AZINES AND HYDRAZINES

The thermal and photolytic decomposition of hydrazine and substituted hydrazines and azines provide a source of many nitrogen containing radicals . For this reason a considerable amount of thermochemical data is now available relating to the bond energies of the bonds involved in these reactions. Friswell and Gowen-lock have recently reviewed the chemistry and thermochemistry of nitrogen containing radicals, and the salient features of their article will serve as an introduction to this section. 

The isoelectronic principle, by which the chemistry of many nitrogen compounds can be related to that of their hydrocarbon counterparts can be useful if used with caution, e.g. account must be taken of the differences in the thermochemistry of the reactions involved s . A comparison of the bond dissociation energies in such isoelectronic sequences is instructive in this regard (Table 27) . 

BOND DISSOCIATION ENERGIES (Z) KCAL.MOLE ) IN ISOELECTRONIC SEQUENCES 

Reliable data for the heats of formation of many nitrogen radicals are available from accurate thermochemical measurements, e.g. from D (H2N-NH2) and A//f° (N2H4, g f one obtains A/ff° (NH2, = 41 +2 kcal.mole . Similarly 

Thermochemical data for alkyl amino radicals show for alkylhydrazines a trend in D (N-N) for these compounds in which the N-N bond was strengthened by increasing the degree of substitution by methyl in NH2 NH2 . From these values it was possible to determine values for the enthalpies of formation of the alkylamino radicals , and to confirm these by electron impact studies. The latter values were found to be in agreement with those obtained from pyrolysis studies. Hydrazine has often been used as a source of amino radicals by pyrolysis flame decomposition shock tube decomposition , electrodeless discharge and microwave discharge , viz. 

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Mild reduction converts azines and hydrazines into disubstituted hydrazines, but under vigorous conditions reductive cleavage of the N-N bond affords amines. Reduction of oximes thus affords a further but seldom used method of converting carbonyl compounds into amines. 

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

A cold solution of BrF3 (0.3 mL. 6 mmol) in CC13F (25 mL) was added over 10 min to a CCI3F solution of adamantanone azine (3 mmol) prepared from adamantanone and hydrazine in stoichiometric proportions. An immediate reaction took place giving the desired product yield 95%. 

Hydrazido(2-) and hydrazido(l-) complexes have also been shown to condense with aldehydes and ketones to give diazoalkane complexes containing the W=N—N=CRiR2 unit.387,388 Treatment of these complexes with LiAlFL, gives secondary amines and ammonia, whereas treatment with acid produces hydrazine, keto azines and N2-free tungsten compounds. Amines can also be produced from organohydrazido(2—) complexes.389,390... 

Bis(azidobenzylidene) azine and Derivatives B i s (a azidoben zyl idene) azi ne i called Bis-[a -azido-benzylidenl-hydrazin or Dibenzhydrazid-azid in Geri, C6HS.C(N3) N.N C(N3).C6HS, mw... 

The reaction of azines 107, prepared in situ from aldehydes or ketones and hydrazine, afforded the Ugi adducts 108. The acid treatment of 108 resulted in the hydrolytic cleavage of the imino group with formation of the hydrazides, which immediately cyclized to phthalazinone amides 109 (Scheme 2.39) [70]. 

Bifunctional 1,2,3-dithiazole 13 bridged by an azine spacer has been prepared from Appel salt 20 and hydrazine, with a goal to determine the extent of communication between the two dithiazole rings as a function of the electronic and steric demands of the bridge (Equation 29) (see Section 6.01.2) <2001IC2709>. 

The presence of a carbonyl substituent in the -position of the hetero-cycle is essential for the cleavage of five-membered rings. The compounds of this type which have been investigated most thoroughly are 3-acylindoles.287, 384-388 At 160-170° 3-acetylindole and hydrazine hydrate give 3-(o-aminophenyl)-5-methylpyrazole, the structure of which was proved by deamination. Other 3-acylindoles, their hydrazones, and azines, react analogously.385 For the mechanism of the reaction see Alberti.384,391 The reaction requires a fourfold excess of hydrazine hydrate,387 preferably a polar solvent,388 and about... 

Starting from isolated hydrazones, reduction to the corresponding hydrocarbons by treatment with base in an aprotic solvent takes place at temperatures significantly below the 200 °C of the Huang-Minlon modification of the Wolff-Kishner reduction. However, hydra-zones cannot be prepared in a one-step reaction between a ketone and hydrazine, since usually azines (R1R2C=N=N=CR1R2) are formed instead. However, semicarbazones are hydrazone derivatives that are easily accessible by the reaction of a ketone with semicarbazide (for the mechanism, see Table 9.2). Semicarbazones can be converted into alkanes with KO/Bu in toluene at temperatures as low as 100 °C. This method provides an alternative to the Wolff-Kishner reduction when much lower than usual reduction temperatures are desirable. 

Starting from previously isolated hydrazones, it turns out that they can be reduced to the corresponding hydrocarbons by treatment with base in an aprotic solvent at temperatures significantly below the 200°C of the Huang-Minlon modification of the Wolff-Kishner reduction. However, hydrazones cannot be prepared in a one-step reaction between a ketone and hydrazine, since usually azines... 

