Semicarbazones addition products

Addition products have been obtained from aminochrome derivatives such as the semicarbazone, with sodium bisulfite. Recently Correia Alves reported the preparation of a compound described as adrenochrome semicarbazone sodium sulfonate (m.p. >300°) by treating a solution of adrenochrome monosemicarbazone (90) in sodium carbonate solution with sulfur dioxide at 40° for several days192 this compound was apparently different from the substance (m.p. 227-228°) obtained in a somewhat similar manner by Iwao193-194 and may be comparable to the compound (83) (m.p. > 300°) previously described in a Belgian patent179 (see Section IV,F). Iwao established the structure of his compound as the sodium salt of epinochrome-3-sulfonic acid monosemicarbazone (93).193... 

The semicarbazone (134) was too water-soluble to isolate readily, but it was possible to isolate other derivatives of the aminochrome-thiol addition products of this type one such compound was the p-nitrophenylhydrazone of the addition product between adrenochrome and )S-mercaptopropionic acid which was readily obtained in pure crystalline form. The structure of this compound (135) was established by consideration of the microanalytical data and spectroscopic (u.v. visible, i.r. and n.m.r) properties. A total of five derivatives of this type have been prepared and fully identified (see Table 63) [249]. 

The experimental procedure to be followed depends upon the products of hydrolysis. If the alcohol and aldehyde are both soluble in water, the reaction product is divided into two parts. One portion is used for the characterisation of the aldehyde by the preparation of a suitable derivative e.g., the 2 4-dinitrophenylhydrazone, semicarbazone or di-medone compound—see Sections 111,70 and 111,74). The other portion is employed for the preparation of a 3 5-dinitrobenzoate, etc. (see Section 111,27) it is advisable first to concentrate the alcohol by dis tillation or to attempt to salt out the alcohol by the addition of solid potassium carbonate. If one of the hydrolysis products is insoluble in the reaction mixture, it is separated and characterised. If both the aldehyde and the alcohol are insoluble, they are removed from the aqueous layer separation is generally most simply effected with sodium bisulphite solution (compare Section Ill,74),but fractional distillation may sometimes be employed. 

Oximes, hydrazines and semicarbazones. The hydrolysis products of these compounds, t.e., aldehydes and ketones, may be sensitive to alkali (this is particularly so for aldehydes) it is best, therefore, to conduct the hydrolysis with strong mineral acid. After hydrolysis the aldehyde or ketone may be isolated by distillation with steam, extraction with ether or, if a solid, by filtration, and then identified. The acid solution may be examined for hydroxylamine or hydrazine or semicarbazide substituted hydrazines of the aromatic series are precipitated as oils or solids upon the addition of alkali. 

Use of nitrous acid to liberate a free keto-acid from its semicarbazone caused formation of hydrogen azide which was co-extracted into ether with the product. Addition of silver nitrate to precipitate the silver salt of the acid also precipitated silver azide, which later exploded on scraping from a sintered disc. The possibility of formation of free hydrogen azide from interaction of nitrous acid and hydrazine or hydroxylamine derivatives is stressed. 

The basic amino group of the 1-position in semicarbazide or thiosemi-carbazide may be used to react by a substitution reaction with activated halides [52], ethers [51], hydroxy [53], phenoxy [54], and amino groups [55] to yield substituted 1-semicarbazides or thiosemicarbazides. In addition, the amino group of the 1-position may add to electron-deficient double bonds [56]. Formaldehyde and other aldehydes may add to all the available free NH groups to give methylol, alkylol, or polymeric products under basic conditions [57]. Aldehydes or ketenes usually give semicarbazone derivatives, and these in turn are used analytically to identify the purity or structure of a known aldehyde [3]. 

Addition-elimination. This mechanism is important for Group 5 nucleophiles, (i.e. ammonia, hydroxylamine, hydrazine, semicarbazide,2,4-dinitrophenylhydrazine) to form their respective products (imines, oximes, hydrazones, semicarbazones, 2,4-dinitrophenylhydrazones respectively). 

In Section 13.1, it was noted that implicit in the theory of kinetic and thermodynamic control is the fact that the kinetic product (Z in Fig. 13.1 and Y in Fig. 13.2), which is produced more rapidly, is also reconverted to starting material more rapidly. The thermodynamic product, on the other hand, being more stable, is not so readily reconverted to starting material. Experimental Procedure E provides tests of the relative stabilities of the two semicarbazone products toward the reverse reaction. The results of these experiments should provide additional evidence as to which of the semicarbazones is the product of kinetic control and which is the product of thermodynamic control. 

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