Fungicidally active 3-amino-propionic acid chloroanilides
United States Patent [191 Enders et al.  
  451 Apr. 22, 1975 [73] Assignee: Bayer Aktiengesellschaft.  
 Leverkusen. Germany [22] Filed: May 10. 1973 [2]] Appl. No.: 359.166  
 [30] Foreign Application Priority Data May 17. 1972 Germany 2324006 [52] U.S. C1. 424/324; 424/267; 424/274 [51] Int. Cl ..A01n 9/20 [58] Field of Search 424/324; 260/558 A [56] References Cited UNITED STATES PATENTS 3.567.776 3/1971 Krcnzcr ct al. 424/324 X OTHER PUBLICATIONS Chemical Abstracts. 7018717311. (1969).  
 Primary ErumincP-Alhert T. Meyers Asa-ism! E.\&#39;uminerLeonard Schenkman Attorney. Agent. or Firm-Burgess. Dinklage &amp; Sprung 1 1 ABSTRACT Compositions and methods of using propionic acid chloroanilides of the formula 3-aminoin which X and Y are each halogen. methyl or trifluoromethyl. provided that at least one of them is halogen. R is alkyl. cycloalkyl or alkenyl of up to 6 carbon atoms, and R is hydrogen, or alkyl or alkenyl of up to 6 carbon atoms. or R and R conjointly form an alkylene group of 4 or 5 carbon atoms. which forms a ring with the nitrogen atoms to which R and R are attached. some of which are new. which possess strong fungicidal. microbicidal. insecticidal and bird-repellent properties.  
 8 Claims, N0 Drawings FUNGICIDALLY ACTIVE 3-AMINO-PROPIONIC ACID CHLOROAN ILIDES The present invention relates to and has for its objects the provison of particular new active compositions in the form of mixtures with solid and liquid dispersible carrier vehicles of certain 3-amino-propionic acid ehloroanilides. some of which are new. and which possess valuable strong fungicidal. microbicidal. insecticidal and bird-repellent properties. and methods for using such compounds in a new way. especially for combating and controlling fungi. microbes. insects and harmful birds with other and further objects becoming apparent from a study of the within specification and accompanying examples.  
  As has been known for a long time. zinc ethylene-l .2- bis-dithioearbamate (Compound A) is used as a fungicide in agriculture and in horticulture; the said compound is of great importance amongst commercially available products (see R. Wegler. Chemie der Pflanzenschutzund Schaedlingsbekaempfungsmittel (Chemistry of Plant Protection Agents and Pestieides&#34;). volume 2. page 65. Berlin/Heidelberg/New York 1970 However. the action is not always satisfactory if low concentrations are used.  
  It has now been found that the 3-amino-propionic acid anilides of the general formula X and Y are each halogen. methyl or trifluoromethyl.  
 provided that at least one of them is halogen.  
 R is alkyl. cycloalkyl or alkenyl of up to 6 carbon atoms. and  
 R is hydrogen. or alkyl or alkenyl of up to 6 carbon atoms. or  
 R and R conjointly form an alkylene group of4 and 5 carbon atoms. which forms a ring with the nitrogen atom to which R and R are attached. as well as their acid-addition salts. display strong fungicidal properties.  
  Preferably. X and Y are each chlorine. bromine. methyl or trifluoromethyl. R is alkyl of up to 6 carbon atoms. cyclopentyl. cyclohexyl or lower alkenyl of 3 or 4 carbon atoms. and R is hydrogen or lower alkyl or alkenyl with. in either ease. up to 4 carbon atoms. or R and R. together with the linking nitrogen atoms. form a pyrrolidine or piperidine ring system.  
  Surprisingly. the 3-amino-propionic acid anilides which can be used according to the invention. as well as their acid-addition salts. display a substantially greater fungicidal action than zinc ethylene-1.2-bisdithiocarbamate. which is known from the state of the art. The present invention thus represents an enrichment of the art.  
