Cyclic hydrazines and hydrazones

In this section examples of polyazamacrocyclic products synthesised by the interaction of simple ligsons, such as hydrazine and its derivatives with mono- and dicarbonyl compounds, are discussed. The main feature of hydrazines as ligsons is the presence of two lone pairs of electrons in the functional groups. Coordination of hydrazines to the metal ion leads to the loss of nucleophilic properties of only one functionality, because steric restraints will not permit the second nitrogen donor to coordinate to a metal at the same time. As a result the nucleophilic properties of the non-coordinated amino groups can be exploited to carry out ring-closure reactions. 

For example, by template condensation of 2,3-butanedione dihydrazone with formaldehyde, a series of nickel(II), cobalt(II) and copper(II) complexes with the neutral macrocyclic ligand L36 were obtained (Eq. 2.1) [1-4]. 

The iron(II) complex of L36 is synthesised directly by interaction of stoichiometric amounts of 2,3-butanedione, hydrazine and formaldehyde on the iron(II) matrix [2]. [Co(L36)(CH3CN)2](C104)3 is synthesised by oxidation of [Co(L36)](C104)2 with molecular oxygen in acetonitrile in the presence of perchloric acid [2]. 

It is possible to carry out 2,3-butanedione dihydrazone interaction with acetaldehyde, propionaldehyde, acetone or cyclohexanone on the nickel (II) matrix, forming macrocycles similar to L36 [2]. 

Attempts to synthesise manganese(II) and zinc(II) octaazamacrocyclic compounds had no success. Complexes of these metals with 2,3-butanedione dihydrazone react with formaldehyde, but in this case products containing the acyclic tetradentate ligand L37 are isolated [2]. 

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Preparative studies have been reported on the phosphorylation of a series of hydrazines and hydrazones and on the phosphorylation of vicinal diamines with diphenyl phosphorochloridate. The cyclic phosphoramidate esters (12) and (13) may be obtained by treatment of the appropriate acyclic... 

However, in some cases azines can be converted to hydrazones by treatment with excess hydrazine and NaOH. Arylhydrazines, especially phenyl, p-nitrophenyl, and 2,4-dinitrophenyl, are used much more often and give the corresponding hydrazones with most aldehydes and ketones.Since these are usually solids, they make excellent derivatives and are commonly employed for this purpose. Cyclic hydrazones are also known, ° as are conjugated hydrazones. a-Hydroxy aldehydes and ketones and ot-dicarbonyl compounds give osazones, in which two adjacent carbons have carbon-nitrogen double bonds ... 

A variety of macrocyclic complexes which have adjacent nitrogen atoms (cyclic hydrazines, hydrazones or diazines) are formed by condensations of hydrazine, substituted hydrazines or hydrazones with carbonyl compounds. The reactions parallel in diversity those of amines, but are often more facile since the reacting NH2 groups is generally not coordinated and the electrophile is thus not in competition with the metal ion. The resulting macrocycles may be capable of coordination isomerism, since either of the adjacent nitrogen atoms can act as donor atom. 

The reaction of lactim ethers with hydrazine and its derivatives proceeds readily. The resulting compounds are highly reactive and can be used in different reactions involving the side chain and the cyclic nitrogen atom.5,54,76> 80-82 For example, the treatment of caprolactam hydrazone (40) with nitrous acid results in pentamethyl-enetetrazole (41),54,80,81 and the use of diiferent lactim ethers gives other tetrazoles.32,35 The synthesis of polymethylenetetrazoles from lactim ethers and HN3,83 and also84 from HN3 and O-acyl lactims (or imidochlorides of lactams), obtained from lactams and sulfochlorides or phosphoryl chloride, may be mentioned. 

A ring contraction involving this reaction has been found in cyclic hydrazones, hydrazines, and triazines. 

The hydrazine behaves as an amine towards a carbonyl compound and forms the imine-like product, a hydrazone. The cyclic rearrangement involves the... 

To 60 mL absolute EtOH there was added 12.2 g 1-(2,5-dimethoxy-4-chlorophenyl)-2-(phthalimido)ethane and 2.9 mL of 100% hydrazine. The solution was held at reflux for 15 min. After cooling, the cyclic hydrazone by-product was removed by filtration, and the alcoholic mother liquors taken to dryness under vacuum. The residue was distilled at 145-155 °C at 0.05 mm/Hg to give 5.16 g of a clear, colorless oil. This was dissolved in anhydrous Et20 and treated with hydrogen chloride gas, producing 2,5-dimethoxy-4-chlorophenethylamine hydrochloride (2C-C) as white crystals with a mp of 220-221 °C. Anal. (Ci0H 5C12NO2) C,H,N. 

A reduction route similar to that of phenylhydrazones [229] seems to be rather general for azomethine derivatives of hydrazine [229] as it s followed by cyclic and acylic phenylhydrazones, semicarbazones, azines, cyclic hydrazones, and acylated cyclic and acyclic hydrazones [231] under pro tic conditions in DMF, acylated hydrazones of aromatic aldehydes are reduced with saturation of the C=N bond and cleavage of the N-N bond at a more negative potential [232]. The suggestion that the cleavage of the N-N bond precedes the saturation of the azomethine bond is also an essential part of the interpretation of many of the ring contractions of heterocyclic compounds (Chapter 18). 

