United States Patent [ 19] [111 3,932,507 Brand Et Al

United States Patent [ 19] [111 3,932,507 Brand et al. [45] Jan. 13, 1976 [54] PROCESS FOR THE CHLORINATION OF Weeks 9, 11 June 1971, Belgian Pat. No. 755,447. AROMATIC ISOCYANIDE DICHLORIDES [75] Inventors: William Wayne Brand, Hopewell; Primary Examiner-*Gerald A. Schwartz David William Reger, Trenton, both Attorney, Agent, or Firm——H. G. Jackson of NJ. [73] Assignee: American Cyanamid Company, Stamford, Conn. [57] ABSTRACT [22] Filed: Apr. 27, 1973 This invention relates to a novel process for the prepa [21] Appl. No.: 355,1 19 ration of 4-chloro-2-alkylphenylisocyanide dichlo rides. More particularly, this invention relates to the [52] US. Cl. ....................... .. 260/566 D; 260/566 D chlorination of ortho substituted phenylisocyanide di [51 l Int. Cl.2 .................... .._ ................ .. C07C 119/00 chlorides exclusively in the para-position. The com [58] Field of Search ............................... .. 260/566 D pounds are useful intermediates in the preparation of ixodicidal, insecticidal, ovicidal and chemosterilizing [56] References Cited agents. OTHER PUBLICATIONS Central Patents Index (Derwent Publications Ltd.) 10 Claims, No Drawings 3,932,507 1 2 PROCESS FOR THE CI-ILORINATION OF nylcarbonimidoyl dichloride and the p-chloro deriva AROMATIC ISOCYANIDE DICI-ILORIDES tive thereof. Bly, Perkins and Lewis, J. Am. Chem. Soc., 44, 2896 (1922), attempted chlorination of BACKGROUND OF THE INVENTION 5 phenylisothiocyanate in carbon tetrachloride and in lt is known that primary aromatic amines and their phenylcarbonimidoyl dichloride but found no evidence derivatives can be converted to arylisocyanide dichlo of ring chlorination in either'solvent system. D. B. Mur rides in good yield by a number of methods,‘v as for phy, J. Org. Chem., 29, 1613, (1964), reported that example the reactions graphically illustrated by the when chlorination of phenylisothiocyanate is carried following equations taught by: E. Kuhle, B. Anders, and out in chloroform using excess chlorine a mixture of G. Zumach, Angewandte Chemie (International Edi p-chlorophenyl carbonimidoyl dichloride, the unsubsti tion), 6, 649 (1967); and J. E. Baldwin and J. E. Pa tuted compound and 2,4-dichlorophenyl carbonimid triok, Chemical Communications, 968 (1968). oyl dichloride, is obtained. Murphy also reported that when excess chlorine was removed from the reaction ' mixture immediately after the initial chlorination was completed, no ring chlorination occurred. In addition, we have found that chlorination of o-formotoluidide with a chlorine source such as sulfuryl chloride or chlo rine gas leads to a mixture of approximately 75% 4 Cl 20 chloro- and 25% 6-chloro-o-formotoluidide. Similar results are also obtained with the acetyl derivative. Since these procedures give isomer mixtures, the addi tional undesirable step of isomer separation is required. It was therefore an object of the present invention to /Cl .25 find a process which would provide a means for chlori nation of o-alkylaniline derivatives exclusively in the para-position; /Cl SUMMARY OF THE INVENTION 30 The invention relates to a novel process for the man ufacture of compounds having the formula: R I 35 40 wherein R represents alkyl C1-C6, including straight and branched chain alkyl and cycloalkyl. The invention also relates to a novel process for the chlorination of o-alkyl-phenylisocyanide dichlorides exclusively in the para-position. We have now discovered that if the chlorination is In these equations the legend “Ar” means aryl. carried out on an o-alkylphenylisocyanide dichloride, Although such reactions are effective for preparing which may be prepared by any of the above or other methods, the chlorine is introduced essentially in the arylisocyanide dichlorides from primary aromatic 50 amines and derivatives thereof, they do not suggest a para-position. The chlorination can be carried out with means for selectively or exclusively chlorinating any chlorine source, for example, sulfuryl chloride or phenylisocyanide dichlorides in the para-position. In chlorine gas. The reaction is normally run at tempera fact to the contrary, the art reporting the above reac tures between 20°-l50°C., preferably at 60°-l20°C., and can be conducted in the absence of solvents or in tions actually indicates that these reactions yield (a) 55 isomeric mixtures of haloarylisocyanide dichlorides, or a chlorinated hydrocarbon solvent-such as chloroform, (b) fail to achieve ring chlorination at all. dichloroethane, methylene chloride or carbon tetra J. V. Nef, Ann. (Justus Liebigs), 270, 267 (1892), chloride. The reaction may also be carried out in a reported that chlorination of phenyl isothiocyanate at solvent such as thionyl chloride. Graphically, the reac 0°C. in chloroform solution yielded a mixture of phe tion may be illustrated as follows: 3,932,507 3 4 wherein R is alkyl C1—C6. We have also discovered a An alternative procedure involves the sequential process for isolation of 4-chloro-2-alkylphenylisocya- addition to a