McFadyen-Stevens aldehyde

McFadyen-Stevens Aldehyde Synthesis (McFadyen-Stevens Reduction)... 

The McFadyen-Stevens aldehyde synthesis - is based on the reaction shown in Scheme 13, in which arenesulfonylhydrazides (40) are decomposed to aldehydes by treatment with base. It is generally presumed that the acylimides (41) are intermediates in the procedure. The arenesulfonylhydrazides can be synthesized either from acid hydrazides and arenesulfonyl chlorides or from acyl chlorides and arene-sulfonylhydrazines. The latter method is somewhat more common in recent work and is reported to give superior yields. ... 

McFadyen-Stevens aldehyde synthesis.1 Use of this hydrazine in place of p-toluenesulfonylhydrazine for the McFadyen-Stevens synthesis of aromatic aldehydes has the advantage that decomposition of the intermediate acyl derivatives proceeds under mild conditions (K2C03 in refluxing CH3OH) however yields are unsatisfactory unless hydrazine is added. 

McFADYEN-STEVENS ALDEHYDE S YNTHESIS 2,4,6-Triisopropylben-zene-sulfonylhydrazine. 

There has been considerable interest in the preparation of 5-oxo-3-pyrazolin-4-carboxaldehydes (listed in Table XXXI) because of their close relationship to antipyrine (2,3-dimethyl-l-phenyl-3-pyrazolin-5-one). The most frequently used preparation of these compounds has already been mentioned (eq. 135, p. 54). This consists of treating the condensation products of 3-pyrazoIin-5-ones and chloral with base.107,196,889,893,896,901,1190 The McFadyen-Stevens aldehyde synthesis has been applied to the preparation of both 5-oxo-3-pyrazolin-3-carboxaldehydes698 and -4-carboxaldehydes.204,892,1634 This is illustrated in eq. 220. The final step is usually carried out in glycerol at... 

Improved McFadyen-Stevens aldehyde synthesis— tion by solid surfaces s. 13, 139 -Catalysis of gas evolu-... 

Glass powder sodium carbonate McFadyen-Stevens aldehyde synthesis s. 13, 139 aliphatic aldehydes s. M. Sprecher, M. Feldkimel, and M. Wilchek, J. Org. Chem. 26, 3664 (1961)... 

A.ldehyde Syntheses. Aromatic (Ar) carboxylic acids are reduced to the corresponding aldehydes by a sequence of steps known as the McFadyen-Stevens reaction. The acid is converted to the hydrazide, derivatized with benzenesulfonylchloride, then decomposed to the aldehyde in hot glycol in the presence of a base ... 

McFADYEN - STEVENS Ester Reduction Reduction of esters to aldehyde via hydrazides. 

Aldehydes have also been obtained by lithium trialkoxyaluminum hydride reduction of 5-nitriles or 5-acid chlorides, and, as the thio-semicarbazones, by the McFadyen-Stevens reaction in surprisingly good yields (50-60%) considering the severity of the reaction conditions. ... 

Acyl sulfonylhydrazides (117) are cleaved with base to give aldehydes. This is known as the McFadyen-Stevens reduction and is applicable only to aromatic aldehydes or aliphatic aldehydes with no a hydrogen. " RCON=NH (see 10-87) has been proposed as an intermediate in this reaction. " °... 

The hydrazide of 2,2-diphenyl-3-hydroxypropanoic acid was reduced with lithium aluminum hydride in 7V-ethylmorpholine at 100° to 3-amino-2,2-di-phenylpropanol in 72.5% yield [1145], Much more useful is reduction of N-arenesulfonylhydrazides of acids to aldehydes McFadyen-Stevens reduction) [284, 285] based on an alkali-catalyzed thermal decomposition according to Scheme 174. 

In the McFadyen-Stevens reaction, microwave irradiation has also been employed to convert carboxylic acids to aldehydes via the p-toluenesulphonyl hydrazides65. The p-toluenesulphonyl hydrazide is mixed with sodium carbonate, glass powder and ethylene glycol, and pre-irradiated at 150 W for a few minutes before the actual reaction conditions were applied. The reaction was successfully used in the synthesis of the alkaloid Nauclefidine (Scheme 4.40). 

