ₂ NH 41.64 4.02 4.01 ^C 2 ^M S 1 ^C Λ 4-CM S- NH 46.89 4.91 4.43

-tΛltL A <f_t-_ Repretenlatlve Halonlc Acid flerlvatlve Cow ^p oundt

O

II

R,0 -C-CH xr Qf

niiH • ιcp _ff t _t |

Representative Halonlc Add flerlvatlve Cowpoundt

Hepretentatlve Halonlc A d Oerlvatlve Cowpoundt

'lO-C-CH _j -C-Y,'-^^

Subttttuentt elemental Analyst* H 1ting

Cowpe—< «'l **1 ^~ -\ Ca culated found Point

NΦ. C H N C H N ^• c

SI C.H. 2-CH ₃ 0-3.4-CI ₂ NH 41.08 4.28 4.48 41.10 4.22 4.61 90-92

SI 2-CH ₃ -4-Br-S-CI NH 43.01 3.92 4.19 41.84 4.31 3.12 132-114

^C 2 ^H S

St 4 (4-CIC^H.O) - NH 61.18 4.83 4.20 61.21 4.94 4.14 86-81

^C 2 ^H 4

60 C ₂ H _S 1- NH 48.44 4.16 3.41 48.91 4.23 3.29 Oil

61 1.96 10.91 6.66 3.12 98-100 s -CCCC] M 11.11 6.46

o

I Os-O

I o ~

-» 0 0 ff ^, 0 *_ -- _" _> -> β» '"- 0 "_ ^l

•» '- —» -- _' — * © *- © <_ O W β tf -

M D -h O O Q —) _' _> l_l _- f>- β fsJ W

v* _» _^ o a. _. _. _—. * u« ι^ 9 ^> v _. -. l» e> -J •> o — o o w _. — i^

46

Example III Preparation of ethyl 1-(2-methyl-4,5-dich1oro- pheny1aminocarbonyPcyclopropaπecarboxylate Into a nitrogen-purged round bottom flask was charged 5.53 grams (0.03 mole) of 2-methyl- 4,5-d1chloroanil1ne, 3.18 grams (0.03 mole) of triethylamine and 190 milimters 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 triethylamine 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 l-(2-methyl-4,5-d1chloropheny1aminocarbonyl)cyclo- propanecarboxylate (Compound 77) having a melting point of 105°C-107°C.

Example IV In a manner similar to that employed in Example.'.III, Compounds 78-96 were prepared and identified in Table B.

Repretentatlve Halonlc Add Derivative Cowpoundt

Melting

Elemental Analyttt

Subttltuentt Polnt ' Calculated found

CMpo-nd TT c H N C H N *C _____

46.38 3.49 4.16 46.69 3.99 4.10 130-132. 12 101-110

41.61 4.14 4.64 41.94 4.34 4.

41.61 4.34 4.64 41.21 4.43 4.46 94-98

41.61 4.34 4.64 41.36 4.48 4.49 104-108

44.64 4.49 4.90 44.92 411 4.84 94.4-96

48.32 4.21 4.21 48.14 4.29 4.16 91-93

40.02 4.42 4.49 40.18 4.69 4.42 92.4-94

39.92 3.34 3.58 40.18 3.41 1.60 128-130

39.92 3.34 3.4B 39.82 3.32 1.46 91-92.4

102-103.

39.92 1.34 3.58 40.02 3.61 1.11

44.04 3.18 4.04 44.28 1.98 1.90 109-110.

44.04 1.18 4.04 44.89 4.29 1.80 94-96

44.04 1.18 4.04 44.16 4.20 1.19 113-116 14 4.14 1.86 119-121 r-4-Cl 46.62 4.19 3.88 48.

lABIj f (Cot.) Repretenlatlve Halonlc Acid Derivative Cowpoundt

Subttltuen|t Elemental Analytlt HeIting

Compound « 2 ''J Calculated found Point

.' »- 1 C H N C H N •c

12 2-E-4-Br 41 •?9 3.91 4.24 46.81 4.01 4.02 102-103

^C 2 ^H 4 tl H 66 .81 6.41 6.00 66.54 6.48 4.80 84-B9

^C 2 ^H 4 14 41 .61 4.34 4.64 41.42 4.42 4.36 (4-(I ^C 2 ^H 4 ι.s-ci ₂

IS C ₂ H _$ 4-C.N 64 .10 4.46 10.14 64.02 4.41 10.(1 129-132 96 C ₂ H _$ 2-CH ₃ -4-lr 41. .54 4.94 4.29 41.12 4.14 4.31 89-91

49

Example V Preparation of 3-r(4-bromo-2-methylphenvD- aminol-3-oxopropanoic acid A 6.0 gram (0.02 mole) portion of ethyl 3-[(4-bromo-2-methylphenyl)amino]-3-oxopropanoate prepared in Example I (Compound No. 75) was dissolved in approximately 80 milliliters 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 drynoss 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)- amino]-3-oxopropano1c acid (Compound 97) as a white solid having a melting point of 163°C-165°C.

Example VI In a manner similar to that employed in Example V, Compounds 98-109 were prepared.

________

Repretenlatlve Halonlc Ac id Der ivat ive '■ ^' rapoundt

Substituents tied lental Anal lysl * He 1 ting

Camp lend «'l - ϊ'ι Calculated round Point ft. C H N C H N •c

91 H 4 Cl 40.(0 1.11 . 6.46 40.61 3.80 6.31 140-141 tt H 2-CH ₃ -4-βr-S-Cl 19.18 2.96 4.41 39.16 3.14 4.44 18I-IB2

100 H l.S-lr ₂ 12.08 2.09 - 4.16 12.34 2.33 4.04 164-164.4

101 H 2-r-4-βr 19.15 2.46 4.01 39.24 2.42 4.94 161-162

102 H 2.4.5-C1 ₃ 38.26 2.14 4.96 38.41 2.12 4.B4 114-114.4

101 H 2-βr-4-CH ₃ NHH(CDCI_/0HSO-d _fc ) : / 2.21(1. 3H) , , 3.4(s.2H) . 144-141

6.94-8.01 (m.4H). 9 .4-9.1 (br *. MJppm.

104 H 2-Br-4-CI 36.94 2.41 4.1* 31. 18 2.11 4.11 159- 161

I0S H 2-Cl-4-Br 36.94 2.41 4.19 31.10 2.60 4.16 165.4-161

106 H 2.4-Br ₂ 32.08 2.09 4.16 32.21 2.23 4.13 141-149

101 H 1.4 βr ₂ 32.08 2.09 4.16 31.96 2.22 4.08 14. 4

101 N 2,4-Cl, NHR(C0CI /0HS0-d ) : J 2.49-2.64 (brt.H) . 3.42 (s,2H) ,

1.11-8.24 (m.3H). 9.86-10.04 (br S.H)ppw.

109 1-C1-4-CH, KHR(CDCI ₃ /-HS0-d _t ) : J 2.30 ( t.3H). 2.44-2.61 (br t. H) . 3.34 (t,2H) .

1.14-1.16 (m. 3H) . 10.04 -10.21 {br s.H)ppw.

51

Example VII Preparation of 1-(2-methyl-4.5-dich1oro- phenylaminocarbonvDcvclopropanecarboxyllc acid A solution containing 0.34 gram (0.006 mole) of potassium hydroxide and 0.109 gram (0.006 mole) of water in 80 millniters of ethanol was prepared in a 250 milllliter round bottom flask. With cooling to a temperature of 0°C in an ice/NaCl bath and stirring, a solution of ethyl 1-(2-methyl-4,5-dichloropheny1am1nocarbony1)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 2554 HCl 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 in a vacuum oven to give 1.85 grams (0.006 mole) of 1-(2-methyl-4,5- d1chlorophenylaminocarbony1)cyc1opropanecarboxy11c acid (Compound 110) having a melting point of 248°C-251°C.

