Hydrazones unsymmetrical

Regioselectivity becomes important, if unsymmetric difunctional nitrogen components are used. In such cases two different reactions of the nitrogen nucleophile with the open-chain educt may be possible, one of which must be faster than the other. Hydrazone formation, for example, occurs more readily than hydrazinoLysis of an ester. In the second example, on the other hand, the amide is formed very rapidly from the acyl chloride, and only one cyclization product is observed. 

The Fischer cyclization has proved to be a very versatile reaction which can tolerate a variety of substituents at the 2- and 3-positions and on the aromatic ring. An extensive review and compilation of examples was published several years ago[3]. From a practical point of view, the crucial reaction parameter is often the choice of the appropriate reaction medium. For hydrazones of unsymmetrical ketones, which can lead to two regioisomeric products, the choice of reaction conditions may determine the product composition. 

The use of diphenyl hydrazone 33 has been used in the synthesis of pyrazoles under modified conditions where the hydrazine is released in situ. Some reversal of regiochemistry is seen in the reaction with unsymmetrical dicarbonyls. With aryl hydrazine and diphenyl hydrazone, the ratio of 41 to 42 is 22 1 and 5 1, respectively. 

The hydrazone group is hydrolyzed (16-2) during the course of the reaction. Yields are high. Aryl iodides are converted to unsymmetrical diaryl ketones on treatment with aryImercury halides and nickel carbonyl ArH-Ar HgX-l-Ni(CO)4 ArCOAr... 

Cyclocondensation of isatin hydrazones 620 with 621 in strong acid gave thiazolo[3, 4 2,3][l,2,4]triazino[5,6-6]indoles 622, which underwent conventional reaction with 2-methyl-3-ethylbenzothiazolium perchlorate 623 to form unsymmetrical cyanines 624 (83URP1054350 85KGS211). The spectral properties of a series of polymethine dyes were examined (88KGS1547). 

The use of the trisylhydrazone 124 of 2-butanone 123 in the coupling process provides access to products containing an ethyl-substimted olefin 126. The starting unsymmetrical hydrazone 124 undergoes deprotonation and alkylation at the terminal a-carbon leading to a single metallated olefinic product 125Li (equation 44). The electrophilic component 2,3-dibromopropene leads to 126, which can be further elaborated via subsequent reactions. 

Hydrazones can also be deprotonated to give lithium salts which are reactive toward alkylation at the j> carbon. Hydrazones are more stable than alkylimines and therefore have some advantages in synthesis.79 The / A Alimcthy I hydrazones of methyl ketones are kinetically deprotonated at the methyl group. This regioselectivity is independent of the stereochemistry of the hydrazone.80 Two successive alkylations of the A A -dimethylby-drazone of acetone can provide unsymmetrical ketones. 

Regioselectivity is not a problem in the metalation and alkylation of SAMP-hydrazones derived from aldehydes, symmetrical ketones and unsymmetrical ketones having one substituent without a-hydrogens. On the other hand, SAMP-hydrazones of unsymmetrical ketones react regioselectively at the less substituted carbon, regardless of the E/Z ratio of the starting hydrazone33. 

Two alternative routes lead to 2-alkyltriazole 1-oxides from a-dicarbonyl compounds (Scheme 50, routes A and B). Unsymmetrical dicarbonyl compounds frequently, but not invariably, give rise to two isomeric hydrazones and two isomeric oximes and hence two isomeric 1,2,3-triazole 1-oxides (81JCS(P1)503). 2-Phenyltriazole 1-oxide is obtained from glyoxal via route A. However, 2-methyl-triazole 1-oxide is prepared from glyoxal by route B in a one-pot process under neutral conditions. 2-Benzyltriazole 1-oxide is obtained similarly. 2,5-Dimethyltriazole 1-oxides are accessible through both routes (86ACS(B)262). 

Copper and nickel Chromium and cobalt N -Np Na-Np Meridional/facial coordination Azo/hydrazone tautomerism Non-planarity due to azo/hydrazone tautomerism Formation of two copper and two nickel complexes by unsymmetrical o.o -dihydroxyazobenzenes78 Detection of isomeric 2 1 chromium complexes 79 proton magnetic resonance80 Isolation of isomeric 2 1 chromium and cobalt complexes 86 87 limited X-ray crystallographic89 90 Proton magnetic resonance80 Detection of five isomeric 2 1 chromium complexes of symmetrical o.o -dihydroxydiarylazo compounds... 

