Hydrazines with ureas

The reaction of hydrazine or a substituted hydrazine with urea is a very convenient and useful method of preparing semicarbazides in good yields (Eq. 2). Table I gives some results of this reaction, and Table II some results of the reaction of substituted ureas with hydrazine to give semicarbazides. 

In Scheme 1 the most useful laboratory method for the preparation of semicarbazides involves the reaction of hydrazines with ureas or isocyanate derivatives (organic and inorganic). 

The most important nonmilitary application is synthesis of maleic hydraz-ide, which is used as a plant-growth regulator for tobacco suckering and tree pruning. Another important nonmilitary chemical is semicarbazide which is obtained by reacting hydrazine with urea ... 

Uracil reacts with hydrazine to give pyrazol-3(2if)-one (944) and urea N-methyl- and dimethyl-hydrazine behave similarly to give the 2-methyl- and 1,2-dimethyl derivatives. The reactions of hydrazines with uridine and related nucleosides and nucleotides is well studied (67JCS(C)1528). The tautomerism and predominant form of uracil are discussed in Section 2.13.1.8.4. 

The pyrazolotriazinecarboxylate 708 underwent cyclization with urea or thiourea to give (84PHA432) pyrazolopyrimidinotriazines 711, and with o-phenylenediamine, p-chloroaniline, or o-aminophenol to give quinolino-pyrazolotriazines 710. The reaction of the pyrazolo[5,l-c][I,2,4]triazine 709 with hydrazine hydrate gave 712, and its reaction with phenyl isothiocyanate gave 713 (83G219). 

The reactions of 5-acyl-2,2-dimethyl-4,6-dioxo-l, 3-dioxanes (1373) with urea, thiourea, sulfamide, hydroxylamine, or 1-substituted hydrazines gave monocyclic six- and five-membered heterocycles (1374-1378) in good yields [79JAP(K) 106466],... 

In the Raschig process (prior to 1924), NaOH, chlorine and ammonia react in aq soln to form dil soln of hydrazine, with Na chloride as a by-product also by oxidation of urea by Na hypochlorite. For its purification can be used fractional distillation, flash distillation or conversion to the slightly sol sulfate, followed by treatment of the latter with coned NaOH soln. 

The second approach uses the more reactive isocyanates, which can be prepared from the corresponding primary amines by treatment with phosgene [254], Oligomers of hydrazine-derived ureas have been prepared as peptide mimetics on PEG in solution [255]. For this purpose, protected pentafluorophenyl carbazates have been used to convert support-bound hydrazines into ureas (Figure 16.25). 

A broad spectrum of hydrogen-containing nucleophiles react with both aromatic and aliphatic isocyanates compounds containing OH groups (H20, alcohols, phenols, oximes, acids), SH groups (H2S, mercaptans), NH groups (NH3, amines, hydrazines, amides, ureas, urethanes), enolizable compounds such as malonic and aceto acetic esters, etc. Some reactions are given in Table 2.5. 

Many of the iV-alkyl and iV-aryl derivatives of urazine have been synthesized and characterized, but the parent substance is not well known. In the past, urazine has been prepared by thermal deammonation of carbohydrazide-iV-carboxamide [eq. (I)],1 fusion of hydrazidicarbamide with hydrazinium hydrogen sulfate [eq. (2)],2 fusion of earbohy-drazide with urea [eq. (3)],3 action of sodium hypobromite on semicarbazide [eq. (4)],4 reaction of dichlorourea with concentrated ammonia [eq. (5)],5 and the reaction between 1,2 hydrazine carboxylic ester and hydrazine hydrate... 

Diketones of the selenophene series are used to synthesize various heterocyclic systems isoxazole, pyrazole, and pyrimidine, as well as a-substituted bis-/3-diketones. Thus, /3-diketones with hydrazine hydrates yielded the corresponding disubstituted pyrazoles.130,131 The presence of the selenienyl radical as a substitutent substantially reduced the basicity of a pyrazole ring (see Section V,C) the electron-accepting ability of the selenien-2-yl radical is especially great.121 The reaction of selenophene /3-diketones with ureas gives substituted pyrimidines.125... 

The production of hydrazine from urea by treatment with sodium hypochlorite is no longer used. Here urea was oxidized with sodium hypochlorite followed by hydrolysis and decarboxylation to yield hydrazine. 

