IL22700A - Dithiazolium salts - Google Patents

Description

PATENT ATTORNEYS · □ ' Q ] Q 3 · 311 U PATENTS AND DESIGNS ORDINANCE SPECIFICATION IMPROVEMENTS IN OR RECAT INO TO OITHIAZOLIUM SALTS (we) HERCULES INCORPORATED (FORMERLY HERCULES POWDER OOMPANv), A CORPORATION ORGA IZED UNDER THE LAW8 OF THE STATE OF DELAWARE, U.S.A., OF 910 MARKET STREET,WILMINGTON, ZONE 99,OELAWARE, U.S.A. , AND WILLIAM RUSSELL DIVELEV, A CITIZEN OF THE U.S.A., OF 4 MORRIS LANE, NEWARK, STATE OF DELAWARE, U.S.A. do hereby declare the nature of this invention and in what manner the same is to be performed, to particularly described and ascertained in and by t following statement :- This Invention relates to new 3,5-bls(substituted amino)-1 ,2,4-dithiazolium salts and to methods for their production.

The new compounds according to the invention have the general ormula wherein X represents an anion of an acid, HX, having an —7 ionization constant of at least 1 x 10 and ^ and g represent a dialkylamino, dicycloalkylamino, diarylamino, allqylarylamino, cycloalhylarylamino or heterocyclic secondary-amino group, They have been found to exhibit defoliating properties.

The compounds of formula I above are readily prepared by oxidation of the 1 ,1 ,5»5*tetra-substituted dithlobiuret in the presence of the above mentioned acid anion.

The acids which form stable salts of this invention are organic or inorganic acids. Suitable acids are those which have an ionization constant of at least 1 x 10 and -6 preferably at least 1 x 10 and include HOI, BBr, HF, HX, fatty acids, particularly acetic acid, chlorinated fatty acids, particularly mono-*, di- and tri-ehloracetic acids, oxalic acid, tartaric acid, dinitrophenols, trinitrophenols, particularly picric acid, benzoic acid, toluic acid and naphthoic acid.

The 3»5-bis(subs itu ed amino)- ,2,4-dithiazolium and other strong acids are stable. Thus the compounds of this invention are obtained only by preparation in the presence of an acid anion capable of forming a salt, and the compounds decompose if reacted with a basic compound so as to remove the acid anion. However, it has been found that one salt can be converted to a salt of another acid by simple displacement or by reacting one salt with a metal salt of another acid. The various salts differ in solubility in water, and the more insoluble salt can be precipitated in the displacement process. On the other hand, the acid of one salt can be substituted by another acid whose metal salt is more insoluble in the solvent used. To this end suitable solvents and suitable metal salts can be selected by any skilled chemist from solubility data in the literature for these metal salts.

