2- Methylthiophene, reaction with

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Bromomethyl-5-methylthiophene gives normal displacement products with amines but it is isomerized on attempted reaction with copper(I) cyanide (Scheme 59) 48MI30200. Whereas 2-hydroxymethylthiophene reacts normally with hydrogen halides to give 2-halomethylthiophenes, reaction of 2-hydroxymethylfuran (2-furfuryl alcohol) with hydrochloric acid results in formation of laevulinic acid (151). 2-Furfuryl alcohol derivatives are... 

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

Reactions with other nucleophiles follow a similar mechanism. For the reaction of Cl with poly(3-methylthiophene) in acetonitrile, the reaction stops at structure 5 (Scheme 2).128 A fully conjugated, Cl-substi-tuted product 6 can subsequently be obtained by electrochemical or chemical dehydrogenation.128 With Br and alcohols, the overoxidation... 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

Substituted 3-hydroxythiophenes are convenient starting-points for the synthesis of the thieno[3,2-Mthiophene system. Shvedov et obtained 50% of 3-chloro-3-ethoxycarbonyl-5-methylthiophene-2-aldehyde (110) from 3-ethoxycarbonyl-4-hydroxy-2-methylthiophene (109) by Vilsmeier formylation at 100°. Reaction with thioglycolic ter formed 3-ethoxycarbonyl-5-methoxycarbonyl-2-methylthieno[3,2-6]-thiophene (111) [. (36)]. 

Bromomethyl-5-methylthiophene gives normal displacement products with amines but it is isomerized on attempted reaction with copper cyanide (347 — 348) (48MI30200). 

Thienylsodium has been prepared from thiophene by treatment with bromobenzene and sodium amalgam (63AHC(l)l). 2-Methylthiophene has also been metallated at position 5 with n-butylpotassium and n-butylcaesium subsequent reaction with C02 gave the carboxylic acid (75BSF1302). 

Marino and Linda130 have measured the relative rates of 2-chloro-thiophene, thiophene, and 2-methylthiophene in the reaction with acetic anhydride and tin tetrachloride in dichloroethane. Additional measurements on two other thiophene derivatives have been made... 

The photochemical substitution of some iodo substituted pyrroles 1446 in the presence of an aromatic compound (benzene, w-xylene, thiophene, 2-chlorothiophene, 2-methylthiophene) varies with the structure of the pyrrole and reaction conditions and gives the corresponding aryl derivatives 1447 and/or dehalogenated product 1448 (Equation 299) <1997J(P1)2369>. 

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