Aralkyl groups

Substitution in position 4 displays a more complex influence. Cyclization of the 4-methyl- and 4-ethyl-thiosemicarbazones of phenylpyruvic acid and of the 4-methylthiosemicarbazone of phenyl-glyoxylic acid (103) was readily achieved (104), whereas it was not possible to cyclize the analogous 4-methyl derivatives of pyruvic and glyoxylic acids. It thus appears that cyclization is hindered by substitution in position 4 and that this unfavorable effect can be partly relieved by the known favorable effect of an aryl or aralkyl group in the a-position. 

Sydnonimines with alkylamine substituents at position N3 were shown to be considerably more potent donors of nitric oxide compared with analogs having alkyl or aralkyl groups at the same position <2004RCB2840>. 

At 30°C. both ki and k2 increase with increasing size of the terf-alkyl and f erf-aralkyl groups. Apparently, the elimination of oxygen from the presumed tetroxide intermediate is accelerated by an increase in the size... 

The nature of the substituent R, an alkyl, substituted aryl, or aralkyl group, is limited by the availability of the open-chain N-substituted 3-aroyl-propionamides (52). 

Eaborn et al.23 26 have studied the cleavage of a number of aralkyl groups from silicon, germanium, and tin under the influence of aqueous or aqueous-methanolic alkali. The cleavages proceed by formation of a carbanion, the latter then reacting with the solvent as in reactions (23) and (24), where OY may be OH- or OMe". 

The expected importance of the Aralkyl groups in 28a for the nonplanarity is confirmed by an X-ray crystallographic study by Huang and coworkers83. A number of N-unsubstituted analogues were found to be nearly planar with twist angles of 3.6°, 8.8° and 18.1° and C1==C2 bond lengths of 138.0, 139.5 and 138.8 pm, respectively. 

Benzimidazoles, too, are readily alkylated either in neutral or basic medium. As with the uncondensed compounds, the former conditions are complicated by salt formation, but to a lesser extent since benzimidazoles are less basic. It is often valuable to vary the initial amounts of alkali and alkyl halide in order to improve yields. The best yields of 1-alkylbenzimidazole (76-83% for primary and 50-60% for secondary alkyl and aralkyl bromides) result with two moles of bromide and 1.5 moles of alkali per mole of benzimidazole (66RCRI22). There is severe steric hindrance to the alkylation of 2-arylben-zimidazoles in alkaline medium, but reactions with the silver salts seem more successful. The rapid and almost quantitative reaction between a benzimidazole and dimethylphenyl-alkylammonium chlorides in aqueous sodium hydroxide provides a very convenient method of introducing a primary aralkyl group (benzyl, a-naphthylmethyl). There has been little systematic study of the dkylation of unsymmetrical benzimidazoles, though much the same criteria should apply as in the uncondensed compounds. In this respect the observation that 1-bromopropane reacts with the anion of 2,6-dimethyl-4-nitrobenzimidazole to give... 

X-ray analysis of an optically active oxaziridine substituted at nitrogen with the 1-phenylethyl group of known configuration led to the absolute configuration (+)-(2/ ,3/ )-2-(S-l-phenylethyl)-3-(p-bromophenyl)oxaziridine of the dextrorotatory compound as expected, C-aryl and Aralkyl groups were trans to each other (79MI50800). 

The parent, 8-azapurine, has been made only by nitrosation of 4,5-di-aminopyrimidine, which is an item of commerce. - - The 7- and 8-alkyl derivatives of 8-azapurine, whether with or without further substituents, require 1,2,3-triazole starting materials (Section IV,B), of which the best source is Hoover and Day s historic condensation of benzyl azide with ethyl cyanoacetate or (better) cyanoacetamide. An 8-aralkyl group has been introduced similarly. In favorable cases, an 8-aryl group can be derived from the action of a benzenediazonium chloride on a pyrimidine that bears enough electron-releasing substituents to activate the 5 position (the Benson synthesis Section IV,A). 

As indicated in Table 22-2. replacement of the A/-mcthyl group in morphine by larger alkyl groups not only lowers analgesic activity, but also confers morphine-antagonistic properties on the molecule (discussed below). In direct contrast to this effect, the A7-phenethyl derivative has 14 times the analgesic activity of morphine. This enhancement of activity by )V-aralkyl groups has wide application, as is shown below. 

Insertion of an aralkyl group into the exocyclic bond at phosphorus in 2-trimethyl-silyloxy-l,3,2-dioxaphospholans and related compounds (47) occurs when they are treated with benzaldehyde under surprisingly mild conditions. ... 

Further reaction of diaziridines is responsible for the formation of bicyclic compounds 122a-c from aldehydes, chloramine and ammonia. The isomers 122a and 122b (R = various alkyl, aryl, and aralkyl groups) are obtained in a kinetically controlled reaction work-up in the presence of ammonium chloride yields an additional isomer 122c as a result of thermodynamic control. 

The addition of alkyl or aryl (or aralkyl) groups to DNA occurs mostly as a result of exposure to exogenous compounds that occur in cigarette smoke, chemotherapeutic agents, and industrial chemicals [135, 136]. All four bases are subject to alkylation, but the N7 position of guanine is by far the most susceptible to attack... 

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