Exhaustive alkylation synthesis

HZ Sommer, HI Lipp, LL Jackson. Alkylation of amines. A general exhaustive alkylation method for the synthesis of quaternary ammonium compounds, (effects of hindrance) J Org Chem 36, 824, 1971. 

Poly(ethylenimine) (PEI) has been examined extensively both in its classical, random branched topology [125] and in its linear form [126]. The various architectural and topological forms of PEI have been reviewed recently [127], Here we describe the first example of this polymer system as an ideal, hyper-branched molecular assembly. Synthesis of a tri-dendron poly(ethyleneimine) dendrimer derived from an ammonia core involved, first the selective alkylation of diethylenetriamine (DETA) with aziridine to produce a symmetrical core cell, namely tris-(-2-aminoethyl)amine. Subsequent exhaustive alkylations of the terminal amino moieties with activated aziridines [2, 127, 128], such as IV-tosyl- or N-mesylaziridine gave very good conversions to the first-generation protected... 

Sommer has described a general exhaustive alkylation procedure for the direct synthesis of quaternary ammonium compounds. As protonation of sterically hindered amines is only slightly affected hysteric hindrance, whereas kinetic nucleophilicity is greatly decreased, the use of a sterically hindered base of greater base strength than the substrate amine will bind up the acid generated on alkylation this system allows quaternization under mild conditions, with the minimum of manipulation. 

The method described in this preparation of mesitoic acid avoids the preparation of bromomesitylene,13 and the yield of acid is essentially the same as that from the two-step synthesis.2-13 This procedure appears to be general and can be used to prepare such acids as a- and /3-naphthoic acids,14 cumenecarboxylic acid, 2,5-dimethylbcnzoic acid, and durenecarboxylic acid. Carboxylic acids could not be obtained from benzothiophene, vera-trole, -dimethoxybenzene, and ferrocene under the conditions of this reaction. Although there has been no exhaustive study, this procedure is probably applicable to a variety of aromatic compounds, especially alkylated aromatics. Aromatic compounds which readily undergo oxidation, e.g., ferrocene, catechol, and hydroquinone, do not lend themselves to this method. 

In CO hydrogenation, the achvity and selechvity to C1-C5 oxygenates over the bimetallic samples are higher than those of the monometallic counterparts [187-190]. Bimetallic catalysts also showed improved activity in the hydroformylation of ethylene compared to either of the monometallic catalysts [191]. The promotion for higher alcohol production is proposed to be associated with the adjacent Ru-Co sites. However, the lack of an exhaustive characterization of catalysts does not allow a clear correlation to be established between the characteristics of the active sites and the catalytic behavior. A formyl species bonded to a Ru-Co bimetallic site has been proposed to be the intermediate in the alcohol synthesis in these systems. A subsequent reaction with an alkyl-surface group would lead to the C2-oxygenate production [187]. 

Any other synthesis that leads to a 2,3-dialkylindole can of course be considered, and several novel reported routes are mentioned later. Vigorous alkylation of a 2-substituted indole can introduce three identical alkyl groups for example, the best route to 1,3,3-triethylFischer s base is exhaustive ethylation of 2-methylin-dole,15 and methylation of 2-phenylindole also introduces three alkyl groups. 

Thermal decomposition of quaternary ammonium salts and bases is most valuable in structural investigations of amines, particularly heterocyclic secondary amines (Hofmann exhaustive methylation). The course of the elimination (A or B) is determined by the nature of the four alkyl groups on the nitrogen atom. The reaction has found little use in the synthesis of pure olefins. The yields are low even when three of the alkyl groups are methyl radicals. Carbon-skeleton rearrangement does not occur. Thus, the only olefin obtained by pyrolysis of pinacolyltri-methylammonium hydroxide, (CHj),CCH(CHj)N(CHj)j OH, is /-butylethylene (50%). ... 

TABLE 2. Synthesis of proton sponges by exhaustive N-alkylation of the corresponding 1,8-diaminonaphthalenes... 

In Figure 7.18, the starting material for the synthesis of patchouli alcohol is the ketone (P20.1). Explain how this can be formed by exhaustive base catalysed alkylation of phenol (Figure P20). 

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