52

Example VIII In a manner similar to Example VII, other Compounds 111-128 were prepared and identified in Table D below.

t α <-

5-3

Example IX Preparation of ethyl 1-(4-bromo-2-methylphenγl- aminocarbonyl)eyelobutanecarboxylate Into a nitrogen-purged reaction flask was charged 2.74 grams (0.01 mole) of 4-bromo-2-methyl- aniHne and 1.49 grams (0.01 mole) of triethylamine dissolved in 200 milliliters of tetrahydrofuran. With vigorous stirring, 2.80 grams (0.01 mole) of ethyl 1-chlorocarbonylcyclobutanecarboxyl te prepared in Example XIX were added and the resulting mixture stirred at ambient temperature for 6 hours. A precipitate of triethylamine hydrochloride 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 millinters) and water, and then dried over magnesium sulfate. Rotary evaporation gave a crude product which was flash chromatographed on silica using 7:3 hexane-ethyl acetate to give 3.68 grams (0.01 mole) of ethyl 1-(4-bromo-2-methy1- pheny1aminocarbonyljcyclobutanecarboxylate (Compound 129) as a white solid. A small sample which was recrystallized from hexane had a melting point of 61°C-64°C.

Example X

In a manner similar to Example IX, Compounds 130-134 were prepared and identified in Table E below.

________

Repretenlatlve Halonlc Add Oerlvat lve Cowpoundt

Substituents Elemental Analysis Melting'

Coined. "'4 Z'5 - Calculated Found Point

NO. C H N C H N ^• c

130 3.5-Cl ₂ 53.18 4.78 4.43 52.84 4.87 4.23 76.5-80

^C 2 ^H 5

111 C ₂ H _S 2.4.5-C1 ₃ 47.95 4.02 4.00 47.25 3.70 3.94 47-49 132 2.4-Cl ₂ 53.18 4.78 ^' 4.43 52.84* 4.67 5.11 Oil ^C 2 ^H 5

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

^C 2 ^H 5 . ₃₄ (-> C ₂ H ₅ 4-C1 59.68 S.73 59.89 5.70 85.5-87

(-) Prepared by tht ϋlxtd anhydrld. proctdurt of Example XXXIII.

55

Example XI Preparation of 1-(3.5-dichloropheny1- am1nocarbonyl)cvclobutanecarboxy11c acid A 2.0 gram (0.006 mole) portion of ethyl 1-(3,5-dichloropheny1aminocarbonyl)cyclobutanecarboxy- late prepared in Example X (Compound 130) was hydrolyzed in the presence of water (0.114 gram, 0.006 mole) and ethanolic potassium hydroxide (0.355 gram, 0.006 mole). The potassium salt of the acid was then acidified with 25% HCl solution and worked up 1n a manner similar to that described in Example VII to give 0.92 gram (0.003 mole) of 1-(3,5-di- chlorophenylaminocarbonyl)cyclobutanecarboxy11c acid (Compound 135) as a beige-colored solid having a melting point of 159°C-160°C.

Example XII In a manner similar to that employed in Example XI, Compounds 136-139 were prepared and identified in Table F below.

Repretenlatlve Halonlc Acid Oerlvatlve Cooφ.-ndt

SubstUuent Eleme. ital Analys is Melting

_______ F Calculated - Found Point

______ C ^' H N - c H N ^• c

136 2.4.S-C1, 44.68 ^' 3.12 4.34 44.88 3.14 4.23 146-147 137 2.4-Cl ₂ " 50.02 3.85 — 50.22 4.30 — 129-132 138 3.4-Cl ₂ 50.02 3.85 — 50.22 4.10 — 151-153 139 4-C1 56.81 4.77 56.99 4.94 159-161

57

Example XIII Preparation of ethyl l-(4-bromo-2-methylphenyl- aminocarbonyl)eyelopeπtanecarboxylate Ethyl 1-chlorocarbonylcyclopentane- carboxylate (3.10 grams, 0.02 mole) prepared in Example XX, 4-bromo-2-methylani line (2.82 grams, 0.02 mole) and triethylamine (1.53 grams, 0.02 mole) were reacted in tetrahydrofuran (200 mmmters) under conditions similar to that described in Example I to give 2.40 grams (0.007 mole) of ethyl 1-(4-bromo-2-methylphenylaminocarbony!)eyelo- pentanecarboxylate (Compound 140) which, after recrystallization from hexane, had a melting point of 64°C-67 ^β C.

Example XIV PreparationOf ethyl 2-(4-bromo-2- methylphenylaminocarbonyDbutanoaτe Ethyl 2-(chlorocarbonyl)butanoate (5.8 grams, 0.03 mole), 4-bromo-2-methylaniline (5.0 grams, 0.03 mole) and triethylamine (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-methylphenylamino- carbonyl)butanoate (Compound 141) as a white solid having a melting point of 98°C-100°C.

Example XV In a manner similar to Example XIV, Compounds 142-152 were prepared and identified irr Table G below.

_______

Repretenlatlve Halonlc Add Oer v.' Cow ^p oundt

142 143 144

144

146

141

148

I4t

141 ISI

152

59

Example XVI Preparation of 3-r(4-bromo-2-methylphenyl)- am1nol-2-bromo-2-methyl-3-oxopropanoic acid A 1.25 gram (0.003 mole) portion of ethyl 3-[(4-bromo-2-methylphenyl)amino]-2-bromo-2-methyl-3- oxopropanoate prepared in Example XV (Compound 144) was hydrolyzed with water (0.06 gram, 0.003 mole) and ethanolic potassium hydroxide (0.21 gram, 0.003 mole). The potassium salt of the acid was then acidified with concentrated HCl and worked up in a manner similar to that described in Example VII to give 1.04 grams (0.003 mole) of 3-[(4-bromo- 2-methy1phenyl)am1no]-2-bromo-2-methy1-3-oxopropanoic acid (Compound 153) as a white solid having a melting point of 133°C-136°C.

Example XVII Preparation of N-butyl 3-r(4-bromo-2- methylphenv1)am1no1-3-oxopropanamide A mixture of 4.90 grams (0.02 mole) of ethyl 3-[(4-bromo-2-methylpheny1)amino]-3- oxopropanoate prepared 1n Example I (Compound No. 75), 358 grams (4.9 moles) of n-butylamine , 150 milimters 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 (Compound 154) having a melting point of 123°C-125°C.

