2- -6- t-butyl

Draw the mechanism of the imaginary reverse reaction, the formation of t-butyl chloride from the alcohol. 

This then is the disconnection corresponding to the reaction. It is the thinking device we use to help us work out a synthesis of t-butyl alcohol. We could of course have broken any other bond in the target molecule such as ... 

This will clearly be made somehow by discormections a and b but the order of events is important. We must discoimect first, that is synthesise last, the bond with the wrong orientation - i.e. meta to the t-butyl group. The reaction will then be intramolecular and orientation doesn t matter. This gives us 399B, and 1 show one possible route from that. 

The /-butoxycarbonyl group (Boc, "t-box ) has been eMens vely used in peptide synthesis, and Boc derivatives of many amino acids are commercially available. The customary reagent for the preparation from the amine is t-butyl azidoformate in water, dioxane/water, DMSO, or DMF. The cleavage by acids of medium strength proceeds with concomitant loss of isobutene and carbon dioxide (L.A. Carpino, 1957, 1973 see section 4.1.2.2). 

J-unsaturated ester is formed from a terminal alkyne by the reaction of alkyl formate and oxalate. The linear a, /J-unsaturated ester 5 is obtained from the terminal alkyne using dppb as a ligand by the reaction of alkyl formate under CO pressure. On the other hand, a branehed ester, t-butyl atropate (6), is obtained exclusively by the carbonylation of phenylacetylene in t-BuOH even by using dppb[10]. Reaction of alkynes and oxalate under CO pressure also gives linear a, /J-unsaturated esters 7 and dialkynes. The use of dppb is essen-tial[l 1]. Carbonylation of 1-octyne in the presence of oxalic acid or formic acid using PhiP-dppb (2 I) and Pd on carbon affords the branched q, /J-unsatu-rated acid 8 as the main product. Formic acid is regarded as a source of H and OH in the carboxylic acids[l2]. 

There are two sequences in which the reaction can be carried out. For most anilines the first step is /V-chlorination which can be done with t-butyl hypochlorite[9]. However, for anilines with ER substituents it may be preferable to halogenate the thioester. The halogenation can be done with Cl2[lbl or SOjCljCU]. For some anilines simply adding f-butyl hypochlorite to a mixture of the aniline and thioester is satisfactory (Entries 1, 4, Table 7.6). 

CycJohexyl free radicals, generated by photolysis of t-butyl peroxide in excess cyclohexane, also possess nucleophilic character (410). Their attack on thiazole in neutral medium leads to an increase of the 2-isomer and a decrease of 5-isomer relative to the phenylation reaction, in agreement with the positive charge of the 2-position and the negative charge of the 5-position (6). 

In the series of 2,5-dialkylthiazoles prepared by Poite and Metzger (492,512), the yields decrease from 5-methyl-2-alkylthiazoles (44 to 75%) to 5-t-butyl-2-alkylthiazoles (0 to 3%). 

Relative Rate of SnI Solvolysis of te/t-Butyl Chloride as a Function of Solvent Polarity ... 

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