Of hydrazones

Many of these compounds ate highly colored and have found use as dyes and photographic chemicals. Several pharmaceuticals and pesticides are members of this class. An extremely sensitive analytical method for low hydrazine concentrations is based on the formation of a colored azine. They are also useful in heterocycle formation. Several reviews are available covering the chemistry of hydrazones (80,89) and azines (90). 

Lead tetraacetate is often used as the oxidizing agent for the conversion of hydrazones into ring-fused systems. 

Analogous to the oxidation of hydrazones to azo compounds, A-unsubstituted pyrazolidines are oxidized to A -pyrazolines. For example, the blcyclic pyrazolidine (415) when treated with silver oxide yields the pyrazoline (416) (65JA3023). Pyrazolidine (417) is transformed into the perchlorate of the pyrazolium salt (411) by reaction with mercury(II) acetate in ethanol followed by addition of sodium perchlorate (69JOU1480). 

A formal ring enlargement of diazirines to five-membered rings is also observed with some hydrazones of ketodiazirines (65CB2509). On attempted preparation of hydrazones (201) from ketodiazirine (200) at 0 C the diazo compounds (202) are plausible intermediates since their transformation to aminotriazoles (203) is known. 

Ring-chain tautomerism of hydrazones of 1,3-dicarbonyl compounds 99MI21. 

Hydrazone 56a was heated for 6 h under reflux in ethanol containing a catalytic amount of hydrochloric acid to afford a mixture of pyrazol-3-one 57a (15%), pyrazole 58a (29%), and hydrazone 59a (49%). The cyclization of hydrazone 56b was much more sluggish. Under similar reaction conditions 5 days was required to give a mixture of pyrazol-3-one 57b (40%), pyrazole 58b (11%), and hydrazone 59b (20%) (80JHC1413) (Scheme 18). 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

An example of the reaction of hydrazones with enynes is reported in a German patent (91GEP4001600). The alkynylpyrazoles were prepared by treating of RNHN=CR C02R2 with CH2=CR 0R" (R =C1, Br R = alkyl) followed by aromatization with acid (Scheme 26). 

Ring-chain tautomerism was observed in a series of l,2,3,6-tetrahydro-l,2, 4-triazine 4-oxides 5 in nonpolar solvents (e.g., CCI4) by NMR spectroscopy. Depending on the nature of substituents R and R, the ratios of the cyclic form of 1,2,4-triazine 5a to the open-chain form of hydrazone 5b were found to be up to 45 55 (77ZOR2617). 

Evidently, analogously to the mentioned cyclization of similar oximes to ben-zisoxazole derivatives (See Section II.A), reaction can take place only in compounds with suitable configuration. However, in case of hydrazones, due to the tautomeric equilibrium of both possible configurations, the reaction usually achieves complete conversion. The usual setup involves heating with the respective hydroxide if an ester group is present, it is partially or completely hydrolyzed to the corresponding acids, which, in addition, can also undergo decarboxylation. 

A series of interesting pyrazolo[3,4-(f pyrimidine derivatives was obtained by a thermal denitrocyclization reaction of hydrazones, e.g. 164 or 166, easily formed from the corresponding aldehyde or ketone hydrazones with halo-nitrouracil derivatives, e.g. 163 (71CC1442, 72CC298). Intermediates 164 or 166 can be isolated and their cyclization in suitable solvents (methanol, DMF, DMSO) provided high yields of the products. Aldehyde hydrazones yielded the corresponding l,7-dihydropyrazolo[3,4-J]pyrimidines, e.g. 165, whereas ketone hydrazones gave l,5-dihydropyrazolo[3,4-pyrimidine derivatives, e.g. spirocyclic compound 167 (Scheme 26). 

Whereas reaction of hydrazones disubstituted in the 4,5-position of the selenazole rings with diazotized arylamines only gives formazans, compounds unsubstituted in the 5-position can be attacked there by the diazonium cation. In fact, the azo coupling in this position is decidedly quicker reaction of 5-benzylidenehydrazino-4-phenyl-... 

The initial step is the formation of hydrazone 2 by reaction of hydrazine with aldehyde or ketone 1 ... 

Having retraced the remarkably efficient sequences of reactions which led to syntheses of key intermediates 14 and 15, we are now in a position to address their union and the completion of the synthesis of the spiroketal subunit (Scheme 6b). Regiocontrolled deprotonation of hydrazone 14 with lithium diisopropylamide (LDA), prepared from diisopropylamine and halide-free methyl-lithium in ether, furnishes a metalloenamine which undergoes smooth acylation when treated with A-methoxy-A-methylcarboxa-mide 15 to give the desired vinylogous amide 13 in 90% yield. It is instructive to take note of the spatial relationship between the... 

Benzotriazepinones 5 are also produced in the reaction of hydrazones of 2-aminoaryl ketones with phosgene (Method B).352... 

The uncatalyzed thermolysis of hydrazone (24) gave, among other products, an indole by loss of the ortho F in a mirror image of the usual Fisher indole synthesis [83JCS(P1)821]. 

Pyrrolo[ 1,2-b [l, 2,4[triazinium salt 30 was obtained (90CB2039) by the reaction of hydrazone 29 with the Vilsmeier reagent prepared from DMF and oxalylchloride (Scheme 9). 

Cyclization of hydrazone 38 with mercuric oxide and EDTA gave dihy-drotriazine 39 (87AP198). On the other hand, methyl hydrazone 38, under 4-electron withdrawal and neighboring group participation reacts with the same reagent to give lactam 40, a useful precursor for the synthesis of the pyrrolo[2,l-c]triazinium salt 41 by cyclization with perchloric acid (87AP258) (Scheme 12). 

Cyclization of hydrazones 318 gave [75CR(C)14I9] pyrazolo[l,5-J][I,2,4]triazine 319 (Scheme 67). 

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

On the contrary, the preparation of hydrazones from the monoacetals of gyloxal is a straightforward process4. b Only one of two possible isomers (Z- or E-isomer) is detectable . 

The use of hydrazone or enamine derivatives of ketones or aldehydes offers the advantage of stcreocontrol via chelated azaenolates. Extremely useful synthetic methodology, with consistently high anti selectivity, has been developed using azaenolates based on (S)- or (R)-l-amino-2-(methoxymethyl)pyrrolidine (SAMP or RAMP)51 58 (Enders method, see Section 1.5.2.4.2.2.3.). An example which illustrates the efficiency of this type of Michael addition is the addition of the lithium azaenolate of (5 )-l-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazone of propanal (R = II) to methyl (E )-2-butenoate to give the nub-isomer (an 1 adduct) in 80% yield with a diastereomeric ratio > 98 2,... 

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