With Semicarbazones

When tellurium dioxide, lithium bromide, and the semicarbazone of methyl phenyl ketone reacted in acetic acid, 6-hromobenzotellurophene was isolated in 9% yield.  

Semicarbazones of other ketones did not react similarly to produce benzotellurophenes. Selenium dioxide is known to convert certain semicarbazones to acetylenes . Tellurium dioxide is expected to elfect a similar conversion. However the 3-bromobenzotellurophene would be the expected product from the reaction of phenylacetylene and a tellurium (IV) bromide acetate. 

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With semicarbazones of lower a-keto acids the reaction proceeds with some difficulty or not at all. Thus, the semicarbazones of pyruvic acid cannot be cyclized and that of glyoxylic acid is predominantly hydrolyzed so that the yield of the cyclization product is only 20-25%. ° This reaction was used in work with a different object, for preparing 6-azauracil, for the first time. 

The mixed chloroacetic-acetic anhydride (538) with semicarbazones of aliphatic aldehydes or ketones (539) affords compounds (540) which cyclize to the 1,2,4-triazinium salts (541) (73ZOR834). 

The reaction of I If(OPr )4 with semicarbazones was proposed to give five-coordinate complexes, in which the ligand acts in a tridentate fashion. However, this was not unambiguously confirmed.740... 

Selenium dioxide reacts with semicarbazones to give selenadiazoles, the thermo-... 

NH2-C0-NH NH2,CH5N30. Colourless crystalline substance m.p. 96" C. Prepared by the electrolytic reduction of nitrourea in 20% sulphuric acid at 10 "C. Forms crystalline salts with acids. Reacts with aldehydes and ketones to give semicarbazones. Used for the isolation and identification of aldehydes and ketones. 

Aldehydes and ketones may frequently be identified by their semicarbazones, obtained by direct condensation with semicarbazide (or amino-urea), NH,NHCONH a compound which is a monacidic base and usually available as its monohydrochloride, NHjCONHNH, HCl. Semicarbazones are particularly useful for identification of con jounds (such as acetophenone) of which the oxime is too soluble to be readily isolated and the phenylhydrazone is unstable moreover, the high nitrogen content of semicarbazones enables very small quantities to be accurately analysed and so identified. The general conditions for the formation of semicarbazones are very similar to those for oximes and phenylhydrazones (pp. 93, 229) the free base must of course be liberated from its salts by the addition of sodium acetate. 

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. 

NHjCONHNHj.HCl) and 1-5 g. of crystallised sodium acetate in 10 ml. of water in a test-tube. Add 1 ml. of acetone, close the tube with a cork and shake vigorously. Allow the mixtme to stand, with occasional vigorous shaking, for 10 minutes it is advantageous to cool in ice. FUter the crystals, wash with a httle cold water, and recrystaUise from water or dilute alcohol. The m.p. of acetone semicarbazone is 187°. 

When semicarbazide Ls heated in the absence of a carbonyl compound for long periods, condensation to blurea, NHjCONHNHCONHj, m.p. 247-250 (decomp.), may result occasionally this substance may be produced in the normal preparation of a semicarbazone that forms slowly. Biurea is sparingly soluble in alcohol and soluble in hot water, whereas semicarbazones with melting points in the same range are insoluble in water this enables it to be readily distinguished from a semicarbazone. 

Wolff - Kishner reduction of aldehydes and ketones. Upon heating the hydrazoiie or semicarbazone of an aldehyde or ketone with potassium hydroxide or with sodium ethoxide solution (sealed tube), the corresponding hydrocarbon is obtained ... 

Dissolve 7 g. of pure oleic acid in 30 ml. of dry ethyl chloride (chloroform may be used but is less satisfactory), and ozonise at about —30°. Remove the solvent under reduced pressure, dissolve the residue in 50 ml. of dry methyl alcohol and hydrogenate as for adipic dialdehyde in the presence of 0 5 g. of palladium - calcium carbonate. Warm the resulting solution for 30 minutes with a slight excess of semicarbazide acetate and pour into water. Collect the precipitated semicarbazones and dry the... 

Extract the dry mixture of semicarbazones with ether only the semicarbazone of (I) dissolves easily. 

To isolate the semicarbazide hydrochloride, the filtered reaction mixture Is treated with excess of acetone and the resulting acetone semicarbazone is decomposed with concentrated hydrochloric acid. 

To decompose the acetone semicarbazone, warm 58 g. with 50 ml. of concentrated hydrochloric acid until it just dissolves. Cool in ice the semicarbazide hydrochloride separates as a thick crystaUine mass. Filter at the pump through a sintered glass funnel, and wash with a small quantity of alcohol and then with ether dry in the air. The yield of pure semicarbazide hydrochloride, m.p. 173° (decomp.), is 35 g. A further quantity of product may be obtained either by saturating the mother liquor with hydrogen chloride or by treating it with twice its volume of alcohol and then with ether. 

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. 

Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

Synthesis from Aldehydes and Ketones. Treatment of aldehydes and ketones with potassium cyanide and ammonium carbonate gives hydantoias ia a oae-pot procedure (Bucherer-Bergs reactioa) that proceeds through a complex mechanism (69). Some derivatives, like oximes, semicarbazones, thiosemicarbazones, and others, are also suitable startiag materials. The Bucherer-Bergs and Read hydantoia syntheses give epimeric products when appHed to cycloalkanones, which is of importance ia the stereoselective syathesis of amino acids (69,70). 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

Alloxan forms an oxime (1007) which is the same compound, violuric acid, as that formed by nitrosation of barbituric acid likewise, a hydrazone and semicarbazone. Reduction of alloxan gives first alloxantin, usually formulated as (1008), and then dialuric acid (1004 R = OH) the steps are reversible on oxidation. Vigorous oxidation with nitric acid and alkaline hydrolysis both give imidazole derivatives (parabanic acid and alloxanic acid, respectively) and thence aliphatic products. Alloxan and o-phenylenediamine give the benzopteridine, alloxazine (1009) (61MI21300). 

Reduced pyrido[4,3-c]pyridazines are obtained from piperidine derivatives such as (371) with hydra2dne e.g. 79AF1835), whilst another related synthesis coupled the enamine (372) with phenacyl bromide semicarbazone to give (373) (74JAP(K)7488897). 

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