III. INDUSTUIAL PHKPARATION 419 



otIuM-, tolalin;^ 7.")%. Both coinpouiids can 1)(> usrd Inr the synthosi.s of the 

 thia/olo, hut tlio chlorine in tho lice alcohol is much more reactive than 

 the chlorine in the ether. With the bromo comj)ouiul, the alcohol is excn 

 less stable in its free form and converts spontaneously to its etlier. Tiie 

 same authors found that a boilinu solution of I % IK'l is more satisfactory 

 than the concentrated acid. 



If the saponification and decarboxylation arc done with hydrochloiic 

 acid in "lacial acetic acid ^ith just the calculated amount of water and 

 acetic anhj'dride is added after the decarboxylation, excellent yields of 

 7-chloro-7-acetopropylacetate are obtained (93 to 95%, Low and Smith^')- 



The use of the acetate was already proposed by Todd et al.,*- but the 

 low yield in the first step of their process (sodium ethyl acetoacetate and 

 /i-bromoetlwl acetate, 25 %) was not encouraging. 



The saponification of a-chloro-a-acetobutyrolactone with sulfuric acid 

 in alcohol at 40 to 50° leads to the formation of a ring ketal, namely 2- 

 methyl-2-ethoxy-3-chlorotetrahydrofurane in a yield of 70 % (Klingenfuss^=*) 



CH2 CHCl 



CH2 C— CH3 



\ / \ 

 O OEt 



The.se ketals do not react with ketone reagents (semicarbazide), but their 

 chlorine is reactive and they can be used for the synthesis of the thiazole 

 ring. 



The starting material for Buchman's method, a-aceto-7-butyrolactone, 

 is easily obtainable*^ from sodium ethyl acetoacetate in alcohol and ethylene 

 oxide, with a yield of 60 %. Both raw materials, ethyl acetoacetate and 

 ethylene oxide, are commercial items. Starting from them, only three steps 

 are required to the necessary 3-halogenopentanolone[4] ; the 3- ields of these 

 steps are good to excellent. 



5. Group D, Nitrogen, Carbon Atom 2, and Sulfur 



n. For Closing the Thiazole Ring 



Thioformamide, XH2 — CH^^, is the easiest source for the remaining 

 three atoms of the thiazole ring. Willstatter and Wirth-*^ reacted formamide 



" Roche Products, J. A. Low, and R. J. Smith, British Pat. 606,026 (August 5, 1948). 



« A. Todd, F. Bergel, and A. Jacob, ./. Chem. Soc. 1936, 1555. 



" M. Klingenfuss, U.S. Pat. 2,123,653 (July 12, 193S) ; British Pat. 496,801 (December 



6, 1938). 

 ** I. L. Knunyantz, G. W. Chelintzew, and K. D. Ossetrava, Covi/pt. rend. Acad. Sci. 



U.R.S.S. 1, 312 (1934) IC A. 28, 4382 (1934)]. 

 *^ R. Willstatter and T. Wirth, Ber. 42, 1911 (1909). 



