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Synlett 2002(10): 1741-1742
DOI: 10.1055/s-2002-34251
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© Georg Thieme Verlag Stuttgart · New York

N,N-Dimethylformamide Dimethyl Acetal

Davor Kidjemet*
PLIVA d.d, Research Division, Prilaz baruna Filipovica 25,HR-10000 Zagreb, Croatia.
e-Mail: Davor.Kidjemet@pliva.hr;
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Publication History

Publication Date:
23 September 2002 (online)

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Introduction

N,N-Dimethylformamide dimethyl acetal (DMF·DMA), as well as other N,N-dimethylfomamide dialkyl acetals (e.g. ethyl, benyzl, t-butyl), are very useful reagents in organic synthesis. All of them are used in two main categories of reactions, namely alkylation and formylation. The mechanism of these reactions probably includes generation of an oxo-stabilized carbenium ion. [1] [2]

As alkylating agents they have been used in the synthesis of esters from acids, ethers from phenols, and thioethers from aromatic and heterocyclic thiols. As formylating agents, formamide acetals are useful in the synthesis of enaminones from active methylene compounds and amidines from amines and amides. These compounds are found to be useful intermediates in the formation and modification of many heterocyclic [1] and biologically active compounds. [3]

The N,N-dibenzyl formamidine group was also found to be effective as a protecting group for primary amines. It is stable under variety of conditions and can be removed by catalytic hydrogenation. [4] All conversions proceed under mild conditions and in high yields.

Many formamide acetals are comercially available. In addition, they can be prepared by addition of chloroform into a refluxing solution of sodium alkoxide in the appropriate alcohol and the secondary amine. [5]

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