  A number of the compounds which can be used according to the invention are already known (see USSR Pat. Spec. No. 233.683). Compounds which have not been described in the literature can be produced either by reacting 3-chloropropionic acid anilides with excess primary or secondary amine at temperatures between +20C and the boiling point of the amine used. or by adding primary or secondary amines to acrylic acid anilides within the aforesaid temperature range. In the reactions mentioned. diluents. such as alcohols 9for example. methanol and ethanol). ketoncs (for example. acetone) or hydrocarbons (for example. benzene and toluene) can also be employed. After completion of the reaction. and after distilling off the excess amine and. if relevant. the solvent. the reaction product can be isolated as the free base after stirring with aqueous caustic alkali solution. or as the hydrochloride after recrystallization from dilute hydrochloric acid. Both the free bases and the acid-addition salts can be employed for the end use according to the invention.  
  The active compounds according to the invention. as stated above. show a strong fungitoxic action. They do not damage crop plants in the concentrations required for combating fungi and have only a low toxicity to warm-blooded animals. For these reasons they are suitable for use as plant-protection agents. to combat fungi. Fungitoxic agents are employed in plant protection for Combating Arc/zimyccres. P/iycomyc&#39;elt&#39;s. Aswmycclcs. BuxidiomyccIt&#39;s and Fungi Imperfecti.  
  The active compounds are especially suitable for use as seed dressings and also for the treatment of soil. Herein. their action is primarily directed against seedborne fungi and phytophathogenic soil fungi: in particular. there may be mentioned bunt diseases of cereals. such as bunt of wheat and loose smuts of oats and also helminthosporioses of barley and of oats. for example. stripe disease of barley. as well as diseases of seedlings. for example in cereals. maize. pulses or cotton. caused by fungi of. for example. the genera Rhizoctonia or Fusarium.  
  The active compounds according to the instant invention can be utilized. if desired. in the form of the usual formulations or compositions with conventional inert (i.e.. plant compatible or herbicidally inert) pesticide diluents or extenders. i.e.. diluents. carriers or extenders of the type usable in conventional pesticide formulations or compositions. e.g.. conventional pesticide dispersible carrier vehicles such as gases. solutions. emulsions. suspensions. emulsifiable concentrates. spray powders. pastes. soluble powders. dusting agents. granules. etc. These are prepared in known manner. for instance by extending the active compounds with conventional pesticide dispersible liquid diluent carriers and/or dispersible solid carriers optionally with the use of carrier vehicle assistants. e.g.. conventional pesticide surface-active agents. including emulsifying agents and/or dispersing agents. whereby. for example. in the case where water is used as diluent. organic solvents may be added as auxiliary solvents. The following may be chiefly considered for use as conventional carrier vehicles for this purpose: aerosol propellants which are gaseous at normal temperatures and pressures. such as Freon; inert dispersible liquid diluent carriers. including inert organic solvents. such as aromatic hydrocarbons (e.g.. benzene. toluene. xylene. alkyl naphthalenes. etc.). halogenated. especially chlorinated. aromatic hydrocarbons (e.g.. chlorobenzenes. etc. cycloalkanes (e.g.. cyclohexane. etc.). paraffms (e.g.. petroleum or mineral oil fractions). chlorinated aliphatic hydrocarbons (e.g.. methylene chloride. chloroethylenes. etc. alcohols (e.g.. methanol. ethanol. propanol. butanol. glycol. etc.) as well as ethers and esters thereof (e.g.. glycol monomethyl ether. etc. amines (e.g.. ethanolamine. etc.). amines (e.g.. dimethyl formamide. etc.). sulfoxides (e.g.. dimethyl sulfoxide. etc.). acetonitrile. ketones (e.g.. acetone. methyl ethyl ketone. methyl isobutyl ketone. cyclohexanone. etc.). and/or water; as well as inert dispersible finely divided solid carriers. such as ground natural minerals (e.g. kaolins. clays. alimina. silica. chalk. i.e.. calcium carbonate. talc. attapulgite. montmorillonite. kieselguhr. etc.) and ground synthetic minerals (e.g.. highly dispersed silicic acid. silicates. e.g.. alkali silicates. etc.); whereas the following may be chiefly considered for use as conventional carrier vehicle assistants. e.g.. surface-active agents. for this purpose: emulsifying agents. such as non-ionic and/or anionic emulsifying agents (e.g.. polyethylene oxide esters of fatty acids. polyethylene oxide ethers of fatty alcohols. alkyl sulfates. alkyl sulfonates. aryl sulfonates. albumin hydrolyzates. etc.. and especially alkyl arylpolyglycol ethers. magnesium stearate. sodium oleate. etc.); and/or dispersing agents. such as lignin. sulfite waste liquors. methyl cellulose. etc.  
