The features of nucleophilic substitution of the nitro group in 4-alkyl-6-nitro-1

E. N. Ulomsky1,2, D. N. Lyapustin1, V. V. Fedotov1, O. S. El’tsov1, I. M. Sapozhnikova1, D. N. Kozhevnikov3, E. M. Mukhin2 1Ural Federal University, Mira Str., 28, Ekaterinburg, 620002, Russia E-mail: ulomsky@yandex.ru; 2Institute of Organic Synthesis named I. Ya. Postovskii Ural Division of RAS, 22 Kovalevskaya Str./20 Academicheskaya Str., 620990, Ekaterinburg, Russia; 3ZAO NPH VMP, 105 Amundsen’s Str., Ekaterinburg, Russia


Introduction
Th e nucleophilic substitution of easily leaving groups is one of the major synthetic approaches in the construction of organic compounds.Th e principles of nucleophilic heteroaromatic transformations are few and well known.Th e fi rst of the conventional mechanisms of the type SNHet is ipso-substitution of easily leaving groups and hydrogen [1,2].Another variant of the substitutive functionalization on the principle of FGI are the transformations on arine mechanism (E, A) [3,4].Finally, chronologically the last of the studied processes of substitution by nucleophiles is ANRORC -multistage process involving in the fi rst stage the disclosure of azine by nucleophile [5].In fact, the disclosure of azines under the action of N-nucleophiles are not uncommon [6][7][8], however not all of these transformations culminate in the substitution of leaving group and reverse cyclization.In the present work we have given the results of the study of the main stages of the transformation of 4-alkyl-6-nitro-1,2,4triazolo [5,1-c] [1,2,4]triazine-7-ones under the action of morpholine and the nature of substitution of the nitro group according to the ANRORC type was installed.
Th e nucleophile was used N-morpholine as the least reactive reagent, allowing us to identify key intermediates.We have found that under the action of three-fold excess of morpholine at room temperature the unusual for stable nitrous heterocycles disclosure of triazine cycle with the formation of adducts with the structure of the hydrazones (2) occurs.
The compounds ( 2) are sustainable, so that their structure is set on the basis of NMR spectroscopy data and elemental analysis (see experimental part).On the other hand, to obtain the holistic integral data of chromatography-mass spectrometry for compounds (2) failed because the hydrazones are converted to the parent compounds (1) and this occurs in the conditions column chromatography on silica gel.
A common feature of the 1 H NMR spectra for compounds (2) is the unusual diff erentiation of the proton signals of the amide fragment, where all eight protons are magnetically nonequivalent (Fig. 1).Such spectral pattern is determined fi rst of all by the peculiarities of the spatial structure of the whole hydrazone fragment of the compounds (2).
Another common feature for the hydrazones ( 3) is the diff erentiation of signals morpholine-amide fragment in the spectrum of 13 C NMR. Th e number of carbon resonance peaks in the spectrum belonging to this doubled fragment (Fig. 2) are doubled.
The spectral correlation pattern HMBC of 1 H-13 C NMR of hydrazone (3b) confirms the attributed structure, because obviously the interaction of protons of morpholine-amide fragment as with unequal C-atoms cycloalkylamine as and carbonyl (Fig. 3).
Another aspect of the studied transformations was the nucleophilic substitution of the nitro group.Th us, the heating of triazolothiadiazoles (1) in excess morpholine leads to the formation of two products ( 3) and ( 4) in comparable proportions.
Th us, it is established that the nucleophilic substitution of the nitro group in 4-alkyl-6-nitro-1,2,4-triazolo[5,1-c][1,2,4] triazine-7-ones is not the type of ipsosubstitution and in accordance with the ANRORC mechanism, including the disclosure of triazine cycle under the action of nucleophile, substitution of the nitro group with the formation of nitrosomorpholine and subsequent cyclization.

The experimental part
NMR spectra 1 H and 13 C were recorded on the spectrometer Bruker Avance II spectrometer (400 MHz for 1 H and 13 C) in DMSO-D 6 , internal standard for 1 H NMR spectra is TMS.Elemental analyses were performed on SSPA automatic analyzer «Carlo Erba 1108».IR spectra were recorded on the Fourier-IR spectrometer «Bruker Alpha, ZnSe».Th e data on gas chromatography-mass spectrometry were obtained on a gas chromatography-mass spectrometer «GCMS-QP2010 Ultra» (Shimadzu, Japan, 2013).Monitoring for the progress of reactions and purity of synthesized compounds was performed by TLC on plates «Sorbfi l» (fi rm ZAO «Sorbpolimer») in the system ethyl acetate.For preparative column chromatography the same eluent and silica gel Sigma-Aldrich 60 Å were used.4-Methyl-6-nitro-4,7-dihydro-1,2,4-triazolo [5,1-c][1,2,4]triazine-7-it is obtained by the method described in [10].trifl uoroacetic acid were suspended, 20 mmol of tert-butanol were added and were heated with the refl ux condenser at 80 о С within 2 hours.Th e solution is evaporated in vacuum, 10 ml of ethanol added and again evaporated.Th e residue was triturated with 15 ml of tert-butylmethyl ether, fi ltered and dried.Yield 2.4g (46 %).