Reagents Simple Acylating Agents

When Gabriel and Jansen, in 1890, converted (2-aminobenzyl)acetamide (60) to 3,4-dihydro-2-methylquinazoline (62) by heating at 240°C, they initiated the most useful of all reactions for making fused 3,4-dihydropyrimi-dines48 These substances are of considerable interest in themselves but 

When no substituent is required in the 2-position of the product, milder conditions suffice. Thus, the mere reduction of o-nitrobenzylformamide with zinc and hydrochloric acid at 20°C liberated enough energy to give 3,4-dihydroquinazoline directly.49 Again, 2-amino-4,5-methylenedioxo-benzylamine, when refluxed with formic acid and sodium formate for half an hour, yielded 6,7-methylenedioxo-3,4-dihydroquinazoline.50 

2-Acylaminobenzylamines are another source of 3,4-dihydroquinazolines, which they form by heating in the solid state48,49,51 or in the presence of an acid52 (e.g., a mixture of sulfuric acid with acetic anhydride or acetyl chloride for cyclizing 2-acetamidobenzylamine).53,54 

To obtain an alkyl group in the 1-position of the product, 2-benzylamino-benzylamine was refluxed with formic acid for 45 min to yield l-benzyl-1,4-dihydroquinazoline (63) in excellent yield.51 Without such an anchoring 

3-Substituted 3,4-dihydroquinazolines were obtained without difficulty by boiling 2-amino-3-(iV-methyl)benzylamine (64) with formic acid.56 

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A simple approach to kinetic resolution is to use a stoichiometric reagent. In the example shown in Scheme 1.3, an enantioenriched alcohol is obtained from a racemate through the addition of an enantiopure-acylating agent [13]. If 1 equivalent of the reagent were used, a 1 1 mixture of diastereomers would result with no kinetic differentiation. Stoichiometric kinetic resolutions thus necessarily employ a sub-stoichiometric amount of the reagent - in the example shown only 0.1 equivalents is used. This method for the separation of enantiomers is described in detail by Maddani, Fiaud and Kagan in Chapter 2. 

Barton and Crich reported the first examples of the uses of 2-substituted allylic sulfur compounds [53]. Their initial experiments with additions of simple alkyl radicals to allyl sulfides, sulfoxides and sulfones were relatively unsuccessful. This failure was largely due to the fact that the nucleophilic alkyl radicals, which were generated by photolysis of the corresponding Barton ester, underwent addition to a second equivalent of Barton ester faster than they added to the allyl transfer agent. Reactions were much more successful with the electron-deficient acrylate reagent 93 (Fig. 4). Crich was later able to show that this same reagent underwent addition reactions with an acyl radical derived from an acyl phenyl telluride [54]. 

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