4-Pyridyl-hydrazine

Inspired by the work of Burk and Feaster ) we attempted to use (2-pyridyl)hydrazine (4.36) as a coordinating auxiliary (Scheme 4.10). Hydrazines generally react effidently with ketones and aldehydes. Hence, if satisfactory activation of the dienophile can be achieved through coordination of a Lewis acid to the (2-pyridyl)hydrazone moiety in water. Lewis-add catalysis of a large class of ketone- and aldehyde-activated dienophiles is antidpated Subsequent conversion of the hydrazone group into an amine functionality has been reported previously by Burk and Feaster ... 

Reaction of dnnamaldehyde 4.35 with (2-pyridyl)hydrazine (4.36) yielded the desired hydrazone 4.37. As anticipated, this compound coordinates readily to copper(II)nitrate in aqueous solution as... 

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

The reaction conditions (neutral, acidic or basic) do have an affect on the regioselectivity of the reaction. Acidic reaction conditions have also been shown to preferentially provide one regioisomer over basic conditions for reactions of aryl hydrazines. Extensive studies with 2-perfluoroacylcycloalkanones and mono-substituted hydrazines were studied to determine the selectivity of various alkyl-, aryl-, and heteroaryl-substituted hydrazines. Reactions of the aryl hydrazine 21 with the trifluoromethyl-substituted cycloalkanone 22 under neutral conditions (methanol, reflux) gave a mixture of isomers 23 and 24, whereas the reaction of the pyridyl hydrazine 25 was shown to give exclusively 26. 

Schwartz, D.A., Abrams, M.J., Giadomenico, C.M., and Zubieta, J.A. (1995) Protein labelling utilizing certain pyridyl hydrazines, hydrazides and derivatives. US Patent No. 5,420,285. 

Bis-[3,5-dinitro-2-pyridyl]-hydrazin. Mit2-Chlor-l,3,5-trinitro-benzol konnen Hydra-zino-pyridine aryliert werden. Alle Verbindungen bilden unter Einwirkung von rauchender Salpetersaure die hochcxplosiven Azo-Verbindungen6 ... 

C6H5N3 mw 119.14 N 35.28% white hygr crysts mp, decompn on being heated. Prepn is by condensation of 2-pyridyl hydrazine with anhydr formic acid... 

Okuda and Robison prepared 7-azaoxindole (90, R = H) in 67% yield by heating 2-aminop3uridine-3-acetic acid at 225° under nitrogen. Their attempts to synthesize 5-azaoxindole from 3-bromo-4-acetamidop5Tidine by creation of an intermediate pyridyne species were unsuccessful. Ficken and KendalR obtained a small amount of 3,3-dimethyl-7-azaoxindole (90, R = Me) by heating l-isobutyryl-2-(2-pyridyl)hydrazine with calcium oxide. They were... 

Nitro-3-chloropyridine-l-oxide is reduced with hydrazine to 4-amino-3-chloropyridine-1-oxide. 2-Chloro4-nitropyridine gives 1,2-bis-(2-chloro4-pyridyl)hydrazine on treatment with hydrosulfide. ... 

Perform the following reactions starting from (2-pyridyl)hydrazine (X) ... 

A suspension of Na-2-hydrazinopyridine (prepared from 2-hydrazinopyridine and NaNHg) in benzene heated 2 hrs. at 80° with a slight excess of ethyl bromide 1-ethyl-l-(2-pyridyl)hydrazine. Y 93%. T. Kauffmann and J. Hansen, Z. Naturf. Ub, 602 (1959). 

The acid-catalysed Fischer indole synthesis is an electrophilic substitution, and the evidence suggests that it occurs less readily with pyridylhydrazones than with benzene derivatives. Some failures with derivatives of 2-pyridyl-hydrazine have been recorded but cyclohexanone and desoxybenzoin 2-pyridylhydrazones were cyclized in about 50 per cent yields with poly-phosphoric acid. Zinc chloride has been used successfully with methyl isopropyl ketone 2-pyridylhydrazone 82, The Brunner oxindole synthesis worked... 

---