CROSS REFERENCE TO RELATED APPLICATION

This application is a eontinuation-in-part of pending U.S. Patent

Application having Serial No. 205,436.

BACKGROUND OF THE INVENTION

The present invention relates generally to biologically active hydroxi- midates, thioLhydroximidates, amidoximes and, more particularly, to ^" novel pesticidally active carbamate and sulf enylated carbamate derivatives thereof.

Carbamate derivatives of hydroximidates and thioLhydroximidates

-have heretofore been previously described. For example, U.S. Patent No.

3,576,834 discloses acyclic compounds of the structure

wherein Q is sulfur or oxygen and the insecticidal and acaricidal activity thereof. Similarly, carba ates of monocyelic . thiolhydroximidates of the structure

OMPI

are disclosed in U.S. Patent No. 3,317,562 as insecticides.

Carbamate derivatives of bicyelie oximes have been previously reported. U.S. Patent No. 3,231,599 discloses compounds of the structure

NOCNHCHg and

(XXI) (xxπ) as insecticidally active compounds.

Further, Belgian Patent No. 766109 reports quinuclicϋne oxime car- bamates of the structure

O

It

also with reported insecticidal activity.

U.S. Patent Nos. 3,317,562 and 3,574,233 further disclose thiabicyclo¬ alkanes and -alkenes of the formulas

The patentees indicate that compounds of the above formulas possess insecti¬ cidal, fungicidal, nematicldal, antibacterial and herbicide! activity. It will be appreciated that . the foregoing thiabicycloalkanes and alkenes are not carbamates.

U.S. Patent No. 4,219,658 discloses lactones and thiolactones of the formulas

as intermediates in the preparation of hydrocarbylthiomethyl-2,2-dimethylcyclo- propane carboxylic acids useful as pesticides.

It has now been surprisingly found, in accordance with the present invention, that substituted heterobicyclic compounds of the formula (I)

as defined hereinafter possess a broad range of useful biological properties, as well as a high degree of activity as arthropodicides, i.e., insecticides, acaricides, aphicides, etc., as well as nematicides.

As ^' detailed hereinbelow, the compounds of the above formula (I) are chemically and biologically distinguishable from the acyclic and monocyclic hydroximidates and thiolhydroximidates, bicyclic oxin.es and thiabicyelo-alkanes and -alkenes described above in reference to heretofore suggested compounds by reason of the mode of action, type of action and level of action demonstrated for the compounds of the present invention, as well as the fact that the compounds of the present invention are not obtainable by previously suggested synthesis methods employed to prepare the prior art compounds which appear to be structurally similar.

Certain of the compounds of the present invention are derived from Diels- Alder adducts of thiocarbonyl compounds with cyclic dienes. The ability of carbon-sulfur double bonds to serve as dienophiles in the Diels-Alder reaction was first reported in 1965 by Middleton [J. Org. Chem. 130, 1390 (1965)] who described the reactions of perfluorinated thioketones, thiophosgene and thio¬ carbonyl fluoride with several dienes, including cyclopentaciene, e.g.,

-^IIS

C:.;PI

' ^'

Since that time, many other examples of such reactions have been reported, including in addition to the above dienophiles such thiocarbonyl compounds as NCC(=S)SCH ₃ [Can. J. Chem. 49, 3755 (1971)] , NCC(=S)NR _χ R [Tetrahedron Letters, 2139 (1977)] RS0 ₂ C(=S)SR' [Tetrahedron 30_, 2735 (1974)] , and

[J. Qrg,. Chem. 45, 3713 (1980)]

A limited number of reports have appeared on further reactions of the initial Diels-Alder adducts. Johnson et al. [J. Ore. Chem. ZΛ, 860 (1969)] describe oxygenation of the sulfur, followed by epoxication of the double bond as depicted below:

The authors indicate that one chlorine can be reduced from the dichloro sulf one by treatment with divalent chromium:

Reduction with lithium aluminum hydride yields the bicyciic thioal ene:

+ LiAlH, -->

In 1973, Reich et al. [J. Qrg. Chem. 38_. 2537 (1973)2 reported the reaction of thiophosgene with cyclohexa dienes, to yield 3,3-dic loro-2-thiabi- cyclo[2.2.2] oct-5-enes, as well as the hydrolysis of these Diels-Alder adducts to the corresDondins, thiolaetones.

,U R_=A cv?ι

./ V - v;::-.;

(X)

Benassi et al. [Synthesis 735 (1974)] describe a similar hydrolysis in the [2.2.1] system during reduction using an aqueous workup procedure:

Raasch [J. Qrg. Chem. 40, 161 (1975)] reports on the addition of halogen or sulfenyl halides to the carbon-carbon double bond of the 2-thiabicyclo[2.2.1] hept- 5-enes with rearrangement to yield the 6,7-disubstituted t_-iabicyclo[2.2.1] - heptanes, e.g.,

In 1976, Allgeier et al. [Tetrahedron Letters, 215 (1976)] also described the reaction of thiophosgene with anthracene to give the Diels-Alder adduct which is subsequently hydrolyzed to the thiolactone. Hong [Dissertation Abstracts International 40, 5672-B (1980)] states that solvolysis with methar.cl of the Diels- Alder adduct from thiophosgene and cyclopentadiene results in ring opening to yield (XIV) in almost quantitative vield.

O

It

(XIV)

For purposes of indexing, Chemical Abstracts classifies compounds of type X above as 2-thiabicyclo[2.2.2] oct-5-en-3-ones. In referring to these compounds, it is important to distinguish nomenclature used for indexing

convenience rom nomenclature signifying chemical type. Thus, Chemical Abstracts refers to both compounds XV and XVI (shown below) as thiabicyclo- alkanones. Chemically, however, compound XV is a thiolactone, i.e., a cyclic thiolester; whereas compound XVI [J. Org. Chem. 43, 4013 (1978)] is a true ketone and specifically a^-thioketone.

Esters and ketones are distinct chemical classes with many distinctly different properties. One of these distinctions is their reactivity with hydroxylamine. Ketones are known to react readily with hydroxylamine to form oximes:

O N-OH tt it RC R ^T + H ₂ NOH > RCR"

Esters or -thiolesters (and their cyclic counterparts, lactones and thiolactones) do not react with hydroxylamine to yield the analogous hydroximϊdates or thiol- hydroximidates.. t t

C=0 + H NOH // C=NOH t ^ t

O(S) O(S) r i Instead they react with cleavage of the carbon-oxygen or carbon-sulfur single bond to yield as displacement products, the hydroxamie acid or, in the case of the lactones and thiolactones, a lactam (Advanced Organic Chemistry, Second Edition, Jerry March, McGraw-Hill Book Company, New York, 1977, p. 386, 388).

An example of the failure of thiolactones to react with hydroxyl¬ amine to yield thiolhydroximicates is reported by Bruice and Fedor [J. Am.

Chem. Soc. 86, 4886 (1964)] . The authors confirm that thiolactones, e.g., thiolbutyrolactone, undergo hydroxylaminolysis in a manner analogous to their thiolester acyclic counterparts.

The hydroximidates and thiolhydroximidates, i.e., NOH NOH rt π -C-O- and -C-S- have been reported" in the literature. At least four methods of preparation have been described. U.S. Patent No. 3,576,834 (and the references therein) describes two of these: (1) the reaction of an iminoether hydrochloride with hydroxylamine and (2) chlorination of an aldoxime to form a hydroxamoyl chloride followed by reaction of the latter with a salt of a mercaptan:

NH-HC1 NOH tt tt

(1) RCOR' + H ₂ NOH RCOR' + NHg-HCl

NOH NOH NOH

It j If _ It

(2) RCH ~> RCC1 — ^R ' ^? > RCSR' + Cl ^"

_

U.S. Patent No. 3,787,470 reports the formation of thiolhydroxamate esters from nitroalkanes and alkyl mercaptans;

NOH ₁ CH ₂ N0 ₉ + R ₂ SH _> ,CS ₂

Faust et al. [Journal fuer Praktische Chemie, Leipzig, 311(1), 61, (1969)] describe the conversion of a thiopyranthione to a cyclic thiolhydroximidate.

It will be seen from the foregoing that applicants have discovered that the Diels-Alder adducts of certain thiocarbonyl compounds with cyclic dienes are converted easily and in high yield to bicyclic thiolhydroximidates which not only possess significant biological activity but which are valuable as

O...PI

intermediates in the synthesis of carbamate and sulfenylated carbamate final products. Moreover, the outstanding arthropodicidal and nematicidal activity exhibited by these compounds is entirely unexpected in light of the prior art set forth ereinabove which relates to the ease of hydrolysis of the thiophosgene adducts, along with the reported inability of the thiolactones thus formed to react with hydroxylamine to yield compounds of the subject invention.

In addition to the above observations relative to the absence of prior art synthesis methods which would allow one to predictably obtain the com¬ pounds of the present invention by analogy, it is likewise Important to note the material differences in biological activity observed with the compounds of the present invention compared to that of the seemingly related prior art compounds described hereinabove. In making such comparisons, it is again important to distinguish between nomenclature used for indexing convenience and nomencla¬ ture signifying actual chemical type. For example, for indexing purposes, Chemical Abstracts would describe the compounds of the present invention, as well as those of formulas (XXIHXXHI) as carbamates of bicycloalkanone oximes. However, in reality, the compounds of formulas (XXIHXXH-) are derivatives of true oximes; whereas, the compounds of the present invention are derivatives of hydroximidates or thiolhydroximidates. The significance of the foregoing distinction is readily apparent when one considers the work of Huhtanen and Dorough [Pesticide Biochemistry and Physiology 6_, 571 (1975)] who have shown that the chemical difference between the ketoxime derivative XXIV and the thiolhydroximidate derivative XXV

NOCONHCH-, NOCONHCH„

IT ³ °

(CH ₃ ) ₃ CCCH ₂ SCH ₃ CH ₃ CSCH ₃

(xxrv) (xxv)

results in surprisingly marked differences in their biological activity. Although both (XXIV) and (XXV) are insecticides, their spectrum of activity, persistence, use pattern and method of application are totally different. It is evident that these documented differences result from the difference in chemical structure between a true ketoxime and a thiolhydroximidate. It will also be appreciated that a similar distinction between the compounds of the present invention and compounds of formulas (XXI)-(XXIII) prevails.

SUMMARY OF THE INVENTION

It. is, therefore, a primary object of the present invention to afford novel substituted heterobicyclic compounds which possess outstanding pesticidal activity.

It is a further object of the present invention to provide novel processes for preparing heterobicyclic hydroximidate, thiolhydroximidate and carbamate compounds.

A still further object of the present invention is to provide arthrc- podicidally and nematicidally active compositions and methods for controlling undesired pests by the application of the novel compounds and pesticidal compo¬ sitions of the invention to their habitat, food supply or breeding sites.

Still another object of the present invention is to provide novel heterobicyclic hydroximidates, thiolhydroximidates, and amidoximes which display arthropodicidal, nematicidal, bactericidal, fungicidal, plant growth regulant and anthelmintic activities, as well as being useful as novel intermediates for the preparation of carbamate and sulfenylated carbamate product derivatives.

These and other similar objects, advantages and features are accom¬ plished according to the products, compositions and methods of the invention comprised of novel substituted heterobicyclic compounds, compositions derived therefrom and pesticidal methods employing same.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

As stated previously, the present invention relates to substituted heterobicyclic compounds of the general formula (I)

wherein

A repres ;eennts S, 0, S(O) m where m is 1 or 2 or NR «-_ where R- is hydrogen, alkyl, aryl or cyano;

^R l ^R l" ^R 2 J reDresents the group -C-a-C -a-C -a-C- _f t q i

R - R "' R "' R ^r 1 1 2 2 where q, independently, is 0 or 1, a, independently, is a single or double bond and R R^, R^', R-"', R ₂ , F_ ₂ ', R ⁿ and R ₂ '" are defined below; .

O

If X is 0, S, NR _g , or N-CR- where R_ is hydrogen or alkyl, or wherein X represents a bridge member selected from „

I -

^R 7 ^R 7 ^R 8 CH

CH , H— C C H , H— C C— H ,

M . ! I I I

where R_ and R„ independently represent hydrogen, halogen, cyano, alkyl, alkoxy, alkoxycarbonyl or alkylthio and b— d independently represent carbon or oxygen and f is 0 or 1:

R.-R,'", inclusive, R„-R ₂ , inclusive, R ₃ and R_, independently represent hydrogen, halogen, hycroxy, cyano, __I__yl, alkoxy, haloalkyl, alkyl- carboxy, arylcarboxy, alkylaminocarboxy, car amoyl, alkylcarbamoyl, dialkylcarbamoyl, aL ylthio, alkylsulfln l. alkylsulfonyl, alkylamino, dialkylamino, alkoxycarbonyl, trifluororr.ethyl, pyrrolidyl, phenyl, nitro, thiocvano, thiocarbamvl, alkvlthiocarbamvl, dialkvlthio-

and G represents alkyl, alkoxy, al ylthio, amino, alkylamino or dialkylamino; or when a is a single bond and at least two of R R."', R or R '" are hydrogen on adjacent C atoms, then R,, R.", R ₂ or ^2" on the same adjacent C atoms together may represent

G-.-PI

R' O — O —

I

— O — C ^■ or O = C

R" O — O —

where R' and R" represent hydrogen or alkyl; or any of R. and R R," and R,"', R ' and R "' .or R ₂ and R ₂ ' represent = 0; or when q, independently, is 0 or 1 and a, independently, is a double bond, R,' R^", ₂ ^m or R ₂ ' are absent; Y represents hydrogen or

O rt R

/

1) -C-N

R 1. 0 where R _g -R _f] independently represent hydrogen, alkyl, hydroxyalkyl, alkenyl, alkyn l, aralkyl, alkoxyalkyl or polyoxy- alkylene; or

O

It R,

/

2) -C-N

\

Z ^' where R _q is the same as defined before and Z represents a) — S — R. t 11

-°>n where n is 0, 1 or 2 and R^, is pyridyl, pyrimidyl, phenyl or phenyl substituted with at least one member selected from hydroxy, alkyl, alkoxy, halogen, nitro, trifluoro- methyl or cyano;

R ₁₂ O

I ¹ -- It b) — S -N -C-OR 1. 3 ⁽⁰⁾ n where n is 0, 1 or 2, and R* ₉ is alkyl, alkoxyalkyl, or

where m is 0, 1, 2 or 3 and R"' is hydrogen, halogen, cyano, nitro, alkyl, alkoxy, alkylthio, alkvlsulfonyl or phenyloxy and R., is alkyl, alkoxyalkyl, naphthyl, alkyl- thioalkvl

CN

where (R ¹ ")- m _^ is as defined before,

CH ₃ S CH ₃ SCH ₂

\ \

C = N — C = N —

CH, (CH ₃ ) ₃ C or 0 where Q-OY represents formula (I) as defined

10 herein;

C) -S-S-N - !— OR. _n where R^- .^ are as defined before;

*i _

(o)_

where n is 0, 1 or 2, R, ,, is phenyl, alkyl, alkoxyalkyl, acyl, alkoxycarbonylalkyl, alkylthioalkyl, carboxyalkyl

15 and R.- is alkyl,

where m is 0-5, p is 0-5 and R,„ is halogen, alkyl, trifluoromethyl, nitro or alkoxy;

C:.:FI

. .

e) — S-NR,„R- _g where R_ ₇ -R.g are alkyl, aryl or together with the nitrogen atom represent

, — tf p or — N S(O) _v where v is

0, 1 or 2 or — -N N-R'"' where R"" is alkyl;

5 f) - S =- - _{I Q} where n is 0, 1 or 2, m is 1 or 2 and R, _g is

--»_, alkyl, cycloalkyl, haloalkyl, cyanoalkyl, alkoxycarbonyl, (alkylthio)carbonyl, alkoxy(thiocarbonyl), alkylthio(thio- carbonyl), aryl or substituted ar l with at least one substituent selected from halogen, cyano, nitro, alkyl, 10 alkoxy, alkylthio, alkvlsulfonvl or phenyloxy, with the proviso that when R, _g is aryl or substituted aryl, m is 2;

where n is 0, 1 or 2, R„ _π is alkyl and ^{are the} same as R, ₇ -R, ₃ as defined before;

^R 23 Λl

15 h) -S -N -P — . ,

\ ^{Λ (0)} n ^MR 25 where n is 0, 1 or 2, M, independently, is S or O and 2* _. ~ ^R 25 - ⁿ - ^e ? ^er --- ^en -ly represent alkyl or R and ₂₅ together represent

20 where R _o -C _c D _! -R _ _π ._ ( independently ' rep ^' resent hydrogen or alkyl;

^R 28 O π ,R 29 i) -S — N — C—N

\ ⁽⁰⁾ n ^R 30 where n is 0, 1 or 2, R _2g is alkyl or aryl and R29~ ^R 30 independently represent hydrogen, alkyl, aryl or aLkoxy;

^R t 3 ^ύ 1 ⁱ ° tt j) - -S -N — C — R ₃₂ where n is 1 or 2, ,, is alkyl and R ₃₂ is fluoro, alkyl, aryl or aralkyl;

^R 33 ° ^k) ^ - -^-^s

⁽⁰⁾ m ^R 34 where m is 0, 1 or 2, n is 1 or 2 and R ₃₃ ~R ₃ _. independently represent hydrogen, alkyl or aryl;

CH, O t -> π

1) -S- CH m (T ⁾ n (CH- A) m— ^■ S-N C— OR. _.o,. where T is O, S or —CH -, m is 1 or 2, n is 0 or 1 and

R _3S = R, ₃ as defined before;

/ ^R 37 m) — Si — R„ _σ where R .- _rι are alkyl or arvl:

^R 39

O

It n) — C — L where L represents alkyl, cyano, alkoxy, aryloxy, alkylthio, arvlthio or — 0N=CR_. _Q R ₄ , where R 4.0--R 4..1 are the same as R ₁ 12 ₀ -R_ 1„3 as defined before; or

V

1 o) — C =CH ₉ where V represents halogen, alkoxy or alkyl¬ thio and the pesticidal utility thereof.