The 3 , 5-bis (dimethylamino) -1 , 2,4-dithiazolium bromide representing a substituted 3 , 5-diamino-l, 2 ,4-dithiazolium salt of this invention, wherein X is Br, may be prepared by the reaction (Procedure A) : (CH3)2N-C-SH · (CH3)2NH + BrCN- (CH3) (CH3)2 Br Similar salts are more advantageously prepared by the following series of reaction (Procedure B) : S S II II (CH3)2N-C-C1 + MeSCN —— > (CH3 ) 2N-C-NCS + MeCl where Me represents alkali metal or ammonium ion, S it (CH3) 2N-C-NCS + (CH3)2NH -) (CH3) 2N-C-NH-C=S N (CH3 ) 2 (CH3) 2N-C-NHC=S CI- (CH3)2N -N(CH3)2 CI Θ N(CH3)2 22700/2 or mo Procedure B has a definite advantage over Procedure A particularl in th© chlorination procedure which produces the chloride directly* Both procedures of preparing the compounds of this invention are illustrated by the following examples in which all parts and percentages are by weight* Examples grooedure A - To a well-stirre aaixtur© of 63*6 parts of cyanogen bromide in 800 parts methylene chloride at room temperature was added in small portions ove a period of about one hour 99*6 parts of dimethylammonium diraethyldithiocarbamate* Cooling was applied to keep the temperature from rising above 30°Q* When the reaction was complete, the precipitated solid was removed by filtration and the products was recovered by distilling off the methylene chloride in vacuo* extracting the product from the residue with hot water and subsequently evaportin the water* !he solid product amounted to 19.63 parts which melted at 264-268°G, (dec*), ihis product is easily crystalliaed in purified form by dissolving in acetone* adding water gradually to turbidity* and allowing to crystallize* the purified crystalline salt sup* 270~272°C. (dec*), analysed 0, 25*5^J H, 5*Q5#f M* 14*6$} S, 22.6$} Br, 28.1$£j mol* wt. 260-270* fhe product forms a monohydrate from which water of hydration is driven off at 100°C* in vacuo* Its formula is corresponding to the above analysis for the purified crystalline salt of 3,5-bis(dimethylamino)-l,2,4-dithia2oliura bromide monohydrate* From the 35-bis dimethlamino)-l 24-dithlazolium bromide acid salt in about 5 times its weight of hot water and adding a chemically equivalent amount of 30$ aqueous potassium thiocyanate. A voluminous salt crystallized out on cooling. This thiocyanate salt melted at 188193°G. (dec*) and after crystallization from methanol melted at 196-198°G, (dee.), analyzed 0, 54.0 j H, 4.85^ IT, 21.9^1 3, 37.?/*; mol. wt. 249-258. Δ pierate prepared in a similar manner melted at 165-174°C.(dee ■S ocedure B (Peroxide oxidation)-A homogeneous mixture of 12.35 parts diraethylthiocarbamyl chloride and 10 parts potassium thiocyanate o in 90 parts acetone was heated at about 55 G» for fifteen minutes, cooled and filtered to remove precipitated potassium chloride. To the filtrate at about 25°G, was added 4.5 parts anhydrous dimethylamine over a 10-minute period. The reaction with the dimethyl amine s complete in this time. To the resulting mixture was added slowly with cooling 26.9 parte of 37$ hydrobromic acid. Then 11.35 parts of 30 hydrogen peroxide was added dropwise with adequate cooling to keep the temperature below 30°C» A light tan solid product separated during the oxidation step and this separated by filtration on completion of the reaction.

A second crop of product was separated from the mother liquor. The combined crops were washed with acetone and dried. They amounted to 12.6 parts and a sample melted at 270-275°C. (dec). This salt was shown by misled melting point and by comparison of infrared spectra to be the same as the salt l^iS- isidimethylamiaoJ-l^^-dithiaaollum bromide monohydrate, produced The melting salts prepared by this oxidation procedure using sulfuric acid in place of hydrobromic acids 3-dimethylamino-5»diethylamin©-lf294-dithia30lium bisulfate m . 211-217°0 (dec) ; 3~dimethylamino-5-di-n-butylamino-l,2, -dlthiazolium bisulfate m.p* 233-5°C. (dec.)j 3-dimethylamino-5-JBorpholino-lf2,4-dithlazolium bisulfate m.p. 170-173°C. (dec); and 3-dimethylamino-5*-piperidino-1 24-dithiazolium bisulfate m.p. 217-*220°0. (dec).

