L-Bromo-3-methylbenzene

Write structures for the following compounds (a) l-bromo-3-methylbenzene, (b) l-chloro-2-propy-Ibenzene, (c) 1,2,4,5-tetramethylbenzene. 

The present method of preparation of 4,4 -dimethyM,l -biphenyl is that described by McKillop, Elsom, and Taylor. It has the particular advantages of high yield and manipulative simplicity and is, moreover, applicable to the synthesis of a variety of symmetrically substituted biaryls. 3,3 - and 4,4 -Disubstituted and 3,3, 4,4 -tetrasubstituted 1,1 -biphenyls are readily prepared, but the reaction fails when applied to the sjmthesis of 2,2 -disubstituted-l,l -biphenyls. The submitters have effected the following conversions by the above procedure (starting aromatic bromide, product biphenyl, % yield) bromobenzene, biphenyl, 85 1 -bromo-4-methoxybenzene, 4,4 -dimethoxy-l, 1 -biphenyl, 99 l-bromo-3-methylbenzene, 3,3 -dimethyl-l,l -biphenyl, 86 4-bromo-1,2-dimethylbenzene, 3,3, 4,4 -tetramethyl-1,1 -biphenyl, 76 l-bromo-4-chlorobenzene, 4,4 -dichloro-l,T-biphenyl, 73 l-bromo-4-fluorobenzene, 4,4 -difluoro-l,l -biphenyl, 73. 

Condensation of l-bromo-2-methoxy-4-methyl benzene (64) with 5,6-dimethoxyaniline acetate (65) in pyridine in the presence of Cu and K2CO3 and subsequent hydrolysis with 20% KOH furnished the di-phenylamine derivative (66) which on treatment with palladium acetate in DMF afforded murrayastine (13). Condensation of l-bromo-3-methoxy-4-methylbenzene (67) with the dimethyl acetal of 6-formyl-5-methoxyaniline acetate (68) furnished the diphenylamine derivative (69) which on hydrolysis and on subsequent cyclisation furnished murray-aline (14). 

For the synthesis of pyrayafoline (41), l-bromo-3-methoxy-4-methylbenzene (67) was condensed with 2,3 [2, 2 dimethyl-A -pyrano-]-aniline acetate (119) to furnish the diphenylamine derivative... 

SrnI processes have been shown to be relevant to the synthesis of simple thianthrenes which is done by irradiating the disodium salt of 4-methylbenzene-1,2-dithiol in the presence of 1,2-bromochlorobenzene (55%) or 1,2-di-iodobenzene (64%). More complex, fused thianthrenes result from l-bromo-2-iodonaphthalene (24%, 2 isomeric products) and 2,3-dichloroquinoxaline (100%). These clearly hold considerable promise for the controlled construction of unsymmetrical thianthrenes (87JOC1089). 

The dihydrooxazol-mediated biaryl coupling of nonracemic 11 with the Grignard reagent derived from l-bromo-2,3,4-trimethoxy-6-methylbenzene yielded (via intermediates of type 12) the two diastereomeric coupling products 13 and 14 in a 6 1 ratio. In this case the relative configuration around the biphenyl axis had to be determined (see p 478)122. 

A kinetic isotope effect, kH/kD = 1.4, has been observed in the bromination of 3-bromo-l,2,4,5-tetramethylbenzene and its 6-deuterated isomer by bromine in nitromethane at 30 °C, and this has been attributed to steric hindrance to the electrophile causing kLx to become significant relative to k 2 (see p. 8)268. A more extensive subsequent investigation304 of the isotope effects obtained for reaction in acetic acid and in nitromethane (in parentheses) revealed the following values mesitylene, 1.1 pentamethylbenzene 1.2 3-methoxy-1,2,4,5-tetramethyl-benzene 1.5 5-t-butyl-1,2,3-trimethylbenzene 1.6 (2.7) 3-bromo-1,2,4,5-tetra-methylbenzene 1.4 and for 1,3,5-tri-f-butylbenzene in acetic acid-dioxan, with silver ion catalyst, kH/kD = 3.6. All of these isotope effects are obtained with hindered compounds, and the larger the steric hindrance, the greater the isotope... 

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