Addition to the Carbonyl Group — The internal, cyclic hemiacetal formation is one of the illustrations of such addition. The H2N-X nucleophiles, with X being NH2 (hydrazine), NHAr (arylhydrazines), OH (hydroxylamine), NHCONH2 (semi-carbazide), NHCSNH2 (thiosemicarbazide), or alkyl (primary amine), produce hydrazones, arylhydrazones, oximes, semicarbazones, thiosemicarbazones, and alkyl imines (Schiff bases), respectively, following the following path 5.4 + 5.15 — 5.16 ->. .. -> 5.21. 

Reactions of cyclic and acyclic 1,2,3-triones with phenylhydrazine give rise to mono- and bis-(phenylhydrazones). The central carbonyl group of a vicinal tricarbonyl system is electron-deficient and highly electrophilic,255 which is why treatment with an aryldiazonium ion affords 2-phenylhydrazones. The structure of such bis(phenylhydrazones) as cyclopentane-1,2,3-trione 1,3-bis(phenylhydrazone), dehydroascorbic acid 2,3-bis(phenylhydrazone), and cy-clobutanetetraone l,3-bis(phenylhydrazone) has been studied by UV, IR,1H-, 13C-, and 15N-NMR spectroscopy.265-268 Quantum-mechanical calculations to predict the most stable tautomeric forms of some 1,2- and l,3-bis(phenylhydrazones) revealed that the chelated bis(hydrazone) structure was usually more stable than the azoene-hydrazine structure.269-271 This does not mean that such structures do not exist, for example cyclobutanetetraone l,2,3-tris(phenylhydrazone) exists in a stable phenylazoene-hydrazine structure (see 49 Scheme 8).257-263... 

The chemical reactivity of all of the compounds of this series is governed by the powerful, electron-withdrawing influence of the sulfonyl groups this renders the acyclic, saturated members liable to eliminations, and the acyclic, unsaturated members susceptible to attack at C-2 by nucleophiles, and makes both the cyclic and the acyclic members unstable in basic solutions. This last feature provides the main source of interest in these compounds, all of which are degraded by aqueous ammonia to diethyl-sulfonylmethane and the aldose derived from the parent sugar by loss of C-1. Treatment with hydrazine in methanol, followed by cleavage of the derived hydrazone, offers a satisfactory means for degrading the acetylated sulfone (148) to n-arabinose (yield, 73%). ... 

The hydrazine derivatives of saccharide are here discussed in sections on saccharide azines, which are formed when one hydrazine molecule reacts with two saccharide molecules saccharide hydrazones and glycosylhy-drazines, which are the tautomeric acyclic and cyclic products formed when one hydrazine molecule reacts with one sugar residue saccharide osazones and poly(hydrazones), which are formed when two or more hydrazine molecules are linked to a saccharide residue and, finaly, hydrazones of carba-sugars and related compounds. 

The reaction of the cyclic carbonate 306 with hydrazine hydrochloride and Pr 2NEt in ethanol at reflux produced the cyclic hydrazone 307 via partial, regioselective hydrazinolysis of 306 followed by intramolecular condensation of the resultant hydrazide with the unmasked hemiacetal group (Equation 51) <2005SL2607>. 

Oxatriazines. (1) Reaction of benzonitrile oxides with hydrazones (Equation 16) - this method gives 3-aryl derivatives (2) reaction of benzonitrile oxides with hydrazine carboxylates and cyclization (Scheme 33) (3) cyclic carbonylation of l,4-disubstituted-4-hydroxy-semicarbazides with (thio)phosgene (Scheme 41) - this method gives 3,6-dione-type derivatives. Methods (1) and (3) both appear quite general and high yielding, with precursors readily available. 

The hydrazones 22 derived from partially protected o-ribose or o-glucose exist in equilibrium with the corresponding cyclic structures (Fig. 4). Subsequent cyclization of the respective hydrazine residue with 1,3-dicarbonyl compounds or unsaturated nitriles gave the pyrazoles 23 and 24 [51-55]. To-sylation of the isopropylidene derivative 23 gave the pyrazolium tosylate 26 via the intramolecular cyclization of 25 [54]. 

Within the last two decades, a number of chemical structures have been proposed as metal deactivators for polyolefins. These include carboxylic acid amides of aromatic mono- and di-carboxylic acids and N-substituted derivatives such as N,N -diphenyloxamide, cyclic amides such as barbituric acid, hydrazones and bishydrazones of aromatic aldehydes such as benzaldehyde and salicylaldehyde or of o-hydroxy-arylketones, hydrazides of aliphatic and aromatic mono- and di-carboxylic acids as well as N-acylated derivatives thereof, bisacylated hydrazine derivatives, polyhydrazides, and phosphorus acid ester of a thiobisphenol. An index of trade names and suppliers of a few commercial metal deactivators is given in Appendix A4. 

The structure of the osazone derived from dehydroascorbic acid remains in dispute. Recently (Vol. 13, p. 95) it was described as the phenylhydrazine-phenylazo-structure (34), but it is now claimed that the bis(hydrazone) formula (35) fits the n.m.r. and u.v. data more satisfactorily. The structure of the bi-cyclic oxidation product of (35) has been shown to be a 3,6-anhydride (36) by n.m.r. and m.s. A n.m.r. study of the formation of dehydroascorbic acid hydrazones revealed that the two 2-phenylhydrazides (37) were formed initially and subsequently underwent dehydration to give the two rotationally isomeric 2-phenyIhydrazones. Reaction of 6-bromo-6-deoxy-isoascorbic acid (D-ery thro) with phenyl hydrazine afforded the cyclized bis(hydrazone) (38). Treatment of D-threo-ascorbic acid bis(phenylhydrazone) with caustic soda afforded the cyclized product (39). The corresponding D-erythro- and L-threo-isomers were also prepared and the side-chains have been modified in various ways. 

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