Dicyanopyrazine with sodium methoxide in methanol with ammonia at reflux gave 5,7-diimino-6//-pyrrolo[3,4-i)]pyrazine (65) (1442) and 2,3-dicyano-5,6-dimethyl(and 5,6-diphenyl)pyrazine with hydrazine by the procedure of Patel and Castle (1339) gave 2,3-dimethyl(and 2,3-diphenyl)-5,8-diaminopyrazino[2,3-rfJ-pyridazine(s) (66) (1435). Fusion of 2-chloro-3-cyano-5,6-diphenylpyrazine with urea and thiourea was reported to give 4-amino-2-hydroxy(and mercapto)-6,7-diphenylpteridine (848). 

High-level ab initio calculations show that diacyl-hydrazines are intrinsically nonplanar with respect to the CO—N—N—CO torsion, and the corresponding rotational barriers are high.171 The global minimum finds the nitrogen lone pairs approximately perpendicular to one another. Thus, their conformational properties are essentially determined by the conformation of their hydrazine and urea constituents. As a result of restricted rotation about the N—N bond, azapeptides cannot adopt extended conformations. This is likely the reason that they are resistant172 to chymotrypsin-like proteases, which bind their substrates in extended forms. 

A similar hydrazine cleavage is employed in a synthesis of t-butylamine, which starts with the condensation of t-butanol with urea to form f-butylurea, " When this... 

Derivation The preferred method is a two-step process (1) reaction of sodium hypochlorite and ammonia to yield chloramine (Nfi,Cl) and sodium hydroxide (2) reaction of chloramine, ammonia, and sodium hydroxide to yield hydrazine, sodium chloride, and water. Noteworthy is the need to carry out the reactions in the presence of such colloidal materials as gelatin, glue, or starch to prevent unwanted side reactions that would reduce the yield of hydrazine. An older method utilized the reaction of sodium hypochlorite or calcium hypochlorite with urea. 

Various cyclopropanecarboxylic acids and esters have been converted to various amides, TV-alkylated amides, and hydrazides by treatment with ammonia, alkylamines, - and hydrazines, respectively. In many cases the acids have been converted via the corresponding acid chlorides generated in situ. Diethyl esters of a variety of cyclopropane-1,1-dicarboxylic acids also react with urea. Generally, all these reactions proceed smoothly and in fairly good yield and give only very small amounts of byproducts due to opening of the cyclopropane ring. 

With regard to the simple diaziridine synthesis under large-scale conditions from ketone, ammonia, and chlorine, - some patents claim a direct preparation of hydrazine products by reaction of diaziridines with suitable reagents. For example, hydrazine dicarboxylic acid diamide is obtained directly from 3-ethyl-3-methyldiaziridine and urea in acidic so-lution. The reaction conditions, however (some hours at 70°-80°C), point to acid hydrolysis prior to reaction with urea. 

Ammonia (NHj), listed as an enzyme inhibitor, has a kinship with urea and such other ammoniacal inorganic compounds as hydrazine sulfate. Not only may they be potential enzyme inhibitors for glutaminolysis, but also for other metabolic reactions. Both urea and hydrazine sulfate are known to have been tried against cancer, apparently with mixed results. 

A number of reactions similar to those noted above have been used to prepare six-membered rings. The ketoaldehyde used to prepare 60 (R = H) reacts with urea to give 4-ferrocenyl-2-pyrimidone (70). The appropriate y-diketone and y-keto acids have reacted with hydrazine to give 71 and 72 (R = CH3 or CeHs), respectively. The Michael addition of cyanoacetamide to 73 in the presence of base gave the compounds 74-76. Ferrocenylphenylglyoxal and o-phenylene-... 

In addition, commercial polyacetals are also stabilized with urea, hydrazine, or with polyamides against thermal degradation these additives react with formaldehyde or its reaction products, such as, for example, formic acid. Secondary and tertiary amines are also added to increase oxidation resistance. 

Amulticomponent condensation of substituted phei lthiourea/urea, aqueous formaldehyde, and substituted aromatic/heteiocychc amines lead to 2-thioxohexaltydio-l,3,5-triazines in aqueous medimn under microwave irradiation in 30-60 s in a quantitative yield with reasonable purity [14], Further, tiiazolo[4,3-a]triazines were also prepared by a one-pot reaction of in sito synthesized tiiazii rl hydrazine with CS2. 

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