Pyrazoles are very common parts of commercially available pharmaceuticals, agrochemicals and dyestuffs. The reaction of fi-diketones with hydrazines is the most widely used method to synthesize pyrazoles. The reaction proceeds via the formation of hydrazone 13 which on subsequent cyclization and dehydration produces the corresponding pyrazole 2. This method usually has the disadvantage that with unsymmetrical diketones generally a mixture of isomeric pyrazoles is formed. Here the authors report no other isomer probably because of the great electronic differences of the two ketones being substituted with an ester vs. an alkyl group. 

Geometrical stereoselectivity can often be achieved in the condensation of unsymmetrical ketones 8 with tosylhydrazine l,2 and this feature means Shapiro reactions direct from an unsymmetrical ketone 8 via E-9 lead to the less substituted vinyllithium 11. On the other hand, a sequential alkylation-Shapiro sequence from a starting symmetrical hydrazone 12 will reliably form the more substituted vinyllithium 14 via Z-9 Retention of Z stereochemistry in Z-9 is dependent on its re-use almost immediately on standing, for example, Z-9 (R = vinyl) equilibrates to an 85 15 ratio E Z-9J ... 

Aza-enolates also react cleanly at carbon with acid chlorides. Good examples come from dimethyl-hydrazones of ketones. When the ketone is unsymmetrical, the aza-enolate forms on the less substituted side, even when the distinction is between primary and secondary carbons. The best of our previous regioselective acylations have distinguished only methyl from more highly substituted carbon atoms. 

This pyrazole synthesis, which undoubtedly profits from the thermodynamic stability of the end products, gives excellent yields (Table VI). Its range of application is limited, however, by the fact that the reaction of 3-substituted unsymmetrical dithiolium salts with substituted hydrazones leads to mixtures of isomers which can be separated only with difficulty. On the other hand, it does permit the preparation of a single 4,5-disubstituted pyrazole from a 3,4-disub-stituted salt and a substituted hydrazine. 

The unsymmetrical aza-analogues of 7t-exTTFs with linear nitrogen-containing spacers were synthesized in the aza-Horner-Wittig reaction of A-(diethoxyphosphoryl)hydrazones 859 derived from l,3-dithiol-2-one, with formyl group-terminated 1,3-dithioles 860 and 861. The hydrazone 859 was prepared in the reaction of diethoxyphosphoryl hydrazine with the dithiolium cation 858 (Scheme 129) <2004TL8211>. 

Both sides of acetone have been alkylated with different alkyl groups, in one operation, by treatment of the A, A -dimethylhydrazone of acetone with n-BuLi, followed by a primary alkyl, benzylic, or allylic bromide or iodide then another mole of n-BuLi, a second halide, and finally hydrolysis of the hydrazone. " Alkylation of an unsymmetrical ketone at the more substituted position was reported using an alkyl bromide, NaOH, and a calix[n]arene catalyst (see p. 122 for calixarenes). ... 

The synthesis of tazobactam from 6-APA (Scheme 6.15) proceeded via the 2- -(chloromethyl)penam ester (81 a), which was first prepared by Gottstein and co-workers [47] during the synthesis of 2-/S-(chloromethyl)-2-a-methylpenam-3a-carboxylic acid 1,1-dioxide (29). 6-APA (8) was converted to 6a-bromopenicillanic acid (77) by treatment with sodium nitrite and hydrobromic acid. Oxidation with peracetic acid in the presence of benzophenone hydrazone gave benzhydryl 6a-bromopenicillanate-l-oxide (78) and reduction with zinc and acetic acid gave benzhydryl penicillanate-1-oxide (79). The unsymmetrical azetidinone disulphide (80) was obtained by heating with 2-mercaptobenzothiazole reaction with copper (II) chloride... 

Running the Fisher indole synthesis on an unsymmetrical phenyl hydrazone gives a mixture of 2,3-disubstituted indoles. For example, reaction of the phenyl hydrazone, 34, with acid can give both 35 and 36 (Eqn. 22.26). Soluble acids and Amberlyst-15 give these two products in a 75 25 ratio at 100% conversion. With an H-M catalyst they are formed in a 65 35 ratio but over a dealuminated H-beta zeolite, the selectivity is reversed and 36 is produced in an 82% yield at 100% conversion.62 n was proposed that the preferential formation of 36 over the H-beta catalyst was the result of a restricted transition state selectivity. ... 

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