As used throughout the instant specification and claims, the expres¬ sions "alkyl" and "alkoxy," unless otherwise defined, are inclusive of straight and branched chain carbon-carbon linkages of from 1 to about 22 carbon atoms, e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, hexyl, heptyl, octyl, decyl, or dodecyl, etc. The expressions "alkenyr and "alkynyl," unless otherwise defined, include the corresponding unsaturated radicals. The expressions ' "cycloalkyl" includes cyclic alkanes of from 3 to about 8 carbon atoms, whereas "aryl" defines unsaturated ring systems of from 6 to about 12 carbon atoms. The term "halogen" includes chlorine, fluorine and bromine. The expression "polyoxyalkylene," unless otherwise defined, includes alkylene moieties of 1-4 carbon atoms and wherein the polyoxyalkylene moiety may contain up to 50 oxyalkylene repeating units.

It will be appreciated by those skilled in the art that the compounds of the present invention may be prepared in various salt forms and, as used herein, the expression "pesticidally acceptable salts" is intended to include those salts capable of being formed with the instant compounds and substituted derivatives thereof in accordance with the invention without materially altering the chemical structure or pesticidal activity of the parent compounds. For example, alkali metal salts of carboxylic acid derivatives of the invention may be obtained by reaction with suitable bases, e.g., sodium hydroxide, potassium hydroxide, etc. Likewise, alkaline earth metal salts may be similarly obtained.

Similarly, quaternary salts of the amino derivatives of the invention may also be obtained, as well as acid addition salts, where necessary to, for instance, alter solubility properties. it will be understood that in the structural formula depicting the compounds of the present invention all unsubstituted bonds are satisfied by hydrogen. It will further be apparent to those skilled in the art that the compounds of the present invention may exist in two geometric forms, the E and Z isomers (i.e., syn- and anti-isomers) around the carbon-nitrogen double bond. Both isomeric forms and their mixtures ^" are encompassed within the scope of the present invention.

The hydroximino derivatives of the present invention, i.e., compounds of formula (I) where Y - hydrogen, are prepared according to the following methods. Hydroximidate (oxabicycio) compounds of the invention can be ob¬ tained, for example, by reaction of chlorosulfonyl isocyanate with appropriately substituted cyclic dienes to form N-chlorosulfcnyl- -Hactams which readily rearrange to the (N-chlorosulfonyl)imino— oxabicyclic intermediate (via cyciiza-

VV IIPPOO

- 15 -

tion through oxygen). See [J. Org. Chem. 41, 3583 (1976)] /and [J. Chem. Soc. Perkin I, 874 (1977)] and the references cited therein. The thus obtained imiπo- oxabicyclic intermediate is then reacted with hydroxylamine to yield the desired hydroximidate. The foregoing general reaction scheme is set forth below with substituent representations corresponding to those in formula (I). It will be recognized that, while the following scheme illustrates the formation of a compound of the present invention having a [2.2.1] bicyclic ring system, the above generally described process is followed to obtain- compounds of the present invention having, for example, a [3.2.1] , [4.2.1] , etc., bicyclic ring system. The specific bicyclic ring system obtained will, of course, be determined by the selection of the appropriate reactants (e.g., employing a eyclohexadϊene reactant in place of the cyclopentadiene reactant below).

As alluded to previously, the bicyclic thiolhydroximidates of the present invention are obtained by a Diels-Alder reaction of certain thiocarbonyl compounds with appropriately substituted cyclic dienes under suitable cycliza- tion conditions to obtain the initial adducts which are then reacted with hydroxylamine to afford the desired intermediates. The foregoing general

reaction scheme is depicted below with substituent representations corresponding to those set forth previously in formula (I):

^R f ^R 4

The bicyclic azahydroximidates of the present invention are prepared in a similar manner to the preparation of the oxa- and thiolhydroximidates previously described. More specifically, the _* appropriate 3-tosyl-2-azabicyclo intermediate [prepared by the procedure of J. Organic Chemistry 39, 564 (1974)] is treated with hydroxylamine to give the desired bicyclic azahydroximidate. Alternatively, conversion of the appropriate lacta to the corresponding thionolactam followed by treatment with hydroxylamine will also afford the desired azahydroximidate. The specific reactants, procedures and conditions are further illustrated in the examples. The hydroximino intermediates can then be converted to the various carbamate derivatives embraced by formula (I) by any of several conventional methods. One preferred method involves the reaction of an isocyanate substi¬ tuted with groups corresponding to R _q or R. _n of formula (I) with the particular hydroximino intermediate. The hydroximino intermediate and isocyanate are reacted in an inert organic solvent at from about 0° C to about 150° C, preferably from about 20° C to about 80° C, and at a pressure from about 1 to 10 atmospheres, usually about 1 to -about 3 atmospheres. Reaction pressures will be determined by reaction temperature, concentration and vapor pressure of the isocyanate. Any inert organic solvent used in the reaction should not contain hydroxy, amino or other groups which will react with the isocyanate function. Useful inert solvents include aliphatic and aromatic hydrocarbons, e.g., hexane,

QMPI /IPO

heptane, octane, benzene, xylene; ethers such as diethyl ether, ethylpropyl ether, etc.; esters such as ethyl acetate, ethyl propionate; ketones such as acetone, methyl ethyl ketone and various chlorinated hydrocarbons such as methylene chloride, perchloroethylene and the like. The reaction may be carried out in the presence of from about 0.1 to about 1.0 percent by weight, based on the weight of reactants, of a tertiary amine catalyst such as triethylamine, N,N-dimethylaniline or the like.

The molar ratio of isocyanate to hydroximino reactant can vary from about 0.1:1 to about 10:1. An ecuimolar amount or slight excess of isocyanate is preferred to insure complete reaction. Reaction times may also vary from a few minutes to several days with a usual reaction time of from about 1/2 to about 6 hours.

Another method for preparing such carbamate derivatives involves reaction of the hydroximino compound with phosgene to obtain the ehloro- formate which is reacted with an amine. A solution of the hydroximino derivative is generally dissolved in an inert solvent such as diethyl ether which is added slowly to a solution of phosgene dissolved in inert solvent in the presence of an HC1 acceptor such as a tertiary amine. Reaction temperatures vary-from about -30° C to about 100° C with usual temperatures of from about 0° C to about 50° C. The resulting reaction mixture, a solution of the ehloroformate in an inert organic solvent can be filtered to remove amine hydrochloride before reaction with an amine in step 2 of the reaction. The amine is added to the ehloroformate solution in the presence of a suitable amine solvent such as water, at temperatures between about -40° C to about 80° C. A larger than molar excess of amine can be used so that the amine acts both as a reactant and as an HC1 acceptor and complete conversion of ehloroformate is obtained. Alternatively, a separate HC1 acceptor, such as a tertiary amine can be used.

It will also be appreciated by those skilled .in the art that the carbamate derivatives of the present invention can be prepared by reaction of N- protected hydroxylamine with an appropriately substituted carbamylating agent,

-C-N.

Z as defined before, deprotection of the resulting intermediate and reaction of the deproteeted intermediate with, for example, the initial Diels-Alder adduct to obtain the products of formula (I).

The sulfenylated carbamates of the invention may be prepared from the carbamates and carbamate precursors obtained in accordance with the foregoing description by methods described, for example, in Angewandte Chemie, International Edition, 16, 735 (1977) and the references referred to therein, J. Org. Chem. 43, 3953 (1978), J. Agric. Food Chem. _26, 550 (1978), U.S. Patent Nos. 4,201,733, 4,148,910, 4,138,423 and 4,108,991.

Essentially, two methods have previously been employed for the preparation of such ^' derivatives. In the first of these, an N-alkyl carbamate is allowed to react with a sulfenyl halide to yield the sulfenylated carbamate in accordance with the following reaction scheme:

O R' O R* tt t rt i

ROC— NH ÷ R"SX -) ROC— NSR" . + HX

In the second method, the sulfenyl halide is allowed to react with an N-alkyl carbamyl halide to yield an intermediate N-alkyl-N-(substituted thio)- carbamyl halide which is then treated with the desired hydroxylic moiety to provide the carbamate.

R O ^• R O

R"SX + H-N-C-Y -) R"S-N-C-Y + HX

R O R O

R"SN-_C-Y + R'OH - R"SN-C OR' + HY

In each of the foregoing reactions, where HX or HY are generated, an acid acceptor is utilized to facilitate the reaction. The foregoing sul enyla tion reactions are normally conducted in an aprotic .organic solvent. Illustrative of aprotic organic solvents which are suitable as reaction solvents in accordance with the present invention are those previously mentioned for use in connection with the preparation of the carbamate derivatives of the invention. The acid acceptor utilized in carrying out the sulf enyla tion reaction may be either an organic or inorganic base. Organic bases useful as acid acceptors are tertiary amines, alkali metal alkoxides and the like. Bases such as sodium hydroxide, potassium hydroxide, sodium carbonate and the like are illustrative of inorganic bases suitable for use in the conduct of this reaction.

OMPI ^/ . ^WI? ° _

Preferred acid acceptors are aromatic and aliphatic tertiary amines, such as triethylamine, pyridine, trϊmethylamine, l,4-diazobicyclo[2.2.2] octane and the like.

When an inorganic base is used as the acid acceptor, phase transfer agents may be used to facilitate the transfer of the acid acceptor across the organic/inorganic phase interface. As useful phase transfer agents, there may be mentioned crown ether compounds, quaternary ammonium halide compounds and the like.

In these reactions, the reaction temperature may be varied between about -30° C to approximately 130° C, preferably between 0° C to about 75° C.

The sulfenylation reactions can be conducted at either subatmo- spheric, atmospheric or superatmos ^' pheric pressures, but conventionally are conducted at atmospheric or autogenous pressure.

Reactants, intermediates or precursor compounds necessary in carrying out the reactions set forth herein are readily obtainable following conventional synthetic methods. For instance, N-methylearbamyl fluoride may be prepared in accordance with the procedure detailed in J. Org. Chem. 43, 3953 (1978) as may N-(N,N-"-dialkylaminosulfenyl>-N-methylcarbamyl fluoride. N-[(N- alkyl-N-arylsulfonyl)aminosulf enyll -N-methylcarbamyl fluoride is prepared according to the methods set forth in U.S. Patent No. 4,148,910. The prepara¬ tions of bis[(N-fluorocarbonyl-N-methyl)amino] sul ide, bisKN-fluorocarbonyl-N- methyDamino] disulfide and N-arenesul enyi-N-methylcarbamyl fluoride are described in U.S. Patent No. 3,639,471. -\3ubst:tuted-cyanoalkanesulfenyl and thiosulfenyl)-N-aLkyIcarbamyl halides are also described in U.S. Patent No. 4,058,549.

The active compounds are well tolerated by plants, have a favorable level of toxicity to warm-blooded animals and can be used for combating arthropod pests, especially insects and arachnids, and nematode pests. They are active against normally sensitive and resistant species and against all or some stages of development, i.e., eggs, larvae, nymphs, cysts and adults. The above- mentioned pests include: from the class of the Isopoda, for example, Qniscus asellus, Arma- dillium vulgar e and Cylisticus convexus; from the class of the Diplopoda, for example, 31aniulι_s guttulatus; from the class of the Chilopoda, for example, Geophiluscarooohagus and Scutigera sop.; from the class of the Symphyla, for example, Scutigerella immaculata; from the order of the Thysanura, for example, Lepisma saccharina: from the order of the Ccliembola, for example, Onychiurus armatus; from the order of the Orthoptera, for example, Blatta

C PI

orientalis, Periplaneta americana, Blattella germanica, Acheta domesticus, Gryllotalpa spp., Locusta migratoria migratorioides, elanoplus differentialis and Schistocerca gregaria; from the order of the Isoptera, for example, Reticu- litermes spp.; from the order of the Thysanoptera, for example, Hercinothrips femoralis and Thrips tabaci; from the order of the He iptera, for example, Lygus spp., Dysdercus spp., Nezara viridula; from the order of the Homoptera, for example, Bemesia tabaci, Trialeurodes spp., Aphis spp., Macrosiphum spp., Myzus spp., Em oas ^' ca spp., Nephotettix cincticeps, Psylla spp.; from the order of the Lepidoptera, for example, Pectinoohora gossvoiella, Plutella maculipenπis, Malacosoma neustria, Porthetria disoar, Bucculatrix thurberiella, Agrotis spp.; Euxoa spp., Earias insulana, Heliothis spp., Prodenia litura, Spodoptera spp., Trichoolusia ni, Carpocaosa pomonella, Pieris spp., chilo spp., Pyrausta nubilalis, Ephestia kuehniella, Galleria mellonella, Choristoneura fumiferana, and Tortrix viridana: from the order of the Coleoptera, for example, Leptinotarsa decemlineata, Diabrotica spp., Epilachna varivestis, Orvzaephilus surinameπsis, Anthonomus spp., Sitophilus spp., Hypera postica, Dermestes spp., Trogoderma spp., Anthrenus spp., Attagenus spp,, Lyctus spp., Conotrachelus nenuphar, Popillia jaoonica. Ptinus spp,,- Tribolium spp,, Tenebrio molitor, Agriotes spp., Conoderus sp., Melolontha melolontha, and Costelytra zealandica; from the order of the Hymenoptera, for example, Diprion spp., Hoplocampa sp ., La≤ius spp., ^' ono orium pharaonis, Vespa spp., and Caliroa cerasi; from the order of the Diptera, for example, Aedes spp., Anopheles spp., Culex spp., Drosoohila melaπogaster, Muse a spp., Fannia spp., Calliphora erythroceohala, Lu cilia spp., Chrysomya spp., Cuterebra spp., Gastrophilus spp., Hyppobosca s p., Stomoxys spp,, Oestrus spp., Hypoderma spp., Tabanus spp., Tannia spp., Qscinella frit, Pegomyia hyσscyami, Ceratitis caoitata, Dacus oleae, and Tipula oaludosa; from the class of the Araehnida, for example, Scorpio maurus and Latrodectus mactans; from the order of the Acarina, for example, Acarus spp., Argas spp., Ornithodoros spp., Dermanyssus gallinae, Eriophyes rib is, Boophilus spp., Rhipicephalus spp., Amblvomma spp., Hyalomma spp,, Ixodes spp., Psoroptes spp., Chorioptes spp., Sarcoptes s p., Tarsonemus spp., Brvobia praetiosa, Panonychus spp., and Tetranyehus spp.; from the order of the Phylum nematoda, for example, species of the following genera eloidogyne, Heterodera, Trichodorus, Xiphinema, Ditylenchus, Pratyieπchus, Tylenchus, Radopholus, Longidorus, and Tylenchorhynchus.

