A NEW SYNTHESIS OF ALDEHYDES FROM ACIDS VIA REDUCTION OF N-ACYL SACCHARINS USING SODIUM DIHYDRO BIS-(2-METHOXY-ETHOXY) ALUMINATENS Ramegowda, MN Modi, AK Koul, JM Bora, CK Narang and NK Mathur
Department of Chemistry, University of Jodhpur, India
Tetrahedron 29 (1973) 3985-3986Abstract: Synthesis of certain aldehydes from the carboxylic acids has been carried by reduction of the corresponding N-acyl saccharins using SDA. The N-acyl saccharins are easily prepared by reaction of an acid with gamma-saccharin chloride, which can be used for the next step of reduction without isolation and purification. This provides a convenient and one step synthesis of aldehydes by combining the two reactions, viz, preparation of the N-acyl compound and its reduction. The method has been successfully applied for the reduction of aliphatic, alicyclic, aromatic and alfa,beta-unsaturated acids to the corresponding aldehydes and the yields obtained are quite satisfactory.
Article: Numerous synthetic routes to aldehydes from carboxylic acid derivatives are known.
1,2 The recent methods of aldehyde synthesis from the acids or their derivatives utilise metal hydride reduction. Normally the metal hydride reduction of acid derivatives, e.g., the esters or acid chlorides gives the corresponding alcohols while the amide derivatives are reduced to amines or alcohols, but during the reduction of tertiary amides and in case of certain phenolic esters, the rupture of -CO-NR2 or -CO-O- bond has frequently been observed, which results in N- or O- deacetylation, respectively. If the hydride is not used in excess, the acyl function can be isolated as the corresponding aldehyde, particularly if the reduction is carried out at a low temperature. A comprehensive survey of such methods of aldehyde synthesis has recently been made by Smith
3 and Weygand
4-6.
In many of these methods, the N-acyl compound is derived from the more acidic R2NH groups such as those in carbazole
7, 3,5-dimethyl pyrazole
8,9, imidazole and pyrrole. This is to be expected because such N-acyl compounds are active trans-acylating reagents and the amine component in such compounds can act as a good leaving group, resulting in easy cleavage of -CO-NR2 bond. The same is true of phenolic esters.
And aldehyde synthesis introduced by Staat
10 involves the reduction of N-acylimidazole. Recently the trans-acylation reactions of N-acylsaccharin were reported from these laboratories
11 and the reactivity of N-acyl saccharin has been found to be comparable to that of N-acyl imidazole. It has now been found that the N-acyl saccharin can be synthesised in one-step from the carboxylic acid and gamme-saccharin chloride which is easily prepared.
9 N-acyl saccharins thys synthesised can be reduced in high yield to the corresponding aldehydes by sodium bis-(2-methoxy-ethoxy) aluminium hydride (SDA). This provides a convenient and one-step synthesis of aldehyde from the carboxylic acid. The main advantage of the proposed method is combining two reactions, i.e., the preparation of N-acyl compound and its reduction in one step. The reductions are successfully carried at O to 5 C whereas in many other cases, temperatures as low as -70 C have to be employed. The method has been successfully applied for the reduction of aliphatic, alicyclic and alfa,beta-unsaturated acids to the corresponding aldehydes.
Experimental:Reagents and material - Sodium bis-(2-methoxy-ethoxy) aluminium hydride (SDA) used in the present investigation was obtained as a 70% benzene solution (supplied by The Institute of Inorganic Synthesis, Czechoslovak Academy of Sciences, Prague), used as such or after proper dilution with dry benzene. 'AnalaR' benzene used as the solvent was dried by distillation over SDA.
Preparation of N-acyl Saccharins -
(a) Via carboxylic acid chloride. A mixture of the acid chloride (1 mol) and sodium salt of saccharin (1.5 mol) was melted together for a few min. The products obtained as such were washed with NaHCO3(aq) and finally recrystallised from ethyl methyl ketone or THF.
(b) From gamma-saccharin chloride. To a soln of gamma-saccharin chloride (1 mol) in methylene chloride was added the carboxylic acid (1 mol) at 0 C.
12 The mixture was kept at this temp for 10 min or such time till the completion of reaction which was ascertained by TLC. Finally the methylene chloride was distilled off and the N-acyl saccharin obtained was subjected to reduction.
Reduction of N-acyl sccharins by SDA. To a suspension of the N-acyl saccharin (1 mol) in dry benzene, was added with stirring, a soln of SDA (0.5 mol) in benzene, in small portions, during 5-10 min at 0-5 C. The stirring was continued at this temp for about 2h, and the product was subsequently decomposed with little water. The benzene layer was separated and the ppt of saccharin and the metal hydroxide was filted off and washed with benzene.
The aqueous layer was extracted several times with benzene and all the benzene extractions were combined and subjected to reduced pressure distillation using rotary flash evaporator. In this manner, the aldehydes were separately collected. The yield of aldehydes was found to be in the range of 70 to 80%. Alternatively the combined benzene solution may be treated with a soln of 2,4-dinitrophenyl hydrazine and the precipitated hydrazones can be weighed. The results obtained by the reduction of various N-acyl saccharins with SDA are given in Table 1.
A controlled experiment between saccharin and SDA showed that saccharin was not reduced by SDA.
Acknowledgements - One of us (AK Kou) is thankful to UGC, New Delhi for the award of Junior Research Fellowhip.
Table 1: # N-acyl saccharin Aldehyde BP (C) Yield (%)
1 N-acetyl saccharin acetaldehyde 18(20) 76
2 N-propyl saccharin propionaldehyde 53(49) 78
3 N-butyryl saccharin butyraldehyde 72(75) 78
4 N-cyclohexanecarbonyl- cyclohexanealdehyde 66(63) 75
saccharin
5 N-benzoyl saccharine benzaldehyde 182(179) 80
6 N-(o-chlorobenzoyl) o-chlorobenzaldehyde 210(213) 65
saccharin
7 N-(p-chlorobenzoyl) p-chlorobenzaldehyde 212(214) 72
saccharin
8 N-(o-toluoyl)saccharin o-tolualdehyde 201(200) 63
9 N-(p-toluoyl)saccharin p-tolualdehyde 206(204) 70
10 N-(p-nitrobenzoyl)saccharin p-nitrobenzaldehyde 103*(106) 75
11 N-cinnamoylsaccharin cinnamaldehyde 253(252) 77
* MP of p-nitrobenzaldehyde
References
1 IT Harrison and S Harrison, Compendium of Organic Synthetic Methods, Wiley-Interscience (1971)
2 IT Harrison, S Harrison, Ibid. (1971)
3 LJ Smith, ER Roger, JACS 73, 4047 (1951)
4 F Weygand, G Eberhardt, Angew Chem 64, 458 (1952)
5 F Weygand, G Eberhardt, H Linden, ibid, 65, 525 (1953)
6 F Weygand, H Linden, ibid 66, 174 (1954)
7 G Wittig, P Hornberger, Ann 577, 11 (1952)
8 W Ried, FJ Koningstein, Angew Chem 70, 165 (1958)
9 E Stephen, H Stephen, J Chem Soc 490 (1957)
10 HA Staab, H Braeunling, Ann 654, 119 (1962)
11 NS Ramegowda, JM Bacchawat, CK Narang, NK Mathur, Indian J Chem 10, 1194 (1972)
12 F Micheel, M Lorenz, Tetrahedron Lett 2119 (1963)
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For those who want to try out this article, do not forget benzene is a highly carcinogenic compound! Better use another solvent system...