60

Example XVIII

Preparation of ethyl 1-chlorocarbonyl- cvclopropanecarboxylate

Into a stirred solution containing 15.1 grams (0.27 mole) of potassium hydroxide in 240 milliliters of ethanol and 4.83 grams (0.27 mole) of water was added dropwise, with cooling at a temperature of 0°C, 50.0 grams (0.27 mole) of dlethyl 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 in 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 milliliters). The ether extract was dried over magnesium sulfate and vacuum stripped to give the monocarboxylic acid as a clear liquid. The clear liquid was dissolved in 300 mmiliters 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-chlorocarbonylcyclopropanecarboxylate (Compound 155). NMR analysis of the product indicated the following:

NMR (CDC1 ₃ ): 1.22-1.50 (t, 3H), 1.75

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

61

Example XIX Preparation of ethyl 1-chlorocarbonylcyclo- butanecarboxylate Diethyl 1 ,1-cyclobutanedicarboxylate (20.0 grams, 0.10 mole) was saponified with 6.59 grams (0.10 mole) of potassium hydroxide in a mixture of 200 milliliters of ethanol and 1.80 grams (0.10 mole) of water and worked up to give the monocarboxylic acid which was reacted with thionyl chloride (8.86 grams, 0.07 mole) in methylene chloride solution as described in Example XVIII. Removal of the solvent gave 7.48 grams (0.04 mole) of ethyl 1-chlorocarbonylcydobutanecarboxylate. NMR analysis of the product indicated the following: NMR (CDC1 ): 1.10-1.44 (t, 3H), 1.7-2.85 (m, 6H), 4.05-4.5 (q, 2H). ppm.__

Example XX Preparation of ethyl 1-chlorocarbonyl- cyclopentanecarboxylate In a manner similar to the procedure described in 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 diethyl 1,1-cyclo- pentanedlcarbox late was converted into 5.67 grams (0.03 mole) of ethyl 1-chlorocarbonylcydopentane- carboxylate (Compound 157). NMR analysis of the product indicated the following:

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

62

Example XXI

Preparation of ethyl 2-bromo-2-chloro- carbonylpropanoate

In a manner similar to the procedure described in Example XVIII, except that refluxing with thionyl chloride in 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 diethyl 2-bromo-2-methylma1onate was converted into 12.94 grams (0.05 mole) of ethyl 2-bromo-2-chloro- carbonylpropanoate (Compound 158). This compound was employed ^' n the preparation of Compound Nos. 144-148 and 152 in Example XV. NMR analysis of the product indicated the following:

NMR (CDC1 ): 1.10-1.47 (t, 3H),

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

2H) ppm.

Example XXII Preparation of ethyl 3-r(4-chlorophenyl)amino1-3- oxopropanoate 4-Chloroanlline (25.4 grams, 0.20 mole) and diethyl malonate (48 grams, 0.30 mole) were reacted in a manner similar to the procedure described by A.K. Sen and P. Sengupta, Jour. Indian Chem. Soc. 46. (9), 857-859 (1969). The reaction afforded a greenish colored solid which was recrystallized from toluene-hexane (1:1) and then from isopropyl ether to give 9.0 grams (0.04 mole) of ethyl 3-[(4-chloropheny1)amino]-3-oxopropanoate (Compound 159) as white crystals having a melting point of 82°C-83°C.

63

Example XXIII Preparation of ethyl 3-r(4-methylthiazol-2-y1) aminol-3-oxopropanoate In a manner similar to the procedure described in Example I, 2-amino-4-methylthiazole was reacted with ethyl malonyl chloride employing triethylamine as the acid acceptor in tetrahydrofuran solution. The ethyl 3-[(4-methy1thiazol-2-y1)amino]-3-oxopropanoate product (Compound 160) (7.5 grams, 0.03 mole) was obtained as an off-white solid having a melting point of 138°C-141°C.

Example XXIV In a manner similar to Example XXIII, Compounds 161-173 were prepared and identified in Table H below.

64

N

64 A

H

I ABU H ( Con! .) Repretentat lve Halonlc Der ivative Cowpoundt

O O

8 a

H _s C ₂ 0-C-CH _r C-NH-

Elewental Analysts Helttng

Compound Calculated found Point _____ c H N C H N ^• c

ιto XX 49.40 4.41 11.44 49.34 4.(4 11.(9 99-100

111 46.(1 4.10 16.31 49.88 4.B3 16.24 132- 136

112 42.84 4.K 6.16 43.01 4.81 (.11 Oi l

^S-^CH ₂ "

111

64 C

Example XXV Preparation of ethyl 2-chlorocarbonyl-3- methyl-2-butenoate Diethyl isopropylidenemalonate (30 grams, 0.15 mole) was saponified with 10.0 grams (0.15 mole) of potassium hydroxide in 200 milliliters of ethanol solution and worked up to give the monocarboxylic acid which was then reacted with thionyl chloride (10 mllimters, 0.1 mole) in methylene chloride solution in a manner similar to the procedure described in Example XVIII. Removal of solvent gave 9.6 grams (0.05 mole) of ethyl 2-ch1orocarbonyl-3- methyl-2-butenoate. NMR analysis of the residue product in COCI solution indicated complete conversion of the carboxylic acid to the acid chloride as evidenced by absence of a downfield carboxylic acid proton. This compound is referred to hereinafter as Compound 174.

Example XXVI Preparation of ethyl 2-T(4-bromo-2-methylpheπyl)- aminocarbonvn-3-methyl-2-butenoate In a manner similar to the procedure described in Example I, ethyl 2-chlorocarbonyl- 3-methy1-2-butenoate (9.6 grams, 0.05 mole) prepared in Example XXV, 4-bromo-2-methylaniline (5.3 grams, 0.03 mole) and triethylamine (4.0 mnimters, 0.03 mole) were reacted to give 2.9 grams (0.009 mole) of ethyl 2-[(4-bromo- 2-methylphenyl)am1nocarbonyl]-3- methyl-2-butenoate (Compound 175) as a white solid having a melting point of n6 ⁰ C-119 ⁰ C.

65

Example XXVII Preparation of 3.4-dichloro-2.5-d1methylannine A solution of 5.0 grams (0.03 mole) of 3,4-d1chloro-2,5-d1methyl-l-nitrobenzene in 70 milliliters of ethanol was hydrogenated at room temperature at 50 psi in the presence of 0.25 gram of 10"/4 palladium on activated carbon as a catalyst. Working up the reaction mixture gave 1.21 grams (0.006 mole) of 3,4-dichloro-2,5-dimethylaniline (Compound 176) as a yellow solid having a melting point of 72°C-76°C.

Example XXVIII Preparation of 4.5-dich1oro-2-methoχyaππine

Part A: Preparation of 2.2-d1methyl-N-(4-ch1oro- 2-methoχyphenyl)propanamide Into a stirred solution containing 10.0 grams (0.06 mole) of 4-chloro-2-methoxyan111ne and 6.42 grams (0.06 mole) of triethylamine in 200 milliliters of tetrahydrofuran was added 7.65 grams (0.06 mole) of trimethylacetyl chloride in a small amount of tetrahydrofuran solvent. The resulting mixture was stirred for two hours at room temperature. Triethylamine hydrochloride precipitated and was filtered off and the filtrate vacuum stripped to give a dark liquid which was taken up in methylene chloride. This solution was washed with 2N HCl (2 x 100 milliliters), then with water (1 x 100 miimiters), dried over magnesium

66

sulfate and solvent evaporated to give a crude product which was crystallized from hexane to give 6.82 grams (0.03 mole) of 2,2-dimethyl-N-(4-chloro- 2-methoxyphenyl)propanam1de as a first and second crop. NMR analysis of the product indicated the following:

NMR (CDC1 ₃ ): 1.32 (s, 9H), 3.91 (s, 3H), 6.83-7.08 (m, 2H), 8.28-8.52 (d, 2H) ppm.

Part B: Preparation of 2.2-dimethyl-N- (4.5-d1chloro-2-methoxy henyl)propanam1de Into a stirred solution containing 6.82 grams (0.03 mole) of 2,2-dimethyl-N-(4-ch1oro-2- methoxyphenyl)propanamide prepared in Part A in 150 miliniters of chloroform was added 3.81 grams (0.03 mole) of sulfuryl chloride over a 40 minute period. The resulting reaction mixture was heated under reflux for a 3 day period, each day cooling the mixture and adding an additional 3.81 grams (0.03 mole) of sulfuryl chloride before continuing the reflux. At the end of 3 days, thin layer chromatographic analysis of the mixture indicated the reaction to be complete. Volatiles were removed from the reaction mixture and 3.70 grams (0.01 mole) of 2,2-d1methyl-N-(4,5-dichloro-2-methoxypheny1)- propanamide (Compound 177) recovered as a light yellow-orange solid by flash column chromatography eluting with dlchloromethane. NMR analysis of this product indicate the following:

NMR (CDC1 ₃ ): 1.34 (s, 9H), 3.92 (s, 3H) , 6.94 (s, H), 8.08 (br s H) , 8.67 (s, H) ppm.