Exemplary of preferred compounds for use in the arthropodicidal compositions and methods of the present invention are compounds of formula (II)

G-.-PI , Y.-IPO

wherein

A represents S or 0; *1 V

J represents the group -C-a-C -a-C -a-C- ι _ q t q i

^R l ^R l" ^{T R} 2 ^{m R} 2' where q, independently, is 0 or 1, a, independently, ^' is a single or double bond and R _p R^, R..", R-" ¹ , R ₂ , ₂ ', R ₉ " and R ₂ '" are defined below;

X is selected from

where R- and R _g independently represent hydrogen or cyano; R--R_ ^! ", inclusive, and R„-R "', inclusive, are hydro-gen or when a is a double bond, R. 1 and R„ ___, and in addition if q ', independently in each ease, is 1,

R," or R ₉ ", are independently hydrogen or halogen and RΛ R ₉ ', '" or R "' are absent; ₃ and R ₄ represent hydrogen, halogen, cyano or alkoxycarbonyl; Y represents

where R _g -R _{ι n} independently represent hydrogen, alkyl, h droxy alkyl, alkenyl or alkynvl; cr

⁰ R " ^9

2) -C-N

Z where R _g is the same as defined before and Z represents

where n is 0, 1 or 2 and R-, is phenyl or phenyl substituted with at least one member, selected from halogen, alkyl, alkoxy, trifluoromethyl, nitro or cyano;

R ₁₂ 0 b) — S-N -C-OR ₁₃

<°>n where n is 0, 1 or 2, R.„ is alkyl and R.„ is alkyl, alkoxyalkyl or Q where Q-OY represents formula (II) as defined herein;

c ⁾ - ^S -N ^s ° ₂ " ^R is where R. , is alkyl and .- is alkyl or

where p is 0-5 and R, _β is halogen, alkyl, trifluoro- methyl, nitro, methoxy, cyano or dialkylamino; d) -S-NR ₁₇ R, _g where R,-,-R-g are alkyl, aryl or together with the nitrogen atom represent

/ \ ' — \

— O or — N S(0) _y where v is Q, 1 or 2

e) - -S -R _q where n is 1 or 2 and R. _g is alkyl, cyanoalkyl or alkoxycarbonyl;

^R 20 ^21 f) -S — -SO„-N

\

(O). R n 22 where n is 0, 1 or 2, R _2Q is alkyl and R- ₂ ^R 22 ^{are the} same as R. ₇ -R,„ as defined before;

where n is 0, 1 or 2, R _{9 g} is alkyl or aryl and R ₂ 9~ ^R 30 independently represent hydrogen, alkyl, aryl or alkoxy; and

R« O

I -* ³ IT h) - S--)-C C-R,-

⁽⁰⁾ m ^R 34 where m' is 0, 1 or 2, n is 1 or 2 and R„„-R ₃ -. independently represent hydrogen, alkyl or aryl.

As preferred compounds for use in the nematiciσal compositions and methods of the present invention, there may be mentioned those compounds of Formula IV:

wherein ^R l ^R l" ^R 2" ^R< >

J represents the group -C-a-C -a-C -a-C- i i q t q i

R ' R ^,!I R "' R ' 1 1 2 ^Λ 2 where q, independently, is 0 or 1, a, _# independently, is a single or double bond and R., R ' R,", R '", R ₉ , ₂ ', R ₉ " and R. " are defined below;

X is selected from

where R„ and R„ are hydrogen; R.-R.'", inclusive, and R„-R '", inclusive, are hydrogen or when a is a double bond, R. and R ₂ , and in addition if q, independently in each case, is 1,

R." or R ", are independently hydrogen or halogen and R,', R ₂ ', R, ^m or ₂ ^m are absent; ₃ and R ₄ represent hydrogen, halogen, cyano or alkoxycarbonyl;

Y represents

0 where R _g -R. _Q independently represent hydrogen, alkyl, alkenyl or alkynvl; or

where R _Q is the same as defined before and Z represents ^a) - — ^R u

⁽⁰⁾ n where n is 0, 1 or 2, R,, is alkyl, phenyl or phenyl substituted with at least one member selected from halogen, alkyl, alkoxy or trifluoromethyl, nitro or cyano;

R ₁₂ O f-- ⁴ tt b) —S-N -C-OR ₁₃

<°>„ where n is 0, 1 or 2, R- ₂ is alkyl and , ₃ is alkyl, alkoxyalkyl or Q where Q-OY represents Formula (IV) as defined herein;

!l4 c) -S-N— S0 ₂ -R ₁₅ where R. .-R-- are alkyl, aryl or substituted aryl with at least one substituent selected from halogen, alkyl, trifluoromethyl, nitro, methoxy, cyano or dialkylamino;

d) -S-NR ^, ₇ R.g where R1 -R1 ₀ ^arε alkylj aryl ^or together with the nitrogen atom represent

_l ^" T b , - or - 11 S(O)_ --___----_ _' -. _{v ^} where v is 0, 1 or 2;

_ _*

^R 28 ° V

' " y 29 e) -S -N C-N

(0) _n ^K 30 where n is 0, 1 or 2, R _9g is alkyl or aryl and _2g -R ₃₀ independently represent hydrogen, alkyl, aryl or alkoxy; and

^R t 3 °3° ° It _f , - S-^C C-R ₃₅

⁽⁰⁾ m ^R 34 where is 0, 1 or 2, n is I or 2 and R ₃₃ ~R ₃₅ independently represent hydrogen, alkyl or aryl. In general, in the foregoing arthropodicidal and nematicidal compo¬ sitions of the invention as well as the methods of selectively killing, combating or controlling such pests, the compounds of the mvention, either alone or in

admixture, will be applied to the pests or their habitat, including growing crops, in an arthropodicidally or nematicidally effective amount of the compound(s) within the range of from about 0.1 to 20 -lb/A and, preferably, 0.25 to 1.5 lb/A, for arthropods and between about 0.125 to 20 lb/A and, preferably, about 0.25 to 4 lb/A for nematodes. The LD _{5 Q} of the carbamate ester derivatives of the invention in rats is generally in the range of 1.5 to 3 g/kg, whereas the sulfenylated- derivatives exhibit considerably reduced toxicities, i.e., up to a 15 fold decrease or greater.

The pesticidally active compounds in accordance with the present invention may be utilized in the form of formulations or compositions with appropriate dispersible pesticide carrier vehicles. As employed typically in the methods of the present invention, such compositions will contain between about 0.1 and 98 percent by weight, and usually between about 1 percent and 90 percent by weight of active compound. The heterobicyclic compounds of the invention are practically insoluble in water and only- sparingly soluble in organic solvents. Accordingly, the compounds of the present invention are formulated in accordance with conventional practices in the form of, for example, wettable powders, dust or emulsifϊable concentrates, water-based flowables, dispersible granules and the like. In such compositions, the active compound of the invention will be combined with suitable dispersing agents (e.g., lignin, sulfite waste liquors, methyl cellulose, etc.), surfactants, such as nonionic and anionic emulsifying agents (e.g., polyethylene oxide esters of fatty acids, polyethylene oxide ethers of fatty alcohols, alkyl sulfonates. aryl sulfonates, alkyl arylpoly- glycol ethers, magnesium stearate, etc.) and appropriate solid pesticidally acceptable carriers or diluents (e.g., kaolins, alumina, silica, calcium carbonate, talc, etc.). In general, in preparing the active compound for incorporation in such formulations, the compound will be subjected to conventional comminuting treatment, such as air milling, hammer milling, ball milling, wet milling, etc., to obtain an average particle size of between about 3 to 5 ji. Depending upon the ultimate intended use and particular storage conditions, other optional adjuvants such as anticaking agents, antifoam agents, freeze-thaw depressants and the like may be incorporated in the compositions. Likewise, the compounds of the present invention may be employed in combination with other pesticidal agents, including, for example, insecticides, miticides, bactericides, fungicides, nema- ticides, herbicides, plant growth regulants, etc. Moreover, the compounds of the present invention have surprisingly demonstrated good activity for destroying parasitic worms. Thus their use as anthelmintic agents is also contemplated herein.

ΓUTE

_/y ^" Y.'IPO

The following nonlimiting examples are afforded in order that those skilled in the art may more readily understand the present invention and specific preferred embodiments thereof with respect to the preparation of starting materials, intermediates and product compounds in accordance with the fore- going description. The assigned structures for the title compounds exemplified below as well as in compound Table 1 thereafter are consistent with nuclear magnetic resonance and infrared spectra and, where applicable, X-ray crystal¬ lography.

EXAMPLE 1 2-Thiabicyclo[2.2.l3 hept-5-en-3-one oxime

A stirred solution of 33 g (0.5 m) of cyelopentadlene in 150 ml of petroleum ether was maintained at 0° to -10° C as 23 g (0.2 m) of thiophosgene was added over 25 minutes. The colorless solution was stripped of volatiles. A solution of the residue in 200 ml of 1,2-dimethoxyethane was added over one hour at 0° C to 2.0 m of hydroxylamine in 500 ml of water. The reaction mixture was stirred overnight and allowed to come -to room temperature. A dried methylene chloride extract was»stripped to yield a semi-solid .residue which was purified by dry column chromatography (silica gel, ethyl ether:hexane::l:l). Two bands were observed.. Extraction of each individually yielded 2.4 g of the less polar material, m. 87-88° C and 5.9 g of the more polar, m. 137-137.5° C. The N R and IR spectra indicate these to be the E and Z iso ers of the title compound. The more polar material was identified as the Z isomer by X-ray crystallography.

EXAMPLE 2A

2-Thiabicvclo[2.2.2] oet-5-en-3-one oxime

Method A

A solution of 735 ml (7.3 m) of 1,3-cyclohexadiene in 550 ml of chloroform was stirred at 30-50° C while 500 ml (7.86 m) of thiophosgene was added over one hour. The mixture was stirred at 60 - 5° C for two hours, cooled, and added over 90 minutes at 25-40° C to a stirred mixture of hydroxylamine (from 2300 g (28 m) of hydroxylamine sulfate, 2700 ml of water, and 1130 g (27.8 m) of sodium hydroxide) and 800 ml of chloroform. The resulting mixture was stirred at 40 - 5° C for four hours, filtered, and the filter cake washed with chloroform. The chloroform laver from the combined filtrate and washings was

- separated, dried, and reduced in volume. After the addition of three liters of carbon etrachloride, the solvent was distilled until a pot temperature of 75° C was reached. The carbon tetrachloride solution was decanted from some gummy insolubles and allowed to cool to yield the title compound as a pale yellow solid, . 118.5-122° C.

Calc'd for C _? N _g NOS : C, 54.2; H, 5.9; N, 9.0; S, 20.7

Found : C, 53.7; ^' H, 6.0; N, 9.0; S, 20.4

Method B

A solution of 0.22 g (0.00085 m) of 3,3-bis-(l,2,4-triazol-l-yl)-2- thiabicyclo.2.2.2] oct-5-ene [J. Qrg. Chem. 45, 3713 (1981)] in 30 ml. of tert-butyl alcohol was treated with 0.75 g (0.011 m) of hydroxylamine hydrochloride. The mixture was heated under reflux, cooled, and partitioned between water and dichlorom ethane. The organic layer was dried over MgSO ,. The residue after removal of solvent was purified by thick layer chromatography to yield 0.036 g of product v/hich was spectrometrically identical with that, obtained in Method A of this example.

EXAMPLE 2B

Reaction of 2-thiabicyclo_2.2.2] oct-5-eπ-3-one with hydroxylamine

A solution of 1.4 g (0.01 m) of 2-thiabicyclo[2.2.2] oct-5-en-3-one [-L Org. Chem. 38, 2537 (1973)] in 30 ml of dimethoxyethane was added to a mixture of 3.01 g (0.04 m) of hydroxylamine hydrochloride and 2.27 g (0.02 m) of sodium carbonate in 30 ml of water and 30 ml of dimethoxyethane at 0° C. The mixture was stirred at 0-10° C for 3 hours. TLC in ethyl acetate/hexane/ethanol (1:1:0.1) showed two intense spots (Rf 0.02 and 0.25). The mixture was extracted with methylene chloride. A white solid precipitated out in the aqueous layer. This was filtered and washed with water and methylene chloride to give 0.34 g of a compound identified by spectral analysis as 4,4'-{N-hydroxycarbamyl)eyclohex-2- enyl disulfide (2), m. 156-158° C, Rf=0.02, H ^T -NMR (D.MSO-d : 5 1.5-2.28 (4H, m, CH ₂ ), 2.65-3.1 (1H, m, CHCO), 3.4-3.7 (1H, m, SCH), 5.73 (2H, s, CH), 8.73 (1H, s, NH), 10.2 (1H, s, OH); IR (KBr): 3150 (NHOH), 1610 cm ^"1 (C=0).

The methylene chloride extract was dried with magnesium sulfate and filtered. After the solvent was removed at reduced pressure, the mixture was chromatographed on dry column silica gel using ethyl acetate/hexane/- ethanol (1:1:0.1) as eluent to give a solid identified by NMR and IR spectroscopy as N-hydroxy-(4-mercaptocyclo-hex-2-enyl)carboxamide (1), m.

Rf=0.25, H ^T -NMR (DMSO-dg): δ 1.95-2.2 (4H, m, CH ₂ ), 2.6-3.05 (1H, m, CHCO), 3.3-3.8 (1H, m SCH), 5.3-6.0 (2H, m, CH), 8.7 (1H, s, NH), 10.2 (1H, s, OH); IR ( Br): 3200 (OH), 3025 (NH), 2550 (SH), 1612 cm ^"1 (C=0). Compound 1 gradually converted to compound 2. None of the 2-thiabicyclo[2.2.2] oct-5-en-3-one oxime was observed.

EXAMPLE 3

2-Thiabieyclo(2.2.2] oct-5-en-3-one oxime

Thiophosgene (296 g of 85%, 2.19 m) was added dropwise to a stirred solution of 167 g (2.08 m) of 1,3-eyclohexadiene in 500 ml of chloroform. The exothermic reaction caused the temperature to rise from 25° C to 68° C with refluxing of the solvent. After 45 minutes, the reaction mixture was cooled and added in portions over four hours to a stirred solution of hydroxylamine (prepared from 480 g (6.9 m) of hydroxylamine hydrochloride in 175 ml water by dropwise addition at 0° C of a solution of 434 g of 89% potassium hydroxide (6.9 m) in 250 ml of water) at -15° C. After being stirred overnight, the reaction mixture was filtered and the filter cake washed with methylene chloride. The combined filtrate and washings were separated and the organic layer dried (MgS0 ₄ ) and reduced in volume at about 20 Torr. After addition of carbon tetrachloride to the residue, distillation of solvent was continued at atmospheric pressure until a pot temperature of 75° C was attained. The hot mixture was filtered. Cooling of the filtrate gave a solid which was recrystallized from carbon tetrachloride to yield 271 g of the title compound.

EXAMPLE 4

Z-2-Thiabieyclo.2.2.1] hept-5-eπ-3-one oxime

Method A

A stirred solution of 14.5 g (0.22 m) of cyclopentadϊene in 50 ml of petroleum ether was maintained at 0 - 5° C as 23 g (0.2 m) of thiophosgene was added over 40 minutes. The colorless solution was stripped of volatiles on a rotary evaporator. A solution of the residue in 100 ml of 1,2-dimethoxyethane was added at -5° C to a stirred slurry of 55.8 g (0.8 m) of hydroxylamine hydrochloride, 115 g (0.4 m) of sodium carbonate decahycrate, 90 mi of water and 100 ml of 1,2-dimethoxyethane. The mixture was stirred overnight as the temperature was allowed to reach 25° C.

CMPI

The upper liquid . layer was separated, combined with a methylene chloride extract of the lower aqueous layer, washed, and dried (MgSO . A small portion was removed and stripped to dryness. The presence of Ξ and Z isomers of the title compound was demonstrated by nuclear magnetic resonance and, thin layer chromatography. The methylene chloride solution was treated with 2.5 ml of trifluoroacetic and allowed to stand at room temperature for four days. The solvent was stripped to yield 23.3 g of pale tan residue. This was confirmed as the Z isomer of the title compound by thin layer chromatography and nuclear magnetic resonance versus an authentic sample.

Method B

Thiocarbonyldiϊmidazole [9.0 g, (10.0 g of 90 percent technical material), 0.05 m] was dissolved in 250 ml of dichloromethane. The solution was treated with 10 ml of freshly cracked cyclopentadiene, and the mixture was refluxed for 4 hours. Evaporation of the solvent gave 16.8 g of a dark brown oil, the NMR of which was consistent with the structure, 3,3-bis(l-imidazolyl)-2- thiabicyclα_2.2.1] hept-5-ene.

A portion (11.1 g, 0.033 m) of the oil was dissolved in 200 ml of absolute ethanol, ^' and the solution was treated with 9.5 g of hydroxylamine hydrochloride. The mixture v/as refluxed for 2 hours. The solvent was evaporated, and the resfdue v/as partitioned between water and dichloromethane. The organic layer and 4 dichloromethane extracts of the aqueous layer were dried (MgSO , filtered with carbon and the solvent was evaporated. The residual brown oil was taken up in dichloromethane and hexane. Upon standing an oil was deposited. The solution was decanted, the solvent v/as evaporated, and residue was triturated with dry ether. The ether soluble material was chro atographed on silica (preparative layer, 50 percent ether in nexanes). The purified material was eluted with acetone; there was obtained 1.51 g of material which was spectrometrically identical with the compound prepared by method 4A.

