Hydrocinnamonitriles
United States Patent Wright, Jr. et al.  
 HYDROCINNAMONITRILES Inventors: Donald Perry Wright, Jr.,  
 Pennington; Donald Frederic Barringer, ,lr., Trenton; Donald Edward McKay, Highland Park, all of NJ.  
 American Cyanamid Company, Stamford,- Conn.  
 Filed: May 21, 1973 Appl. No.: 362,617  
 Related US. Application Data Division of Scr. No. 250,338, May 4, 1972, Pat. No. 3,793,456, and a continuation-in-part of Ser. No. 141,444. May 7, 1971, abandoned.  
 Assignee:  
 U.S. CL... 260/465 E; 260/332.3 R; 260/347.7;  
  424/275; 424/285; 424/304 lnt. Cl. C07c 121/78 Field of Search 260/465 E References Cited UNlTED STATES PATENTS 2/1972 Buchel et al 260/465 Apr. 29, 1975 Primary Examiner-Lewis Gotts Assistant Examiner-Dolph H. Torrence Attorney, Agent, or FirmHarry H. Kline ABSTRACT The present invention relates to insecticidal methods and compositions employing a, ,B-dioxohydrocinnamonitriles having the formula:  
 Ra ll 5 Claims, No Drawings HYDROCINNAMONITRILES This is a division of application Ser. No. 250,338, filed May 4, 1972, now US. Pat. No. 3,793,456, issued on Feb. 19, 1974, and a continuation-in-part of application Ser. No. 141,444, filed May 7, 1971, now abandoned.  
  The present invention relates to the use of certain hydrazones in insecticidal methods and compositions. It further relates to certain novel hydrazones used therein and to the preparation thereof.  
  More particularly, the invention relates to insecticidal methods and compositions employing hydrazones of a, B-dioxohydrocinnamonitriles having the formula:  
  NHN=C 1 where R, R R and R are defined as follows: R is halo, loweralkyl (C -C loweralkoxy (C -C,), cyano, nitro, trifluoromethyl, phenylazo or p-chlorophenoxy; R, is hydrogen, halo, trifluoromethyl or loweralkyl (C,-C R is hydrogen or halo; and R is phenyl, halophenyl, dihalophenyl, alkyl (C -C phenyl, loweralkoxy (C C,) phenyl, l-naphthyl, 2-furyl, or Z-thienyl. It further relates to the novel hydrazone compounds thereof having unexpectedly high insecticidalactivity, having the formula:  
 wherein Y is hydrogen, chloro or loweralkyl (C -C n is 0, l or 2; and m is l or 2. Especially preferred compounds therein are: a,B-dioxo-, a-[(3-chloro-otolyl)hydrazone]hydrocinnamonitrile, a,B-dioxo-, a-[- (3,4-dichlorophenyl)hydrazone]hydrocinnamonitrile,  
 a,B-dioxo-, a-[ (2 ,4-dichlorophenyl )hydrazone ]hydrocinnamonitrile, p-chloro-a,B-dioxo, a-[(pchlorophenyl )hydrazone]hydrocinnamonitrile and chlorophenyl )hydrazone 2 hydrocinnamonitrile, a,B-dioxo-, oz-[(m-chlorophenyl)hydrazone]; hydrocinnamonitrile, a,B-dioxo-, a-[(o-chlorophenyl)hydrazone]; hydrocinnamonitrile, a,fl-dioxo-, a-[(4-chloro-o-tolyl)hydrazone]; hydrocinnamonitrile, a,B-dioxo-, a-[(2,5-dichlorophenyl)hydrazone]; hydrocinnamonitrile, p-chloro-a,/ 3-dioxo-, a-[(p-chlorophenyl)hydrazone]; hydrocinnamonitrile, a,B-dioxo-, a-(p-tolylhydrazone); Z-furanpropionitrile, a,B-dioxo-, oz-[(p-chlorophenyl)hydrazone]; 2-thiophenepropionitrile, a,B-dioxo-, a-[(p-chlorophenyl)- hydrazone]; 1-naphthalenepropionitrile, a,B-dioxo-,  
 -a-I(p-chlorophenyl)-hydrazone]; acetanilide, 4&#39;-[(athetic method may be illustrated as follows:  
  0 u 1) R NO ax E 2) a cocn cm W III I wherein R is selected from the group consisting of an alkali metal, such as lithium, potassium or sodium and C -C loweralkyl groups, such as methyl, ethyl, npropyl, iso-propyl, n-butyl, t-butyl and the like and HX represents a mineral acid, such as l-lCl, H SO HNO and the like. R, R R and R are as above.  