Procedure B - (Chlorine oxidation) - A vessel provided with a cooling jacket, thermometer, condenser, and inlet tube was charged with 2300 parts acetone and 270 parts of potassium thio-cyanate and stirred until homogeneous. Then 334 parts of dimethyl thiocarbamylchloride was added and the mixture stirred and heated at about ,55 °C. for 10 minutes. The mixture became yellow and potassium chloride separated. The mixture was cooled, filtered (suction) , and the salt cake washed with acetone. The filtrate (including washings) was charged back into the same vessel. Then 121.5 parts of dimethylamine was passed in at a rate of 1 to 1.5 parts per minute, with stirring and cooling to keep the temperature below 30 °C. After stirring for an additional 0.5 hour, the mixture was aspirated for 5 minutes to remove excess amine. Following removal of the amine, 173 parts chlorine were introduced into the solution at a rate of 1 to 2 parts per minute while stirring and cooling to keep the temperature below 30 °C. The mixture became orange-colored and a solid began to separate almost immediately. Then the mixture became yellow as the reaction progressed and the solid became voluminous. After the chlorine addition was completed, the solid product was filtered (suction) ,. washed with acetone twice and dried in the air overnight. The dried product amounted to 500 parts 3 , 5-bis'(dimethylamino) -1, 2 , 4-dithiazolium chloride , representing a conversion of about 82% based on acid chloride and a yield of about 92% based on chlorine used, in the average run. The products were usually light tan or very light yellow in color. The product is further purified by making a concentrated aqueous solution (1/2 part water, 1 part product) ,. warming slightly, filtering, and reprecipitating the product from the filtrate with acetone. The purified product is white and melts at 267-270 °C. (dec.) - a - ixocedure B ¾iith either peroxide oxidation or chlorine oxidation can be employed to make all of the compounds of this invention. fhus, when for instance, is the dicyclohexylamino radical, an equivalent quantity of dicyclohexylthioearbamyl-chloride is used in place of dimethylthiocarbamyl-chloride in the foregoing example.

When fig, for instance,is the dicyclohexylamino radical, an equivalent amount of anhydrous dic clohexylamine is used in place of the anhydrous dimethylamine in the foregoing example. When , for instance is the cyclohexylphenylamino radical, an equivalent quantity of cyclohexylphenylthiocarbamylchloride is used in place of dime hylthiooarbamate in the foregoing example. When R^, for instance, is the cyclohexylphenylamino radieal, an equivalent amount of anhydrous cyclohexylphenylamine is used in place of the anhydrous dimethylamine in the foregoing example.

-Procedure B is preferably carried out in an organic solvent medium rather than an aqueous medium, and at least the firs two stages are preferably carried out in the absence of water for best yields. Solvents which are suitable for all steps of the process using oxidizing agents are the hydrocarbons, ketones, chlorinated hydrocarbons, alcohols, ethers, dioxane, and dimethylformamide. Solvents boiling below 150 °C. are preferred. When a halogen is used as the oxidizer as in the chlorination step, hydrocarbons, ketones, and chlorinated hydrocarbons are preferred solvents.

In Procedure B the oxidizing agent is any of the well-known oxidizing agents for the oxidation of a sulfhydryl (-SH) to disulfide (-S-S-) . This class of oxidizing agents is well known in the art as exemplified by the disclosures in Organic Chemistry. "An Advanced Treatise", Vol. I, page 851, Gelman (John Wiley and Sons, N.Y. , 1943) page 851-2, and Reactions of Organic Compounds , W. J. Hickinbottom (Longmans, Green and Co., 1948) page 131, and in the patent art on hair waving wherein the sulfhydryl group is oxidized to a disulfide group in the process of setting.

Active oxygen such as that obtained from gaseous oxygen (e.g. , air) or nascent oxygen formers are suitable sulfhydryl-to-disulfide oxidizing agents. Hydrogen peroxide, preferably 25-30% concen-tration, as well as elementary halogens are particularly suitable sulfhydryl-to-disulfide oxidizing agents. Other suitable oxidizing agents are organic peroxides and hydroperoxides, peroxy acids, and peroxyanhydrides. Peracids may be added in the form of their metal salts using sufficient acid for the purpose in addition to that for forming the salt of this invention. The oxidation may also be carried out by electrolysis.

In the oxidation step using a halogen as the oxidizing agent the halogen undergoes reduction producing the required anion to form a salt.

The oxidizing reaction temperature is normally about room temperature and since heat is given off in the reaction, cool preferably below about 30 °C. The oxidation will take place even at temperatures below 0°C. and the lower limit is not critical, but will vary somewhat with the oxidizing reagent used.

The nitrate was prepared by Procedure B by substituting a chemically equivalent amount of 68% HNO3 for HBr in the oxidation step with hydrogen peroxide as the sulfhydryl-to-disulfide oxidizing agent. Similarly, the hydrochloride salt was prepared by substituting 38% hydrochloric acid for the HBr in the oxidation step with the hydrogen peroxide. The dihydrogen phosphate was prepared by substituting 85% phosphoric acid in chemically equivalent amount for the HBr in the oxidation step with the hydrogen peroxide. Similarly, the acid sulfate, the acetate, the trichloro-acetate, the monochloracetate , and the picrate were prepared.