EXAMPLE 5

6,7-Dibromo-2-thiabicycio[2.2.1] heotaπ-3-one oxime

A solution of 0.036 m of bromine in 167 ml of carbon tetrachloride was added over 30 minutes at 23-30° C to a stirred slurry of 5.0 g (0.035 m) of 2- thiabicvclo(2.2.1] heot-5-en-3-one oxime in 50 ml of carbon tetrachloride. After

a further 30 minutes, the solvent was removed to yield 10.6 g 'of white solid residue, m. 168° C. Reerystallization from acetone gave 6.9 g of the title compound as a white solid m. 168° C (dec).

Calc'd for C _Q H ₇ Br ₂ NOS : C, 23.9; H, 2.4; N, 4.7. Found : C, 24.0; H, 2.4; N, 4.7.

EXAMPLE 6

5(6)-Chloro-2-thiabicyclo{2.2.1] hept-5-en-3-one Q[(methylamino)carbonyI] oxime

To a solution of 5 g (0.035 m) of 2-thiabicyclo_2.2.1] hept-5-en-3-one oxime in 200 ml of methylene chloride was added, over 15 minutes at 25-30° C, 5.7 g (0.042 m) of sulfur l chloride. The mixture was stirred at room temperature for 45 minutes, then stripped to dryness to givQ 8.1 g of tan solid residue which was extracted with 300 ml of boiling methylene chloride. Cooling yielded 1.8 g of a dϊchloro-2-thiabicyelo_2.2.1] heptan-3-one oxime. Calc'd for C _Q H ₇ C1 ₂ N0S : C, 34.0; H, 3.3; N, 6.6, Found : C, 33.7; H, 3.2; N, 6.5.

A solution of 63 g (0.3 m) of the dichlorc—oxime,*' 29 g (0.35 m) of dihydropyran, and 0.4 g of p-tolueπesulfonic acid in 500 ml of methylene chloride was stirred for 16 hours at room temperature. The residue after removal of solvent was taken up in 400 ml of ether. The solution was neutralized with sodium bicarbonate, filtered, and stripped to yield an oil v/hich was purified by dry column chromatography (silica gel; hexane:ether:acetone:3:l:0.3) to yield 37.5 g of a diastereo merle mixture of dichlorobicyclo[2.2.1] heptan-3-one 0-(2- tetrahydropyranyDoxime. A portion of this was treated with ether to give a solid which was reerystallizεd from hexane-acetone. A white solid, m. 129-131° C, was obtained.

Calc'd for C^-Cl^NO^S : C, 44.6; H, 5.1: N, 4.7.

Found : C, 44.5; H, 5.3; N, 4.8.

A solution of 19.5 (0.064 m) of the above protected tetrahydrc- pyranyl-oxime in 250 ml of ether was treated under argon at -10° C with 14.4 g (0.13 m) of potassium tert-butoxide. The mixture was stirred 16 hours at Q° C and four hours at room temperature, filtered, and the filtrate shaken with water. The dried ether layer was stripped to yield 9 g of yellow solid. A solution of 6.1 g of this in 200 ml of methanol v/as treated with 2 ml of concentrated hydrochloric acid, stirred for 16 hours, treated to neutrality with sodium bicarbonate and concentrated to dryness. The residue was taken up in methylene chloride. The dried solution was stripped to vield 3.3 g of vellow oil. A solution of 2.8 g (0,016

m) of this oil, 2 ml of methyl isocyanate and one drop of triethylamine in 50 ml of methylene chloride was stirred at room temperature for 18 hours. The dark solution was treated with charcoal, filtered and stripped of solvent to give 3 g of yellow viscous oil. Dry column ehromatographic purification (silica gel- acetone:hexane::2:3) provided 1.7 g of the title compound as a viscous oil which could not be induced to crystallize.

Calc'd for C ₈ H _g ClN ₂ 0 ₂ S : C, 41.3; H, 3.9; - N, 12.0; Cl, 15.2. Found : ^' C, 40.8; H, 4.5; N/ 11.7; Cl, 15.3.

EXAMPLE 7 2-Oxabicyclo[2.2.2] oct-5-en-3-one oxime

To a 0° C solution of hydroxylamine [from 4.2 g (0.06 m) of hydroxylamine hydrochloride, 8.6 g (0.03 m) of sodium carbonate decahydrate and 30 ml of water] in 50 ml of 1,2-dimethoxye thane was added dropwise, with stirring under nitrogen, 4.4 g (0.02 m) (N-chlorosulfonyl)imino-2- oxabicyclo[2.2.2] oct-5-ene [J. Chem. Soc, Perkin I, 874 (1977)] in 200 ml of 1,2- . dimethoxyethane. After being stirred for 18 -hours, the mixture was filtered to give 0.5 g of solid. Ether extraction of the filtrate yielded an addition 1.3 g of product. The combined solids were recrystallized from ethanol to provide the title compound as a white solid, m.p. 153-4° C. Calc'd for CgH^N^ : C, 60.4; H, 6.5; N, 10.1.

Found : C, 60.7: H, 6.8; N, 10.2.

EXAMPLE 8

2-Thiabicyclo(2.2.2] oct-5-en-3-one Q-(2-tetrahydropyraπyI)ox:me

A solution of 10 g (0.06 m) of 2-thiabicyclo[2.2.2] oct-5-en-3-one oxime, 9 g (0.1 m) of 98% dihydropyran, and a catalytic amount of p- toluenesulfonic acid in 30 ml of methylene chloride was heated under reflux overnight. Sodium bicarbonate was added to neutrality. The residue after removal of solvent was purified by dry column chromatography (silica gel-ethyl acetate:hexane::l:l) to give 14.4 g of yellow solid. Recrystallizaticn from ether- hexane yielded 10.1 g of the title compound as a white solid, m. 84-5° C. Calc'd for C^H _j yNOgS: C, 60.2; H, 7.2; N, 5.9.

Found : C, 60.0; H, 7.2; N. 5.9.

EXAMPLE 9

5,6-Dihydroxy-2-thiabicyclo[2.2.2] octan-3-one 0-<2-tetrahydropyranyl)oxime

A mixture of 8 g (0.033 m) of the product of Example 8, 5.3 g (0.039 m) of N-methylmorpholϊne N-oxide, 4 ml of 2.5% osmium tetroxide in t-butaπol, and 20 ml of acetone was stirred for four hours then extracted with ethyl- acetate. The organic solution was washed with brine, dried, and stripped to give 12 g of crude product which was purified fay dry column chromatography (silica gel, ethylacetate:hexane::l:l) to yield 5.8 g of the title compound as a white solid, M. 124-6° C. Calc'd for C ₁₂ H _ιg N0 ₄ S: C, 52.7; H, 7.0; N, 5.L

Found : C, 52.6; H, 7.4; N, 5.0.

EXAMPLE 10

5,6-Dimethoxy-2-thiabicyclo[2.2.2] octan-3-one oxime

To a suspension of 1.4 g (0.03 m) of 60% sodium hydride in mineral oil was added a solution of 4 g (0.015 m) of the product of Example 9 in tetrahydrofuran. The mixture was stirred until gas evolution ceased, then cooled to 0° C and treated with 2.3 g (0.015 m) of methyl iodide. This mixture was stirred at 40° C. After slow addition of a little me hanol, followed by water, the mixture v/as extracted with methylene chloride. The organic solution was washed with brine, dried and stripped to give 6 g of oil which was purified by high performance liquid chromatography to yield an oil.

A solution of 1.8 g (0.0033 rn) of this oil and 3 drops of 5N hydrochloric acid in 80 ml of methanol was heated under reflux overnight. Water was added. A methylene chloride extract of this mixture was dried and stripped to yield 1.25 g of the title compound as a solid.

EXAMPLE U

2-Thiabicyclo[3.2.2] non-5-en-3-one oxime

A solution of 29 g (0.3 m) of 1,3-cycloheptadiene, 46 g (0.4 m) of thiophosgene, and 25 ml of eyclohexane was heated under reflux for 24 hours, then stripped of vola tiles under reduced pressure. The oily residue was taken up in 150 ml of methylene chloride and stirred with 1.5 m of hydroxylamine in 200 ml of water at room temperature for three days. The separated organic layer was dried over magnesium sulfate and stripped to yield 25.7 g of viscous oil.

C Λ?Ϊ

Purification by dry column chromatography using silica gel and l:4::ether:hexane as eluent. There was obtained 14 g of yellow solid. Recrystallization of 2 g portion from 1:1 ether-hexane yielded 1.4 g of the title compound as white crystals, m. 130-132° C. Calc'd for CgH^NOS : C, 56.8; H, 6.6; N, 8.3: S, 18.9. Found : C, 57.1; H, 6.7; N, 8.2; S, 18.5.

EXAMPLE 12

2-Thiabicyclo[3.2.2] nonan-3-one oxime

Air was passed through a stirred solution of 3.4 g (0.02 m) of the product of Example 11, 20 ml of 85% hydrazine hydrate, and 0.1 g of. cupric acetate in 50 ml of isopropyl alcohol for six hours at room temperature. The mixture was poured into 300 ml of water. A methylene chloride extract was washed with water, dried over magnesium sulfate, and stripped to yield 3.7 g of solid residue. Dry column chromatography on silica gel using l:4::ether.hexane yielded 3.1 g of the title compound as a white solid, m. 146-8° C. Calc'd for C _g H ₁₃ NOS : C, 56.1; H, 7.7; N, 8.2; S, 18.7.

Found : C, 56,0; H, 7.9; N, 7.9; S. 18.6. . -

EXAMPLE 13

2-Thiabicyclo[2.2.1] heotan-3-one Q-[(methylamino)carbonyl] oxime

A solution of 6.6 g (0.046 m) of 2-thiabicyclo[2.2.1] heptan-3-one oxime, 2.9 g (0.05 m) of methyl isocyanate, and 60 ml of methylene chloride was stirred at room temperature for 17 hours. Removal of solvent gave 9.1 g of yellow-tan solid which was purified by dry column chromatography on silica gel using ether-acetone as eluent. There was obtained 5.2 g cf the title product as a cream colored solid, m. 121-2° C.

Calc'd for CgH ₁₂ N ₂ O ₂ S : C, 48.0; H, 6.0; N, 14.0.

Found : C, 47.8; H, 6.1; N, 14.1.

EXAMPLE 14

2-Thiabicvclo[2.2.1] oct-5-en-3-one Q-(aminocarbonyl)oxime

To a cold, stirred solution of 11 g (0.11 m) of phosgene in 20 ml of methylene chloride was added 12.1 g (0.1 m) of N,N-dimethylaniline. To this was

OMPI

added over one hour a solution of 14.1 g (0.0091 m) of 2-thiabicyelo[2.2.2] oct-5- en-3-one oxime in 100 ml of methylene chloride. The solution was stirred at 0° C for two hours, then treated with a solution of 14.7 g of 29% aqueous ammonia in 40 ml of water. After a further 30 minutes, the organic layer was separated, washed twice with cold water, twice with cold dilute hydrochloric acid, and finally with water. The dried (MgSO solution was stripped to give 16.6 g of solid residue- Purification by dry column chromatography over silica gel using ethyl acetate:cyclohexane::10:6 yielded 3.3 g of solid." The title compound was obtained as a white solid, m. 145-7° C, by recrvstallization from methylene chloride-petroleum ether.

Calc'd for CgH^N^S : C, 48.5; H, 5.1; N, 14.1.

Found : C, 48.4; H, 5.2; N, 14.0.

EXAMPLE 15

2-Thiabieyclo[2.2.1] hept-5-en-3-one Q-[(methylamino)carbonyl] oxime exo-2- -oxide

A solution of 18 g (0.091 m) of 2-thiabicycxo[2.2.1] hept-5-en-3-one O- [(methylamino)earbonyl] oxime in 300 ml of methylene chloride was treated over 15 minutes with a solution of 16.5 g (0.095 m) of 80.5% metachloroperoxybenzolc acid in 300 ml of methylene chloride. The temperature rose to 35° C during the addition. After 15 minutes additional stirring, the reaction mixture was washed with 2 x 600 ml of 5% aqueous sodium bicarbonate. The aqueous washes were saturated with sodium chloride and extracted twice with methylene chloride. Stripping of the dried (MgSO j extract gave 6.8 g of solid residue. Recrvstal¬ lization of a portion of this from acetone-hexane yielded the title compound as a pale tan solid, m. 118° C (dec).

Calc'd for CgH^N^S : C, 44.9; H, 4.7; N, 13.1.

Found : C, 44.7; H, 4.7; N, 13.1.

EXAMPLE 16

2-Thiabicyclo[2.2.1] heot-5-en-3-one Q-[(methylamino)carbonyl] oxime enco-2- -oxide

The procedure of Example 15 was repeated. The methylene chloride solution after the sodium bicarbonate wash v/as dried and concentrated to give 8.1 g of dark oil. Purification by dry column chromatography followed by

medium pressure liquid chromatography gave 0.87 g of solid. Trituration with ether and hexane yielded 0.32 g of the title compound as a tan solid, m. 59-77° C (dec).

Calc'd for CgH _1Q N ₂ 0 ₃ S : C, 44.9; H, 4.7; N, 13.1. Found : C, 44.2; H, 5.1; N, 12.6.

EXAMPLE 17

2-Thiabicyclo[2.2.1] hept-5-en-3-one Q-[(methylamiπo)σarbonyl] oxime 2,2-dioxide

To a stirred solution of 6.77 g (0.034 m) of 2-thiabicyclo[2.2.1] hept-5- en-3-one 0-_(rnethylamino)carbonyl] oxime in 169 ml of methylene .chloride was added a solution of 16.1 g (0.075 m) of 80.5% metachloroperoxybenzoic acid. The temperature rose to 33° C. After being heated at 35-40° C for five hours, the reaction mixture was cooled slowly without stirring to 0° C. The precipitated metachlorobenzoic acid was separated. The solution was stripped to dryness.

After being slurried with two portions of ether, the residue was recrystallized from hexane-acetone to yield 1.6 g of the title compound as a white solid, m. 132° C (dec).

Calc'd for CgH^N^S : C, 41.7; H, 4.4; N, 12.2.

Found : C, 41.3; H, 4.7; N, 12.0.

EXAMPLE 18 5,6-exo-Epoxy-2-.hiabicyclo[2.2.l! heotar.-3-one Q-[(methyIamino)carbonyl] oxime 2,2-dioxide

A solution of 7.5 g (0.0325 m) of the product of Example 17 and 7.0 g (0.0325 m) of 80.5% metachloroperoxybenzoic acid in 730 ml of ethyl acetate was heated at reflux for 5 hours. After addition of a second equivalent of peracid, the mixture was heated for 3.5 hours, allowed to cool, and stripped to yield 19.9 g of white solid residue. This was slurried with two portions of ethyl ether to leave 5 g of crude product as residue. Purification by dry column chromatography followed by recrvstallization from acetone-hexane gave 0.26 g of title compound as a white solid, m. 178-9° C (dec). Calc'd for CgH _1Q N ₂ 0 ₅ S : C, 39.0; H, 4.1; N, U.4.

Found : C, 38.9; H, 4.3; N, 11.2.

O PI

EXAMPLE 19

5,6-Dihydroxy-2-thiabicyclo[2.2.2] octan-3-one Q-[(methyIamino)carbonyl] oxime

To a solution of 6.5 g (0.048 m) of N-methylmorpholine N-oxide and 5.0 g (0.024 m) of 2-thiabicyclo[2.2-2] oct-5-en-3-one 0-t(methylamino)car- bonyl] oxime in 20 ml of acetone was added 15 ml of a 0.5% solution of osmium ^' tetroxide in tert-butanol. The reaction mixture was stirred at room temperature for 48 hours, then treated with a slurry of 1 g sodium bisul ite, 15 g of magnesium silicate, and 50 ml of water. After being stirred for 30 minutes, the mixture was filtered. The filtrate was extracted with ethyl acetate, then with methylene chloride. Evaporation of the dried organic solution gave 4.8 g of viscous oiL Purification by dry column chromatography yielded 3.5 g of the title compound as a white solid, m. 123-5° C.

Calc'd for C _g H ₁₄ N ₂ 0 ₄ S : C, 43.9; H, 5.7; N, 11.4.

Found : C, 43.8; H, 6.1; N, 11.3.