  The relative quantities of the ingredients employed can be widely varied. For optimum yields, it is generally preferred to react equimolar quantities of the aniline and nitrite. Lower alcohols C -C water and mixtures thereof are among the preferred solvents for use in carrying out the synthesis. It is also preferred to employ a mineral acid in sufficient quantities to produce an acidic pH in the aqueous or alcoholic solvent and to adjust the reaction temperature to temperatures within the range of from about 10C. to about +10C. The preferred temperature is about 0C.  
  Sodium and potassium nitrite and methyl, ethyl or nbutyl nitrite are among the preferred diazotizing agents which are particularly well suited for use in the syntheses.  
  Preferred mineral acids include sulfuric, hydrochloric and hydrobromic acid. It is generally preferred to employ a slight excess of the acid over and above the stoichiometric amount required to form the substituted benzene diazonium salt.  
  After formation of the desired diazonium salt, the reaction mixture is preferably reacted further by adding it to a mixture of the appropriate aroylacetonitrile and a weak base, such as sodium or potassium acetate while the temperature is maintained at from about lC. to about +l0C. The desired hydrazone of the a,B-dioxohydrocinnamonitrile is produced thereby and may be recovered from the reaction mixture by any convenient means, such as, by filtration, centrifugation and the like.  
  It has been found that the hydrazones of Formula 1 and especially the novel hydrazones a,B-dioxo-, a-[(3-chloro-o-tolyl)hydrazone] hydrocinnamonitrile and a,l3-dioxo-, a-[(3,4-dichlorophenyl)hydrazone] hydrocinnamonitrile are useful as insecticides. They are particularly effective for controlling lepidoptera and mosquitoes, especially in the larval stages.  
  The insecticidal methods of the present invention involve contacting the insect to be controlled or the locus or area where insect control is desired with an insecticidally effective amount of one or more of said hydrazones. Application of the active ingredient at a rate of from between about 0.5 and about 15 pounds per acre of the active ingredient is generally sufficient to achieve the desired insect control.  
  For application of the hydrazones, it is generally preferred to employ them in combination with conventional pesticidal adjuvants and formulation aids. They may be advantageously employed with the use of either solid or liquid adjuvants and applied in the form of dusts, dust concentrates, wettable powders, emulsifiable concentrates and the like.  
  Field application of these formulations may be made by conventional equipment, such as power dusters, boom and hand sprayers, spray dusters, addition to irrigation water, and the like.  
  The active ingredient may be initially formulated with a concentrated composition, comprising the active ingredient in a solid or liquid adjuvant which serves as a formulation aid or conditioning agent, permitting the concentrates to be further mixed with a suitable solid or liquid carrier.  
  Useful liquid adjuvants in which the toxicant is dissolved. suspended or distributed include, for example, xylene, benzene, lower alcohols C,C fuel oil or the like, with or without an emulsifying agent. For application, the resulting solution can be further diluted with either water or an organic diluent, such as deodorized kerosene. Concentrations in the range of from about 5 to about 95 percent are generally suitable for initial so- Q-NHZ NaNO H2S04 Qu N H804, CF CF;  
 lution. When diluted for application, suitable solutions may contain the active ingredient in concentrations of from about 0.5 to about 5000 ppm.  
  Suitable solid adjuvants include, for example, attapulgite, kaolin, talc or diatomaceous earth in granular or finely ground form. The active ingredient can be conveniently formulated with the solid adjuvants as dusts, dust concentrates, wettable powders, granulars and the like.  
  Dusts are generally prepared by grinding together from about 1 to 10 percent by weight of the hydrazone with a finely divided inert diluent such as attapulgite, kaolin, diatomaceous earth, talc, or fullers earth. These formulations can then be applied with dusting equipment to the foliage of agronomic crops or fields, meadows, forests or the like which are to be protected from insect attack or where insect control is desired. Application is generally sufficient to provide between about 0.5 and 15 pounds per acre of active material.  
