Halide To alkyl

Reaction of dibenzylamine with ethylene oxide affords the amino alcohol, 82. Treatment of that product with thionyl chloride gives the a-sympathetic blocking agent, dibenamine (83). (Condensation of phenol with propylene chlorohydrin (84) gives the alcohol, 85. Reaction with thionyl chloride affords the chloride (86). Use of the halide to alkylate ethanolamine affords the secondary amine (87). Alkylation of this last with benzyl chloride... 

Alkylation of phenothiazine with l-chloro-2-methyl-3-bromopropane affords the methylated analog (80) of the intermediate above. Use of this halide to alkylate the piperazine... 

The low structural specificity of the antihistamines has already been noted. It is perhaps not too surprising, therefore, to find Lhat attachment of the basic side chain directly onto one of the. iromatic rings affords active compounds. In an unusual reaction reminiscent of the Claisen rearrangement, benzyl chloride affords the substituted phenol, 46, on heating with phenol itself. Alkyl-.ition of 46 with 2-dimethylaminoethyl chloride gives phenyltolox-.imine (47).Alkylation of that same intermediate (46) with 1-bromo-2-chloropropane, leads to 48. Use of that halide to alkyl-,ite piperidine gives the antihistamine, pirexyl (49). ... 

Kamal and Chouhan prepared the TSIL [bmim][SCN] to convert alkyl halides to alkyl thiocyanates. This [bmim][SCN] was prepared by ion exchange of [bmim][Cl] with KSCN in acetone. Alkyl halides were reacted with this TSIL to give quantitative amounts of the corresponding alkyl thiocyanates with high yields. Scheme 31. The product was then easily extracted with ether. 

The characteristics of the addition of HBr to double bonds are similar to those of the addition of HC1. However, in acetic acid 1,2-dimethylcyclohexene gives more anti addition if HBr is the addend.25 Also, as Figure 7.1 shows, when HX is added to a double bond in acetic acid, the ratio of alkyl halide to alkyl acetate increases sharply as the concentration of HBr is increased but is almost independent of the concentration of HC1. Fahey suggests that the much larger acid dissociation constant of HBr (AXd = 103-104) is responsible for both of these facts. Hydrobromic acid acts as a better halide source, and Ad3 addition is favored.26... 

Figure 7.1 Variation in the alkyl halide to alkyl acetate product ratio with HX concentration for reaction in HOAc at 25°C. From R. C. Fahey, C. A. McPherson, and R. A. Smith, J. Amer. Chem. Soc., 96, 4534 (1973). Reprinted by permission of the American Chemical Society.

Lower ratios of amine halide to alkyl halide have been used successfully but with concomitant lower yields of the desired tetramine. Excess diamine is recovered during the work-up procedure and may be used for subsequent preparations, t Large losses may occur if care is not taken to separate all liquid from the solid residue. iThis can be prepared easily and inexpensively in solution from NiCOa and HCIO4. 

Trimethylsilyl azide (TMSN3) is a more easily handled, stable alternative to hydrazoic acid. It has found many uses in organic synthetic applications. Most recently it has been found to readily convert hindered alkyl halides to alkyl azides in the presence of a Lewis acid. Thus, tertiary alkyl azides can be formed from tertiary alkyl chlorides, trimethylsilyl azide and tin tetrachloride. In this work the azides were converted to the benzamides132 (equation 135). Similar conditions were used by Olah and coworkers133 to prepare secondary and tertiary cyclic azides in good yields (equation 136). 

We have seen that most ester condensations use alkoxides to form enolate ions. With simple esters, only a small amount of enolate is formed the equilibrium favors the alkoxide and the ester. The alkoxide often interferes with the desired reaction. For example, if we want an alkyl halide to alkylate an enolate, alkoxide ion in the solution will attack the alkyl halide and form an ether. 

Answer This is an alkylation reaction. In step 1, we are using LDA to form an enolate. And then in step 2, we are using an alkyl halide to alkylate. 

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