EXAMPLE 20

5,6-isoPropylidenedioxy-2-thiabicyclo[2.2.2] octan-3-one O-l [(meth-rlamino)- carbon l] oxime

A mixture of 1 g (0.004 m) of the product of Example 19, 2 ml of acetone, 0.13 g of p-toluenesulfonic acid, and 50 ml of methylene chloride was heated overnight at reflux. After addition of 0.03 g of sodium acetate, the mixture was stirred for 30 minutes, filtered, and stripped to yield 1.26 g of white solid residue. Purification by dry column chromatography over siiiea gel using ethyl acetate: hexane:ethanol::l:l:0.1 gave 1 g of the title compound as a white solid, m. 126-8° C. Calc'd for ^C ₁₂ ^H ₁ 8 ^N 2°4 ^{S: C} ' ⁵ °' ^H ' ^δ ' ³ ' ^N » ⁹ ' ⁸ *

Found : C, 50.2; H, 6.5; N, 9.7.

EXAMPLE 21

2-Thiabicyclo[2.2.2] oct-5-en-3-one Q-[(t-butyldimethyl)s.ly i] oxime

A solution of 15.5 g (0.1 m) of 2-thiabieycio[2.2.2 oct-5-en-3-one oxime, 18.1 g (0.12 m) of t-butyldimethylsilyl chloride and 17.0 g (0.25 m) of i idazole in 300 ml of ethyl ether was stirred overnight at room temperature, then filtered. The filtrate was washed with saturated brine, dried, and stripped

O./.PI ~

to yield 7.2 g of solid residue which Was purified by dry column chromatography to give 6.4 g of the title compound as a white solid, m. 78-9° C. Calc'd for C. ₃ H ₂₃ NOSSi : C, 57.8; H, 8.6; N, 5.2.

Found : C, 57.6; H, 8.8; N, 5.2.

EXAMPLE 22

N _> N'-thiobis[(methylimino)carbonyloxy] -2-thiabicyclo[2.2.2] octan-3-imine

A solution of 10.7 g (0.05 m) of 2-thiabicyclo[2.2.2] octan-3-one O- [(methylamino)carbonyl] oxime in 30 ml of pyridine was cooled at 0° C as 3.8 g (0.028 m) of sulfur monochloride was added over five minutes. The mixture was stirred at 0° C overnight, poured onto ice and water, arid filtered. The filter cake was washed with cold dilute hydrochloric acid, then with water and dried to yield 12.2 g of solid, m. 158-62° C. Recrystallization from hot 2-butanone gave the title compound as an off-white solid, m. 174-6° C (dec). Calc'd for C ₁₈ H ₂ gN ₄ 0 ₄ S ₃ : C, 47.1; H, 5.7; N, 12.2. Found : C, 47. ^' 3; H, 5.9; N, 12.3.

EXAMPLE 23

2-Thiabicyclo[2.'2.2] octan-3-one Q-[N-methy.-N-(.N-methyl-N-(butoxy- earboπ pamino] thio)carbonyl] oxime

To a stirred solution of 10.7 g (0.05 ) 2-thiabicyclo[2.2.2] octan-3- one 0-[(methylamino.earbony_] oxime and 4.4 g (0.055 m) of pyridine in 100 ml of methylene chloride at 0° C was added 10.9 g (0.055 m) of butyl N-chlorothio-N- methylcarbamate. After being stirred overnight as it was allowed to come to room temperature, the reaction mixture was diluted with 2Q0 ml of ethyl ether, then washed with three 150 ml portions of water. The organic solution was dried over magnesium sulfate, filtered, and the filtrate stripped of solvent. The residue was purified by dry column chromatography (silica gel, hexane:ethyl ether::l:l) to yield 12 g of the title substance as a white powder, m. 77.5-30° C. Calc'd for C _][5 H ₂₅ N ₃ 0_ _i S ₂ : C, 48.0; H,.6.7; N, 1L2. Found ^* : C, 48.0; H, 6.9; N, 1L2.

OMPI > IPO

EXAMPLE 24

2-ThiabicycIo[2.2.2] octaπ-3-one Q-[N-(N-fluorocarbonyl-N-methyl)aminothio] -

N-methvIaminoearbonvloxime

To a cooled (-10° C) solution of 18.4 g (0.1 m) of bis[N-fluoroearbonyI- N-methyl)amino] sulfide and 15.7 g (0.1 m) of 2-thiabicycio[2.2.2] octan-3-one oxime in 200 ml of methylene chloride was added, over 30 minutes, 14.0 ml (0.1 m) of triethylamine. After being stirred at -10° C for 40 minutes, the reaction mixture was poured directly onto a silica gel dry column which was developed with ether:hexane::l:L This gave 26.4 g of solid. Purification on HPLC and dry column chromatography using ether yielded the title compound as a solid, m. 98- 100° C. Calc'd for C _u H ₁₆ F ₃ 0 ₃ S ₂ : C, 41.1; -H, 5.0; N, 13.1; S, 20.0.

Found : C, 4L2; H, 5.3; N, 13.3; S, 20.1.

EXAMPLE 25 2-Thiabicyclo[2.2.2] octan-3-one Q-(N-methyl)-N[N-methyl-N-(l-methylthio- ethylideneamino-oxycarboπyl)am ino thio] am inocarboπyloxim e

To a stirred solution of 3.2 g (0.01 m) of the product of Example 24 and 1.05 g (0.01 m) of methylthioacetohydroxamate in 50 ml of methylene chloride was added 1.4 ml (0.01 m) of triethylamine- The reaction mixture was stirred overnight, washed with water, dried and stripped to give 4.3 g of a white solid. Purification by dry column chromatography (silica gel, ether) yielded 3.25 g of the title compound as a white solid, m. 176-9°-C. Calc'd for ^c ₁₄ --- _*22 N ₄ 0 ₄ S ₃ : C, 41.4; H, 5.5; N, 13.8; S, 23.7. Found : C, 41.2: H, 5.8; N, 13-7; S, 23.4.

EXAMPLE 26

2-Thiabicyclo[2.2.1] heot-5-en-3-one 0-[N-methyl-N-(2-cyano-2-propylthio- sulfenyl)] aminocarbonyloxime

A solution of 6.1 g (0.043 m) of 2-thiabicyelo_2.2.1] hept-5-en-3-one oxime and 9.0 g (0.043 m) of N-methyl-N(2-cyano-2-propylthiosulfenyl)amino- carbonvl chloride in 200 ml of methylene chloride was treated with 4.4 g (0.43 m) of triethylamine. After being stirred overnight, the mixture was washed with three portions of water, dried, and stripped to give 14.6 g of brown gum.

Purification by dry column chromatography (silica gel, ether:hexane::9:l) yielded 8 g of the title compound as an off-white solid, m. 76-8° C.

Calc'd for C ₁₂ H ₁₅ N ₃ 0 ₂ S ₃ C, 43.8; H, 4.6; N, 12.8.

Found : C, 43.5; H, 4.8; N, 12.6.

EXAMPLE 27 2-Thiabicvclo[2.2.1] heot-5-en-3-one 0-{N-methylH(N-methvl)-N-(p-toluene- sulfonyDaminosulfenyl] aminocarboπyloxime

A solution of 6.8 g (0.048 m) of 2-thiabicyclo[2.2.1] -hept-5-en-3-one oxime and 14.0 g (0.048 m) of (N-methylHN-methyl-N-(p-toluenesulfonyl)- amino] sulf enylaminocarbonyl fluoride in 100 ml of methylene chloride was treated with 4.8 g (0.048 m) of triethylamine- After being stirred for 72 hours, the solution was washed with water, dried, and stripped to give 13.2 g of dark viscous residue. Purification by dry column chromatography (silica gel, ethyl ^" ether) yielded 6 g of the title compound as a brown solid, m. 120-122° C. Calc'd for C ₁₆ H _ιg N ₃ 0 ₄ S ₃ : C, 46.5; H, 4.7; N, 10.2.

Found C, 46.2; H, 4.7; N, 10.2.

EXAMPLE 28

2-Thiabicyclo[2.2.2] octan-3-one Q-(N-methyl)-N-(3-trifluoromethylphenylthio)- aminocarbonvloxime

To a stirred suspension of 5.36 g (0.025 m) of 2-thiabieyclo[2.2.2] - octan-3-oπe 0[(methylamino)carbonvl] oxime in 50 ml of carbon tetrachloride was added 3.96 g (0.025 m) of l,5-diazabicyclo[5.4.0] -undec-5-ene. The reaction mixture was cooled at -10° C during the addition of 6.38 g (0.03 m) of 3- trifluorobenzenesulfenyl chloride in 25 ml of carbon tetrachloride. After being stirred for 18 hours, the reaction mixture was filtered. Stripping of the filtrate gave 6 g of an oil which was purified by dry column chromatography (silica gel, ether) to give 3.1 g of solid. Recrystallization from ethanol yielded the title compound as a white solid, m. 60-2° C. Calc'd for C ₁₆ H ₁₇ F ₃ N ₂ 0 ₂ S ₂ : C, 49.2; H, 4.4; N, 7.2. Found : C, 49.1; H, 4.7; N, 7.L

EXAMPLE 29A

4-Cyano-2-thiabicyclo[2.2.2] oct-5-en-3-oπe Q-(N-methyl)-N(4-t-butylphenyl- thio.aminocarbonyloxime

To a stirred mixture of 5.9 g (0.03 m) of 4-cyano-2-thiabicyclo- [2.2.2] oct-5-en-3-one oxime and 7.24 g (0.03 m) of N(p-t-butylphenylthio)-N- methylcarbamyl fluoride in 150 ml of methylene chloride was added 3.04 g of triethylamine in 50 ml of methylene chloride. After being stirred for 72 hours, the reaction mixture was stripped. Purification of the residue by dry column chromatography gave a solid which was recrystallized from ethanol to yield 3.8 g of the title compound as a_ white solid, m. 148-9° C.

Calc'd for C ₂₍ -H ₂₃ N ₃ 0 ₂ S ₂ : C, 59.8; H, 5.8; N, 10.5. Found : C, 59.8; H, 6.0; N, 10.6.

EXAMPLE 29B

2-Thiabicyclo[2.2.2] oct-5-ene-3-one O-<N-methyl)-N-(4-tertbutylphenylthio)- aminocarbonyl oxime, hydrate

A flame dried 3-neck flask was equipped with a gas inlet tube, mechanical stirrer and injection septum. Under nitrogen atmosphere, 4.37 g (.03 m) 2,2,6, 6-tetramethylpiperidine was dissolved in 100 ml THF (distilled from LAH) with stirring, while 18.8 ml of a 1.6 molar (in hexane) solution on n- butyllithium was injected through the septum. The reaction mixture assumed a yellow color. Stirring was continued for 10 minutes, after which the reaction mixture was cooled to -78° . Over a two-minute period, a solution of 6.38 g (.03 m) of 2-thiabicyclo[2-2.2] oct-5-ene-3-one 0-(N-methylaminoearbony_.oxime in 100 mL THF was added- Stirring was continued for 5 minutes, 6.03 g (.03 m) p-t- butylbenzεnesulfenyl chloride in 100 -ml tetrahydrofuran was added dropwise during 15 minutes, and the reaction mixture was allowed slowly to come to ambient temperature over an 18-hour period. The reaction mixture was then quenched with saturated aqueous ammonium chloride, extracted with 300 ml ether and water washed five times. The ether extract was dried over MgS0 ₄ , filtered and the solvent removed under reduced pressure to give 9 g of a brown oil which was chromatographed on a silica gel dry column (ether) to give 2.51 g (21 percent) of the title compound as a yellow oil. Crystallization was induced by trituration with ether. Recrystallization from ethanol afforded pure product (0.6 g), m. 119-120° C.

OM?I

Calc'd for C _ιg H ₂₄ N ₂ 0 ₂ S ₂ -H _j O : C, 57.8; H, 6.6; N, 7.1. Found : C, 57.8; H, 6.3; N, 7.1.

EXAMPLE 30

N,N ^τ -dithiobis[(methylimino)carbonyloxy] -2-thiabicyclo[2.2.1] hept-5-en-3-imine

A solution of 10.1 g (0.1 m) of triethylamine in 25 ml of methylene chloride was added over 30 minutes at 0° C to a stirred solution of 14.1 g (0.1 m) of 2-thiabicyelo[2.2.1] hept-5-en-3-one oxime and 10.8 g (0.05 m) of bis[(N- methyl-N-fluorocarbonyl)amino] disulfide in 200 ml of methylene chloride. The mixture was allowed to warm to room temperature, stirred for 20 hours, and stripped to give a semisolid residue. After being passed through a short column of silica gel (ethyl acetate as eluent), the material was purified by dry column chromatography (silica gel, methylene chloride:acetone::95:5) to give a brown syrup. Trituration with ether gave 10.2 g of the title compound as a tan solid, m. 148-150° C (dec). Calc'd for C ₁₆ H ₁₈ N ₄ 0 ₄ S ₄ : C, 41.9; H, 4.0; N, 12.2; S, 28.0.

Found : C, 41.9; H, 4.2; N, 12.1; S, 27__ . "

EXAMPLE 296

2-Azabicyclo[2.2.1] heot-5-en-3-one oxime

To a solution of hydroxylamine (from 2.1 g (0.03 m) of hydroxylamine hydrochloride, 4.3 g (0.015 m) of sodium carbonate, 10 ml of water and 200 ml of tetrahydrofuran) at 0° C was added 5.16 g (0.021 m) of 3-tosyl-2- azabicyclo[2.2.1] hepta-2,5-diene (prepared by the procedure of J. Organic Chemistry, 39, 564 (1974)) in 50 ml of tetrahydrofuran. After being stirred overnight, during which time the temperature was allowed to warm to 25° C, the organic layer was separated, dried, and stripped of solvent. Purification of the residue by chromatography (silica gel: l:l::dichloromethane:ethyl acetate) gave 0.8 g of material whose spectra were consistent with the title structure.

EXAMPLE 297

2-Methyl-2-azabicyclo[2.2.2] octan-3-one oxime

A slurry of 33.0 g (0.218 m) of 4-(me _hylamino)benzoic acid and 4.0 g of 5% rhodium on alumina catalyst in 350 ml of water was shaken under 1500 psig of hydrogen for 24 hours. The insolubles were removed by filtration. The slurry

O PI

from partial removal of water under reduced pressure was diluted with 300 ml of NiN-dimethylformamide and chilled. The precipitated solid was filtered, washed with several portions of cold acetone, and dried to yield 23 g (75%) of 4- (methylamino)eyclohexanecarboxylic acid. The crude acid in 200 ml of dlphenyl ether was heated at 230-250° C for 20 minutes with removal of water. Removal of the diphenylether under reduced pressure gave 10.6 g (52%) of 2-methyl-2-azabicyclo[2.2.2] octan-3-one.

A solution of this in 100 ml of toluene was added to a mixture of 28.3 g (0.07 m) of 4-methoxyphenylthionophosphine sulfide in 100 ml of toluene- After 3 hours under reflux, the cooled mixture was filtered and the filtrate evaporated to dryness. The oily residue was purified by column chromatography (silica gel: 3:l_:ether:petroleύm ether) to yield 8.8 g of 2-methyl-2-azabicyclo[2.2-2] octan- 3-thione.

A solution of the thione in 50 ml of acetone was added to 80.9 g (0.57 m) of methyl iodide under nitrogen at room temperature. After being stirred overnight, the mixture was chilled and filtered under nitrogen to give 10.6 g of solid. A partial solution of this solid in 75 ml of chloroform was added dropwise to a stirred solution of hydroxylamine (from 5 g (0.072 m) hydroxylamine hydrochloride, 15.5 g (0.054 m) of hydrated sodium carbonate, 10 ml of water, and 150 ml of chloroform) at 0° C. After 6 hours, during v/hich the mixture was allowed to warm to room temperature,, the organic phase was separated, dried and stripped to yield 4.4 g of residue whose spectra were consistent with the title structure.