67

Part C: Preparation of 4.5-dich1oro-2- methoxyanlliπe The 2,2-dimethyl-N-(4,5-dichloro-2-methoxy- phenyl)propanamide (3.70 grams, 0.01 mole) prepared in Part B was dissolved in ethanol: 12N HCl (1:1), the mixture heated under reflux overnight and then freed of volatiles under rotary evaporation. Partition between 2N HCl and dichloromethane gave an acid-soluble fraction which was worked up to give 1.1 grams (0.01 mole) of pure 4,5-dichloro-2- methoxyaniline as determined by thin layer chromatographic analysis. The dichloromethane faction from above was freed of solvent giving starting material which was again refluxed overnight with ethanol: 12N HCl and worked up to give an additional 1.2 grams (0.01 mole) of pure 4,5-d1chloro-2-methoxyan1line as determined by thin layer chromatographic analysis. NMR analysis of the product indicated the following:

NMR (C0C1 ₃ ):63.88 (s, 5H) , 6.73-6.90

(d, 2H) ppm.

68 ,

Example XXIX

Preparation of 1-(4-bromo-2-methylphenylamiπo- carbonyDcyclobutanecarboxylic acid

A 3.0 gram (0.009 mole) portion of ethyl l-(4-bromo-2-methylpheny1aminocarbonyl)cyc1obutane- carboxylate prepared in Example IX (Compound 129) was hydrolyzed in a manner similar to that described in Example XI to give 2.19 grams (0.007 mole) of 1-(4-bromo-2-methylphenylaminocarbonyl)cyc1obutane- carboxylic acid, Compound 181, having a melting point of 154°C-155°C.

Example XXX

Preparation of ethyl (chlorocarbonyl)methoxyacetate

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 milliliters 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 mmniter-portion of ethanol was added and the mixture then refluxed for about 5 hours after which 1t 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 diethyl methoxymalonate, employed in the subsequent steps without purification.

69

Part 8. 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 milliliters 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 milliliters) to remove unsaponified diester. Acidification to pH=1 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 millinters of methylene chloride was stirred for about 17 hours and then evaporated free of volatile materials. As NMR examination indicated the reaction to be incomplete, the above thionyl chloride treatment 1n methylene chloride was repeated for a period of about 65 hours. A third treatment with 8.63 grams of thionyl chloride in 150

70

milliliters of methylene chloride was finally given, refluxing for a period of approximately 7 hours. Removal of volatiles under reduced pressure gave 6.0 grams (0.03 mole) of ethyl (chlorocarbonyl) ethoxyacetate, Compound 211. NMR analysis of the product indicated the following:

Η NMR (CDC! ) S 1.16-1.53(t, 3H, CH ) , 3.58(s, 3H, CH 0), 4.13-4.56 (q, 2H, CH ₂ ) 4.62 (s, H, CH) ppm.

Example XXXI

Preparation of ethyl 3-T(3,5-d1chloroph£nyl)aminol-

-2-methoxy-3-oxopropanoate

3,5-Dichloroaniline (2.69 grams, 0.02 mole) and ethyl (chlorocarbonyl)methoxyacetate (3.0 grams, 0.02 mole), prepared in Example LIII (Compound 211), were reacted in the presence of triethylamine (1.68 grams, 0.02 mole) in 200 m1ini1ters of methylene chloride in a manner similar to that described in Example I to give 1.34 grams (0.004 mole) of ethyl 3-[(3,5-d1chloropheny1)amino]-2-methoxy-3-oxopropano- ate, Compound 213, having a melting point of 89.5°C-92.5°C.

Example XXXII 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 miliπiters of methanol and 5.55 grams (0.3 mole) of water

71

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 diester. 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. NMR analysis of the product indicated the following:

Η NMR (COCI ) δ 3.54(s, 3H, alpha CH 0), 3.86(s, 3H, ester CH 0) , 4.51 (s, H, CH), 9.36(s, H, CO H) ppm.

Example XXXIII

Preparation of methyl 3-r(4-bromo-2-fluoro- pheny1)aminol-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-f1uoroan1l1ne in approximately 100 miimiters of dry tetrahydrofuran was fed

72

dropwise a solution of 3.87 grams (0.02 mole) of 1 ,3-dicyclohexylcarbodiimide in about 30 milliliters 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 (MgSO.) and solvent vacuum evaporated to give a colorless liquid. Flash column chromatography of !he latter on silica, eluting with hexane-ethyl acetate (7:3) gave, after workup, a liquid which crystallized on standing. Recrystallization 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-methoxy-3-oxopropanaote, Compound 215, having a melting point of 51°C-53°C.

Example XXXIV

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 in TableHa below.

TABLE H a Re _p resentative Halonlc Add Derivative Compounds

-

_

.91 101-103

49.49 4.15 4.81 49.88 4.29 4

217 4-CF3

218 4-Br 43.73 4.00 — 43.73 4.04 — 55-59

— 40.44 3.22 — 117-121

219 3.4.5-Cl ₃ 40.46 3.09

74

Example XXXV

Preparation of t-butyl 3-1 ^" (3,5-dichlorophenyl)amino1

-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 milliliters of carbon tetrachloride was added a mixture of 4.94 grams (0.07 mole) of anhycrous t-butyl alcohol, 4.50 milliliters (0.06 mole) of pyridine and 25 milliliters 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 aπ-c 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 milliliters of methylene chloride and partitioned with 100 milliliters of saturated aqueous sodium bicarbonate following which the organic phase was extracted with cold 10% hydrochloric acid (3 x 100 miiniiters), then with cold water (3 x 100 miimiters) after which it was dried (MgSO ) 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.

75

Part B Preparation of mono-t-butyl methoxymalonate

t-Butyl methyl methoxymalonate (7.57 grams, 0.04 mole), prepared in Part A, was saponified with potassium hydroxide (2.45 g, 0.04 mole) in a mixture of 25 miimiters of methanol and 668 microliters (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. NMR analysis of the product indicated the following:

*H NMR (C0C1 ) δ 1.45(s, 9H, t-butyl), 3.5d(s, 3H, CH 0), 4.45(s, H, CH), 10.51(s, H, CO H) ppm.

Part C Preparation of t-butyl 3-r(3.5-dichloro- phenyl)am1nol-2-methoxy-3-oxopropanoate

Mono-t-butyl methoxymalonate (5.42 grams, 0.03 mole), prepared 1n Part B, 3,5-dichloroaniline (4.62 grams, 0.03 mole) and 1 ,3-dicyclohexyl- carbodiimide (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-d1chlorophenyl)amino]-2-methoxy-3-oxopro- panoate having a melting point of 129.5°C-131.5°C.

76 ^•

Example XXXVI

Preparation of methyl 3-,(3.5-dich1orophenyl)aminol-

-2-methoxy-3-th1oxopropanoate

A mixture of 3.50 grams (0.01 mole) of methyl 3-[(3,5-dich1orophenyl)amino]-2-methoxy- 3-oxopropanoate (Compound 233, Example LXX), 2.42 grams (0.006 mole) of 2,4-bis(4-methoxypheny1)-l ,3- d1thia-2,4-diphosphetane-2,4~d1sulfide and 35 mil11li ers of anhydrous 1 ,1-dimethoxyethane was stirred at room temperature 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-dich1oro-phenyl)amino]-2-methoxy- 3-thioxopropanoate, Compound 238, having a melting point of 144°C-147°C.

