Rhodium (Chief Bee)
02-06-03 22:31
No 405212
      Acids to aldehydes using Red-Al & Saccharin  Bookmark   

Reaction of carboxylic acids with saccharin chloride (or reaction of acid chlorides with sodium saccharin) followed by reduction with Red-Al to give the aldehyde, Yields 70-80%. 

../rhodium/pdf /acid2aldehyde.red-al.pdf

Could somebody please type the article and post it below?

Edit: I have removed the above PDF and uploaded the HTML version at ../rhodium/chemistry /redal.saccharin.html
(Hive Bee)
02-07-03 11:47
No 405255
      acid > aldehyde
(Rated as: excellent)


NS Ramegowda, MN Modi, AK Koul, JM Bora, CK Narang and NK Mathur
Department of Chemistry, University of Jodhpur, India

Tetrahedron 29 (1973) 3985-3986

Abstract: 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.

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
 5    N-benzoyl saccharine        benzaldehyde         182(179)       80
 6    N-(o-chlorobenzoyl)         o-chlorobenzaldehyde 210(213)       65
 7    N-(p-chlorobenzoyl)         p-chlorobenzaldehyde 212(214)       72
 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

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)

--- THE END ---

For those who want to try out this article, do not forget benzene is a highly carcinogenic compound! Better use another solvent system...

Abusus non tollit usum
(Chief Bee)
02-07-03 12:18
No 405263
      Kudos  Bookmark   

Wonderful! Great job! Nice typography too, making it a breeze for me to convert the post to a HTML document.
(Hive Bee)
02-07-03 13:37
No 405275
      np  Bookmark   

With pleasure.

For some reason(s) - my current blood EtOH content might be partially responsible - "saccharin" re-triggered one of my old dreams, viz. making TMA-2 (and its analogues) using fructose (I don't remember if it was d or l-fructose) as initial precursor. Under pressure, the fructose was converted to 1,3,4-trihydroxybenzene (I seem to remember ca 50% yield). The latter is an excellent starting key for TMA-2 and its analogues. Doh! I'm getting off-topic... I better get looking for my old refs.

Abusus non tollit usum
(Hive Addict)
02-07-03 14:14
No 405281
      IŽd love to hear more about the ...  Bookmark   

IŽd love to hear more about the 1,3,4-trihydroxybenzene formation.
BTW. Do you really drink solvents? shocked

(Hive Addict)
02-07-03 18:47
No 405335
      damn  Bookmark   

I was afraid this would happen.  Rhodium, check your pm's.  (hey foxy2, better?)
(Hive Addict)
02-07-03 18:50
No 405337
      Cancer  Bookmark   

For those who want to try out this article, do not forget benzene is a highly carcinogenic compound! Better use another solvent system...

Toluene always instead of benzene, unless we are talking reactions of course...

GC_MS: Now that is TYPING! wink And also; how do you menage to make such nice looking tables, you drunk!?

Your tables have always been puzzling me... And please GC_MS, dig up those refs! wink

Accept No Imitations, There Can Only Bee One; www.the-hive.ws
(Hive Bee)
02-07-03 21:36
No 405373
      EtOH  Bookmark   

I checked my urine this noon for EtOH-content (via GC-FID). It was about 1.25 g/L, ca 8 hours after I drank my last glass of beer. Some bees might see that I probably was very drunk last night...

Abusus non tollit usum
(Hive Addict)
02-07-03 21:46
No 405379
      Beer my ass!! You were in the solvent cabinet...  Bookmark   

Beer my ass!! You were in the solvent cabinet again. wink

(Hive Bee)
02-08-03 10:52
No 405569
      b33r  Bookmark   

I use beer as solvent in my organic reactions. Much more OTC then regular denaturated alcohol. Happy now? wink

Abusus non tollit usum