Hydroxyl reaction with dimethyl formamide

Hasegawa and Fletcher25,37 studied the reaction of some aldoses, mainly 2-acetamido-2-deoxyaldohexoses, with 2,2-dimethoxypro-pane-N V-dimethylformamide-p-toluenesulfonic acid at 25 and 80°. The products obtained at the two temperatures differed markedly, and, again, lack of activity at the anomeric hydroxyl group in the presence of N,N-dimethylformamide was noted. To account for this phenomenon, it was postulated that the dimethyl acetal ofA/JV-dimethyl-formamide, presumably formed in situ, reacts to afford highly labile (dimethylamino)methylene acetals which may thereby permit insertion of isopropylidene groups in abnormal positions. 

The reaction is carried out by adding the dry peptide (carefully dried in vacuo at 100 C over phosphorus pentoxide) dropwise, to a dispersion of silica particles, in anhydrous A, 7V-dimethyl formamide. The reaction is allowed to proceed under dry nitrogen at about 90°C to 95 C. If the isocyanate reacts with a hydroxyl group on the peptide then a carabamate bond is formed in the manner depicted below. 

Benzylation of eucomin (3) with benzyl bromide and potassium carbonate in dimethyl formamide gives 5,7-di-O-benzyleucomin (43). If acetone is used as solvent additional C-benzylation at C-6 or C-8 takes place (25, 24). Again sodium acetate shows complete selectivity towards the activated hydroxyl at C-7 (64). Similarly 7-0(p-bromophenacyl)euco-mol (32) is isolated from the reaction of eucomol (10) with p-bromo-phenacyl bromide and sodium acetate or pivalate in acetone (74). 

Abstract - This work is concerned with the origin of effects on rate equilibrium processes when reactions are performed in dipolar aprotic media such as dimethyl sulfoxide and dimethyl-formamide compared to typical hydroxylic media. An example of processes studied in our laboratory is the competition between proton abstraction and a-complex (Meisenheimer adduct) formation in the interaction of nitroaromatic compounds with basic systems (e.g. 1,3-dinitrobenzene in DMF-D20-Na0D). Other reactions studied are the base catalyzed isotopic exchange of D2 in aqueous DMSO mixtures, and also isotopic exchange of fluoroform. It has been found possible in certain cases to dissect the initial state and transition state contributions to the reaction rates from the kinetically measured enthalpies of activation and the thermodynamically evaluated enthalpies of transfer of the reactants. This procedure affords insight into transition state properties and behaviour. 

A mixture of 2, 3 -0-isopropylideneuridine, 2-mercaptopyrimidine, and dimethyl-formamide dineopentyl acetal refluxed in benzene under anhydrous conditions -> thioether (Y 73%) refluxed 0.5 hr. with Raney-Ni W4 in ethanol 2, 3 -0-isopropylidene-5 -deoxyuridine (Y 70%). - This reaction affects prim, hydroxyl groups selectively therefore, protection of the functional groups is not required. F. e. s. A. Holy, Tetrah. Let. 1972, 585. 

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