Heterocycles from hydrazines

In a recent review of heterocyclic compounds no further mention is made of the three-membered ring structures for the condensation products from hydrazine and carbonyl compounds. However, the products obtained from azodicarbonyl derivatives with aliphatic diazo compounds were formulated as diaziridines [Eq. (1)]. Recent investi-... 

A variety of heterocycles can be prepared from the reaction of bifunctional amines and related compounds with 1,3,5-triazine (equation 3). Similarly, 1,2,4-triazole is formed from hydrazine hydrochloride (Scheme 9) <63AG(E)309). 

Dimethyl-lO-ethylphenotellurazine reacted with sulfuryl halides or bromine in diethyl ether solution to quantitatively precipitate re,7e-dihalides. The dihalides were recrystallized from chlorobenzene. The dihalides can be reduced to the parent heterocycle with hydrazine or sodium sulfide. ... 

The effect of temperature and stoichiometry on the thiomethylation of hydrazine has been reported <2004RCB1717>. Heterocyclization of hydrazine with an excess of a CH2O-H2S mixture (1 6 4), in the temperature range from 0 to 20 °C, gives the tricyclic 11 and tetracyclic 360 nitrogen-and-sulfur-containing heterocycles. The nature of the product is affected substantially by the reaction temperature. At 20 °C, compound 11 is obtained in 30% yield and 360 in 18% yield. With a ratio of hydrazine CH20 H2S of 1 6 4, and a 0°C reaction temperature, an increased yield of 360 to 31% was observed (Scheme 74). PMR and initio calculations were used to confirm the structures of the products and are discussed further in Sections 9.09.2 and 9.09.3.1. 

Heterocycles related to indoles can also be prepared using the Buchwald-Hartwig amination strategy. For instance, indazole 15 can be prepared from hydrazine 14. Benzimidazole derivatives may also be prepared from the intramolecular guanidinylation of aryl bromides. And oxindoles can be prepared from the intramolecular amidation of aryl bromides. ... 

The formation of carbamates is also possible from hydrazines, imines, cyclic guanidines, and nitrogen heterocyclic compounds. For example, reaction of hydrazine with DMC gives methyl hydrazinofor-mate, which then further reacts with another molecule of hydrazine to yield carbonic dihydrazide (N,N -diaminourea). 

An ethanolic soln. of 2,3-dibenzoyl-2,3-dihydro-5-phenylfuran and 95%-hydrazine refluxed 2 hrs. l,2,4a,8a-tetrahydro-3,5,8-triphenylpyridazino[4,5-c]pyridazine. Y 50%. F. e., also fused heterocyclics from functionalized 1,3-dipoles, s. B. E. Landberg and J. W, Lown, Soc. Perkin I 7975, 1326. 

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). 

In this section formation of pyrazoles from the reaction of heterocycles with compounds other than hydrazines will be discussed. 

One of the extensively investigated applications of enamines to heterocyclic syntheses is based on the bifunctional character of enamine acylation products. Thus the vinylogous ureas and thiorueas obtained from enamines and phenylisocyanate and phenylisothiocyanate (-433) have been converted to aminopyrazoles and thiouracils with hydrazine (566) and phenylisocyanate (567). 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

The preparation of pyrazoles from heterobut-l-en-3-ynes and hydrazine provides the main pathway to the synthesis of these fundamental heterocycles [67HC (22)284 74MI2],... 

In much the same vein, reaction of the heterocycle, 145 (obtainable from phthalic acid and hydrazine), with phosphorus oxychloride gives the dichloride, 146. Double displacement of halogen by means of hydrazine leads to dihydralazine (147)... 

Amino-5-hydrazinopyrazole dihydrochloride 300 is a good source for the synthesis of this type of heterocyclic compound [78JCS(P1)885] and it was prepared by reaction of malononitrile with two equivalents of hydrazine. Reaction of 300 with ethyl pyruvate afforded 301. Unstable hydra-zone 302 formed when 300 was boiled with diacetyl rapidly cyclized to 303. Reaction of 300 with benzil gave 304 directly, which gave an acetyl derivative and resisted reductive deamination. On the other hand, a polymer was isolated from the reaction of 300 with glyoxal (Scheme 65). 

The potential of such reaction sequences for the generation of molecular diversity was also demonstrated by the synthesis of a library of heterocycles. Epoxide ring-opening with hydrazine and subsequent condensation with (3-diketones or other bifunctional electrophiles gave rise to a variety of functionalized heterocyclic structures in high purity [34]. A selection based on the substrate derived from cyclohexene oxide is shown in Scheme 12.12. 

Diamino-substituted complexes of type 37 were first obtained by Fischer et al. [12] in two steps via the 1,2-addition-elimination product 34 from di-methylamine and 35 (Scheme 6). The (3-aminoallenylidene)chromium complexes 36, which can be prepared either from 33 [47,48] or directly from 35 [33], can also be transformed to l,3-bis(dialkylamino)-substituted complexes of type 37 (e.g., R2=z Pr) by treatment with dimethylamine in excellent yields [33]. Although the complex 37 is accessible by further reaction of the complex 34 with dimethylamine, and 34 itself stems from the reaction of 35 with dimethylamine, the direct transformation of 33 to 37 could not be achieved [12]. In spite of this, heterocyclic carbene complexes with two nitrogens were obtained by reactions of alkynylcarbene complexes 35 with hydrazine [49] and 1,3-diamines [50]. 

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