  Dust concentrates are usually prepared in the same manner as dusts but generally from about 25 to percent by weight of the active hydrazone and from 75 to 25 percent by weight of diluent are used.  
  wettable powders are prepared in the same fashion as the dust concentrates, however, from about 1 to 5 percent by weight of an emulsifying agent and from about 1 to 5 percent by weight of a dispersing agent are usually included in such formulations. Polyethylene glycols, methoxy polyethylene glycols, sodium lignosulfonate, calcium dodecylbenzene sulfonate and the like are among the emulsifying agents and dispersing agents which can be used in these formulations. in practice, the wettable powders are generally dispersed in water and applied as a dilute spray to the vegetation or water where insect control is desired.  
  Usually, concentrations of the active ingredient of from about 10 to 1000 ppm dispersed in the water of ponds, lakes, creeks, swamps and such will give excellent control of mosquito larvae. Excellent insect control and plant protection in fields, forests, crop lands and the like is generally achieved by application of the active ingredient at rates of from about 1 to about 15 pounds per acre.  
  The invention is further illustrated by the following examples which are not to be taken as limitative thereof. In each case, the parts and percentages are by weight unless otherwise indicated.  
 EXAMPLE 1 Preparation of a,B-dioxohydrocinnamonitrile a-(a,a,oz,a&#39;,a&#39; ,a&#39;-hexafluoro-3,5-xylyl )hydrazone NaOAc 0.02 mole) in Found EXAMPLE 1? Preparation of a,B-dioxo-a-[(p-chlorophenyl)hydrazone1- hydrocinnamonitrile C1 -N=C EXAMPLE 18 Preparation of a,B-dioxo-, a-[ 3-chloro-o-tolyl )hydrazone]hydrocinnamonitrile Analysts, percent A solution of p-chloroaniline (2.5 g.  
 30 ml. of 10 percent aqueous hydrochloric acid was cooled to -5C., and a solution of sodium nitrite (1.5 g., 0.02 mole) in 5 ml. of water was added dropwise. The resulting solution was stirred for one-half hour. Excess nitrous acid was destroyed by addition of sulfamic 20 acid, and the resulting solution was filtered. The filtrate was added dropwise over a period of 15 minutes to a mixture of benzoylacetonitrile (2.9 g., 0.02 mole) in 30 ml. of methanol, ml, of water, and g. of solid sodium acetate at 0C. The resulting mixture was stirred overnight. The desired product was isolated by filtration, washed with water, and dried in vacuo at 80C., yielding 5.0 g. (88 percent).  
 Purification was effected by successive recrystallizations from aqueous ethanol to give a product having an m.p. of l175.5C.  
 in lieu of the TABLE I Percent Yield c.)  
  Calcd. for C l-l F N O: C, 53.00; H, 2.35; F, 29.59; N, 10.91. Found: C, 52.77; H, 2.33; F, 30.55; N, 10.92.  
 EXAMPLES 2-16 Preparation of various a,B-dioxohydrocinnamonitrile hydrazones A variety of a,B-dioxohydrocinnamonitrile hydrazones of Formula 1 were prepared by the general procedure of Example 1, employing the appropriately substituted aniline and cinnamonitrile,  
 &#39;tated as a flocculent white solid. This mixture was stirred and maintained in an ice bath while a solution of the sodium nitrite (1.72 g., 0.0250 mole) in a little water was added dropwise. The yellow diazonium salt solution was then filtered to remove a small amount of 5 precipitate. The B-oxohydrocinnamonitrile (3.62 g., 0.0250 mole) was slurried in 25 ml. of 28 ethanol. and  
 a solution of sodium acetate (12.30 g., 0.150 mole) in 40 ml. of water was added. This mixture was stirred and maintained in an ice bath while the diazonium salt solu- 10 tion was added dropwise. Thereafter, the solution was stirred with cooling for an additional hour and the desired product produced as a solid precipitate was recovered by filtration. It was washed with water, and air dried to yield 8.07 g. (84 percent yield) in the form of 15 a yellow-orange solid having an m.p. of l85-l9lC. The product was purified and recrystallized from ethanol with a little added water to yield 5.93 g. (62 percent) of a yellow-orange solid having an m.p. of l9l.0-193.5C. Identification was by infrared spectrum and the following elemental analysis:  
 a,a,a,a&#39;,a&#39;,a-hexafluoro-3,5-xylidene and B-oxohydrocinnamonitrile used therein, to produce the hydrazones set forth in Table I below. R which is shown in 35 Table l, is in each case l-l.  