Other salts of this invention are also readily prepared by displacement of HBr from the hydrobromide either directly with the corresponding acid or its monosodium salt or similar salt of another metal and the corresponding acid. The organic acid salts of this invention are particularly readily produced by this latter method.

The compounds of this invention have been shown by polarographic analysis, molecular weight determinations, and nuclear magnetic resonance analysis (NMR) to have a cyclic structure with a heterocyclic ring rather than the acyclic structure. The formula set forth above accordingly fits all of the facts now available. Compounds having this ring structure, in which the ring appears to have a positive charge whereby the anion is held, are believed to be novel. It is further believed that such compounds are produced only from tetra-substituted dithiobiurets in the oxidation process. The cyclic compounds produced by oxidation of dithiobiurets of lower substitution are distinctly differ-ent in being stable in the absence of anions whereas the present compounds are stable only in the presence of anions „ While the 3 , 5-dialkylamino-l , 2 , 4~dithiazolium salts of this invention decompose when neutralized by addition of an alkali, all of the salts with strong acids of this invention are all quite stable.

The salts of this invention were all shown to have defoliating properties when made into a 0.15% aqueous emulsion or solution and sprayed on leaves of growing plants. Further testing on nearly mature cotton plants caused excellent defoliation with such a solution or emulsion at 1 to 3 pounds per acre. The defoliant action appears to be characteristic of all compounds having the dithiazolium salt structure and to be greater in those compounds having R-^ and R2 groups with less than 8 carbon atoms than in those compounds having larger R-^ and R2 groups.

The following are representative data on defoliation activity on cotton: Defoliation % after R2 X lb/acre 4 Days 8 Days (CH3)2N- (N-Bu) 2N- HSO4 1 100 100 (CH3)2N- C6H5x HS04 1 75 83 N- CH3/ (CH3)2N- (N-Pr) 2N- HS04 1 58 92 (CH3)2N- (N-Pr) 2N- HSO4 3 92 100 (CH3)2N- (i-Pr) 2N- HSO4 1 67 67 (CH3)2N- (i-Pr) 2N- HSO4 3 100 100 (CH3) 2N- (C2H5) 2N- HSO4 1 100 100 (CH3)2N- (N-C12H25)2N- HS04 1 50 50 (CH3)2N- (N-C12H25)2N- HSO4 3 92 100 (CH3) 2N- (CH3)2N- N03 1 83 92 (CH3)2N- (CH3)2N- N03 3 83 100 - - In the compounds of this invention the following are representative of and R2: dialkylamino -dimethylamino, dieth lamino, dipropylamino, dih tylamino, dilaurylamino, didodecylamino, methylstearylamino, distearylamlno; dioycloal-gylamino->dicyclohexylamino; diar.ylamlno-di en lamino, ditolylamino; tolylphenylamino, dinaphthylaminoj alkylarylamino^methvlphenvlamlno, butyltolylamino} ef^loalkylarylamino^oycloheaylphenylamino heterocyclic eee-amino-rpjperidino and morpholino^ R, and R9 may be the same or different,..

Claims (1)

1. 1 salts of the formula wherein X represents an anion of an having an ionization constant of at least 1 x and and represent a cycloalkylarylamino or heterocyclic A compound according to Claim 1 in which X is chlorine and and represent dimethylamino A compound according to Claim 1 in which X is te and and 2 represent dimethylamino A compound according to Claim 1 in which X is represents dimethylamino and represents A compound according to Claim t in which X is and and represent salts of formula I in Claim I substantially as described with reference to the A method of preparing a compound according to any one of Claims 1 to 6 which comprises reacting at a reaction temperature below about a dithiobiuret of the S compound to a disulfide compound in the presence of an as defined in Claim A method according to Claim 7 in which the oxidizing agent is elementary chlorine and X is method of preparing salts of formula I in Claim 1 substantially as described herein with reference to the A defoliating composition comprising as an active ingredient a amino salt of formula I in Claim as described insufficientOCRQuality