As mentioned above, there are two particular types of amide which can be induced to decompose to aldehydes without requiring reducing agents. They are the Reissert compounds, to be discussed first, and the sulfonylhydrazides involved in the McFadyen-Stevens method, to be discussed second. 

In the classical McFadyen-Stevens method, the Ar group in (40) is generally phenyl or p-tolyl and the conditions for the decomposition are sodium or potassium carbonate in ethylene glycol at 160 °C for ca. 2 min. This procedure is suitable for the synthesis of aromatic aldehydes, and appears to have been quite widely used. Table 10 shows a few examples many more are tabulated elsewhere. It can be seen that the best yields are obtained with electron rich aromatic nuclei. 

Finally, Nair and Schechter developed a version of the McFadyen-Stevens which does appear to be genuinely useful for aliphatic aldehydes, provided that they are reasonably volatile. The salts (42) are produced from the corresponding tosylhydrazides by treatment with NaOMe/MeOH followed by evaporation, and are then heated to 140-155 °C under a vacuum. The product aldehydes RCHO are collected in a cold trap. The method was used for butanal (68% yield), 2-methylpropanal (71% yield), 3-phe-nylpropanal (85% yield) and 10-undecenal (60% yield). Yields were also good for simple aromatic aldehydes. 

McFadyen-Stevens reaction. Base-catalyzed thermal decomposition of aroylbenzenesulfo-nylhydrazines to aldehydes. 

Mit Hilfe der Kurzzeitpyrolyse gelingt es, die McFadyen-Stevens Reaktion auch auf enoli-sierbare Aldehyde auszudehnen. Trotz der sehr kurzzeitigen thermischen Belastung ent-steht neben den Aldehyden in 60-70%iger Ausbeute auch etwa 10-20% an Alkohol und Carbonsaure268. 

The use of 2,4,6-tri-isopropylbenzenesulphonylhydrazides (in place of the tosylhydrazide) allows milder conditions to be used for the preparation of aromatic aldehydes by the McFadyen-Stevens reaction. Addition of hydrazine hydrate and traces of cupric sulphate suppresses formation of aromatic ester and alcohol by-products. Reduction of oxazolinium salts by sodium borohydride, as part of the well known sequence for the conversion of carboxylic acids into aldehydes, can lead to ring cleavage to form amino-alcohols. It is now reported that over-reduction is much less marked if potassium tri-s-butylborohydride is used as reducing agent (Scheme 2) ... 

The amides and hydrazides of pyridine-carboxylic acids arc of some importance, though their chemistry is not marked by unusual properties. Nicotinamide is, of course, an important compound, and isonicotinic acid hydrazide (isoniazid) is an antitubercular drug. Substituted derivatives are used as antidepressants. In general, however, these compounds show normal chemical behaviour. The amides undergo hydrolysis, dehydration and Hofmann bromination without difficulty. Their reduction has been much studied as a route to pyridine aldehydes. The Sonn-Muller reduction is not very satisfactory in this series, but the McFadyen-Stevens reaction is useful . Nicotinic acid diethylamide gives only poor yields of the aldehyde upon reduction with lithium aluminium hydride, but yields from the methyl-phenylamide are high. Most satisfactory is the reduction of nicotinic acid dimethylamide with lithium diethoxyaluminium hydride . 

Vacuum pyrolysis of sodium (or lithium) salts of l-acyl-2-p-tosylhydrazines realizes a simple method for the preparation of aldehydes and represents a modification of the McFadyen-Stevens procedure that is applicable to base-sensitive aldehydes [equation (10)]/°... 

The Darzens reaction and the McFadyen-Stevens reaction are also useful aldehyde syntheses involving elimination reactions. 

McFadyen and Stevens (cf. Bayer344h) obtained aldehydes from the corresponding carboxylic acids in yields of up to 60% by intramolecular disproportionation of aromatic and heterocyclic l-acyl-2-(benzenesulfonyl)hydrazines induced by an alkali carbonate in ethylene glycol at 160° but this method fails for aliphatic and, / -unsaturated carboxylic acids. 

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