Reactions of Hydrazines and Hydroxylamines

In contrast to the reaction products of the 1,3-dipolar cycloaddition to linear enones (chalcones and their derivatives), spiro- 1-pyrazolines 25-28 are stable heterocycles. Their isomerization into spiro-2-pyrazolines 29-31 can be carried out under acidic conditions at room temperature for 24 h in the case of the cis isomers, and for more than 1 month in the case of trans isomers [30, 41, 42, 43]. 

These reactions are carried out most efficiently under acidic conditions—in the presence of mineral or organic acids—or without catalysis [35]. For example, Palaska et al. [12] and Fathi et al. [54] reported the synthesis of pyrazolines 34 in high yields by the reaction of unsaturated ketones 32 and phenylhydrazine 

Another method for the preparation of polymers containing pyrazoline fragments was suggested in [18]. Poly (9i/-fluoren-2,7-ylene)- / -[3,5-bis(l,4-phenylene)-4,5-dihydro-1-phenylpyrazole] 53 was synthesized by the reaction of pyrazoline 51 and fluorene-2,7-bis(trimethylene boronate) 52 in toluene in the presence of a catalyst, Pd(PPh3)4, with 85% yield. 

The regioselectivity of pyrazole 55 formation is completely the reverse of that of pyrazoline 57 in the reaction of ketones 54 with hydrazines without DPPH. In addition, heterocycles 56 cannot be obtained from 57 by the action of DPPH. These facts show that the radical-initiated treatment of a, 3-unsaturated ketones with hydrazines does not occur via the initial pyrazoline 57 formation. 

TV-Thiocarbamoyl derivatives of pyrazoline can be synthesized by the reaction of oc,(3-unsaturated carbonyl compounds with thiosemicarbazides under basic conditions [14, 62, 63, 64, 65]. 

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The expected products are obtained in the reaction of hydrazines and hydroxylamines (109,200.201,248 imidoyl chlorides. For example. 

V. Kumar, R. Aggarwal and S. P. Singh, Reaction of Hydrazines and Hydroxylamine with Trifluorometyl-P-diketones Synthesis of Trifluoro-methylpjrazole and Isoxazole Derivatives , Heterocycles, 2008, 75, 2893. 

In the above-mentioned reactions with hydrazine and hydroxylamine, the actual reducing species is diimide (NH=NH), which is formed from N2H4 by the oxidizing agent and from NH2OH by the ethyl acetate.The rate of this reaction has been studied.Although both the syn and anti forms of diimide are produced, only the syn form reduces the double bond, at least in part by a cyclic mechanism ... 

Cobalt hexacyanoferrates and Prussian blue have shown high activity in oxidations of hydrazine and hydroxylamine [80-82], Electrocatalytic activity in this reaction has also been found for nickel [83] and manganese [69] hexacyanoferrates. 

The most usable and well-known pathway for the synthesis of five-membered nitrogen-containing heterocycles is condensation involving a,P-usaturated carbonyls and 1,2-binucleophilic compounds, e.g., derivatives of hydrazine and hydroxylamine (Scheme 2.8). The procedure based on these reactions was successfully applied for a long period [45, 46, 47, 48, 49, 50, 51, 52, 53]. 

Pyra/olincs and oxazolincs (339, Ing. 132 see also 262 in Sec. B.2) are pre-pared - - by the well-known reaction with hydrazines and hydroxylamines, respectively. Investigations carried out with isotopes allow the exclusion of an elimination-addition mechanism for the reaction, at least in the case of the oxaz.olinc synthesis. ... 

The resin-bound reagents thus obtained were reacted with a variety of nucleophiles to give different heterocycles (Scheme 13). So, reaction with hydrazine or hydroxylamine gave respectively pyrazoles and isoxazoles in excellent yields (94-99%, 34 examples) and excellent purities (> 95%). Reaction with guanidines afforded 2-aminopyrimidines. 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

This is by far the most important reaction of tetrazolium salts and accounts for the bulk of their many applications. A large variety of reagents can reduce tetrazolium salts, e.g., 53 to formazans, e.g., 51. Ascorbic acid, hydrazine, and hydroxylamine have been recommended for the preparation of formazans from tetrazolium salts.245 Stronger reducing agents such as ammonium sulfide, sodium amalgam, sodium dithionite, and catalytic hydrogenation can further reduce the formazans to the amidrazones, e.g.,... 

Nitropyrido[l,2-A]quinolin-6-ium-l 1-olate (6%) was isolated from a reaction mixture obtained by photoirradiation of crystalline photochromic 2-(2, 4 -dinitrobenzyl)pyridine for 10 days <2004JP0865>. Reaction of l-(3-chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium perchlorate with hydrazines and hydroxylamine in refluxing MeOH afforded 9,10-dimethoxy-6-methyl-, -4,6-dimethyl-l,2,3,4-tetrahydropyridazino[6,l-tf]isoquinoli-nium, and 9,10-dimethoxy-6-methyl-l,2,3,4-tetrahydro[l,2]oxazino[3,2- ]isoquinolinium, perchlorates, respectively <2004CHE1131>. 

Unlike the 3-position, the 5-position is very susceptible to nucleophilic substitutions and additions. Thus, a series of publications report that 5-fluoroalkyl-l,2,4-oxadiazoles 94 undergo reaction with hydrazine or hydroxylamine to furnish 3-fluoroalkyl-l,2,4-triazoles 95 (X = NH) and 3-fluoroalkyl-1,2,4-oxadiazoles 95 (X = 0), a reaction that proceeds via addition of the nitrogen nucleophile to the 5-position (Scheme 9) <2005JOC3288, 2004EJ0974, 2003JOC605>. 

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Reactions of 4H-Pyrans and 4H-Thiopyran with Amines, Hydrazines, and Hydroxylamines... 

The standard syntheses for pyrazoles (17) and isoxazoles (19) involve the reactions of (3-dicarbonyl compounds (18) with hydrazines and hydroxylamine, respectively. These reactions take place under mild conditions and are of very wide applicability the substituents Y can be H, R, Ar, CN, C02Et, etc. 

Thioxo and alkylmercapto groups are easily replaced by other groups. The sulfur in the 5-position of the 1,2,4-triazine ring is the most reactive and is replaced initially. Water, alcohols, amines, hydrazine and hydroxylamine can replace the thioxo or alkylmercapto group. Scheme 10 summarizes these reactions. Since the preparation of 3-thioxo-l,2,4-triazines is very easy and proceeds in high yield, these replacement reactions at the 3-position are of much preparative value. 

Dihydropyrimidines 296 react very easily with water, forming 6-oxy derivatives 297 even during storage of 296 in solvents containing water and special catalysts [248]. There are examples of other addition reactions with water [326, 327, 328, 329, 330, 331], alcohols [82, 332], hydrazine and hydroxylamine [333]. 

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