Example XXXVII Preparation of 2-cvclopropeny1-1-carboethoxy-1-rN-

(2-methyl-4-bromophenyl) lcarboxamide

Part A. Preparation of diethyl bis(2.3-tr1methv1- s11yl)cyc1opropeπe-1.1-dicarboxylate

A 50 milliliter 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 bis(trimethylsilyl) acetylene and 0.40 gram (0.001. mole) of cupric ace- tylacetonate. Using an oil bath the temperature of

w ^*

77

the stirred mixture was raised to 145°C. Using a syringe pump 39.3 grams (0.21 mole) of diethyl diazomalonate were added over 36 hours. Heating at 1450C was continued for an additional 12 hours after all of the diazomalonate 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 diethyl bis(2,3-trimethylsilyl)cyc1opropene- 1 ,1-dicarboxylate as a yellow liquid. NMR analysis of the product indicated the following:

Η NMR (CDC1 ₃ ): b 0.23(s,18H), 1.20 (t, 6H), ^* ι.l7(q, 4H) ppm.

Part B. Preparation of diethyl cyclopropene-1 ,1- dicarboxylate ^»• -

A 500 miπmter round-bottom flask was equipped with a magnetic stirrer and N inlet. The flask was charged with 21.0 grams (0.07 mole) of diethyl bis (2,3-trimethyls11yl)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 mil11liters 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 diethyl cyclo-

78

propene-1 ,1-dicarboxylate as a yellow oil. NMR analysis of the product indicated the following: ^■ H NMR (CDCl ₃ ): _> 1.25 (t, 6H) , 4.23 (q, 4H); 7.08 (s, 2H).

Part C. Preparation of mono-ethyl cvclopropene-1.1- dicarboxylate

A 250 milliliter 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 diethyl- cyclopropene-1 _> 1 -dicarboxylate and 50 milliliters of ethanol. The stirred mixture was cooled in an ice bath and a solution of 1.33 grams (0.03 mole) of NaOH in 5.0 mi11inters of water was added dropwise. 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 ice water, and extracted twice with ether. The basic aqueous phase was acidified with ice cold 10% HCl, and extracted three times with ethyl acetate. The ethyl acetate was dried (MgSO.) and the solvent removed .under reduced pressure to leave an orange colored solid. This was recrystallized from hexane- ethyl acetate to give 3.65 grams (0.02 mole) of mono- ethyl cyclopropene-1 ,1-d1carboxy1ate as a light yellow solid having a melting point of 76.00C-77.50C. NMR analysis of the product indicated the following:

•H NMR (C0Cl ₃ ):c- 1.20 (t, 3H), 4.25 (q, 2H), 6.80 (s, 2H), 11.5 (br s, IH) ppm.

79

Part D. Preparation of 1-carboethoxy-l-ethoxy- carbonyloxycarboπyl-2-cvclopropene A 250 milliliter round-bottom flask was equipped with a magnetic stirrer and an addition funnel with N_ inlet. The flask was charged with 1.30 grams (0.008 mole) of mono-ethyl cyclopropene- l,1-d1carboxylate, 50 nil111liters of dry THF, 2.3 grams (0.02 mole) of potassium carbonate (anhydrous), and 450 milligrams of dicyclohexano-18- crown-6 ether. The stirred reaction mixture was cooled to 00C, and 0.90 gram (0.008 mole) of ethyl chloroformate 1n 10 milliliters of THF was added dropwise. The mixture was stirred for 2 1/2 hours at OOC. At this time an aliquot from the reaction mixture showed a very strong anhydride carbonyl stretch at 1820 cm in the infrared indicating the formation of the mixed anhydride 1-carbo- ethoxy-l-ethoxycarbonyloxycarbonyl-2-cyclo- propene. The balance of the reaction mixture containing the mixed anhydride was carried on to Part E.

Part E. Preparation of 2-cyclopropenyl-l-carbo- ethoxy-1-rN-(2-methy1-4-bromophenv1) 1 carboxamide

A solution of 1.40 grams (0.0075 mole) of 2-methyl-4-bromoan111ne in 10 mlimiters of tetrahydrofuran was added dropwise to the reaction mixture from part D at OOC. The mixture was allowed to come to room temperature and stirred for 2 hours. The reaction mixture was filtered and the

80

filtrate concentrated under reduced pressure to give an orange colored solid. This solid was washed with ether and recrystallized from hexane-ethyl acetate to give 1.5 grams (0.004 mole) of 2-cyclopropenyl-1- carboethoxy-l-[N-(2-methyl-4-bromophenyl) ]carboxamide, Compound 256, as a white crystalline solid having a melting point of 1510C-1530C.

Example XXXVIII

Effect of Representative Malonic Acid Derivative Compounds on Crop Yield Enhancement- Plant Axillary Stimulation

Plant axillary stimulation may be indicative of increased plant reproductive sites resulting in increased plant biomass and/or increased crop yield. Treatment of plants with certain malonic acid derivative compounds such as those compounds Identified in Table I below results in enhanced axillary stimulation.

Solutions of the test compounds identified in Table I were prepared by dissolving 68.8 milligrams of the particular compound in 5.5 mil11liters of acetone and then adding water to a final volume of 11.0 miimiters. If clouding of the solution occurred as the water was added, the use of water was discontinued and acetone was added to a final volume of 11.0 miinnters. The resulting stock solutions contained 6255 parts per million by weight of the particular compound. The test concentrations in parts of the test compound per million parts by weight of final solution employed in the axillary stimulation tests in Table I were obtained by appropriate dilution of the stock

81

suspensions with acetone and water (50/50 volume/volume). Seeds of snapbeans, wheat, velvetleaf, cucumber, sunflower, flax, buckwheat, tomato, perennial rye, marigold, soybean, barnyard grass, wild oats and pea were planted in a sandy loam soil in a flat having the following dimensions: 3.5 inches in width x 7.9 inches in length x 1.0 inches in height. Twelve to fourteen- days after planting at the time the first trlfoliolate of leaf snapbean was at least 3.0 centimeters long, each concentration of the test compounds identified in Table I was applied to one flat as a foliar spray by use of an aspirated spray apparatus set at 10 pslg air pressure (all flats sprayed at a rate of 4 pounds per acre). As a control, a water-acetone solution containing no test compound was also sprayed on a flat. When dry, all of the flats of plants were placed in a greenhouse at a temperature of 80°F i 5°F and humidity of 50 percent + 5 percent. Visual Indications of axillary stimulation activity were observed and recorded 10 to 14 days after treatment.

Visual observations of axillary stimulation were recorded employing a system of numerical- ratings. Numerical ratings from "0" to "10" were used to designate the degree of axillary stimulation activity observed in comparison with the untreated control. A "0" rating Indicates no visible response, a "5" rating indicates 50 percent more axillary stimulation than the control, and a "10" rating indicates 100 percent more axillary stimulation than the control. This rating system

82

indicates the degree of axillary bud growth on broadleaf plants and the degree of tillering on grasses in comparison with an untreated control ^, The results are reported in Table I.

