McFadyen-Stevens synthesis

The McFadyen-Stevens synthesis (66. 99) and its Newman-Caflish modification. 

The conversion of esters to hydrazides and of hydrazides to the sulfonyl derivatives occurs in good yield in the McFadyen-Stevens synthesis, but the decomposition of sulfonyl derivatives gives low yields of the desired products, for example, thiazole hydrazide (28) with 10% excess of PhSOjCl in pyridine gave a 75% yield of l-phenylsulfonyl-2-(4-methyl-5-thiazo ecarbonyl)hydrazine (29) (66). The Newman-Caflish modification of the McFadyen-Stevens synthesis gave 37% 4-methyl-5-thiazole-carboxaldehyde (30) (Scheme 27). 

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 Synthesis (McFadyen-Stevens Reduction)... 

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). 

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. ... 

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. 

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-... 

Malonic ester synthesis, 60, 74 Mannich reaction, 157 Markovnikoff addition, 178 anti-, 178, 180 Markovnikoff s rule, 29 McFadyen-Stevens reaction, 50 Michael condensation, 157 Michael reaction, 94... 

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)... 

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