solution of suspension of the sul?de (plus nide dichlorides. The reaction mixture is stripped of base Where required), of the isocyanide dichloride, solvent and then diluted with an inert chlorinated hy- 5 followed by methylene bromide. Alternatively, the drocarbon solvent such as methylene chloride, chloro- Sul?de Plus base may also be added to a SOlUIlOn Of the form, dichloroethane or carbon tetrachloride. The re- isocyanide dichloride, followed by addition of meth)" sulting solution is then washed with water, dried, and lene brolflld? The Same requirements on Stolchlome Stripped of so|vent to give the purified product_ The try, reaction temperatures, reagents, and solvents apply compounds are useful intermediates in the preparation 10 to this modification as speci?ed for the above proce of ixodicidal, insecticidal, ovicidal and chemosterilizing dure The present invention is further illustrated by the age_n IS. examples provided below which are not to be con DETAILED DESCRIPTION strued as limitative. ' The 2-substituted para-chlorophenylisocyanide di- 5 EXAMPLE 1 chloride is an especially desirable product since it is an 4-Chloro-o-tolylisocyanide Dichloride CH3 CH 3 Cl vCH3 C1 Q-NHCHO + soc12 + $02012 _~_> -N=C< C1 502012 —> 01- _N=c< (:1 intermediate useful in the preparation of the highly To a solution of 67.5 g. (0.5 mole) of o—formo-tolui effective ixodicidal, insecticidal, ovicidal and chemos- 25 dide in 450 ml (6.2 mole) of thionyl chloride was added terilizing, 2-alkyl-(4'-chlorophenylimino)-l,3-dithie- over 1/2 hr. 162 ml. (2 mole) of sulfuryl chloride. The thanes used for the control of insects and ixodides. reaction mixture was stirred at room temperature over The process is particularly advantageous since it night. It was then heated at re?ux for 2% hr., after yields the 2-alkyl-4-chlorophenylisocyanide dichloride which another 30 ml. (0.375 mole) of sulfuryl chloride as a product virtually free of isomeric contamination 30 was added dropwise over 15 minutes as re?ux was and readily convertible to the desired 2-substituted continued. After another We hr. of re?ux, the reaction (p~chlorophenyl-imino)-l ,3-dithietane. These latter- could be seen by gas chromatography ( 140°, 4 ft. SE-30 named dithietanes may be prepared by a one-step pro- on Gaschrome Q, 100-120 mesh) to be essentially com cedure from phenylisocyanide di-chlorides, thereby 35 plete. The solvent was evaporated to afford a crude eliminating the necessity of isolation and puri?cation of reaction product contaminated with small amounts of intermediates. One such procedure involves the addi- thionyl chloride and sulfuryl chloride. This solution was tion of a sul?de source represented by the formula diluted with 250 ml. of methylene chloride and then Hut SM(2_,,'), wherein a’ is an integer 0, 1 or 2; M is was shaken with two 100 ml. portions of water. The an alkali metal, ammonium or primary-secondary- or 40 organic layer was dried over anhydrous magnesium tertiary-alkyl(C,-C4) -amrnonium group such as aque- sulfate, ?ltered, and stripped of solvent to afford a high ous (NI-L028; NazS, KSH or H28, to a solution of methy- yield of product which gas chromatography showed to lene bromide, an appropriate base, where needed, and contain about 9% o-chloro product and 91% p-chloro the isocyanide dichloride. If a’=0 in the sul?de, no product. Gas chromatographic examination of aliquots additional base is needed; if a’=l, one equivalent of 45 removed during the reaction showed that 6-chloro-o base is vneeded per equivalent of sul?de; and if a’=2, tolylisocyanide dichloride was present soon after the two equivalents of base are needed per equivalent of reaction was begun to the extent of 9% of the total sul?de. Any common base can be used, as for example reaction mixture, and its relative amount remained alkali metal hydroxides, alkali metal bicarbonates, al- constant during the ‘course of the reaction. The forma kali metal carbonates, or perferably tertiary-alkyl(- 50 tion of this isomer is due to the contamination of the C1~C4)-amines. Preferably used are 2 to 3 equivalents thionyl chloride by sulfuryl chloride which gives some of methylene bromide to each equivalent of the isocya- non-selective chlorination of o-formotoluidide. It is nide ‘dichloride. The reaction can be run at tempera- merely carried along in the reaction as an impurity in tures between 0°C. and 60°C., and preferably at 20°C. the o-tolylisocyanide di~chloride. After conversion of to 40°C. The solvent used can be any polar aprotic 55 the o-formotoluidide and the contaminants 4- and 6 solvent or aqueous mixture of an organic solvent which chloro-o-formotoluidide to their respective isocyanide is inert to the reactants such as water, pyridine, sulfo- dichlorides, further chlorination by addition of sulfuryl lane, ethylene glycol dimethyl ether, diethylene glycol chloride is restricted to forming 4-chloro-o-tolylisocya dimethyl ether, esters of lower alkanols, or an aqueous nide dichloride from o-tolylisocyanide dichloride.

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