83 ^"

TABLE I

Effect of Representative Malonic Acid

Derivative Compounds on Crop Yield Enhancement -

Axillary Stimulation on Snapbean Plants

Compound Axillary Stimulation

No. Rating

Control 0

1 1

2 2

3 1 5 1

8 1

9 1 11 1 15 1

21 1

22 5

23 2

24 2

25 1

26 3

27 1

28 1

34 5

35 1

36 1

37 1

38 1 40 1

84

TABLE I , Cont . _

Effect of Representative Malonic Acid Derivative Compounds on Crop Yield Enhancement Axillary Stimulation on Snapbean Plants

Compound Axillary Stimulation No. Rating

43 1 46 3 47 50 57 58 66 67 2 68 2 69 2 70 2 71 1 75 6 79 80 82 83 84 86 88 90 92 95

85

TABLE I ( Cont . )

Effect of Representative Malonic Acid

Derivative Compounds on Crop Yield Enhancement -

Axillary Stimulation on Snapbean Plants

Compound Axillary Stimulation

No. Rating

98 1

99 1

100 1

101 1

102 2 105 1

107 1

108 1

110 2

111 2

112 1

114 2

11 5 1

116 1

117 1

120 1

121 1

122 1

123 1

125 2

126 2 129 1 135 1

86

TABLE I ( Cont . )

Effect of Representative Malonic Acid

Derivative Compounds on Crop Yield Enhancement -

Axillary Stimulation on Snapbean Plants

Compound Axillary Stimulation No. Rating

140 1

141 2

144 2

145 1

146 1

148 2

149 1

150 1 159 2 168 1 173 1 175 4

87

TABLE I

Effect of Representative Malonic Acid Derivative

Compounds on Crop Yield Enhancement -

Axillary Stimulation on Wheat

Compound Axillary Stimulation No. Rating

Control 0

1 2

2 1

14 2

22 1

66 3

67 3

69 1

88 1

96 4

97 3

83 2

175

144

129

116

117

121

146

145

88

The results in Table I demonstrate that treatment of plants with certain malonic acid derivative compounds provides signficantly enhanced axillary stimulation which may be indicative of increased plant reproductive sites resulting in increased plant biomass and/or increased crop yield.

Example XXXIX Effect of Representative Malonic Acid Derivative Compounds on Crop Yield

Enhancement-Wheat Solutions of Compound 75 were prepared by dissolving either 0.48 grams, 0.96 grams or 1.92 grams of the compound into 800 millinters acetone. Water plus 0.2 percent by volume of SurfelK spray adjuvant were added to each of the above solutions to a final volume of 1600 mii iters. SurfelK spray adjuvant 1s commercially available from Union Carbide Corporation, Danbury, Connecticut.

The above formulations were applied to wheat by utilizing a statistical treatment procedure involving 42 separate plots. Each plot consisted of 8 rows individually 30 feet 1n length and about 0.75 feet between rows.- The entire plot was treated with the prepared solutions containing the active ingredient identified 1n Table J below. The experiment was designed as a randomized complete block of six different repetitions in which each repetition included the following:

89

(1) an untreated control;

(2) treatment with 0.48 grams/plot of Compound 75 at time T designated in Table J;

(3) treatment with 0.96 grams/plot of Compound 75 at time T, designated in Table J;

(4) treatment with 1.92 grams/plot of Compound 75 at time T.. designated in Table J;

(5) treatment with 0.48 grams/plot of Compound 75 at time T„ designated in Table J;

(6) treatment with 0.96 grams/plot of Compound 75 at time T- designated in Table J; and

(7) treatment with 1.92 grams/plot of Compound 75 at time T. designated in Table J.

The above formulations were applied to each plot by use of a carbon dioxide backpack sprayer set at about 30 psig air pressure. The planting, application and harvesting times for each crop are detailed 1n Table J. The harvested wheat crops for yield determination Included the inner 20 feet of the middle 4 rows in each plot (5 feet in from ends of the middle 4 rows). The values obtained for each plot in each repetition were averaged to obtain the results in Table 3.

Two weeks prior to harvest, the wheat plants from 2 separate 1 square foot sections of each plot were sampled (subsamples) and the number of Inflorescences and seeds per Inflorescence were determined. The values of the subsamples per plot together with the values obtained for each plot in each repetition were averaged to obtain the results in Table J.

IA8U J

Effect of Repretentatlve Halonlc Add Derivative Compounds on Crop yield tnhancewent - Wheat

Compound Concentration Application Infloretcence Seeds per Actual Yield ______ liming' per square foot Inflorescence (ktlogr_M-/plot)

Control 66 29 4.9

Z-mφQunύ IS 0.48 12 29 5.3

O

0.96 64 30 5.0

1 .92 64 31 4.0

Compound 15 JD.4B 61 28 5.0

0.96 . 64 29 5.0

1.92 66 28 4.0

• first application at flag leaf emergence (1.). 49 days after planting; second application at fla« leaf fully-expanded (1 ), S3 days after planting; and harvesting occurred 19 days after planting-

91

The results in Table J demonstrate that treatment of wheat with certain malonic acid derivative compounds provides significantly increased yields in comparison with untreated control wheat. As demonstrated in Table J, the increased yield may be attributable to an Increase in the number of inflorescences or an increase in the number of seeds per inflorescence or a combination thereof.

Example XL

Effect of Representative Malonic Acid Derivative

Compounds on Crop Yield

Enhancement-Alfalfa

Solutions of Compound 75 were prepared by dissolving either 70 milligrams, 140 milligrams or 280 milligrams of the compound Into 87 miimiters of acetone. Water plus 0.2 percent by volume of Triton X-100 surfactant were added to each of the above solutions to a final volume of 174 miimiters. Triton X-100 surfactant is commercially available from Rohm and Haas Company, Phildelphla, Pennsylvania.

The above formulations were applied to alfalfa by utilizing a statistical treatment procedure involving 24 separate plots. Each plot measured 5 feet by 10 feet. The entire plot was treated with the prepared solutions containing the active Ingredient in Table K below. The experiment was designed as a randomized complete block of six different repetitions 1n which each repetition included the following:

92

(1) an untreated control;

(2) treatment with 70 milligrams per plot of Compound 75 at 45 days after planting;

(3) treatment with 140 milligrams per plot of Compound 75 at 45 days after planting; and

(4) treatment with 280 milligrams per lot of Compound 75 at 45 days after planting.

The above formulations were applied by use of a carbon dioxide bicycle sprayer set at about 30 psig air pressure. Three weeks after treatment, eight plants per plot were harvested. The plants were separated into stems and leaves. p ^" >aced in a drying oven and dried for a ι|riod of 48 hours at a temperature of 90°C. The leaf and stem components were weighed separately and these results are reported in Table K. Total dry weight and leaf/stem ratio were calculated from tfve leaf and stem dry weight data and these results are reported in Table K. The values obtained for each plot in each . repetition were averaged to obtain all of the results in Table K.

Ύ\

1A11E K

Effect of Representative Halonlc Add Derivative Cowpoundt on Crop Yield tnhancewent - Alfalfa

Leaf Stem Iota)

Compound Concentration Dry Ut. Dry Ht. Dry Ut. Leaf/Stem % Increase ^■

#t- (grawt/plot) (grant) _a_._!U f _rawt) Ratio 1ϋ.LE_l-____-_.__L_la

Contrαl 2.31 1.45 3.91 1.54

Compound 75 0.7 2.16 1.51 4.-8 1.83 19 1.4 3.12 1.51 4.(3 2.09 36 2.8 3.20 1.40 4.(0 2.14 52

94

The results in Table K demonstrate that treatment of alfalfa with certain malonic acid derivative compounds provides significantly increased yields in comparison with untreated control alfalfa. As demonstrated in Table K, the treated alfalfa exhibited an increase in leaf dry weight, a decrease in stem dry weight and an increase in total dry weight (leaf and stem) in comparison with untreated control alfalfa. A significant increase in leaf-stem ratio for treated alfalfa versus untreated control alfalfa is demonstrated by the results in Table K.

Example XLI .

