Thiophenes, nitro-, synthesis

Benzo[6]thiophene, 4-N-methylcarbamoyl-biological activity, 4, 913 Benzo[6]thiophene, 2-methyl-3-vinyl-cycloaddition reactions, 4, 795 Benzo[fc]thiophene, 2-( 1 -naphthyl)-synthesis, 4, 915 Benzo[6]thiophene, 2-nitro-reduction, 4, 815 synthesis, 4, 923 Benzo[6]thiophene, 3-nitro-cycloaddition reactions, 4, 789 Benzo[6]thiophene, 4-nitro-synthesis, 4, 923 Benzo[6]thiophene, 5-nitro-synthesis, 4, 923... 

Benzo[b]thiophene-2-carboxylic acid, 5-nitro-synthesis, 4, 923... 

Thiophene, 2-amino-3-cyano-5-phenyl-synthesis, 4, 888-889 Thiophene, 3-amino-4,5-dihydro-cycloaddition reactions, 4, 848 Thiophene, 2-amino-3-ethoxycarbonyl-ring opening, 4, 73 Thiophene, 2-amino-5-methyl-synthesis, 4, 73 Thiophene, 2-anilino-synthesis, 4, 923-924 Thiophene, aryl-synthesis, 4, 836, 914-916 Thiophene, 2-(arylamino)-3-nitro-synthesis, 4, 892 Thiophene, azido-nitrenes, 4, 818-820 reactions, 4, 818-820 thermal fragmentation, 4, 819-820 Thiophene, 3-azido-4-formyl-reactions... 

Thiophene, 3-methyl-4-phenyl-phototranspositions, 4, 743 Thiophene, 2-(methylthio)-3,4-disubstituted synthesis, 4, 876, 931 Thiophene, nitro-... 

Thiophene, 3-nitro-4-(phenylsulfonyl)-cine substitution, 4, 817, 825 Thiophene, oxo-synthesis, 4, 125... 

Substituted nitrothiophenes serve as precursors for a variety of condensed thiophenes. The synthesis of thienopyrroles has been reviewed <85S143>. Treatment of (2-nitro-3-thienyl)methyl phenyl sulfone (497) with diethyl maleate in the presence of K2CO3 and 18-crown-6 gave the thienopyridine A -oxide (498) in 38% yield <92acs689>. The reaction apparently proceeds by Michael addition, followed by elimination of phenylsulfinate and cyclization. The starting material can be prepared by vicarious nucleophilic substitution discussed earlier. 

Ethylene, /3-(dimethylamino)-nitro-in pyrrole synthesis, 4, 334 Ethylene, dithienyl-in photochromic processes, 1, 387 Ethylene, furyl-2-nitro-dipole moments, 4, 555 Ethylene, l-(3-indolyl)-2-(pyridyl)-photocyclization, 4, 285 Ethylene, l-(2-methyl-3-indolyl)-l,2-diphenyl-synthesis, 4, 232 Ethylene, (phenylthio)-photocyclization thiophenes from, 4, 880 Ethylene carbonate C NMR, 6, 754 microwave spectroscopy, 6, 751 photochemical chlorination, 6, 769 synthesis, 6, 780 Ethylene oxide as pharmaceutical, 1, 157 thiophene synthesis from, 4, 899 Ethylene sulfate — see 2,2-dioxide under 1,3,2-Dioxathiolane... 

In this chapter we describe a novel, safe and efficient large-scale synthetic approach to tricycle thienobenzazepines. The key steps in the synthesis include a chemoselective hydrogenation of an aryl-nitro functionality in the presence of a 3-bromo thiophene and a subsequent palladium-catalyzed intramolecular aminocarbonylation telescoped sequentially after simple catalyst and solvent exchange. 

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. 

Direct nitration of dibenzothiophene occurs in the 2-position, while prior oxidation of the sulfur atom to either the sulfoxide or sulfone causes nitration to be directed to the 3-position. These two reactions form the starting point for the synthesis of most of the known derivatives of dibenzothiophene, which normally proceed via the derived amines. This has now been further illustrated by the synthesis of both 1-nitro- and 4-nitrodibenzothiophene from iV -derivatives of 2- and 3-aminodibenzo-thiophene, respectively, as described below. The synthesis of these two compounds thus completes the series of mononitrodibenzothiophenes. Unfortunately hopes of s3mthesizing nitrodibenzothiophenes via the chlorocyclohexanone route have been almost certainly ruled out by the failure to produce 2-nitrodibenzothiophene by this route (Section IV, A). 

Chakrabarti and coworkers at Eli Lilly in the United Kingdom have reported the initial discovery and synthesis of olanzapine (Schemes 5 and,6). The thiophene 22 was synthesized by adding a DMF solution of malononitrile to a mixture of sulfur, propionaldehyde and triethylamine in DMF. The anion of amino thiophene 22 underwent a nucleophilic aromatic substitution with 2-fluoronitrobenzene to provide 23. The nitro group was reduced with stannous chloride and the resulting anihne cyclized with the cyano group to form amidine 24. Finally, a mixture of N-methylpiperazine and 24 were refluxed in DMSO/toluene to afford olanzapine (2). 

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