  Such active compounds may be employed alone or in the form of mixtures with one another and/or with such solid and/or liquid dispersible carrier vehicles and/or with other known compatible active agents. especially plant protection agents. such as other fungicides. microbicides. insecticides and bird repellents. or acaricides. rodenticides. bactericides. nematocides. herbicides. fertilizers. growth-regulating agents. etc.. if desired. or in the form of particular dosage preparations for specific application made therefrom. such as solutions. emulsions. suspensions. powders. pastes and granules which are thus ready for use.  
  As concerns commercially marketed preparations. these generally contemplate carrier composition mixtures in which the active compound is present in an amount substantially between about 01-95 percent by weight. and preferably -90 percent weight. of the mixture. whereas carrier composition mixtures suitable for direct application or field application generally contemplate those in which the active compound is present in an amount substantially between about 0.000ll0 percent preferably 0.0l-1 percent. by weight of the mixture. Thus. the present invention contemplates over-all compositions which comprises mixtures of a conventional dispersible carrier vehicle such as (l) a dispersible inert finely divided carried solid. and/or (2) a dispersible carrier liquid such as an inert organic solvent and/or water preferably including a surface-active effective amount of a carrier vehicle assistant. e.g.. a surface-active agent. such as an emulsifying agent and- /or a dispersing agent. and an amount of the active compound which is effective for the purpose in question and which is generally between about 0.0001-95 percent. and preferably 0.01-95 percent. by weight of the mixture.  
  The active compounds can also be used in accordance with the well known ultra-low-volume process with good success. i.e.. by applying such compound if normally a liquid. or by applying a liquid composition containing the same. via very effective atomizing equipment. in finely divided form. e.g.. average particle diameter of from 50-100 microns. or even less. i.e.. mist form. for example by airplane crop spraying techniques. Only up to at most about a few liters/hectare are needed. and often amounts only up to about to 1.000 g/hectare. preferably 40 to 600 g/hectare. are sufficient. In this process it is possible to use highly concentrated liquid compositions with said liquid carrier vehicles containing from about to about 95 percent by weight of the active compound or even the percent active substance alone. e.g.. about 20-100 percent by weight of the active compound.  
  In dressing. amounts of active compound of 50 mg to 50 g. preferably of 200 mg to 10 g. are in general employed per kilogram of seed.  
  In the treatment of soil. which can be carried out by overall. band or spot application. concentrations of 1 to 1.000 g of active compound per cubic meter of soil. preferably 10 to 200 g per cubic meter, are generally required at the place of the intended effect.  
  Furthermore. the present invention contemplates methods of selectively killing. combating or controlling pests. e.g.. fungi. microbes. insects and harmful birds. and more particularly methods of combating fungi. which comprises applying to at least one of correspondingly (a) such fungi. (b) such microbes. (e) such insects. and (d) the corresponding habitat thereof or of harmful birds. i.e.. the locus to be protected. a correspondingly combative or toxic amount. i.e.. a fungicidally. microbicidally. insecticidally or bird-repellent effective amount. of the particular active compound of the invention alone or together with a carrier vehicle as noted above. The instant formulations or compositions are applied in the usual manner. for instance by spraying. atomizing. vaporizing. scattering. dusting, watering. squirting. sprinkling. pouring. fumigating. dry dressing. slurry dressing. moist dressing. wet dressing. and the like.  