 Cl H  
 / ENC16 NH; HCl KNO .Ste I Dec.  
 manna m mm mm m m mmmnma mum u m m &#34;Humane now an muuummm mun mnmm new un 22a 11$ magma mun nmmm mnmmaum nun uunn www mm no M Human m mum m m H mmuummm awn use mmnumnn mum mmmm ame: can an: LllLlZL Z21 call Manama man can nanuunu mum awn mmmmmmm H H mm. n 1 111 mmmll l l m emnumww 3. Mama W m 1.1.; a lzzm mmmmamm $88 nnewnn nnnenenw m. m B N .|C  
  0H0 mmm w mmmmmw 2&#34; Lmmmmmmu added dropwise, maintaining the temperature at C. The diazonium salt solution was then added to a solution of 5.81 grams (0.04 m.) of benzoylacetonitrile and 30 grams (0.365 m.) of sodium acetate dissolved in 300 ml. of water and 200 ml. of methanol, over approximately minutes with rapid stirring at room temperature. The mixture was stirred for 1 hour at room temperature, and the bright yellow solids were collected by filtration. The crude product was recrystallized from 300 ml. of ethanol to 50 ml. of methyl ethyl ketone, water was added at reflux until the cloud point was reached (approximately 50 ml. necessary). 9.45 grams (80 percent theory) of yellow needles were obtained. Melting point is 133 to 133.5C.  
  Analysis. Calculated for N OCIC H C, 64.56; H, 4.03; N, 14.12. Found: C, 64.16; H, 4.00; N, 14.08.  
  As in the case of the preparation of a,B-dioxo-, a-[(3-chloro-o-toly1)hydrazone] hydrocinnamonitrile, the other novel hydrocinnamonitrile insecticides mentioned above, e.g., a,B-dioxo-, phenyl)hydrazone] hydrocinnamonitrile, can also be prepared by reacting the appropriately substituted aniline at a temperature of from about l0C. to about +C. with a compound of the formula R NO in a solvent rendered acidic by the addition of a mineral acid to form a diazonium salt solution of said aniline, and reacting the diazonium salt in solution to form said hydrazone by adding said diazonium salt to a mixture of a weak base and an aroylacetonitrile, e.g.,  
 wherein R is a member selected from the group consisting of alkali metals and C -C loweralkyl groups.  
  Step 2 Cl CH NEN CP cocn c m NaOAc ESE/l) 5.66 grams (0.04 m.) of 3-chloro-o-t0luidine was dis- E solved in 60 ml. of 3N HCl (0.186 m.), and the solution XAMPFE 19 was cooled to 36 grams (004 m) of potassium Preparation of various afi-dtoxohydrocinnamonitrile nitrite, which was dissolved in 10 ml. of water, was then hydrazones A variety of a,B-dioxohydrocinnamonitrile hydrazones of Formula I were prepared by the general procedure of Example 1, employing the appropriately substituted aniline and cinnamonitrile. The compounds produced are set forth in Table 11 below.  
 TABLE II 0 Bl -Rg NHN==C Bi CN R B: Ra  
 Z-Cl 8-0] H Z-Cl. H  
 bra-04H K Z-CH: H  
 S-CL H mm H 8-CFa 6-CF H G-CICuHsO H H EXAMPLES 20-33 The insecticidal activity of the compounds of Formula I is demonstrated by the following tests using the test procedures set forth below.  
