Alkylating agents selectivity

The hydrogen atom of position 3 of the derivative 18a is expected to display acidic properties. Thus when treated with sodium methoxide in methanol-di, the ester I8a underwent racemization with incorporation of deuterium at position 3. In principle, the carbanion 148, the species formally involved in the foregoing reaction, may isomerize to the enethiolate 149 by a jS-elimination process. There is good evidence (Section V,C,2,b) that such isomerizations do occur and are reversible (Section V,B,4,b). Normally, alkylating agents selectively trap species of type 149 thus compound 150 was isolated when the derivative Ifo was treated with sodium hydride and methyl iodide. However, in the presence of potassium t-butoxide and methyl iodide, the derivative 140c was converted into 151 evidence for the intermolecular nature of the reaction was provided by the observation that the same product was formed when a 1 1 mixture of the derivatives 18c and 140c was treated with the base. ... 

Studying alkylations, we developed a series of selective ionic alkylating agents. Although Meerwein s trialkyloxonium and dialkoxycar-benium salts are widely used as transfer alkylating agents, they lack selectivity and generally are incapable of C-alkylation. 

Tertiary, benzyl, and aHyhc nitro compounds can also be used as Friedel-Crafts alkylating agents eg, reaction of (CH2)3CN02 (2-nitro-2-methyl propane [594-70-7]) with anisole in the presence of SnCl gives 4-/-butylanisole [5396-38-3] (7). SoHd acids, such as perfluorodecanesulfonic acid [335-77-3], and perfluorooctanesulfonic acid [1763-23-1] have been used as catalysts for regio-selective alkylations (8). 

Selective monohalo alkylations were achieved when chlorobromoalkanes such as l-chloro-S-bromo-S-methjIbutane were used as halo alkylating agents (47). The bromine is replaced preferentially ... 

The monoacetate 9a (R1 = Ac) and the diacetate 10a (R1 = R2 = Ac) are obtained by treatment of 8 with acetic anhydride in anhydrous pyridine at room temperature 4 the oxo group in position 5 of 8 is more reactive towards acetylation. Similarly, the S,S-dioxidc of 8 can be converted to the bisacetylated S,5-dioxide of 10a in 78 % yield.74 Methylation of 8 with diazomethane gives 9c (65 % yield), along with 14 % of the 3-methoxy compound 11. Other alkylation agents, such as dimethyl sulfate in the presence of potassium carbonate, selectively give 9c, albeit in lower (30 %) yield.90 The dimethyl enol ether 10c (R1 = R2 = Me) is obtained by a subsequent methylation of 9c (R1 = Me) with dimethyl sulfate and potassium teri-butoxide.90... 

Noncovalent Association of the Alkylating Agent can Direct Reaction to Selected Atoms and Selected Sequences in DNA... 

J. A. Hartley, Selectivity in alkylating agent-DNA interactions, in Molecular Aspects of Anticancer Drug-DNA Interactions Vol. 1 (Eds. S. Neidle, M. Waring), CRC Press, Boca Raton, FL, 1993, 1. 

Alkylation of enamines requires relatively reactive alkylating agents for good results. Methyl iodide, allyl and benzyl halides, a-halo esters, a-halo ethers, and a-halo ketones are the most successful alkylating agents. The use of enamines for selective alkylation has largely been supplanted by the methods for kinetic enolate formation described in Section 1.2. 

There are several means to maximize the yield in the desired monoalkylation product high aromatic/alkylation agent ratio, association of a transalkylation unit to the alkylation unit, and use of a shape selective zeolite as catalyst. 

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