HALOMETHYL THIOPHENES

Whereas 2-hydroxymethylthiophene reacts normally with hydrogen halides to give 2-halomethyl-thiophenes, reaction of 2-hydroxymethylfuran (2-furfuryl alcohol) with hydrochloric acid results in formation of laevulinic acid (350) via the intermediate (349). The conversion of 2-furanacrylic acid... 

The reaction of 3,4-bis(halomethyl)thiophenes with sodium sulfide and primary amines gives l//,3//-thieno[3,4-c]thiophenes (103) and 5,6-dihydro-47/-thieno[3,4-c]pyrroles (104), respectively. Some of the cyclizations are adversely affected by ortho substituents (X) (69JOC333). The method has been used to prepare l,3,4,6-tetrahydrothieno[3,4-c]pyrrole 2,2-dioxides (73JHC785). 

Hydroxy group of 8-hyd oxy-2-cycloalkyl-2,3,4,6,ll,lla-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-diones was alkylated with allyl bromide, 2-(bromodifluoromethyl)pyridines, l-(bromodifluoromethyl)- and l-(bro-momethyl)benzenes, halomethyl derivatives of different heterocycles (pyridine, pyrazine, pyrazole, pyrrole, thiazole, thiophene) in the presence of CS2CO3 or K2CO3 (98MIP7). Hydroxy group of 8-hydroxy-2-cyclopentyl-... 

Storage at ambient temperature may lead to explosively violent decomposition. See other 2-halomethyl-furans or -thiophenes... 

See Other GAS EVOLUTION INCIDENTS, 2-HALOMETHYL-FURANS OR -THIOPHENES... 

See also 2-HALOMETHYL-FURANS OR THIOPHENES, NITROBENZYL COMPOUNDS, a-PHENYLAZO HYDROPEROXIDES... 

These methods are limited in scope. Direct thiation has been reported for the transformation of vicinal diketones to [3,4]-annelated thiophenes <1996CHEC-II(7)49>. Thionations and selenations of vicinal halomethyl ketones with thioacetamide or iV,iV-diethylselenopropionamide as sulfur and selenium donors, respectively, have also been reported <1996CHEC-II(7)49>. In a recent example, thieno[3,4-f]pyrazoles 160 were readily prepared from aryl 5-bromomethyl-l//-l-phenylpyrazole-4-yl ketones 159 by reaction with thioacetamide (Equation 35) <1998JHC71>. Additionally, an example of an amination cyclization by reaction of 161 with benzylamine to afford pyrrolo[3,4-i/ thiazole 162 has been described (Equation 36) <1998JHC71>. 

The material is unstable and gradually decomposes, even when kept cold and dark, with liberation of hydrogen chloride which accelerates the decomposition [1]. If kept in closed containers, the pressure increase may cause an explosion [2]. Amines stabilise the material, which may then be kept cold in a vented container for several months [3]. See other GAS EVOLUTION INCIDENTS, 2-HALOMETHYL-FURANS OR -THIOPHENES... 

Griffing, J. M. et ai, J. Amer. Chem. Soc., 1948, 70, 3417 It polymerises at ambient temperature and must therefore be stored cold. See other 2-HALOMETHYL-FURANS OR -THIOPHENES... 

Thus, halomethyl selenophenes are highly reactive and in their properties closely resemble the corresponding thiophenes. 

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