Ammonium nitrate in acetic acid, an efficient reagent for the nitration of perimidines and the one-pot synthesis of 6(7)-aminoperimidines

Full text of DOI:10.1007/s10593-011-0748-6

Chemistry of Heterocyclic Compounds, Vol. 47, No. 2, May, 2011 (Russian Original Vol. 47, No. 2, February, 2011)
AMMONIUM NITRATE IN ACETIC ACID, AN EFFICIENT
REAGENT FOR THE NITRATION OF PERIMIDINES AND
THE ONE-POT SYNTHESIS OF 6(7)-AMINOPERIMIDINES
A. V. Aksenov1*, A. S. Lyakhovnenko1,
T. S. Perlova1, and I. V. Aksenova1
Keywords: aminoperimidines, ammonium nitrate, nitroperimidines, perimidines, zinc, reduction, nitration.
Nitro compounds are important intermediates in the synthesis of differently functionalized arenes. We
have previously proposed a method for the nitration of perimidines using nitric acid (d 1.5) in acetic acid [1].
The product yields for mononitration at a peri position (the 6(7)-nitroperimidines 2 are 8% for perimidine 1a
and 46% for the 2-methylperimidine (1b). We have proposed that the low yield is linked to an incorrect choice
of nitrating conditions. It was found that refluxing the perimidines 1a-c (1 mmol) with NH4NO3 (0.12 g,
1.5 mmol), and glacial acetic acid (25 g) for 5-10 min (TLC monitoring), cooling, neutralization of the reaction
mixture to pH ~ 8 with sodium carbonate solution, and filtration of the precipitate obtained gave the 6(7)-nitro-
perimidines 2a-c in 76-83% yields.
R
R
R
N
NH
N
NH
N
NH
NH4NO3
AcOH
Zn
AcOH
NH2
NO2
1a–c
3a–c
2a–c
1–3 a R = H, b R = Me, c R = Ph
Treatment of the reaction mixture before neutralization with zinc powder (0.32 g, 5 mmol), refluxing for
30 min (TLC monitoring), filtration to remove the excess zinc, neutralization of the mother liquor, and filtration
gave the corresponding 6(7)-aminoperimidines 3a-c in 62-69% yields.
_______
Dedicated to the anniversary of L. I. Belen'kii.
* To whom correspondence should be addressed, e-mail: alexaks05@rambler.ru.
1Stavropol State University, 1 Pushkin St., Stavropol 355009, Russia; e-mail: k-biochem-org@stavsu.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 304-305, February, 2011. Original
article submitted January 31, 2011.
0009-3122/11/4702-0245©2011 Springer Science+Business Media, Inc.
245

Finally, it should be noted that only traces of 4(9)-nitroperimidines are formed in the course of the
nitration using the proposed system of reagents.
1H NMR spectra were taken on a Bruker WP-200 instrument (200 MHz) using DMSO-d6 with TMS as
internal standard. Monitoring of the reaction course and the purity of the synthesized compounds was carried out
on Silufol UV-254 plates in the solvent system ethyl acetate and ethyl acetate−alcohol (1:1).
6(7)-Nitroperimidine (2a). Yield 0.177 g (83%); mp 240-242ºC (water) (mp 240-241oC [1]). 1H NMR
spectrum, , ppm (J, Hz): 6.45 (1H, d, J = 8.2, H-9(4)); 6.72 (1H, d, J = 8.2, H-4(9)); 7.27 (1H, dd, J = 8.5, J = 8.2,
H-8(5)); 7.62 (1H, s H-2); 8.03 (1H, d, J = 8.3, H-5(8)); 8.08 (1H, d, J = 8.5, H-7(6)); 10.58 (1H, br. s, NH). Found,
%: C 62.15; H 3.26; N 19.66. C11H7N3O2. Calculated, %: C 61.97; H 3.31; N 19.71.
2-Methyl-6(7)-nitroperimidine (2b). Yield 0.184 g (81%); mp 233-235ºC (aqueous alcohol) (230-
235ºC [1]); The 1H NMR spectrum was similar to that given in [1].
1
2-Phenyl-6(7)-nitroperimidine (2c). Yield 0.220 g (76%); mp 207-209ºC (aqueous alcohol). H NMR
spectrum, , ppm (J, Hz): 6.47 (1H, d, J = 8.2, H-9(4)); 6.74 (1H, d, J = 8.3, H-4(9)); 7.55 (4H, m, H-8(5), 3,4,5-Ph);
8.02 (1H, d, J = 8.3, H-5(8)); 8.07 (1H, d, J = 8.5, H-7(6)); 8.93 (2H, d, J = 7.3, 2,6-Ph); 10.55 (1H, br. s, NH).
Found, %: C 70.71; H 3.78; N 14.54. C17H11N3O2. Calculated, %: C 70.58; H 3.83; N 14.52.
6(7)-Aminoperimidine (3a). Yield 0.126 g (69%); mp 261-262ºC (ethyl acetate) (mp 261-262ºC [2]).
The 1H NMR spectrum was similar to that given in [2].
6(7)-Amino-2-methylperimidine (3b). Yield 0.132 g (67%); mp 274-275ºC (ethyl acetate) (mp 274-275ºC
[2]). Dihydrochloride mp ˃ 310ºC (mp ˃ 310ºC [3]). The 1H NMR spectrum was similar to that given in [2].
6(7)-Amino-2-phenylperimidine (3c). Yield 0.161 g (62%); mp 288-289ºC (ethyl acetate) (mp 288-289ºC
[4]). The 1H NMR spectrum is similar to that given in [4].
This work was carried out with the financial support of the Russian Fund for Basic Research (grant
10-03-00193a) and within the framework of the Federal Target Program "Science, Academic and Teaching Staff
of Innovative Russia for the years 2009-2013" (State contract No. 16.740.11.0162).
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