Effect of Representative Malonic Acid Derivative Compounds on Crop Yield Enhancement-Soybeans Solutions of Compound 75 were prepared by dissolving either 0.39 grams, 0.78 grams or 1.56 grams of the compound into 650 milliliters acetone. Water plus 0.2 percent by volume of SurfelK spray adjuvant were added to each of the above solutions to a final volume of 1300 millinters. SurfelK spray adjuvant is commercially available from Union Carbide Corporation, Danbury, Connecticut.

The above formulations were applied to soybean plants by utilizing a statistical treatment procedure involving 42 separate plots. Each plot consisted of 4 rows individually 20 feet in length and about 3 feet between rows. The middle two rows of each plot were treated with the prepared solutions containing the active ingredient

95

identified in Table L below. The experiment was designated as a randomized complete block of six different repetitions in which each repetition included the following:

(1) an untreated control;

(2) treatment with 0.39 grams/plot of Compound 75 at time T. designated in Table L;

(3) treatment with 0.78 grams/plot of Compound 75 at time T.. designated in Table L;

(4) treatment with 1.56 grams/plot of Compound 75 at time T. designated 1n Table L;

(5) treatment with 0.39 grams/plot of Compound 75 at time T designated in Table L;

(6) treatment with θ ?| grams/plot of Compound 75 at time T„ designated in Table L; and

(7) treatment with 1.56 grams/plot of Compound 75 at time T designated in Table L.

The above formulations were applied- to each plot by use of a carbon dioxide backpack sprayer set at about 30 psig air pressure. The planting, applicaton and harvesting times are detailed in Table L. The harvested soybean crops for yield determinaton included the inner 10 feet of the middle 2 rows in each plot (5 feet in from ends of

* ^*• ! the middle 2 rows). The values* obtained for each plot (kilograms of soybeans/plot) in each repetition were averaged to obtain the results 1n Table L.

Four weeks following the applications at time T-, eight soybean plants were sampled from each plot to determine the number of fruits (pods) per plant. The values obtained for each plant were averaged to obtain the results in Table L.

wi

Effect of Repretentatlve Halonlc Add Oerlvatlve Cowpoundt on Crop Yield Enhancement - Soybean.

Compound Concentration Application Podt per Actual Yield No. (grant/plot) Timing' Plant (ktlograw/plot)

Control 14 I.II

Compound 15 0.39 flowering (1 1 71 1 .21 0.18 flowering (1 ) 91 1.4B 1.44 flowering (1 ) 8) 1 .31

Compound 15 0.39 3 weekt after flowering (! ) 102 1.04 0.11 3 weekt after flowering-(1 ) 174 1 .41 1.46 3 weeks after flowering (1 1 122 1 .13

* rirst application at flowering (1 ), 71 days after planting; second application at 3 weeks after lowering (1 ), 98 days after planting; and harvesting occurred 180 days after planting.

97

The results in Table L demonstrate that treatment of soybean plants with certain malonic acid derivative compounds at certain rates provides significantly increased yields in comparison with untreated control soybean plants. As demonstrated in Table L, in addition to an increase in actual yield (kilograms of soybeans/plot), the treated soybean plants exhibited an increased number of pods per plant in comparison with untreated control soybean plants.

Example XLII Effect of Representative Malonic Acid Derivative Compounds on Crop Yield J

Enhancement-Soybeans

Solutions of Compound 75 were prepared by dissolving either 0.75 grams or 1.5 grams of the compound into 125 miimiters acetone. Water was added to each of the above solutions to a final volume of 250 miimiters.

The above formulations were applied to soybean plants by utilizing a statistical procedure involving 36 separate plots. Each plot consisted of 4 rows individually 25 feet in length and 2.5 feet between rows. The middle two rows of each plot were treated with the prepared solutions containing the active ingredient identified 1n Table M below. The experiment was designed as a split-plot design with six different repetitions. The experiment was divided Into two blocks as follows: Block 1 consisted of those plots treated at first flower and Block 2 consisted of those plots treated at 3 weeks .

98

after first flower. Randomized within each block were:

(1) an untreated control;

(2) treatment with 0.75 grams of Compound

75; and

(3) treatment with 1.5 grams of Compound

75,

The above formulations were applied to each plot by use of a carbon dioxide backpack sprayer set at about 30 psig air pressure. The planting, application and harvesting times are detailed in Table M. The middle two rows of each plot were harvested for yield determinations. The values obtained for each plot in each repetition were averaged to obtain the results in Table M.

Four weeks prior to harvest, 5 soybean plants were sampled from each plot to determine the number of fruits (pods) per plant. The values obtained for each plant were averaged to obtain the results in Table M.

IABU M

Ef fect of Repretentatlve Halonlc Add Oerlvat lve Cowpoundt on Crop Yield Enhancement - Soybean!

Compound Concentration Application Podt per Actual Yield

____. (grjmt/plot) Timing* Plant . ._U-gi.w-.pl_t)

Control first flower (1 ) 49 3.14

- Compound 14 0.14 f lrtt f lower (! ) 10 4.11 1.50 f irst f lower (I ) 13 3.94

Control 3 weeks after flrtt flower (1 ) (9 3.50 Cowpound 14 0.14 3 weekt after flrtt flower (1 ) 14 3.5( 1.50 3 weekt after first flower (1.) (1 3.IB

• Application at first flowering (I.), 52 days after planting; application at 3 weekt after first flowering (1.). 11 days after planting; and harvesting occurred 1(1 dayf after planting.

1 00

The results in Table M demonstrate that treatment of soybean plants with certain malonic acid derivative compounds at certain rates provides significantly increased yields in comparison with untreated control soybean plants. As demonstrated in Table M, in addition to an increase in actual yield (kilograms of soybeans/plot), the treated soybean plants exhibited an increased number of pods per plant in comparison with untreated control soybean plants.

Example XLIII Effect of Representative Malonic Acid Derivative Compounds on Crop Yield Enhancement-Snapbeans Solutions of Compound 75 were prepared by dissolving either 1.56 milligrams, 3.13 milligrams or 6.25 milligrams of the compound in 5 milliliters of acetone and then adding water to a final volume of 10 miimiters.

Into 10.2 centimeter diameter plastic pots containing a perlite-vermicullte potting mix (1:2 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. Ten to twelve days after planting at the time of full expansion of the primary leaves, each concentration of Compound 75 (each pot was sprayed with 1 m1imiter of solution) was applied to 10 snapbean plants as a foliar spray by use of an aspirated spray apparatus set at 10 psig air pressure. Untreated plants were included as

1 01

controls. When dry, all of the plants were placed in a Sherer Model FAL22R controlled environment chamber with day/night temperatures of 80°F/65°F and a daily 15 hour photoperiod. Sixty-seven days after planting, the plants were removed from the controlled environment chamber, harvested and the total number of fruits (pods) per plant was determined. The values obtained for each plant were averaged to obtain the results in Table N below.

TABLE N

Effect of Representative Malonic Acid Derivative Compounds on Crop Yield Enhancement - Snapbeans

Compound Concentration No. of Fruit (pods) No. (ppm) per Plant

Control — 34

Compound 75 156 44

313 45

625 44

The results in Table N demonstrate that treatment of snapbean plants with certain malonic acid derivative compounds provides significantly increased yields in comparison with untreated

1 02

control snapbean plants. A significant increase in the number of fruit (pods) per treated snapbean plants versus untreated control snapbean plants is demonstrated by the results in Table N.

Example XLIV

Effect of Representative Malonic Acid Derivative Compounds on Plant Chlorophyll Content

Increased chlorophyll content can be an indication of increased photosynthetic activity resulting in increased biomass and/or increased crop yield. Treatment of plants with certain malonic acid derivative compounds, e.g., Compound 75, as described hereinafter results in enhanced levels of chlorophyll.