The following compounds were prepared using the foregoing synthesis procedures with appropriate selection of substituted dienes, dienophiles and carbamylating agents to obtain the derivatives of formula I set forth in Tables I-V

TABLE I

EX. MELTING CALCULATED POUND NO. a RANGE°C N N

31 S double C(-=0)t.--C-!_ 110-119 48.5 5.1 14.1 40.5 5.2 13.0

32 S double C(=0)NI1CII_ 09- 91 48.5 5.1 14.1 40.6 5.2 14.2

34 No Example

50 S doubl C(-=0)N(CII )S-N(CII )C( ^« 0) 156 45.1 4.2 13.1 44.0 4.4 12.9

70 S doubl C (=0) N (Cll ₃ ) S- C ₆ U C (Cll ) -4 99-100 59.6 6.1 7.7 59.7 6.2 7.7 e

7n S double C(=0)N(CII ₃ )S-N(CII )S0 NtCil ) 109-110 36.0 5.0 15.3 36.0 5.1 15.3 m H double C(--O.N(CII.)S-C ιι.. oil 54.9 4.6 9.1 54.5 4.0 0.7

.1 (i .» i - — i no S double c(-o.N(c.._)s-NC._„α_„oc_ι..cπ.- 115-116 45.7 5.4 1.3.3 45.5 5.3 13.2

J __. 2. £

101 S double C(=0)N(CI1,)SC_II CII.-2 115-116 56.2 5.0 0.7 56.0 5.3 0.5 J υ i 11.2 S double C(--0)N(C )S0 ll.C 1-4 64- 60 -47.3 3.0 0.2 49.1 4.0 0.1 3 6 4 117 S double C(=0)N(CI1 .SC i ll -4 73- 74 56.2 5.0 8.7 56.2 5.2 0.6 3 6 4 3

163 26.8 2.0 7.0 27.1 3.0 7.9

TABLE I (Cont'd)

125 double C(=0)N(CH ₃ )SN(CH ₂ CH ₂ CH ₃ )SO ₂ C ₆ H ₄ - 85- 07 50.0 5.3 9.5 50,0 5.6 9,0

CU ₃ -

12G S double II C (-Ω) NII 1I Cll Cl! 69- 71 53.1 6.2 12.4 53.0 6,5 12.3

120 S double II C( = <0)NIICII Il Cl! 72- 75 53.1 6.2 12.4 53,0 6.3 12.5

129 S double 11 C(=0)N(C....)i_N(C.I- - n)SO„C.H.CH - oil 50.1 5.5 9.2 50.3 5.9 9.0 J 4 9 2 6 4 3

130 _J ϊi 1 nij 1 e 5, 6- c( 0> iic.n 150 60.0 4.6 6.4 59,8 4.6 6.2

If. V ¹ ! .C(= 0)0) - λ

131 f _> in<|le 5,6- C(-0)N1ICU, 149-150 45.6 5.1 , 8.9 45.6 5.2 0.9 tcιι ₃ c(=o)ol ₂

135 double II C(= 0)N(CH-.)SC,.II _Λ Br-4 67- 69 43.6 3.4 7.3 43.4 3.4 7.1 3 6 4 137 __.ii.cjlo 5,6- [CII..NIIC- C(~-0)NI1CI1 200-202 41.6 5.2 16.2 41.5 5.4 16.0

(-0)0]

138 sinqle 5,6-OCII 0- C(-=0)NIICH_ 190-192 41.9 3.9 10.0 42.0 4.0 10.0

TABLE I (Cont'd)

139 double C(=0)N(C1I.-)S1.(C1I(CII_)_)SO Λ\ - 155-157 49.0 5.2 9.5 40.8 5.4 9.6 C.. ₃ -4 ^J 3 2 2 6 4

143 single 5,6-Cl, 137-138 34.0 3.3 6.6 33.7 3.2 6.5

147 single 5(6)-CH HH- C(=0)NIICIL 60- 80 41.5 5.2 14.5 41.9 5.9 14.2 C(=0)0-6(5) (HO)-

140 S double 11 C(=0)N(CII )SC ILC1- 112-113 49.3 3.8 0.2 49.2 4.1 0.1 J 0 4

J 9 S double 11 C (=0) N (CIL ) SN (CILCILCIL ) S0_C _c IL syrup 47.0 4.9 9.0 40.0 5.3 9.6 3 2 2 3 2 6 5

152 S single 5(6)C ₆ 1I ₅ C- C(=0)NIICIL 107-109 53.6 4.8 0.3 51.6 4.8 0.0

(=0)0-6(5)- (110)

153 S single 5(6)-110-6(5)- 162-165 53.6 4.0 0.3 52.2 4.0 0.1 -C,.ILC(-=0)-0

6 D

TABLE I (Cont'd)

157 S double H C(-0) 110*111 53,6 5,4 12.5 53.5 5,5. 12,5 160 S single 5,6-(110). C(=0)NI1CII. 98-101 41.5 5.5 11.0 41.5 5.6 11.8

.1 1 double 7-Br C(=0)NIICII 87- 92 34.7 3.3 10.1 34.8 3.4 10.0

K.7 double. C (-0) N (CIL.) HH (Cll CIl CU ) so ₂ - 100-111 44.2 4.4 9.1 44.5 4.5 9.3

C LC1-4 6 4

.170 double C(---0)N(CII ) . ( ιι ₂ cιι ₂ cιι ₃ )so ₂ cπ ₃ 91- 94 39.4 5.2 11.5 39.3 5.6 11.4

172 double C(=0)N(CII ₃ )SN(CH )C(=0)0CII ₃ 93- 95 41.6 4.0 13.2 41.7 4.9 13.2

170 double C(-=0)N(CII ₃ ) ₂ 07- 95 50.9 5.7 13.2 50.0 6.1 13.3

02 single C(=0)N(CII )SN- 139-140.5 40.7 5.7 9.5 40.4 5.7 9.0

TABLE I (Cont'd)

105 S double 11 C(=-0)NII, 126-127 45.6 4.4 15.2 45,7 4,5 15.3

107 S double II c(-o)N(cιι ₃ )sN(ακcιι ₃ > ₂ )so ₂ N(cπ ₃ ) ₂ _ _n4 39.6 5.6 14.2 39.5 5.9 13.9

1 1 S double II C(=0)N11, 135-130 45.6 4.4 15.2 45,4 4,4 15.2

209 S double 4-C(= =0)0CH. C(-=0)NHC|| 112-113 46.9 4.7 10.9 46.0 4,4 11.0

212 S double H C (=0) N (CH ₃ ) SN .C ₁₂ -- ₂₅ --. S0 ₂ N (CH ₃ ) ₂ 02- 04 50.7 7.8 10.8 51.0 8.0 10.4

214 S double H C(=0)N(CIL)SN(ClI )C IL 91- 93 53.7 5.1 12.5 53.6 5,0 12.1 J i b

220 S double 4-C(= =0)ocπ C(=0)NIICIL oil 46.9 4.7 10.9 46.6 5,0 10.5

221 S double 1-C(= =0)0CII C(=0)N1ICH. 102-106 46.9 4.7 10.9 46.7 4.6 10.8

227 S single 11 C(=0) (CH ₃ )SC ₆ II ₄ C(CH ₃ ) . 121.5-125 59.3 6.6 7.7 59.5 6.6 7.7

220 Ξ double 11 C(=0)N(CII )._N(C _M .I- n)SO.C H αi -4 oil 54.0 6.5 0.2 54.2 6,7 0.1. i H i./ -. 6 3

EX. MEI.TING CALCULATED FOUND NO. R RANGE °C H - N H N

33 S double II 112-114 50.9 5.7 13..2 50..6 6.1 12.8

35 S double 5(6)-CH ₃ -7- C(=0)NI1CII oil 50.2 7,5 10,9 58,3 7,8 10,2 (0)CII(CH ₃ ) ₂ -

36 S single 11 C(-^0)NIICIL 115-116.5 50,4 6.6 13.1 50.4 6.7 12.4

37 S double, II C(=0)NIICII 122-124 50.9 5.7 13.2 50.7 5.6 12.6

30 S double 7,0-Cll ₂ - C(=0)NI1CII 124.5-125.5 53.6 5.4 12.5 53.3 5.0 12.3

3 S single 7,0-CII _? - C (-^0) NI1CII 124-125 53.1 6.2 12.4 52.9 6.4 12.3

40 a double 5(6)-(C.I ~ C(=-0)NIICII oil 42.8 5.0 7.7 43.0 6.3 7.6 Cll ₂ 0) ₂ P( ^» 0) 1 .-. double 4-CN C(-=0)NIICII 153-157 50.6 4.7 .1.7.7 50.2 4.7 17.5

42 s double 11 C(=-0)NHCII CH 92- 94 53.1 6.2 12.4 53.0 6.3 12.1 CIL 94- 95 53.1 6.2 12.4 52.9 6.3 12.2

TABLE II (Cont'd)

44 S double 7 (8) -C(=0) OCIL II oil 50.7 5.2 6.6 50.1 5.5 6.2

45 S double 1(4)C( =O)0CU, 178-180 50.7 5.2 6.6 50.5 5.2 6.5

46 double 7(0)C(=-0)0CIL C(=0)NHCIL 139-142 40.9 5.2 10.4 48.8 5.3 10.3

47 S double 4C DC (=0)( C(=0)NIICIL 122-125 48.9 5.2 10.4 48.5 5.3 10.4

40 S double 4-CN 196-199 53.3 4.5 15.5 53.1 4.7 15.3

49 S in le 11 C (=0) N (CM ) S-N (CIL) C (=0) 0CII CII 77-70.5 44.9 6.1 12.1 44.0 6.3 11.8

50 S double 11 C(- =o)N(cπ )s- N(CII ₃ )C(=0)O(CII ₂ ) ₃ CH ₃ 94.5-95 48.2 6.2 11.2 48.0 6.5 11.2

51 s single 11 C (-0) N (CIL ) S-C.ll -C (CIL ) -4 140-140.5 60.3 6.9 7.4 59.7 7.1 7.5 3 6 4 3 3

52 s single 11 C (=0) N (CII ₃ ) S-N (CII ₃ ) C (=0) OCH,,- 104-104.5 44.6 6.1 11.1 44.5 6.4 11.0

CIl ₂ OCH ₃

53 S double 1 (4) -C(=0) 0- C(-- )NHCI 123-125 50,7 5 ₄ 7 9.9 ₅₀ .6 5.9 9.9

CH ₂ C.l ₃

TABLE II (Cont'd)

double 1(4)C(=0)- C(=0)NI1CIL oil 50.7 5.7 9.8 50.? 6.0 9.3

OCH ₂ CH ₃

56 single 11 C(=0)M(CIL)S-N(CIl_)C(-=0) _t OCπ(CIL)„ 93-95 46.5 6.4 11.6 46.7 6.5 11.6

J J i Δ 57 S double II C (=0) N (CII ₃ ) S-N (CH ₃ ) C (=0) Q 190 47.6 4.9 12.3 47.8 5.0 12.2 5 S single II C(=0)NIICII CIL 82-83 52.6 7.4 12.2 52.6 7.4 12.1 60 single II 95-96 46.8 6.7 12.5 47.1 6.4 12.7 61 S double 5(6)-Bϊ C(-=0)NI1CII.. oil 37.1 3.0 9.6 37.5 4.2 9.5 62 S double 5(6)-Br C(^0)NI1CI1., 07-09 37.1 3.0 9.6 37.0 4.0 7.5 3 S double 5(6)-Br 142-145 35.9 3.4 6.0 36.2 3.5 6.0 64 S double 5(6)-Br 126-120 35.9 3.4 6.0 36.0 3.6 5.9 65 S sin i*. II C (- 0) N (CH , ) S-N (CIL ) C (=0) OCIL 96-99 43.2 5.7 1.2.6 43.1 6.0 12.4 3 3 3 66 S single II C(»0)N(CH_,)SNC _r π- _n oil 51.0 7.0 12.7 51.2 7.2 12.4 3 5 10 67 S single II C (=0) N (CH ) S (-=0) -C ₆ H ₄ C- (CH ₃ ) ₃ -4 156-150 57.0 6.6 7.1 57.8 6.9 6.9 60 S double II C( ^» 0)N(CI1..)S-C,I1 C(CII ) -4 -H 0 119-120 57.0 6.6 7.1 57.9 6.3 7.1 3 (> 4 3 3 2

125 53.0 4.4 16.9 53.1 4.5 16.2

TABLE II (Cont-t)

71 S double II C(=0)N(CIL)S-C_H -C(CIL) ,-4 122-123 60,6 6,4 7.4 60.3 6.7 7.3 3 6 4 3 3 72 S double 5-(6)-Cl C(=0)NIICII., oil 43.0 4.5 11.3 43.7 4.7 11.1 73 S double 5(6)C1 116-119 44.3 4.2 7.4 44.1 4.2 7.3 74 S double 5(6)C1 C(=0)N1IC1I 61-64 43.8 4.5 11.3 43.5 4.7 11.3 75 S double 5(6)C1 C(=0)NIIC1I. 101-104 43.8 4.5 11.3 43.7 4.6 11.3 76 double 5(6)C1 110-1-13 44.3 4.2 7.4 44.0 4.5 7.1 77 S single 11 C(=0)N(CII ₃ )S-l.(CH ₃ )SO ₂ N(CH ₃ ) ₂ oil 37.7 5.0 14.6 37.1 6.1 14.8 79 S single II C(=0)N(CIL)S-C I _r 97-98 55.9 5.6 8.7 55.8 6.0 8.6 3 6 5 00 S double C(=-0)N(CIL)SCVII _r 112.113 56.2 5.0 8.7 56.4 4.0 0.7 3 6 5 .02 S double 4 - CN C(=--0)N(C!I..). ^c .C.lL 139-141 55.6 4.4 12.2 55.5 4.3 12.2 3 6 5 03 S double 11 c (=0) N ( π ₃ ) -k.ιι ₂ cιι ocπ ₂ άι ₂ 112-113 47.4 5.0 12.7 47 .4 6.0 12.7

TABLE II (Cont'd)

94 s single 4-CN 222-225 52.7 5.5 15.4 52.7 5.6 15.3

95 s single 4-CN C(=0)NI.C1I, 170-180 50.2 5.5 17.6 49.0 5.4 17.5

96 s double 4-C1 105-100 44..3 4.2 7.4 44.4 4.4 7.1

97 s double 4-C1 C(-=0)NIICIL 104-106 43.8 4.5 11.3 43.9 4.6 11.1

90 s single II C(=0)N(CIL S-C ₆ «. ₄ -CH ₃ -2 110-119 57.1 6.0 0.3 57.3 6.0 0.4

9 s double II C(=0)N(CII. - ₆ H ₄ -CH ₃ -2 120-121 57.5 5.4 8.4 57.2 5.7 0.3

100 s sin le II C(-*0)N(CI1. 119-120 54.5 5.7 7.9 54.5 6.0 8.0

102 s si gle II C(-*0)N(C11. SN(CIL)S0_C_H .CH -4 154-156 47.5 5.4 9.8 47.2 5.6 9.5 3 2 6 4 3

103 s double 4-CN C(=-0)M(CII S-C II CH -3 158-159 56.8 4.0 11.7 56.4 4.7 11.6 6 4 3

104 s double II C(=-0)N(CII. S-C.1 CP -3 93-94 49.5 3.9 7.2 50.0 4.2 7.2 6 4 3

105 s double 4-CN C(--0)N(CII. -C ₆ .« ₄ C ₃ -3 140-149 49.4 3.4 10.2 49.6 3.6 10.2

1 6 s double 11 C(=-0)N(CII SC _G .. ₄ C.I ₃ -3 77-70 57.5 5.4 0.4 57.1 5.5 0.2

107 s double 11 C(=0)N<CIL SC_IL(OCIL)~4 77-78 54.4 5.4 7.9 54.0 5.2 0.0 6 4 3

100 a double 4-CN C("0)N(CII. ..(CI. ₃ )Γ,O ₂ C ₆ H ₄ CΠ ₃ -4 100-102 47.0 4.4 12.4 47.9 4.6 12.5 II ) CN 125.5-127 45.5 5.0 12.2 45.5 5.2 12.1 C1-4 110-111 50.5 4.0 7.0 50.3 5.0 7.9

TABLE II (Cont'd)

Ill S double 11 C(=0)N(CH. .C,ILCl-4 108-109 50.8 4.3 7.9 50.8 4.4 7.8 6 4

113 S double 4-CN C(=0)N(CIL)SC,II l-4 156-158 50.6 3.7 11.1 50.4 3.8 11.1 3 6 4

114 S double 4-CN C (=0) N (CIL ) S-N (CILCIL&L ) S0_C,H .- 142-149 50.0 5.0 11.7 49.6 5.1 11.6 CH ₃ -4 ³ 2 2 3 2 6 4

115 double C (=0) N (CIL ) S-N (CIL CH CIL ) SO C, H - 110-115 50.1 5.5 9.2 49.6 5.7 9.2

