Semicarbazide, reaction with aldehydes

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

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]. 

SEMICARBAZONES. The products of the reaction between an aldehyde or a ketone with semicarbazide are termed semicarbazones. 

Reaction CXXXl. Formation of Semioxamazones.—Semioxamazide, NH2.CO.CO.NH.NH2, possesses similar properties to semicarbazide, and reacts well with aldehydes, but with ketones the reaction does not seem to be generally applicable. 

Protection of peptide aldehydes as semicarbazones serves two purposes (1) it reduces or eliminates racemization during chromatographic separation, and (2) the semicarbazone protects the aldehyde functional group during subsequent peptide coupling reactions. Crude aldehydes can be immediately reacted with semicarbazide hydrochloride to give the corresponding semicarbazones. The semicarbazones are purified on a silica gel column and are subsequently deprotected with 37% formaldehyde/HCl. To determine the optical purity, the aldehydes are immediately reduced with sodium borohydride followed by determination of the optical rotation of the alcohol (Table 3).[5]... 

Ketones and aldehydes also condense with other ammonia derivatives, such as hydroxyl amine and substituted hydrazines, to give imine derivatives. The equilibrium constants for these reactions are usually more favorable than for reactions with simple amines. Hydroxylamine reacts with ketones and aldehydes to form oximes hydrazine and its derivatives react to form hydrazones and semicarbazide reacts to form semicarbazones. The mechanisms of these reactions are similar to the mechanism of imine formation. 

A compound containing the C=N—NH — CONH2 group, formed by the reaction of a ketone or aldehyde with semicarbazide. (p. 853)... 

A number of reactions of nitrogen-containing nucleophiles with aldehydes and ketones involve addition of the nitrogen to the carbon of the carbonyl group, followed by elimination of water to produce a double bond. Common examples are reactions of primary amines to produce substituted imines, reactions of secondary amines to produce enamines, reactions of hydrazine or substituted hydrazines to produce hydrazones, reactions of semicarbazides to give semicarbazones, and reactions of hydroxylamine to produce oximes. Usually these reactions are run with an acid catalyst. 

C=N- Reaction with ammonia, primary amines, hydrazine, hydroxyl-amine, semicarbazide, Girard D reagent Ketones [206], aldehydes [206] irreducible under given conditions better developed waves with some reducible compounds simultaneous determination of pyridoxal and pyridoxal-5-phosphate [193], 17-ketosteroids [238],... 

The periodate oxidation of 165 and its derivatives gave 195, which could be transformed into a variety of derivatives (194 and 196) (80MI8) upon reaction with amines, hydrazines, semicarbazide, or thiosemicarbazide (Scheme 44). The thiosemicarbazones 196 were cyclized to the thiadiazoles 199 and thiadiazolines 198, which are of chemotherapeutic interest (80MI8). The aldehyde also affords the expected dimedone derivative 197. 

D Reactions of Semicarbazide with Cyclohexanone and 2-Fur aldehyde in Bicarbonate Buffer Solution... 

Further evidence in support of this proposed two-step mechanism was obtained by studying the reactions of a series of /lara-substituted benzaldehydes with semicarbazide to determine the electronic effects upon the individual steps of the reaction . The equilibrium con- stants for the formation of semicarbazide addition compounds show a Unear logarithmic correlation with Hammett s substituent constants, with a p value of +1-81. The aldehydes are therefore destabilized, relative to the addition intermediate, by electron-withdrawing substituents. The rates of acid-catalyzed dehydration show an almost equal and opposite p value of — 1-74, indicating that dehydration is euded by substituents capable of electron donation (Figure 3)... 

Catalytic reduction of the nitrile 79 in the presence of semicarbazide affords initially the semicarbazone of 80. Hydrolysis-interchange, for example in the presence of pyruvic acid, gives the aldehyde 80. Condensation with the half ester of malonic acid leads to the acrylic ester 81 the double bond is then removed by means of catalytic reduction (82). Base catalyzed reaction of the... 

Semisynthetic enzymatic oxidation of peptide alcohols employs equine liver alcohol dehydrogenase. Amino alcohols with nonpolar side chains and Z-Om[CH2OH] worked as effective substrates while polar amino alcohols such as H-Arg[CH2OH] and H-Lys[CH2OH] failed as substrates. To attain complete oxidation, semicarbazide was present in the reaction mixture to immediately trap the aldehyde, and flavin mononucleotide was used to oxidize the NADH to NAD+, which serves to oxidize the alcohol 41] Configurational stability was confirmed by NMR spectroscopy as in the case of Ac-Phe[CH2OH], which was prepared by sodium borohydride reduction of Ac-Phe-H 4 1... 

A mortar was charged with the aldehyde or ketone (1 mmol), hydrazine derivative or semicarbazide (1 mmol), sodium hydroxide (0.04 g, 1 mmol) and silica gel (0.1 g). The reaction mixture was ground with a pestle in the mortar. When TLC showed no remaining aldehyde or ketone, the reaction mixture was poured into a mixture of dichlorometliane (20 mL) and 5% HC1 (10 mL). The ethereal layer was washed with saturated NaHC03, dried (MgS04), and evaporated by rotary evaporation to give the pure product. 

A paste of a mixture of aromatic aldehyde (5 mmol) and hydroxylamine (5 mmol), semicarbazide (5 mmol), or tosylhydrazine (5 mmol) in methanol (few drops) was exposed to microwaves (heating and cooling at intervals of 15 s and 1 min for the specific time). After completion of the reaction (TLC) the product was extracted with 3x5 mL CH2CI2. Removal of the solvent under reduced pressure gave pure product in excellent yields. 

Dissolve 1 g of semicarbazide hydrochloride and 1.5 g of crystallised sodium acetate in 8-10 ml of water, add 0.5 g of the aldehyde or ketone and shake. If the mixture is turbid, add alcohol (acetone-free) or water until a clear solution is obtained shake the mixture for a few minutes and allow to stand. Usually the semicarbazone crystallises from the cold solution on standing, the time varying from a few minutes to several hours. The reaction may be accelerated, if necessary, by warming the mixture on a water bath for a few minutes and then cooling in ice-water. Filter off the crystals, wash with a little cold water and recrystallise from water or from methanol or ethanol either alone or diluted with water. 

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