N-Phenyltrimethylacetimidoyl Chloride1

[50993-08-3]  · C11H14ClN  · N-Phenyltrimethylacetimidoyl Chloride  · (MW 195.71)

(strong iminating agent, used in forming imines2 and amidines,3 and in peptide synthesis1,4)

Physical Data: bp 112 °C/13 mmHg.

Solubility: sol most organic solvents.

Form Supplied in: liquid; must be synthesized.

Preparative Method: the amide precursor (1) is treated with a chlorinating agent such as Phosphorus(V) Chloride1 or Thionyl Chloride3 (eq 1).

Purification: redistill under reduced pressure.5

Handling, Storage, and Precautions: irritant and moisture sensitive. Incompatible with strong bases (see Aldrich safety index for trimethylacetyl chloride).6

Addition-Elimination Reactions.

Most reactions of N-phenyltrimethylacetimidoyl chloride involve an addition-elimination reaction (similar to the reactions of the oxa analogs, the acid chlorides) with a C-,7 O-,1 N-,8 P-,9 or As-centered10 nucleophile. However, the imine products (2) can isomerize, the double bond shifting to give enamine derivatives (3) (eq 2).

Cyclizations.

Several N-, P-, and As-containing heterocyclic compounds have been synthesized using N-phenyltrimethylacetimidoyl chloride (eq 3).11,12

Peptide Synthesis.

N-Phenyltrimethylacetimidoyl chloride was initially used to activate the carboxylic acid group on N-tosylalanine (4) to form peptide links with amines (eq 4).1


1. Cramer, F.; Baer, K. CB 1960, 93, 1231.
2. Tanaka, M.; Kobayashi, T. S 1985, 967.
3. Paul, H.; Wolf, U.; Rund, M.; Henning, M.; Paul, L. East Ger. Patent 151 447 (CA 1982, 96, 180 997u).
4. Fieser, L. F.; Feiser, M. FF 1967, 1, 854.
5. Harwood, L. M.; Moody, C. J. Experimental Organic Chemistry; Blackwell: Oxford, 1989; p 147.
6. The Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, WI, 1987; Vol. 2, p 3479C.
7. Knorr, R.; Weiss, A. CB 1982, 115, 139 (CA 1982, 96, 162 225m).
8. Lunazzi, L.; Macciantelli, D.; Tassi, D.; Dondoni, A. JCS(P2) 1980, 717.
9. Issleib, K.; Schmidt, H.; Meyer, H. JOM 1978, 160, 47 (CA 1979, 90, 87 572t).
10. Herzog, S. ZC 1978, 18, 452 (CA 1979, 90, 137 933j).
11. Heinke, J.; Tzschach, A. PS 1985, 25, 345 (CA 1987, 106, 18 694w).
12. Heinke, J.; Tzschach, A. JOM 1978, 154, 1 (CA 1978, 89, 129 616x).

Richard A. Ewin

King's College London, UK



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