3 2 2 3 2 6 4

C.l ₃ -4

116 S double 4-CN C (=0) N (CIL ) S-C LCH -4 122-124 56.8 4.8 11.7 56.7 5.0 11.9 3 6 4 3

11.0 S sin le 11 C(=0)N(C1I..)S(- II Cll -4 74-75 57.1 5.8 8.3 57.0 6.3 8.3 3 6 4 3

119 S single II C(=0)N(CIL)SC_ II -NO -2 167-168 49.0 4.7 11.4 49.1 5.0 11.3 3 6 4 2

120 S double II 107-108.5 51.1 5.0 9.0 50.9 6.0 9.0

121 S double 4-CN C (=0) N (CIL ) SN (C .IL -n) SO_C ..H 149.5-150.5 51.0 5.3 11.3 50.6 5.5 11.2

3 4 9 2 6 4- ^aι ι ^~Λ

123 S doub e 11 C( O)N(CH ).»--N(CII )C(=-0)Q 194-195 44.4 4.6 11.5 44.4 4.6 11.2

124 S sin e II C(=0)N(CII )£5SM(CI1 ₃ )C(=-0)Q 104 44.1 5.3 11.4 43.0 5.4 1.1.3

127 S double II C(=-0)NHCI1 CU ₂ CH 04-05 55.0 6.7 11.7 54.7 7.1 11.5 )SC II Br-4 - 137-130 44.9 4.3 7.0 44.0 4.3 6.9

TABLE II (Cont'd)

133 S double 11 C(- 0)N(CII..)SC _/ .ILBr-4 128-129 45.1 3.8 7.0 45.0 3.0 7.0 3 6 4

134 S single H 150-152.5 53.5 7.1 8.9 53.4 7.2 9.1

136 S double 4-CN C(- 0)N(CIL)SC..IL-C1~2 166-167 50.6 3.7 11.1 50.6 3.7 11.2 3 6 5

140 S double II C(=-O)N(CII )SN(CII(CH ) )S0 C H T 181-181.5 50.1 5.5 9.2 50.0 5.0 9.1 CII -4

141 double 4-CN C(=-0) N (CIL) SN (CH (CIL) SO.C || 202-203 50.0 5.0 11.7 49.9 5.3 11.8 3 3 2 2 6 4

Gil -4

142 S single 11 c (=0) N (cn 116-118 50.5 4.0 7.0 50.6 4,9 .7.8

145 S double H C (=0) N (CIL ) SN (CIL ) C (=0) 0CIL 120-122 43.5 5.2 12.7 43.5 5.4 12.4 3 3 3

150 S double 4-CN C (=0) N (CIL ) SN (CILCILCIL ) SO„C _r IL 122-123 48.9 4.7 12.0 48.6 4.9 12.2 3 2 2 3 2 b

151 S double II C ( -0) N (CHI ) SN (CH CH CH ) SO Cgllg 92-96 49.0 5.2 9.5 49.3 5.5 9.6

1.55 Ω ..ing e 11 C(-0)N(Cll )S ₍₎ ll ₃ (NO ₂ ) ₂ -2,4 206-200 43.7 3.9 13.6 43.5 3.9 13.6

156 S double 11 C(-=0)NIICII CI1--CII 90-91 55.4 5.9 11.8 55.0 6.1 11.8

Hill S nlnglo II ⁽ '.{' ^■ ) H «'ll , ) SN (C .11 -n) S0,C II - 123.5-126.5 50.9 6.2 0.9 50.9 6.4 9.0 Cll ₃ -4 ^{J 4 J λ 6 4}

)SC U V 66-67 52.9 5.0 8.2 52.8 5.3 8.3

TABLE II (Cont'd)

162 S single II C(=0)N(C1I ₃ ); ;t-( ii ₂ cιι ₂ CH ₃ ). ¹⁰ -_ ^C Λ ^H 9.5 48.7 5.7 9.7 2 6 5__ 120-131 48.7 5.7

163 S double 11 C(=0)N(CII )SN(CII CIl CII ) SO CH 115-117.5 41.1 5.6 11.1 40.0 5.9 11.0

165 S double 4-CN C (=0) N (CIL ) SN (CILCILCIL ) SO_C H - 155-156.5 45.5 4.2 11.2 45.5 4.2 11.2 Cl-4 ^{" 3} 2 2 3 2 6 4

166 double C (=0) N (CIL ) S-N (CILCILCIL ) SO - 142-143.5 45.4 4.7 8.8 45.3 4.7 8.9 . 3 λ λ 1 I

C LC1-4 6 4

168 S double 4-CN C(=0)N1ICII C11-=CH 03-05 54.7 5.0 16.0 54.4 5.2 15.9

169 S single II C(=0)N(CII )SN(CII CU CH )S0 ₂ CH ₃ 119.5-121.5 40.9 6.1 11.0 41.2 6.4 11.0

171 S double 4-CN C(=0) N (Cll ₃ ) SN (Cil ₂ CIl ₂ CH ₃ )S0 ₂ CH ₃ 155-156.5 41.6 5.0 13.0 41.4 5.3 13.0

173 S double II C( = 0)N(CII. )SN(CII )C(=0)OCH 79-00 46.8 5.9 11.7 46.2 6.1 11.6

176 S double 4-CN C(=0)N(ClL)SC _r ILF-4 112-115 52.9 3.9 11.6 53.1 4.0 11.3 3 6 4

177 s double II C(=0)N(CII ) 110-119 53.1 6.2 12.4 52.0 6.5 12.2

179 s single II C (-0) M (Cll ) SN (CIl (CH ₃ ) ) SO N (Cl^) ₂

90-92 40.9 6.4 13.6 41.0 6.7 13.5

100 s double 4-CN C(=0)N(CII ₃ ) ₂ 174-176 52.6 5.2 16.7 52.2 5.4 16.6

TABLE II (Cont'd)

186 single C (=0) (CH ) SN (CH ₃ ) C (=0) ON- ( 160-161.5 53.0 6.9 12.0 53.6 7.4 11.7

2-CIL-2,5-(-C(C»L) ~)C L) 3 3 2 6 7

100 S double II C(-=0)N(CII ₃ )S-N(CII(CH ₃ ) ₂ )SO ₂ N(CII ₃ ) ₂ 126-120 41, 1 5.9 13.7 41.3 6.2 13.0

109 s. double 4-CN C(-0)N(CH )SN(CH )C(=0)OCII 130-131 43 8 4.5 15.7 43.8 5.1 15.4

1.90 s double 4-CN C (=0) N (CIL ) S-C II (OCH, ) -2 163-164 54 4 4.6 11.2 54.2 4.5 11.3 3 6 4 3

192 s single II C(-=0)N(CII )SN(CII )C(=0)OCH(CN)- foam 57 0 5.0 10.6 57.0 5.0 ^• 10.3

C _r ll.( C ll,.)-3 6 4 6 5

193 S single 5,6- (Cll O) C(-0)MIICIL 156-157 40.2 6.6 10.2 40.0 6.9 10.4 194 S single H C( ^« 0)N(CH )SSCH CH CH CH emi solid 46.7 6.6 0.4 46.4 6.7 0.2 195 S single II C (-=0) N (CIL ) SN (CIL ) C (-=0)OCILC,H . - glass 56.6 5.4 0.2 56.0 5.5 0.2 J 3 2 6 4

TABLE II (Cont'd)

201 S double 4-CN C(-=0)NIICII Cll 104.5-105.5 52.6 5.2 16.7 52.7 5.2 16.9

202 s double 4-CN C(=0)NI1CII C1I CH 50.5-53.0 54.3 5.7 15.0 54.2 5.0 15.7

203 s single II 115-116 54.6 6.0 12.0 54.0 6.1 11.9

204 s single II C (=0) N (CIL) SN (CIL ) C(---0) NIIC L 67.5 51.2 5.6 14.0 51.1 5.7 14.0 3 3 6 5

205 s double 4-CN C(=0)NIICII(CH ₃ ) ₂ ^■ 112-113.5 54.3 5.7 15.0 54.8 5.0 15.9

206 s double 4-CN C(=0)N(CH )CIl OH 124-126 49.4 4.9 15.7 49.0 4.7 15.9

207 0 double II C(-=0)N(CIL)SC LC(CIL) -4 129-130 63.3 6.7 7.8 63.1 6.7 - 8.1 3 6 4 3 3

200 s single II C(=0) (ClI ₃ ) N(C ₁₀ Il ₂₅ )S0 ₂ N(CH ₃ ) ^' ₂ 92-93 51.4 8.3 10.4 51.2 8.4 10.6

210 o double II C(--0)N(CII )SN(CH )C(=0)OQ 176 51.2 5.2 13.3 50.0 5.4 12.9

211 0 sin le II C(---0)NI-CI 111-112 54.5 7.1 14.1 54.0 7.4 14.3

213 s double II C(=0)N(CIL)SN(C-_IL _r n)SO„N(CIL)„ 76-70 51.6 7.9 10.5 51.7 0.1 10.3 3 12 25 2 3 2

215 s double 4-CN (=0) N (CIL ) SN ( L _r n) SO N (CIL ) . 116-117 51.5 7.4 12.5 51.2 7.6 12.5 3 12 25 2 3 2

216 s double II C (=0) N (CH ) CH OC (=0) CH oil 50.7 5.7 9.8 50.7 5.9 9.7

TABLE II (Cont'd) 19 double C (=0) N (CIL ) SN (C ₀ H. _n) S0_C_lLClL-4 oil 54.0 6.7 0.0 54.3 6.0 7.5 3 0 17 2 6 4 3

222 double 4-CN C(--O) N ( H ) SSC1I CH ₂ CH ₂ cπ ₃ 101-102.5 47.0 5.4 11.0 46.9 5.3 12.1

223 0 single II 165-166 59.6 7.0 9.9 59.2 7.0 10.0

224 0 double II 153-154 60.4 6.5 10.1 60.0 6.5 9.9 226 S double II C (=0) N ( CH ) SSCII CH CH CH 62-64 47.0 6.1 8.4 47.3 6.1 8.7

229 S double 4-CN C (---()) N (CIL ) St. (Cll (Cll.. ) ,. ) S0..C." II, 177-179.5 48.9 4..0 12.0 49..2 4,0 12,0 3 3 2 2 6 5

230 S double 4-CN C(-=0)N(CIL)SN(C_.I1 -n)SO„C _r IL- 133.5-135 54.5 6.2 10.2 54.5 6.3 10.0 3 0 17 2 6 ll. _j -4

T1 S double 4- N 0( 0)N(C.IL)t.N(l.lL)C(-n)O(CIL) , .CIL 9 933--9955 56.4 7.5 11.0 56.7 7.7 11.0

3 11 3

234 double c( )u(r ^! ii (c:ιι )C(- )oo, 195 47.6 4.9 12.3 47.0 5.0 12.2

235 S double 4-CN L ϋ)N(CII..)SC I CII - 171-172 56.0 4.0 11.7 56.6 4.7 1.1.7 3 6 4 3

236 S ϋiivjlo <:(-Ό)N(CII Λr.r.v. IL oil 50.0 5.1 7.9 51.2 5.2 7.4

\ (> 5 N(cιι ₃ ) ( ₄ π ₉ -n). ₂ oil 54.5 7.1 14.1 54,6 7.3 13.7 N (CH ) SC (CII ₃ ) ₂ C (=0) CII ₃ 120-129.5 51.0 5.4 11.9 50.7 5.4 12.0

TABLE II (Cont'd)

239 double 4-CN C(=0)N(CH )! :N(C ₁₂ II ₉₅ -n)C(=0)N- 61.5-65 57.3 7.9 13.4 57.2 7.8 13.3 ^(α, 3»2

240 double 4-CN C(=0)N(Cll )SN(CII C(=0)0CH - 139.5-141.5 48.1 4.6 10.7 48.1 4.6 10.7

CIL) SO C 11 Cll -4 3 2 6 4 3

241 double 4-CN C(=0)N(CII )SN(CI1 Cll CH iSO C ll. ^> 122-125 48.3 4.9 11.3 48.3 4.8 11.2

(OCII. )- 2 J A b 4

242 S double 4-CN C(=0)NII(CH ) Cll 59-60 64.4 8.5 10.7 64.6 8.0 10.8

243 S double 4-C1 C(--0)NI_CII Cll CH oil 48.1 5.5 10.2 47.7 5.8 10.0

244 S dou le 4-C1

24 ' ^" > S doub e 4-CN

246 S dou le -CM

247 S double 4-CN C (=0) N (CIL ) SC (-0) 0C- „H -n 74-76 57.4 7.3 0.7 57.1 7.6 0.8 3 12 25

248 S double 4-CN C(=0)N(CH )SN(Cπ.,CH CH iPlSl- 09.5-91 42.7 5.7 11.7 42.6 6.1 11.9 lO ll^.H..^

TABLli. II (Con't)

253 double 4-C1 C(-0)N(CII )SN(C II -ι.)C(«0)H- 77-70.5 54.1 7.0 10.5 53.9 7.8 10.5

<_'_>_ ^{3 l2} "

254 s double 4-CN c (=o) N (cπ ₃ ) s-N (c ₍ .ιι ₅ ) SΌ ₂ (CΠ ₃ ) ₂ 170.5-100 46.2 4.5 15.0 46.4 4.5 15.0

255 s double 4-CN C(=0)N(Cll,)SSC IL oil 50.9 4.0 11.1 50.7 4.2 10.9 3 6 5

256 s dou l 4-CN C(-O) N (CII ) SSC ΙI C(CIL) -4 110-120 55.4 5.4 9.7 55.4 5.3 9.6 3 6 4 3 3

257 s double 4-CN C (=0) N (CIL ) SC -IL (OCIL ) -4 122-123 54.4 4.6 11.2 54.1 4.6 11.2 3 6 4 3

250 s double 4-CN C(=0) N (CII ₃ ) SN (CH ) C _Q H ₁₇ -n 89-91 55.6 7.4 13.6 55.7 7.3 13.6

259 s double 4-CN C(=0)N(CIL)SN(ClLClI CIL)SO^CILC IL 154-156 50.0 5.0 11.7 50.1 5.0 11.7 3 2 2 3 2 2 6 5

260 s double 4-CN c(---o)NHcπ ₂ cπ(CH..) _{2 Q5 Q7}

55.0 6.1 15.0 55.6 6.3 15.0 c

261 s doubl 4-CN C(-=0)N(CH )HN{CII )C(=---0)NIICH ₃ 136-137 43.9 4.0 19.7 44.0 4.9 19.7 _.

2 2 s double 4 -CN C(=--0)N(CII..)SH(CII.,C|l.CII ) - 129-130 44.1 5.6 11.4 43.9 5.7 il.5

263 .5 double 4-CN

264 S double 4-CN

265 s double 4-CN

266 s double 4-CN

267 s double 4-CN

260 .'] double -CM C (' 0) N (CH.,) SN (Cll . ) C(- 0) N (C 41 -l>) 05-06 53.0 6.9 15.4 52.0 7.0 15.5

V 4 9

270 NH donble II C(-O)NIICIL 120-129 55.4 6.7 21.5 55.6 6.9 21.6

271 S doubl 4-CN C(--Ό)N(CII ₃ )SC. ₂ II _2I . oil 60.4 0.1 9.6 60.1 0.3 0.9 N (Cll ₃ ) SNCII ₂ C.'ll ₂ ⁽ XJIlT tl 59-63 47.4 5.1 15.0 47.1 4.9 15.5

TABLE II (Cont'd)

274 double 4-CN C(=0)NIICI! OCIL 109.5-111.5 49.4 4.9 15.7 49.3 4.9 15.7 275 double II C(=0)N(CII ₃ )SSC(CH ₃ ) ₃ 99.5-103 47.0 6.1 8.4 46.9 6.4 8.5 276 double 4-CN C(=0)N(CII )SN(CI1 Cll CH ) SO - 87-90 46.2 4.5 15.0 46.4 4.6 14.6

(C _r ll N)-3 ^J 5 4

277 S double 4-CN C(-=0)NHC H -n 47-49 60.9 7.5 12.5 60.8 7.9 12.6 270 S double II C (=-0) N (CII ) SN (CILCH CH ) SO - 94-98 46.1 5.0 12.7 45.9 5.1 12.6 (C _r II N)-3 ^J 2 J 2

5 4

279 S double II c (=O) (cn ₃ ) ssc ₁₂ π ₂₅ -n 36-38 56 _t 7 8.2 6.3 56.8 8.4 6.6 280 so ₂ double 4-CN C(=0)NIICH 196-198 44.6 4.1 15.6 44.3 4.1 15.3 201 s double 4-CN C(-0)NIICII C II. 105-106 61.3 4.8 13.4 61.2 4.9 13.3 2 6 5 202 s double 4-CN C (=0) NIICIL (C1LCIL 0) -.CILCIL oil 54.4 6.8 10.6 54.0 6.9 11.0

2 λ Λ λ Δ 206 s double H C(=-0)N(CIL)SSC _^ 11 C(CIL)-4 83-05 55.8 5.9 6.9 56.1 6.0 7.1