  It will be realized. of course. that the concentration of the particular active compound utilized in admixture with the carrier vehicle will depend upon the intended application. Therefore. in special cases it is possible to go above or below the aforementioned concentration ranges.  
  The synthesis. unexpected superiority and outstanding activity of the particular new compounds of the present invention are illustrated. without limitation. by the following examples:  
 EXAMPLE 1 Seed dressing test/bunt of wheat (seed-borne mycosis) To produce a suitable dry dressing. the active compound was extended with a mixture of equal parts by weight of talc and kieselguhr to give a finely powdered mixture with the desired concentration of the active compound.  
  Wheat seed was contaminated with 5 g of the chlamydospores of Tilletia caries per kg of seed. To apply the dressing. the seed was shaken with the dressing in a closed glass flask. The seed. on moist loam under a cover of a layer of muslin and 2 cm of moderately moist compost soil, was exposed to optimum germination conditions for the spores for 10 days at 10C in a refrigerator.  
  The germination of the spores on the wheat grains. each of which was contaminated with about 100.000 spores. was subsequently determined microscopically. The smaller the number of spores which had germinated. the more-effective was the active compound.  
  The active compounds. the concentrations of the active compounds in the dressing. the amounts of dressing used and the percentage spore germination can be seen from the following Table l:  
 1 a b l s- Sued dIUtJUillgj teat/tram, of. wheat Active compound Activu coiawoun&#39;i conihiunnt of (llE&#39;Ll .lgior germ cenbrutiun in the used in nation in 75 111 =i in 71 by seed weight w; &#39;Inout dressing 10 ll CH -Ifi1-C-S- Zn 1O 1 5 CH -NibC-li II (kn own) (A) -1-n1-cmun -011 4111411 10 1 tjlQ-Mi-UU-Uli 121 -1111 1 U. 000 w H01 9 1 0.1.0; y uu cah l 1 0.05  
  v c NH-LO 011 011 NH 0 11 10 1 0.,  
  C H 01 -NH-CO-CH CH N 2 5 10 1 0.000 5 1 0.005 cf 5 Ul-G-NH-CO-CH -CH iO 10 1 o 000 -NIi-UO-1J1i-,C&#39;ri -NH-C H 10 1 0.000 3 1 (U05 RC]. 1 1 0.5  
 Cl @FHH-CO-Ci-i -CH NH-C 4H9 1 0 1 O 5 1 HBLQNH CO (J12 (1H2 llh C4119 10 1 0.05  
 c (10) HCl cl- -I-111-c0-Un -CH -NH-C 11 -41) 10 1 0 005 1 5 1 0.05 Cl (6) 0 H01 01 iru-00-cn -cn -in1@ 10 1 0.005  
  The production ofthe compounds used in this inveng f 3- hl0mpmpi0nic acid 3 4-dichl0r0anilide tion IS illustrated by the following Examples. were introduced into 200 g of cyclohexylamine and the 7 mixture was stirred for 3 hours at C. Thereafter, the EXAMPLE cyclohexylamme was distilled off in vacuo and the residue was recrystallized from a large amount of water with the addition of a little hydrochloric acid. 59 g of (1) 6; 3-cyclohexylaminopropionic acid 3.4-dichl0r0anilide hydrochloride of melting point 249-25lC were obtained.  
 EXAMPLE 3 HCl 8 R is alkyl. cycloalkyl or alkenyl each of up to 6 carbon atoms. and R is hydrogen. or alkyl or alkenyl each of up to 6 carbon atoms. or an acid-addition salt thereof.  
