Chemistry of Heterocyclic Compounds, Vol. 42, No. 3, 2006
RECYCLIZATION OF INTERMEDIATES IN AN
ENAMINE REARRANGEMENT OF A PYRIMIDINIUM
SALT WHEN TREATED WITH ISONIAZIDE
G. G. Danagulyan and D. A. Tadevosyan
Keywords: 2-hydrazinopyridine, isoniazide, pyrimidinium iodide, rearrangement intermediates,
Kost–Sagitullin rearrangement.
In a paper devoted to study of the reaction of 2-(ethoxycarbonylmethyl)-1,4,6-trimethylpyrimidinium
iodide (1) with carboxylic acid hydrazides, we reported on synthesis of derivatives of
1
,2,4-triazolo[4,3-a]pyridine [1]. In particular, in that paper we discussed the hypothesis that when salt 1 was
treated with isonicotinic acid hydrazide (2) (isoniazide), cyclization to form triazolopyridine 4 occurs through a
step involving formation of the intermediate 2-hydrazidopyridine 3 (the product of a Kost–Sagitullin
rearrangement). However, as shown by later X-ray diffraction studies, during the reaction we do not obtain
triazolo[4,3-a]pyridines 4 but rather their isomers: derivatives of pyrazolo[1,5-a]pyrimidine 5 [2] (Scheme 1).
In studying the reaction of the intermediates for recyclization 6 and 7 with isoniazide 2, we obtained a
compound with a structure matching that of the initially proposed structure for the intermediate product of
"
rearrangement with transamination" (compound 3). Probably during the reaction, the pseudobase 6, by
eliminating a water molecule, is converted to the anhydro base 7, which also undergoes the indicated
transformation. Upon recyclization of compounds 6 and 7, the pyridone 8 and also a slight amount of the
demethylation product 9 are formed.
Thus for the first time we have observed a Kost–Sagitullin rearrangement with insertion of a carboxylic
acid hydrazide moiety into the molecule of the reaction product.
1
13
The H and C NMR spectra were obtained on a Varian Mercury-300 spectrometer (300 MHz and
6 MHz respectively), internal standard TMS; the mass spectra were recorded on an MK-1321 spectrometer with
7
direct injection of the sample into the ion source with ionization energy 70 eV.
-(Ethoxycarbonyl)methylidene-1,4,6-trimethyl-1,2-dihydropyrimidine (7). The pseudobase 6
1.5 g, 6.6 mmol) in CHCl (10 ml) was heated for 5 min, the solvent was distilled off, and 1.43 g (96%) of the
2
(
3
1
anhydro base 7 was obtained, R 0.62 (i-PrOH–ammonia, 1:1). H NMR spectrum (CDCl ), δ, ppm (J, Hz): 1.28
f
3
(
3H, t, J = 7.1, CH CH O); 2.22 (3H, s, 4-CH ); 2.30 (3H, s, 6-CH ); 3.19 (3H, s, 1-CH ); 4.16 (2H, q, J = 7.1,
3 2 3 3 3
OCH CH ); 4.46 (1H, s, H-2'); 5.76 (1H, s, H-5). Found, %: C 63.56; H 7.35; N 13.78. C H N O .
2
3
11 16
2
2
Calculated, %: C 63.44; H 7.74; N 13.45.
Reaction of Pseudobase 6 with Isoniazide 2. A mixture of compound 6 (0.9 g, 4 mmol) and hydrazide
2
(1.1 g, 8 mmol) was heated in absolute ethanol (10 ml) for 35 h, the solvent was distilled off, and the following
were obtained by preparative fractionation on a column (toluene–acetone, 3:1): 0.21 g (17%) of
3
_
3
-ethoxycarbonyl-4,6-dimethyl-2-(pyridine-4-carbonyl)hydrazino-1,2-dihydropyridine (3); mp 86-87°C, R 0.64
f
_________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Yerevan
75091; e-mail: gdanag@email.com. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3,
pp. 463-465, March, 2006. Original article submitted February 10, 2006.
4
14 0009-3122/06/4203-0414©2006 Springer Science+Business Media, Inc.
Danagulyan