3 6 4 3 207 o single II C(=0)NHC ₁₂ H _2rj -n 69-72 68.1 10.3 0.0 67.9 10.3 8.0 200 double 4-CN C(=0)NllC _lr ll -n 71-73 67.1 9.2 9.4 67.3 9.2 9.2 1 33 209 !(0) double 4-CN C(=-0)NHCII 170-179 47.4 4.4 16.6 47.1 4.3 16.3 290 double 1-CII -4-CN- C(=0) NIICIL 130-140 52.6 5.2 16.7 53.1 5.3 16.8 291 s double 1-CII -4-CN 200.5-201.5 56.2 6.2 14.4 55.8 5.3 14.4 292 NCIL sincjle II C(=0)N11CH oil 56.8 8.1 19.9 55.5 8.2 19.4

TABLE III

EX. MELTING CALCULATED FOUND

NO. Λ a H Ϋ RΛNGE°C C U C \l N ^'

04 S double H C(-=0)NIICH oil 53.1 6.2 12.4 53.4 6.5 12.1

05 s double 11 C(--O) MUCH Cll oil 55.0 6.7 11.7 55.1 6.0 11.3

06 S ii ingle II C(-0)NIIC(C1I ₃ ) ₃ 111-113 57.0 0.2 10.4 57.7 8.5 10.4

07 S double II (.(■ ^■ 0)MIIC(CIL)_ 07-09 50.2 7.5 10.4 50.3 7.6 10.5 3 ,3 3 S . ingle II C( -O) NIICIL 112-114 52.6 7.1 12.3 52.0 7.2 12.2

225 0 double II II 126-127 62.7 7.2 9.1 62.7 7.4 8.9

231 0 double 11 C(--0)N1ICI1 ₃ oil 57.1 6.7 13.3 57.0 7.0 12.8

TABLE IV

EX. CALCULATED FOUND NO. RANGE °C H N II N

232 0 H II 141-151 63.6 6.0 9.3 63.5 6.1 9.4

269 0 II C(=0)NIICH 137-138 57.7 5.8 13.4 57.5 S.9 13.3

205 0 5 _# 6,7,8-(H) -5,8-Br -6,7-dehydro C(=0)NIIC1L 166-167 32.6 3.3 7.6 32.8 3.4 7.8

TABLE V

203 6,7-H -7-C1-8-SC Jl -n C(=0)NIICIL 103-104 55.7 7.7 ; 8.9 55.9 7.8 8.6 λ 12 25 : 294 6,7-11 - C(=0)N1ICIL oily solid 54.5 7.1 14.1 53.7 7.4 13.8

TABLE VI

EX. MELTING CALCULATED POUND NO. W RANGE°C II N H

146 -oc.. ₂ cπ ₂ - -HC=C(C1)- C (-»0) NHCfl 140-142 41.2 4.2 10.7 41.6 4.4 10.4

174 ^ C(=0)NHCH 172.5-174 65.0 4.5 9.0 65.5 4.5 8.9

¹ ' ² - ^C 6 ^,, 4

175 1,2-C L 216-218 71.1 4.4 5.5 ^' 70.0 4.1 5.6

³ < ² ~ ^C 6 ^U 4 6 4

BIOLOGICAL ACTIVITY

The compounds were evaluated for biological activity against the following representative pests: Southern com rootworm (Diabrotica und- ecimpunctata howardi), Mexican bean beetle (Epilachna varivestis), Southern armyworm (Spodoptera eridania), housefly (Musca domestica), bean aphid (Aphis fabae) and red spider mite (Tetranychus urtieae). A combination of contact, stomach poison and systemic tests are run on these insects.

The formulation used for insecticide testing contains a final concen¬ tration of 0.0128 percent or 128 p.p.m. test chemical, 4 percent acetone and 0.01 percent (100 p.p.m.) Triton X-155 surfactant. Accompanying reference insecticides, if any, are formulated by these procedures as are the checks which contain a standard amount of solvent and a surfactant, but no test chemical. The foregoing stock formulations are utilized with appropriate dilution to obtain the desired pound/acre application rates. The test procedures employed are as follows.

BEAN APHID SPRAY AND SYSTEMIC TEST

This test determines the insecticidal activity of the compound being tested against the bean aphid, Aphis fabae. Stock formulations containing 128 p.p.m. of each test chemical are prepared using 12. S mg of the test chemical, 4.0 ml acetone containing 0.25 percent (V/V) Triton X-155 and 96.0 ml deionized water and are used in both soil drench and spray treatments. The stock formulations are diluted to obtain the appropriate lower concentrations main¬ taining the concentration level of all adjuvants. The bean aphid is cultured on nasturtium plants (var. Tall Single), no. attempt being made to select insects of a given age in these tests. Single nasturtium test plants growing in soil in individual 3-inch fiber pots are then infested with populations of 100 to 200 aphids.

In the spray application, 50 ml of stock or diluted formulation is uniformly sprayed onto the plants. In the systemic application, 1L2 ml of stock or diluted formulation is applied to the soil containing the plant. A dosage of 11.2 ml of formulation containing 128 p.p.m. of test chemical is equivalent to a dosage of the test chemical of 4 pounds per acre (lb/A).

The plant test units under fluorescent lights are given bottom watering for the duration of the test. Percentage mortality is determined three days after treatment. Results of this test, as expressed in I_C . _n values, are shown in Table VII as A (aphid contact spray) and AS (aphid systemic soil drench).

RED SPIDER MITE SPRAY AND SYSTEMIC TEST

This test determines the acaricidal activity of the compound being tested against the red spider mite, Tetranyσhus urticae. Stock formulations containing 128 p.p.m. of each test chemical are prepared by the procedure above and are used in both the soil_ drench and spray treatments. The stock culture of mites is maintained on Scarlet runner bean foliage. Approximately 18 to 24 hours before testing, mites are transferred to the primary leaves of a Lima bean plant (var. Sieva) grown in 3-inch pots.

The spray and systemic application methods described before are used to apply the test formulations to the infested plants and soil. After three days, one of the two leaves treated is examined and mortality is determined. Results of this test, as expressed in LC _n values, are shown in Table VII as (mite contact spray test) and MS (mite systemic soil drench test).

HOUSEFLY SPRAY TEST

This test determines the insecticidal activity of the compound being tested against adult houseflies, Musca domestica. Stock formulations containing 128 p.p.m. of each test chemical are prepared using the procedure described previously and are diluted to obtain the appropiate lower concentrations.

Ten adult flies are plaeed in a cylindrical screen cage 1 1/2 by 4 inches fabricated from 20-mesh stainless steel screening and are sprayed with 50 ml of the stock or diluted formulation. The flies are supplied food and drink from a sucrose solution by draping a paper wick over the outside of the screen cylinder and are able to feed and drink ad libitum. Percent mortality obtained is determined three days after treatment. Results of this test, as expressed in LC- ₀ values, are shown in Table VH as HF (housefly spray test).

SOUTHERN ARMYWORM LEAF SPRAY TEST

Paired fully expanded primary leaves excised from Scarlet runner bean plants are maintained in plastic tubes containing water and sprayed with the test formulation prepared as described previously. After the spray deposit on the leaves is dry, the paired leaves are separated. One leaf is placed onto 1.5 percent water agar and infested with 10 newly hatched Southern armyworm larvae. The covered test receptacle is held at 72° F for four days and then the percent mortality is determined. Results of this test, as expressed in- LC ₅₀ values, are shown in Table VIE as AW (Southern armyworm spray test).

MEXICAN BEAN BEETLE LEAF SPRAY TEST

This test determines the insecticidal activity of the compound being tested against the Mexican bean beetle, Epilachna varivestis. The test procedure is the same as that described for the Southern armyworm with the exception that one-day old larvae of the Mexican bean beetle instead of newly hatched Southern armyworm larvae are used.

These tests are held at 72° F for four days when mortality and feeding inhibition are determined. The feeding inhibition is an indication of the repellent properties of the test material. Results of this test, as expressed in LC- ₀ values, are shown in Table VII as BB (Mexican bean beetle leaf spray test).

TABLE VII

TABLE VII (Cont'd)

TABLE VII (Cont'd)

TABLE VII (Cont'd)

TABLE VII (Cont'd)

TABLE VII (Cont'd)

TABLE VII

ROOT-KNOT NEMATODE TEST

This test is an evaluation of the effectiveness of the compound being tested against infection by root-knot nematodes, Meloidogyne s p.

Pasteurized greenhouse soil, diluted by two-thirds with clean washed sand, is infested with about 15 g of nematode infested tomato roots and soil. The test formulation contains 0.056 g of test compound, 4.0 ml stock emulsifier solution (0.25 percent Triton X-155 in acetone by volume) and 96.0 ml deionized water, giving a concentration of 560 p.p.m. Lower concentrations are achieved by dilution. Treatment is accomplished by adding 50 ml of the formulated compound into a plastic bag which contains enough infested soil to fill two 4-inch round pots. This is thoroughly mixed, then returned to the pots, after which 5 cucumber seeds (Ohio MR17 var.) are planted per pot.

Two standards are included with each test, Phenamiphos and Aldicarb are most often used, with Carbofuran and Ethoprop used as substitutes. Standard formulations are treated at 140 p.p.m. with lower eoncentrations achieved by dilution.

Roots are removed from the soil after three weeks of growth and rated for gall (root-knot nematode infection) formation. A rating of infection from 0 to 10 is recorded: 0 = no galls or complete control and 10 = heavily galled roots comparable to controls. Each of the root systems is rated separately. The average of each treatment is substracted from the average of the control check, that sum is then divided by the average of the control check and multiplied by 100 to obtain a percent nematode control. Percent control equals:

, _{Q Q} average of control check - average of treatment average of control check

The results obtained with selected compounds of the invention are shown in Table VUL

TABLE VIII

Compound Example No. Percent Control At Indicated Rate Dosage (lb/A)

8 * 2 1 0.5 0.25 0.125

PHENAMIPHOS ¹ 76 . 57 30 14 _ _

ALDICARB ² - 78 66 49 .. 14 - -

33 100 99 86 80 76 63 -

3 - 95 - 74 - - - -

36 100 100 100 84 50 24 -

37 - 62 - 41 - - -

33 - 86 - 49 - - -

41 - 100 97 92 83 70 67

43 - 96 - 42 - - -

49 100 100 100 87 67 22 -

50 100 100 100 74 57 5 -

52 100 - 62, 59 31 0 -

58 - 100 - Z5 30 13 -

59 100 79 ' ' -76 0 14 - -

61 100 - 58 - 8 - -

67 - 100 - 90 - - -

68 - 99 - 72 - - -

70 - Z5 - 48 - - -

71 - 98 - 7 - - -

72 - 100 - 73 - - -

77 - 66 - 25 - - -

79 - 100 - 78 - 20 -

80 - 100 - 95 - 42 -

82 - 100 100 95 73 so 69

83 - 100 - 90 - 51 -

8* - 100 - 100 - - -

85 - 100 - 59 - - -

88 - 100 83 98 52 64 48

90 - 100 - 91 - - -

92 - 100 93 93 73 64 49

95 - 99 - 100 - 87 -

97 — 100 94 87 64 50 22

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TABLE VIII (Cont'd)

274 70 44 22 276 88 78 52

1 ' 2 = Mean of all replications.

= Not tested.

SOUTHERN CORN ROOTWOR (LARVAEOF SPOTTED CUCUMBER BEETLE)

The test organisms are six- to ten-day old larvae of a chlorinated hydrocarbon resistant strain of Diabrαtica ϋπdecimpunctata howardi Barb. On the day before test compounds are to be screened, to one ounce polystyrene cups (one cup per test compound) are added: one level teaspoon (5 cm ) air dried greenhouse soil, five corn seeds (Zea mays L. var. Popcorn) treated with thiram and a second teaspoon of dry soil. The following day, 0.45 ml of standard 128 p.p.m. formulation and 2.0 ml of water are added and the cups are capped. The sample cups are stored under conditions of high humidity in a room at 72-78° F. After four days, the corn seedlings will have shoots 0.5 to 1 inch long, and they will have heaved the covering soil. At this time, 5 to 10 larvae are dropped into each test unit. The cups are then returned to the holding room. Three days after infestation, the test is read. Percentage mortality is determined at the dosage rate. The results are summarized in Table IX.

TABI _E IX

Compound Rate Corn Root .Torm Example No. (PPM) (Percent Mortality)

82 128 100

113 12 S 100

64 100

32 20

170 128 33

64 46

172 128 55 9

In addition to the foregoing evaluations, certain of the thiol- hydroximidate compounds of the invention were subjected ^• to the following special tests to determine the presence of other significant biological properties for these compounds.

PLANT GROWTH REGULANT ACTIVITY

Compounds of the invention were evaluated relative to plant growth regulant activity against three plant species in a petri dish test. The test is divided into a primary test where 500 μg and 100 i chemical per petri dish (100 x 25 mm, disposable) are tested simultaneously and a secondary test where 50 ug, 10 μg and 1 μg chemical per petri dish are tested simultaneously. Compounds which pass the primary test are further evaluated in the secondary test. A special petri dish test may also be_ run to evaluate particular test compounds, in which case all five rates, i.e., 500, 100, 50, 10 and lμ% per petri dish, are tested simultaneously. According to the test procedure, three plant species are planted in a petri dish which has been treated with the test substance. The three species are as follows: 1) a mixture of approximately 50 percent light-sensitive and 50 percent light-insensitive lettuce (Lactuca sativa L. 'Grand Rapids'); 2) soft red winter wheat [Tritieum aestivum L. (Aestivicum Group) 'Abe'] ; and 3) pasture- type perennial ryegrass (Lolium pereπne L. 'Linn'). Wheat and perennial ryegrass seeds are surface-sterilized with 1 percent sodium hypochloride for 10 minutes and 5 minutes, respectively.

Each test compound is formulated in acetone and aliq ots of the test formulation are placed on three layers of sterilized filter papers (Whatman No. 1, 8.26 cm diameter) in each petri dish. As soon as the acetone evaporates, 7 ml of deionized water are added into each petri dish with an appropriate automatic dispenser. Then, 5 to 8 wheat seeds, 10 to 15 perennial ryegrass seeds and 10 to 15 lettuce seeds are placed on the filter paper of each petri dish. Dishes are then covered and seeds are germinated for 3 days at 20° C at a relative humidity of 65 in the dark. The dishes are then removed from the dark growth chamber and maintained in lighted environmental growth chambers for 4 days.

At the end of the seventh day of planting, growth and developmental responses/characteristics are evaluated.

The compounds of Example Nos. 1, 2, 11, 12, 44, 45, 48, 54, 63, 64, 73, 76, 94 and 134 exhibited growth retardant activity. Seed germination, root length and hypocotvl length of lettuce were inhibited (i.e., between 15 percent and 85 percent inhibition compared to untreated controls) at rates ranging from about 100 jjg/dish to 2000 ^g/dish. Root and coleoptile growth of wheat and ryegrass was inhibited at rates ranging from 10>ιg/dish to 2000 jig/dish.

Growth stimulation activity was observed with growth of lettuce treated with these ' compounds was stimulated at rates ranging from about 50 jug/dish to 500jιg/dish.

ANTTFUNGAL ACTIVITY

Preselected thiolhydroximidates of the invention were incorporated into an agar based fungal growth medium. Spore siispensions of five different fungus species were prepared. Drops of each suspension were incubated for 24 or

48 hours. The spores were observed microscopically and rated as indicated in Table X.

o,,--?ι / v -". I-P-TO- ¹

TABLE X

Λlleπiarla llcliu iliosporlum OotrylU Collelotricluiin Collelotricluiin solani ory/ne cinerea la|;t-nariιιm trllolioruiϊi

Compound fix. No. (I_.a0pi_.il) 2 ι"C 2. hr 2 <Λ. 24 r 20°C 2<ι hr 20°C .8hr 20°C .8 hr

II 2 1 1 0 0

6. 2 '/ 0 0 0

73 1 0 0 0 0

76 ύ 0 0 0 0

!_.____

0 - no ι;eπιι.ι.ali->n, no ι;ro llι

1 - ι;<.-ιιιιlnaιloιι, no growth

2 - some growth 3- -.50% inhibition 4 - slight inhibition

While the invention has been described and illustrated with reference to certain preferred embodiments thereof, those skilled in the art will appreciate that various changes, modifications and substitutions can be made therein without departing from the spirit of the invention. For instance, dosage rates other than the prefered ranges set forth hereinabove may be applicable as a consequence of variations in soils with respect to permeability, natural plant productivity, prior chemical treatment, etc., as well as difference in environ¬ mental conditions, ^' including light, moisture, temperature, wind and the like. Likewise, the specific results observed with respect to pest control may vary depending on whether the active compounds of the present invention are used alone or in combination with each other or other known agents as well as the specific type of formulation employed in applying same to the pests or their habitat and such expected variations in results are contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be limited only by the scope of the claims which follow.