Diethoxymethyl Acetate1

[14036-06-7]  · C7H14O4  · Diethoxymethyl Acetate  · (MW 162.19)

(reactive orthoformic acid derivative in which the acetate group can be easily substituted by a variety of nucleophiles, e.g. alkoxy, amino, thiolo, and carbon nucleophiles1)

Alternate Name: DEMA.

Physical Data: mp 27 °C; bp 70 °C/15 mmHg; d 0.993 g cm-3.

Solubility: sol most common organic solvents.

Form Supplied in: colorless liquid or solid of 99% purity; widely available.

Preparative Method: best prepared from triethyl orthoformate and formic acid/acetic anhydride.2

Handling, Storage, and Precautions: the compound is sensitive to moisture and should be handled and stored under dry conditions. At temperatures above 120 °C it decomposes into ethyl acetate and ethyl formate.

DEMA is often used as a more reactive alternative for Triethyl Orthoformate. In contrast to the latter it reacts under neutral or basic conditions with nucleophiles due to the better leaving ability of the acetoxy group compared to the ethoxy group. The acetate group can be easily exchanged for other carboxylic groups, leading to different diethoxymethyl esters.2 Reactions with alcohols or thiols under basic conditions yield mixed orthoformates (eq 1).1,3

Preparation of the same compounds from triethyl orthoformate needs acid catalysis, which also leads to disproportionation of the formed mixed orthoester. The high reactivity of DEMA with amines is used in the synthesis of heterocyclic ring systems, e.g. formation of purines from vicinal diamines (eq 2).4

Analogous results have been reported for the synthesis of pyrimidines.5 In the older literature, mixtures of triethyl orthoformate and acetic anhydride have been used, from which DEMA is supposed to be formed in situ.1 The same holds for the reaction of acidic methynes with DEMA or triethyl orthoformate/acetic anhydride, leading to acetals or enol ethers (eq 3).

The advantages of the in situ procedures over pure DEMA have not been systematically investigated. The applicability of DEMA in the synthesis of acetals from the reaction with Grignard reagents has been demonstrated,6 and the results compared with those of the related reagent Diethyl Phenyl Orthoformate. It has been demonstrated that, prepared in this way, a-stannyl acetals (eq 4) are useful synthons in further synthesis.

DEMA has also been used for the introduction of an acetoxy group in the synthesis of the related reagent 2-acetoxy-1,3-dioxolane (eq 5).7

Diethoxymethyl formate, which is easily prepared from DEMA,2 has been used in one of the first syntheses of formic anhydride.8

Related Reagents.

Acetic Anhydride; Acetic Formic Anhydride; Diethyl Phenyl Orthoformate; N,N-Dimethylformamide Diethyl Acetal; Triethyl Orthoformate.

1. (a) Simchen, G. MOC 1985, B.E5, 57. (b) DeWolfe, R. H. Carboxylic Orthoacid Derivatives; Organic Chemistry, A Series of Monographs Vol. 14. Academic: New York, 1970. (c) Pindur, U. In The Chemistry of Acid Derivatives, Suppl. B.; Patai, S., Ed.; Wiley: New York, 1992; Vol. 2, Part 2, Chapter 17. (d) Ogliaruso, M. A.; Wolfe, J. F. In Synthesis of Carboxylic Acids, Esters and their Derivatives; Patai, S.; Rappoport, Z., Eds.; Wiley: New York, 1991.
2. Scheeren, J. W.; Stevens, W. RTC 1966, 85, 793.
3. Scheeren, J. W.; Stevens, W. RTC 1969, 88, 897.
4. FF 1967, 1, 243. For some recent applications see: Gaffney, B. L.; Kung, P. P.; Jones, R. A. JACS 1990, 112, 6748. Patil, S. D.; Schneller, S. W. JHC 1991, 28, 823. Harnden, M. R.; Jarvest, R. L. JCS(P1) 1991, 2073. Patil, S. D.; Schneller, S. W.; Hosoya, M.; Snoeck, R.; Andrei, G.; Balzarini, J.; De Clerck, E. JMC 1992, 35, 3372.
5. For recent applications see: Lee, L. F.; Sing, Y. L. JOC 1990, 55, 380. Bigge, C. F.; Wu, J. P.; Drummond, J. R. TL 1991, 32, 7659.
6. Beaudet, I.; Duchene, A.; Parrain, J. L.; Quintard, J. P. JOM 1992, 427, 201.
7. Scheeren, J. W.; Van Der Veek, A. P. M.; Stevens, W. RTC 1969, 88, 195.
8. Schijf, R.; Scheeren, J. W.; Van Es, A.; Stevens, W. RTC 1965, 84, 594.

J. (Hans) W. Scheeren

University of Nijmegen, The Netherlands

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