Freifelder obtained an 82% yield of benzylhydrazine by hydrogenating a freshly prepared hydrazone over Pd-C in ethanol at 0.3 MPa H2 in less than 30 min.83 However, when the hydrazone was allowed to stand for several days to a week, the yield dropped to 45-48%. In the hydrogenation of phenylacetone hydrazone, Biel et al. observed that the formation of large amounts of jV,iV -bis(l -phenyl-2-propylidene)hydrazine took place when hydrogenation proceeded slowly and incompletely with such catalysts as Pd-C, rhodium, ruthenium, and platinum oxide, and with solvents such as alcohol, water, ethyl acetate, tetrahydrofuran, and dioxane. The A(A%disubstituted hydrazine was obtained when the hydrogenation proceeded slowly to completion, as over platinum oxide in aqueous acetic acid. With Raney Ni in ethanol, the azine and l-pheny-2-propylamine were formed almost exclusively. 1-Phenyl-2-propylhy-drazine was obtained in acceptable yields of 55-70% by use of platinum oxide or supported platinum in alcoholic acetic acid at a pressure of 13.8 MPa H2. The products obtained over platinum oxide in various conditions are summarized in eq. 8.40.78... 

A convenient synthesis [Eq. (13)] of 2-ary lidenehydrazono-4-thia-zolidinone (43) from ethyl thiocyanoacetate (44), arylideneazines (45), and hydrazine hydrate (46) has been reported.79 Presumably, the reaction proceeds via the intermediary hydrazone, which condenses with 44 to give 43. Subsequently, condensation of 43 with the aromatic aldehyde, generated in situ from disproportionation of the azine with hydrazine, affords the 5-arylidene derivative. The reaction of 44 with ammonium acetate and an aromatic aldehyde gives 5-arylidene-2-imino-4-thiazolidinones.80... 

A mixture of 112 g. (1.0 mole) of acetone azine and 32 g. (1.0 mole) of anhydrous hydrazine is placed in a 300-ml. round-bottomed flask fitted with a reflux air condenser and drying tube, and kept at 100° for 12-16 hours. (Caution This reaction and the subsequent distillation should be carried out behind a protective screen.) The crude product is then rapidly distilled through a water-cooled condenser and the colorless fraction boiling at 122-126° collected, n22D 1.4607 (Note 7). It weighs 111-127 g. (77-88%, Notes 7 and 8) and is essentially pure acetone hydra-zone (Note 9). 

The distillation gives a small forerun, b.p. 120-128°, containing hydrazine and acetone hydrazone. There is virtually no distillation residue. The submitters carried out the preparation of both acetone azine and acetone hydrazone on a fourfold scale with comparable results. 

The procedure for acetone azine is essentially that of Curtius and Thun.5 The method for acetone hydrazone is adapted from that of Staudinger and Gaule.8 The hydrazone has been prepared directly from acetone and hydrazine, but this is much less satisfactory.6... 

Upon heating a mixture of benzaldehyde and hydrazine salt in the presence of styrene (2 1 6 molar mixture), in addition to 1,5-diazabicyclo [3.3.0] octane, 3,5,6-triphenyl-l,4,5,6-tetrahydropyridazine was obtained as byproduct. The latter was the only product when a 2 1 2 ratio was used. The pyridazine formation is explained on the basis of cycloaddition of benzaldehyde azine to styrene, followed by tautomerization (87JOC2277). Similarly, other diazadienes add ethyl vinyl ether to give also 1,4,5,6-tetrahydropyridazines [83JCS(PI)1803j. 

It has been suggested [47] that 2-benzoylpyridine azine is reduced via the azo and hydrazine derivatives, rather than through the route suggested previously for benzalazine [1]. It would be rather exceptional if a hydrazine were reducible at the same potential as the azine. 

Electrochemical reduction of 2,2,6,6-tetramethyl-4-oxopiperidine (I) azine or a mixture of I and hydrazine at a lead cathode in neutral medium gave a nearly quantitative yield of 4-amino-2,2,6,6-tetramethylpiperidine II [49]. 

The electrochemistry of hydrazones, azines, and other derivatives of hydrazine is complicated by the possibility of tautomerization. The following forms must be considered [54,55] ... 

All experimental data on the behavior of 3,5-disubstituted 1,2,4-tri-azines in the SN reactions indicate a greater reactivity of the C-5 position. An exception is the reaction between ethyl-3,5-dimethylthio-l,2,4-tria-zine-6-carboxylate (80) and hydrazine or amines, which results in a mixture of 3- and 5-hydrazino (amino) derivatives, 81 and 82 (Scheme 50) (76JCS(P2)2521, 76JMC845 77JHC729 87MI4). 

Cleavage of diaziridines to a carbonyl compound and hydrazine or a substituted hydrazine can be carried out with almost any diaziridine. In order not to obtain the hydrazine as a solution of its salt, techniques were elaborated to transform dialkyldiaziridines from either acetone or butanone into hydrazones under the influence of catalysts and to trap them as azines... 

The reductive removal of hydrazine substituents under oxidising conditions from azines and some azoles is conceptually related to oxidative removal of thiols (e.g. 29.1.1.2). In this case, the intermediacy of a diimide seems likely, as illustrated below. ... 

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