Succindialdehyde

[638-37-9]  · C4H6O2  · Succindialdehyde  · (MW 86.10)

(useful annulating reagent for constructing heterocycles)

Alternate Name: butanedial.

Physical Data: oil, bp 62 °C/14 mmHg.

Solubility: v sol water, alcohol, ether.

Preparative Methods: easily made by acidic hydrolysis of its stable, commercially available synthetic equivalent 2,5-Dimethoxytetrahydrofuran (or its diethoxy analog), followed by extraction with ether and distillation (eq 1).1

Handling, Storage, and Precautions: succindialdehyde rapidly polymerizes and has to be used immediately after distillation. Use in a fume hood.

Annulations.

Succindialdehyde is largely used as an annulating agent in the synthesis of pyrrole and pyrrolidine derivatives. Use of 2,5-dimethoxytetrahydrofuran as a precursor of the dialdehyde may be preferred in some instances. A familiar example is the Robinson-Schöpf cyclization (eq 2)2 (for similar reactions see also Glutaraldehyde).

Using the same methodology, 2,5-dicyanopyrrolidines can be prepared with cyanide as nucleophile (eq 3); in this example, succindialdehyde is used as its bis-sodium bisulfite adduct.3

Pyrrolidines are formed by reductive alkylation (eq 4),4 whereas in the absence of any nucleophilic reagent the double condensation of succindialdehyde with a primary amine gives a pyrrole (eq 5).5

Succindialdehyde can also be considered as a linear C4 unit useful in the synthesis of natural products. It has been used as starting material in the synthesis of squalene;6 the first step consists of the addition of a Grignard reagent to both aldehyde functions (eq 6).

The diol thus obtained can be cyclized to give a 2,5-dialkyltetrahydrofuran, as in the example (eq 7) using Mitsunobu conditions.7

Succindialdehyde has also proved useful in the synthesis of the anthracycline skeleton (eq 8) via two aldol-type reactions.8

A formal phenyl homologation can be achieved by the double aldol condensation of phthalaldehyde with succindialdehyde. In this example, succindialdehyde is generated in situ from 2,5-dimethoxytetrahydrofuran (eq 9).9

Related Reagents.

Diethyl Succinate; Malondialdehyde.


1. Fakstorp, J.; Raleigh, D.; Schniepp, L. E. JACS 1950, 72, 869.
2. (a) Robinson, R. JCS 1917, 111, 762. (b) Schöpf, C.; Lehmann, G. LA 1935, 518, 1.
3. Takahashi, K.; Saitoh, H.; Ogura, K.; Iida, H. H 1986, 24, 2905.
4. Costello, G. F.; James, R.; Shaw, J. S.; Slater, A. M.; Stutchbury, N. C. J. JMC 1991, 34, 181.
5. (a) Hinshaw, J. C. JOC 1975, 40, 47. (b) Jacobi, P. A.; Buddhu, S. C. TL 1988, 29, 4823.
6. Faulkner, D. J.; Petersen, M. R. JACS 1973, 95, 553.
7. Chiarino, D.; Fantucci, M. JHC 1991, 28, 1705.
8. Morris, M. J.; Brown, J. R. TL 1978, 2937.
9. Mallouli, A.; Lepage, Y. S 1980, 689.

Henri-Philippe Husson

Université René Descartes, Paris, France

Jacques Royer

CNRS, Gif-sur-Yvette, France



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.