Thienylacrylic acids

The rate of saponification of ethyl 2-thenoate, in contrast to ethyl 3-thenoate, was found to be considerably slower than predicted from the pKa of the acid, showing that the reactivities of thiophenes do not parallel those of benzene. The first explanation, that this was produced by a steric effect of the ring sulfur similar to the case in or /lo-substituted benzenes and in ethyl 1-naphthoate, could not be upheld when the same effect was found in ethyl 2-furoate. It was later ascribed to a stereospecific acid strengthening factor, involving the proper relation of the carboxylic hydrogen and the heteroatom, as the rate of saponification of 2-thienylacrylic acid was in agreement with that predicted from the acid constants. ... 

The synthesis of the representative compound of this series, 1,4-dihydro-l-ethyl-6-fluoro (or 6-H)-4-oxo-7-(piperazin-l-yl)thieno[2/,3/ 4,5]thieno[3,2-b]pyridine-3-carboxylic acid (81), follows the same procedure as that utilized for compound 76. Namely, the 3-thienylacrylic acid (77) reacts with thionyl chloride to form the thieno Sjthiophene -carboxyl chloride (78). Reaction of this compound with monomethyl malonate and n-butyllithium gives rise to the acetoacetate derivative (79). Transformation of compound 79 to the thieno[2 3f 4,5]thieno[3,2-b]pyhdone-3-carboxy ic acid derivative (80) proceeds in three steps in the same manner as that shown for compound 75 in Scheme 15. Complexation of compound 75 with boron trifluoride etherate, followed by reaction with piperazine and decomplexation, results in the formation of the target compound (81), as shown in Scheme 16. The 6-desfluoro derivative of 81 does not show antibacterial activity in vitro. 

Starting from 2-thienylacrylic acid (244), thionyl chloride and pyridine, the chlorinated thieno[3,2-6]thiophene derivative (245) was formed along with the more highly chlorinated product (246), which was isolated as its methyl ester (247 Scheme 83). In refluxing toluene or chlorobenzene, product (245) was not observed and only the ring-chlorinated acid chloride (246) was isolated in 13% yield. A number of analogs were prepared via this reaction <76AHC(19)123). 

A new type of trichlorogermyl group/hydrogen replacement was found in the reaction of trichlorogermane with -thienylacrylic acid (equation 26). 

Eprosartan was developed in 1997 using a different lead-optimization from S-8308. The main structural change was not the extension of the N-benzyl group, but in order to mimic the C-terminal end of angiotensin II the 5-acetic acid group was replaced with an a-thienylacrylic acid and a 4-carboxy-substituent was introduced, as in the case of the above optimization (Fig. 5.7). 

Reactions of Carboxy- and Cyano-thiophens.—/8-Thenoylacrylic acid reacted with pyrrole to give (109) in good yield. The solid-state photo-oligomerization of the 2-thienylacrylic acid derivative (110) has been investigated. Some amides between thiophen-2-carboxylic acid and anthranilic acids have been prepared, in connection with work on their hypoglycaemic activity. ... 

C7H5NOS2, 1,2-Benzodithiol-3-one oxime, 34B, 189 C7Hg02S, trans-p-2-Thienylacrylic acid, 32B, 185 C7Hg03S, 2-Carboxy-3-acetylthiophene, 38B, 351 C7Hg03S, 3-Carboxy-2-acetylthiophene, 38B, 351 C7Hg03S, 3-Carboxy-4-acetylthiophene, 38B, 351 C7HSS4, 1,2,4,5-Benzotetrathiepine, 45B, 369... 

A similar correlation between solid crystal packing and resulting photochemical reactions was documented by Schmidt and coworkers. " It was demonstrated that the arrangement of molecules within their crystal lattice predicts the photoproduct. This was well illustrated with tra s-p-2-thienylacrylic acid. This more stable form, referred to as the g-modification, produced a photopolymer upon radiation. The metastable form, known as the b-form, primarily yielded a dimer with the two molecules forming a cyclobutane ring. The differences in the photoproducts were directly correlated with their crystal packing. 

Block, S., Filippakis, S. E. and Schmidt, G. M. J. Topochemistry. Part XVII. The crystal structures of two modifications of trans-P-2-thienylacrylic acid.. Chem. Soc. B 233-238, 1967. 

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