Alkylation of the Alpha Position

As a result, the product of a reductive amination must have at least one proton at the alpha position. In the case of tri-ferf-butyl amine, there are three alpha positions, and none of them bears a proton. Each of the alpha positions has three alkyl groups and no protons. 

The lack of clear-cut hallucinogen-type activity for the 2-aminotetralins could be explained in several ways. The known deleterious effect of molecular bulk in the alpha-position would seem to direct attention to the steric effect of the reduced ring of the tetralins as detrimental to activity. In 18b, however, it has been noted (156) that the 5-methoxy group is forced out of plane by the adjacent 6-methyl and 4-methylene groups. The importance to activity of maintaining the methoxy groups coplanar with the aromatic ring has been emphasized earlier. Both substituent orientation and N-alkylation must also be important to activity, and it may not be realistic to make direct comparisons between the phenethyl-amines and the 2-aminotetralins. 

Hie mechanism by which the mixed function oxidase converts a nitrosamine into a carcinogenic compound is not clearly understood (]5). Hiese enzymic oxidations can occur at the alpha, beta, gamma, or omega position of an alkyl chain attached to the nitrosamine function. Regardless of whether or not these other oxidations are significant in carcinogenicity, it has been dorvon-strated that hydroxylation at the alpha position does indeed produce a carcinogen (33). Hie discussion which follows will be limited to those factors relative to oxidation at the a-position. 

Shono and others have shown that electrochemical oxidation of amides in nucleophilic media results in incorporation of the nucleophile into the alpha-position of the N-alkyl group via an intermediate iminium species (equation 36). This so-called anodic alpha-functionalization reaction has been shown to be of considerable synthetic value. The reaction has been extensively reviewed98. 

Similar to these results, 2-alkyl-2H-tetrazoles substituted at the 5-position leads to deprotonation-silylation on the alpha position of the alkyl chain on the nitrogen.158... 

The introduction of an alkyl substituent at the alpha position in relation to the aldehyde group causes a decrease in odour intensity. 

Earlier, (2) PMCA, -(CH2-C(C1)C02CH3 was reported to plasma etch at a rate greater than 1.8X Si02> and this was attributed to the weak C-Cl bond. PTCEMA has a PE etch rate ratio of 2.3, thus, the presence of the weak C-Cl bond at either the alpha-position or on the ester alkyl group apparently enhances the PE decomposition of these resists. To further study this phenomenona, the obvious system with both alpha-Cl and the trichloroethyl ester group, PTCECA, was synthesized and studied. As predicted, (see Table I) PTCECA and the 29/71 TCECA/MMA copolymer both etch faster than PMMA reference. These values are significantly larger than the desired less than one value. EBR-9, the Toray Japanese E-beam resist, is structurally similar to... 

Addition of small amounts of tertiary amines to benzophenone-type initiators was reported by Sander et al. to produce dramatic enhancement of initiating efficiency. This effect was determined to be caused not only by the good hydrogen bonding properties of the alkyl groups in the alpha position to nitrogen, but also by... 

The best known of these is the ozonation of tertiary amines to amine oxides (II) (i). Henbest and Stratford (11) and Shulman (17) have shown that competing with this is an ozone attack on the alpha position of an alkyl side chain to produce various decomposition products of III. Henbest (11) showed that amine oxide formation is favored in chloroform and methanol, while side chain oxidation is predominant in hydrocarbon solvents. Also of considerable interest are the reported conversions, during ozonation, of phenylenediamines to Wursters salts (VII) (8, 14), of liquid ammonia to ammonium ozonate (VA) at a low temperature 18), and of amines to amine hydrochlorides (VB) in chlorinated hydrocarbon solvents 17, 19), Finally, an early report states that azobenzene and quinone are obtained upon ozonation of aniline (15). 

The dienophile must be a five-membered maleimidyl ring with an unsubstituted reactive double bond. Substituents would again collide with the walls of the catalytic pocket. A hydrophobic side chain (alkyl or aryl) makes a major contribution to RNA binding. Branching is not allowed at the alpha position (next to the maleimide ring), due to steric clash with the walls. The ribozyme distinguishes between different enantiomers of chiral substrates and accelerates cycloadditions with both enantio- and diastereoselectivity. 

Reaction of diorganocuprates with a,a -dibromo ketones provides a new method for the a-alkylation of a ketone a nucleophilic attack of the cuprate on the intermediary cyclopropanones could explain the reaction (Posner and Sterling, 1973 Posner et al., 1973). The cyclopropyl group can be introduced at the alpha position of ketones as well (Carlson and Mardis, 1975). 

Benzimidazole Derivatives - The activity of hydroxy benzyl benzimidazole (HBB) against picornaviruses has been a stimulus to continued study of its derivatives. 2-(alpha-Amino benzyl)benzimldazole (ABB) and 1-phenyl ABB were significantly effective in reducing cytopathic effect of ECHO-12 virus at nontoxic concentrations. Alkylation or acetylation of the amino function resulted in loss of antiviral activity. The presence of a 5- or 1-methyl group in the N-methylamino series Increased the activity against ECHO-12. The addition of a phenyl substituent in the 1-position of the alpha nethoxy and alpha-amino derivatives of HBB also Increased the activity against the ECHO viruses. 

Aldehydes that have available only one hydrogen in the alpha position, such as the a-alkyl aldehydes (—CHR—CHO), are less acidic than those containing a —CH2— group in the alpha position. This is due to the electron-release effect of the alkyl group which displaces the C—electron pair nearer to the proton and makes the proton removal by the basic catalyst more difficult. Aldolization of such aldehydes would, therefore, require strongly basic catalysts. 

Olefin formation also occurs when the alpha carbon (the one attached to -X the beta carbon is one position removed from alpha) is a secondary or tertiary alkyl carbon and more especially when an alpha-phenyl or alpha-vinyl group is present. 83 Whereas these olefin-forming reactions frequently do not require the presence of an added base, some reactions are accelerated by a base. The latter base-accelerated reactions came to be designated E2, in contrast to El reactions.84... 

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