Solutions of Compound 75 were prepared by dissolving either 1.56 milligrams, 6.25 milligrams or 25.0 milligrams of the compound in 5 miimiters ^" of acetone and then adding water to a final volume of 10 milliliters.

Into 10.2 centimeter diameter plastic pots containing a perlite-vermiculite potting mix (1:2 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. Eleven days after planting at the time of full expansion of the primary leaves, each concentration of Compound 75 (each pot was sprayed with 1 mlinnter of solution) was applied to 10 snapbean plants as a foliar spray by use of an aspirated spray apparatus set at 10 psig air pressure. Untreated plants were included as

1 03

controls. 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. Eleven days following treatment, 15 disks (10 millimeters diameter) were punched from the primary leaves of each plant. Each set of 15 disks were weighed, placed 1n a test tube and stored on ice 1n a dark environment. Each set of disks were then homogenized in a Waring blender with 20 miimiters 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 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) ^• of chlorophyll = (8.02)(absorbance at 663 nm) grams of leaf weight of leaf disks (grams) tissue

The values obtained for the control and Compound 75 were averaged to obtain the results in Table 0 below.

1 04

TABLE 0

Effect of Representative Malonic Acid Derivative Compounds on Plant Chlorophyll Content

Chlorophyll Content

Compound Concentration (milligrams chloro- No. (ppm) phyll/grams leaf tissue)

Control 60.1

Compound 75 156 72.6

625 78.7

2500 82.1

1 05

The results in Table 0 demonstrate that treatment of plants with certain malonic acid derivative compounds provides significantly increased levels of plant chlorophyll in comparison with untreated control plants. This increase in plant chlorophyll content may be indicative of increased plant biomass and/or increased crop yield.

Example XLV

Effect of Representative Malonic Acid

Derivative Compounds on Plant

Nitrate Reductase Content

Nitrate reductase 1s a substrate-lnducible enzyme which mediates the conversion of nitrate to nitrite. The inducible nature of nitrate reductase and the dependence of the enzyme level on substrate level provides the plant with a mechanism for controlling growth. Nitrate reductase catalyzes the rate-l1m1t1ng step in the conversion of nitrate into proteins. Thus, Increased levels of nitrate reductase may Indicate increased potential for grain and protein production. See, for example, Beevers, L. and R.H. Hageman, 1969, Nitrate Reduction in Higher Plants, Annual Review of Plant Physiology 20: 495-522.

Solutions of Compound 75 were prepared by dissolving either 1.56 milligrams, 6.25 milligrams or 25.0 milligrams of the compound 1n 5 miniliters of acetone and then adding water to a final volume of 10 ml11inters.

Into 10.2 centimeter diameter plastic pots containing perHte-vermicuUte potting mix (1:2

1 06

volume/ olume) were sown three snapbean seeds (Phaseolus vulgaris var. Cranberry). Five to seven days after planting, the plants were thinned to one plant per pot. Eleven days after planting at the time of full expansion of the primary leaves, each concentration of Compound 75 (each pot was sprayed with 1 mmmter of solution) was applied to 10 snapbean plants as a foliar spray by use of an aspirated spray apparatus set at 10 psig air pressure. Untreated plants were included as controls. 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. Seven days after treatment, groups of 5 disks (diameter of 1 centimeter each) were cut at random from the primary leaves. The disks were weighed and then infiltrated under vacuum twice for about 3 minutes in 30 miimiter beakers containing 10 mπilliters of a particular medium. The medium consisted of 0.1 M phosphate buffer (pH 7.5), 0.02 M postassium nitrate and 0.1 percent (volume/volume) Triton X-100. Triton X-100 surfactant is commercially available from Rohm and Haas Company, Philadelphia, Pennsylvania.

The beakers were then covered and incubated for 90 minutes at a temperature of 32°C. At the beginning of the Incubation period and at 20 minutes and 80 minutes into the Incubation period, nitrate released into the medium was determined by removing a 0.2 miimiter aliquot from each beaker and placing it in a test tube. Into the test tube was added 0.25 miimiters of 1 percent (weight/volume)

1 07

sulfanilamide in 3N HCl and 0.25 miimiters of 0.02 percent (weight/volume) N-(l-naphthyl)- ethylenedia ine dihydrochloride. The test tubes were allowed to stand for 20 minutes before mesuring the optical densities at 540 nanometers on a Beckman DB spectrophotometer. Nitrate reductase activity was expressed as micromoles ( M) of nitrite formed per gram of fresh leaf weight per hour. The values obtained for the control and Compound 75 were averaged to obtain the results in Table P below.

TABLE P

Effect of Representative Malonic Add Derivative Compounds on Plant Nitrate Reductase Content

Nitrate Reductase

Compound Concentration Activity (micromoles No. (ppm) Nθ2-/gram/hour)

Control 1.81

Compound 75 156 6.56

625 4.71

2500 4.06

The results 1n Table P demonstrate that treatment of plants with certain malonic acid derivative compounds provides significantly

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increased levels of nitrate reductase in comparison with untreated control plants. This increase in plant nitrate reductase content may be indicative of increased plant protein production and/or increased crop yield.

Example XLVI

Effects of Representative Malonic Acid Derivative

Compounds on Crop Yield

Enhancement - Wheat Tillering

Solutions of the test compounds identified in Table Q below were prepared by dissolving the compounds in acetone/water (50:50 volume/volume) containing 0.05 percent volume/volume of Triton X-100 surfactant commercially available from Rhom and Haas Company, Philadelphia, Pennsylvania. As detailed below, these solutions of test compounds were applied to wheat at a concentration of 0.06, 0.12, 0.25, 0.50 and 1.0 pounds of active ingredient per acre.

Wheat seeds (var. Olaf) were planted in a sandy loam soil 1n flats having the following dimensions: 5.5 inches In width x 9.0 Inches 1n length x 3.0 inches in height. The wheat seeds were sown in 2 different arrangements as follows: 4 rows (5 inches in length) per flat, 10 seeds per row (Flat No. 1); and 2 rows (5 inches in length) per flat, 5 seeds per row (Flat No. 2). Eleven days after planting at the 2-3 leaf growth stage of wheat, each concentration of the test compounds identified in Table Q was applied to a separate flat

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as a foliar spray by use of an aspirated spray apparatus set at 10 psig air pressure (all flats sprayed at a concentration of 120 gallons per acre). As a control, a water-acetone solution containing no test compound was also sprayed on separate flats. When dry, all of the flats were placed in a greenhouse at a temperature of 80°F _ 5°F and humidity of 50 percent _ 5 percent. Measured indications of tillering activity were observed and recorded 15 days after treatment for wheat sown in Flat No. 1 arrangements and 20 days after treatment for wheat sown in Flat No. 2 arrangements.

The number of vegetative shoots per seed was determined by actual count. The results reported 1n Table Q reflect the average of 3 repetitions. The percent increase tillering is based upon the untreated control.

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TABLE 0

Effect of Representative Malonic Acid Derivative

Compounds on Crop Yield

Enhancement - Wheat Tillering

Percent

Compound Rate (Pounds Tillering Increase No. per Acre) .Shoots/Seed) in Tillering

Control* 2.0 0

75* 0.06 2.5 25

0.12 2.7 35

0.25 2.6 30

0.50 3.5 75

m* 0.06 4.8 140

0.12 5.5 175

0.25 5.7 185

0.50 6.1 205

Control** — 6.5 0

75** 0.25 6.6 2

0.50 7.8 20

1.0 8.6 32

0.030 12.1 86

0.060 13.8 112

^♦ Flat No. 1 arrangement. **F1at No. 2 arrangement.

1 1 1

The results in Table Q demonstrate that treatment of wheat with certain malonic acid derivative compounds provides significantly Increased tillering in comparison with untreated control wheat.