  CH =CH-CH 2. The method according to claim 1. m which X and Y are each chlorine. bromine. methyl or trifluoroofd3 -Q:liOII&#39;OPR;SIOHI(. un 1&#39; wi- Y &#39;f F methyl. R is alkyl of up to 6 carbon atoms. cyclopentyl. Lrc intro &#39;UCc into 0 g o tmmt. an IllL yclohexyl or alkenyl of 3 or 4 carbon atoms. and R ture was stirred for 1 hour at ..0C and thereafter for m is hydrogen or alkyl or alkenyL each of up to 4 Carbon 1 hour under reflux. The allylamme was then distilled Mon off and the residue was recrystallized from dilute hy- 3 The method according to claim 1 wherein id idrochlorlc acid. 50 g of 3-allylammo-prop onic acid de is 3{Yclohewlaminchpmpionic acid 3 3.4-dichlorozmilide hydrochloride of melting point dichloroanilide f the f l l94l95C were obtained.  
 EXAMPLE 4 -Nd-CO-CH -CH -NH H C fi Cl n m. w s1 \-m1-c0-en..-cn,-N (2) 2O 4. The method accordmg to claim 1 wherein said am- C 4 lide is 3-allylamino-propionic acid 3.4-dichloroanilide of the formula 1.000 g of 3-chloropropionic acid 3.4-d1chloroamlide were introduced into 1.000 g of diethylamine over the C course of minutes and the mixture was stirred for l N 1\IHWCO-CI&#39;IZDCHZMIFII hour at C and 1 hour under reflux. Thereafter the i C CH =CH-CH excess diethylamine was distilled off and the residue was Stirred with 500 ml f waten T pmduct was fi]- 5. The method according to claim 1 wherein said anitered off. washed with water and recrystallized from diy &#39;p p ilcld lute methanol. 1.095 g of 3-diethylamino-propionic 3Q di hl ilid f th f l acid 3.4-dichloroanilide of melting point 65-67C C H were obtained. Cl CO CH CH 2 5 The following compounds of the general formula (I) 2 2 were produced by methods analogous to those above: 0 2 5 Compound No. X Y R R Properties 4 Cl Cl CH&#34; H Hydrochloride. melting point l65-l68C 5 Cl Cl C.|H.. H Hydrochloride. melting point l94-l9oC 6 Cl Cl C H.,(i) H Hydrochloride. melting point l97-l98C 7 Cl Cl (CH2). Hydrochloride. melting point l95-l98C 8 C F, C I C .H,, H Hydrochloride. melting point 207-209C &#39;9 Cl CH C ,H,, H Hydrochloride. melting point 208-2 l0C 10 CH Cl (1H5. H Hydrochloride. melting point 2 14-2mc Other compounds which may be similarly prepared 6. The method according to claim 1 wherein said aniand employed include: lide is 3-methylamino-propionic acid 3.4-  
 3-diallylamino-propionic acid 3-fluoro-4- dichloroanilide of the formula trifluoromethylamide. 3-dimethylamino-propionic acid 3.4-dibromoanilide. Cl and the like. NH--CQ--CK CH IU&#39;I--CI-l It will be appreciated that the instant specification f and examples are set forth by way of illustration and not limitation. and that various modifications and changes may be made without departing from the spirit 7 The method according to c|aim 1 wherein i iand scope of the present mvemmnlide is 3-butylamino-propionic acid 3.4-dichloroanilide What is claimed is: f the f m l. A method of combating fungi which comprises applying to the fungi or their habitat a fungicidally effective amount of a 3-aminopropionic acid anilide of the C1 r formula NH CO 2 2 4 9 R- C]. -Na-c0-ca--ca -Ni \l/ 2 R Y 8. The method according to claim 1. wherein said anilide or its salt is applied to the seed or soil habitat in in which X and Y are each halogen. methyl or trifluoromethyl.  
 provided that at least one of them is halogen.  
 an amount of 50 mg. to 50 g. per kg. of&#39;seed or per 0.05