 Southern Armyworm (Pradenl&#39;a eridania Cram.)  
 beaker containing 25 ml. of water. The test compound is formulated as an emulsion containing 0.1 gram of test material, 0.2 gram of Alrodyne 315 emulsifier, a nonionic polymeric emulsifier by Alrose Chemical Company, ml. of acetone and 90 ml. of water. This 1000 ppm emulsion is diluted ten-fold with 65 percent acetone&#39;35 percent water to give 100 ppm. One milliliter of the 100 ppm emulsion is pipetted into 225 ml. of water in a 400 ml. beaker and stirred vigorously. The  
  f zm i g&#39; g i&#39; aretmade. i as periem 10 larvae in 25 ml. of water are added, giving a concentra- T m th a W i i g i i i tion of 0.4 ppm. Mortality counts are made after 24 e311 eaves ire di d ppim l g 3 es T f hours at 80F. Data obtained are provided below in F a 9 ey are P Table w. R which is unshown in Table IV below, is petrl dlshes llned on the bottom wlth a molst filter &#39;ln each case H. paper and ten thlrd-lnstararmyworms are added to each dish. The dishes are covered, held at 80F, 60 percent relative humidity for 2 days and then examined TABLE IV and mortallty counts made. Untreated leaves are used as controls. Kill,  
  Ex. Mosquito Larvae,  
  No. R R, R2 Concentration 0.47: To a E w b Coo ud Orm 34 m-Cl H phenyl 92 H I h H 2Cl 5Cl phenyl s reseus) 36 2CH3 4Cl phenyl lOO Compounds to be tested are made up as 0.1 percent 37 =l 2 phenyl 76 1 ti /35 t t t S In 25 38 Benzo phenyl 100 so u ons ln ace one-waer mnr ures. ma eaves 39 H p chk,mphcnyl 100 from cotton plants are then dlpped 1n the selected test 40 p I H lhieflyl 100 solutions and air dried. After drying, they are placed in 2; g:% S 82? 82 a small medicine cup with a dental wick saturated with water and one third-instar tobacco budworm and held 30 in a constant temperature and humidity room for 3 da s. A t nd of the holdin eriod all cu s ar ext he 6 g p p e EXAMPLE 43 amlned and mortallty counts made. At least 10 repli- Cates per test Solution r used- Foliar Residual Activity of Phenylhydrazones The data obtalned are m each case set forth m Table lll below. R which is unshown in Table III, is in each The foliar residual activity of the phenylhydrazones case H. and commercial standards is shown in Tables V, VI, VII- TABLE Ill 74 Control Ex. Soutllem Armyworm, Tobacco Budworm, No. R R R2 Concentration 0. l9? Concentration 0.1%  
 20 p-Cl H phenyl lOO 90 21 m-Cl H phenyl lOO 22 2-Cl 5Cl phenyl lOO 9O 23 p-Cl 0---CH phenyl 100 24 pCH H phenyl 9O 6O 25 --cl-l 5 No phenyl 60 26 Benzo phenyl 50 60 27 p-Cl H p-chlorophcrlyl l 00 2s p-Cl H furyl 100 60 29 p-Cl H thicnyl 100 80 3O p-Cl H naphthyl I00 90 31 3CF 1 5CF phenyl lO0 100 32 p-Cl H. a 100 100 33 p-phenylazo H phenyl l00 100 EXAMPLES 34-42 The larvicidal activity of the compounds of Formula 60 l is demonstrated in the following tests using mosquito larvae. The test procedure is as follows:  
 Mosquito Larvae (Anopheles quadrimaculalus Say) Groups of 25 larvae of the common malaria mosquito are transferred with a medicine dropper to a 50 ml.  
 lent of 86 gallons per acre. Following application, the treated plants are placed on greenhouse benches and permitted to dry. At various time intervals thereafter, treated leaves are removed from the plants, placed in petri dishes with moist filter papers on the bottoms thereof and containing or southern armyworms or gypsy moth larvae. Mortality counts are made after 3 days of exposure.  
  For bioassays with tobacco budworms, the excised leaves are cut into five sections, and each section is placed in a 1 ounce plastic medicine cup containing a 1 inch dental wick saturated with water, and one-third lnstar tobacco budworm. Mortality counts are made after 3 days of exposure.  
