3- Thenyl chloride

The chloromethylation of thiophene has come somewhat into discredit, partly because of the lachrymatory nature of 2-thenyl chloride, partly because this reaction is highly dependent on the conditions used. Formalin in concentrated hydrochloric acid has been used for chloromethylation, as has the anhydrous system, formaldehyde and hydrogen chloride." The use of a-chloromethyl methylether has also been recommended. The sensitivity of chloromethylation to the experimental conditions is illustrated by the fact that addition of zinc chloride gives di-(2-thienyl)methane as the main product and... 

The thenyl chlorides appear to be more reactive in nucleophilic aliphatic substitution than the benzyl analogs. Thus, 2-thenyh chloride gives, in the reaction with sodium cyanide in ethanol, a mixture of ethyl 2-thenyl ether (25% yield) and 2-thenyl cyanide (32% yield), whereas benzyl chloride gives a high 3deld of benzyl cyanide uncontaminated with benzyl ether. When 2-thenyl chloride and benzyl chloride were allowed to compete for a deficiency of sodium amyloxide, 2-thenyl chloride reacted three times faster. In acetone solution 2-thenyl cyanide is obtained smoothl. ... 

The Grignard reagent from 2-thenyl chloride can be obtained by the use of the "cyclic reactor.However, rearrangement occurs in its reaction with carbon dioxide, ethyl chlorocarbonate, acetyl chloride, formaldehyde, and ethylene oxide to 3-substituted 2-methylthio-phenes, Only in the case of carbon dioxide has the normal product also been isolated. 

A solution of 20 g (0.121 mol) of N-(2-pvridvl)-N, N -dimethvl-ethylenedlamine in 25 cc of toluene was added to a slurry of sodamide in 100 cc of toluene representing 2.8 g of sodium. The mixture was refluxed for one hour. To this mixture was added over a period of % hour a solution of 16 g (0.121 mol) of 2-thenyl chloride in 25 cc of toluene. The resulting reaction mixture was refluxed for 3 hours. Thereafter, water was added and the toluene layer was separated and washed with water. 

The reactions of 2-tlienylchloride and 5-chloro-2-thenylchloride were also investigated (11). It was found that the chloride of 2-thenylchloride is readily replaced by nucleophilic reagents. In analogous reactions, 5-chloro-2-thenyl chloride was converted to the corresponding acetate and thiocyanate. Certain properties of 2-thenylchloride were found to be different from its analog benzylchloride. It is more prone to solvolysis in the presence of bases, consequently alcohols are often undesirable reaction by-products with 2-thenylchloride. 

Acid-catalyzed reaction of the thienylethanol (86) with carbonyl compounds gave fused pyrans (87) (75JHC591). The chloromethylation of thiophene can give 2-thenyl chloride and 2,5-bis(chloromethyl)thiophene, depending on the reaction conditions (52HC(3)187). 

Thenyl chloride is more reactive than benzyl chloride. The rates of formolyses (ki x 104s-1) in 20% dioxane at 20 °C are as follows (75H(3)l) benzyl chloride, 0.85 2-thenyl chloride, 1.51 and furfuryl chloride, 695.0. The rates of reaction with various amines also increase in the same order. Normal replacement of the chlorine in 2-thenyl chloride by CN takes place in 30% aqueous MeCN with NaCN or KCN (conditions under which an abnormal product is exclusively formed with furfuryl chloride). 

Chloro 2 thenyl Chloride 2-Chloromethy > thiophene Chloride (5) or 5 Chloro 2 (chloro methyl) thiophene, C1.C-S-C-CH2C1 ... 

HCHO were heated 2 hrs at 40° at 2 hrs at 60°. It was Rosenthal(Ref 6) who pointed out the spontaneous explosive nature of 5 chloro 2 -thenyl chloride and noted that it may be safely stored by placing a loosely stoppered vessel contg this liq within a metal container in a refrigerator... 

Note See also 5 -Chloro-2-thenyl Chloride Refs l)Beil 17, 37 2)A. Biedermann, Ber... 

Reactive halogen compounds such as benzyl chloride, 2-thenyl chloride, 2-bromoacetylthiophene, (C HjS)COCH,Br , and 2-chloromethyl-thianaphthene (C,H5S)CHjCl are readily converted to esters by treatment with the sodium salts of carboxylic acids. A small amount of tri-ethylamine has proved to be an effective catalyst. Acetates are oftentimes made by heating halides with fused sodium acetate in glacial acetic acid, e.g., p-ethylbenzyl acetate (93%). The reaction is of little value for the preparation of simple aliphatic esters. Secondary and tertiary halides give increasing amounts of olefin by dehydro-halogenation. 

Thenyl chloride is a lachrymator anc, in addition, has a tendency to decompose violently in tightly stoppered bottles. It can be stored for a considerable period, in an ice chest without decomposition, but it is best to use the material as soon as possible after distillation. 

Rejtrmces. Blicke and Burckhalter, J. Am. Chem. Sec., 44, 478 (1942). The method has been checked in the Socony-Vacuum Laboratories. In cases where di-(2-thienyl)methane can be conveniently separated irom the end-products, the crude reaction mixture can be conveniently utilized without resorting to distillation of the 2-thenyl chloride. Over-all yields normally are improved in this manner. The author has found that it is convenient to prepare this compound using equimolar quantities of hydrochloric acid, thiophene, and formaldehyde, omitting the use of hydrogen chloride. The yields tire comparable when the above proced ire is employed. 

Very recently, methods of stabilizing 2-thenyl chloride under storage conditions have been reported. Zienty, U. S. Pats. 2,457,079-081, describes the addition of about 0.5% of a heterocyclic amine such as alkylpyrrolidines, morpholines, or a tertiary amine such as 7V-alkyldicyclohcxylamine in order to stabilize the material toward polymeiization on storage. 

---