 TABLE V Fuller residual activity 0! phenylhydmzonaa on lime bean plants blnmyod with southern armywarma o! mfldna Rate, on 1 in pounds per 0 2 8 4 we Percent nma&#39;tality Formmatlon Structure w? as COZ=NNHCI 1 no no 109 100 %WP-ChecL o o o 0 W1 14 50 m 50% -C0(|J=NNH-Cl 1 so m 20 Cu&#39;N w c1 14 so 49 50% 1) 1 so so as :0 as so so mm c 1 100 a) so so mwr-chwk m a) o no TABLE VI Follar residual activity of phenylhydramnea on time bean plants Eyed with southern arm oltmpinnta 30% m in m par 9 l 8 8 an F Structure PM mummy 1s 100 ea 78 m 1 1m 16!) um l 1m 89 t8 1 m1 260 76 mo E 1m 1m (-25 1 109 mu m 16B TABLE JUL-Continued Felts: residual wtlvity of experimental umecticic&#39;tea and standards on cotton plants aged in the greenhouse and btomyed with various Insects Age of residue on plants tn weeks Tobacco budwomr Bentham srmyworm Gypsy moth larvae Rate, pounds013801284&#39;0128 Formupar latlon Structure acre Percent mortality after 8 days of %WP k 13 2E 53 0..-.. $0 75 25... 1100mm) 0..-..16090809912557510 0 aoaaeacasowomoeseoaa tmomoeiefleomnmlwmesmrmmea M100 m to n mo mo m0 100 we amoraworaromoicomomm 1 Southern armywcxms mall-used second luster, not third.  
 EXAMPLE 44 EXAMPLE 45 Field Evaluatlon of Test Compounds 30 The effectiveness of the phenylhdrazone in the con- Test materials were applied at the rate ofl pound actrol of imported cabbage worm (Pieris rapae) on 3 ltual ingredient in 57 gallons of water per acre. Applicafoot rows of cabbage was determined using the application was made by a C0 power-pack sprayer with three tion procedure of Example 44. The results obtained are flat-tip spray nozzles at a pressure of 25 p.s.i. and at a 3 set forth in Table X below.  
 TABLE X amma structure Emulation cabham CmN 5 1% WP 1.0 a -oo--o=rs--NH--c1 Control 6.7  
  50 tractor speed of4 miles per hour. The foliage of 60-foot EXAMPLE 46 rows of potatoes were treated on schedule for control of Colorado Potato Beetle (Leptinomrsa decemlineata Effectiveness of test compounds against insects of the The data obtained for the test compound and untreated Order C0 P r8 i5 ShOWn m the follo ing testcontrol are set forth in Table IX below, 55 The test procedure employed to determine the effi- TABLE IX 2 Fatal 1 Ln &#34;&#39;3 Formatu potato v Stream Lama 524mm lea/row TABLE XI Ule oi eevenl phenylhydruonee ended! where Y is hydrogen, chloro or lower alkyl (C -C cucumber beetle (Diabiotfee net adult spotted panama houmdi) and 531i Mexican been beetle (Epiladma animus) Adult Adult Conapotted Mexican centntion cucumber bean Structure in p.p.m. beetles beetle Cl M GEN 80 100 co-i:=N-Nn 01 G1 I, 80 50 C=N co-c=n-xm c1 CH 01 LG 80 50 C=N O0-c=N-NH GEN 1.000 so an ooo-e=N-Nn--o1 24:7 mortality data. 4-day mortality data.  
 EXAMPLE 47 m is l or 2; and  
 nis0,lor2.  
  2. The compound of claim 1, a,B-dioxo-, (ll-[(3- chloro-o-tolyl )hydrazone]hydrocinnam0nitrile.  
 3. The compound of claim 1, a,B-dioxo-a-[(3,4-  
 4O dichlorophenyl)hydrazone]hydrocinnamonitrile.  
  4. The compound of claim 1, p-chloro-a,B-dioxo-,a- [(p-chlorophenyl )hydrazone hydrocinnamonitrile.  
 TABLE X11 U oi drew in i liar treatment in ileld control 0! the (all ermyworm m (Spodopt mfrupipcrdd) oneorn is ental Total 118!- worms Famedientper intluee Structure letien we replicate.  
  GEN 60%WP... 1 76 ool=N-m1--ci O1 50%WP... l 19 GEN ool&#39;=N-NH can mm... 1 ae c1-C -co-l:=N-Nn- 01 0mm as 65 v We claim: 5. The compound of claim 1, p-chloro-a,B-d1oxo-al. A hydrocinnamonitrile compound having the formula:  
 [phenylhydrazone]hydrocinnamonitrile.