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ISSN 2522-1841 (Online) AZ9RBAYCAN KIMYA JURNALI № 2 2018 ISSN 0005-2531 (Print)
UDC 547.44+547.8
THREE-COMPONENT SYNTHESIS ON THE BASIS OF VARIOUS BENZYLIDENEMALONONITRILES
F.N.Naghiyev, A.R.Asgarova, I.G.Mammadov, A.M.Maharramov
Baku State University farid.orgchemist@gmail.com Received 07.09.2017
There has been revealed the formation of substituted imino- and imidazopyridines by the one-pot, catalyst free three-component reaction of some benzylidenemalononitriles with malononitrile and various amines. Structures of all synthesized compounds were confirmed by NMR and X-Ray spectroscopy.
Keywords: 2-thiophenemethylamine, malononitrile, benzylidenemalononitrile, NMR, X-Ray.
Introduction
Derivatives of pyridine are the main part of various natural products and nitrogen-containing heterocycles very important in bioorganic and medicine chemistry. This group compounds demonstrate antiinflammatory, antioxidant, antipyretic, antitumor, anticanser, antiphtisic, analgetic, antiviral etc. properties [1-8].
One group of authors [9] synthesized 3,4,5-substituted 1,4-dihydropyridines with high yield from the amine hydrochloride salts, aldehydes and acetals in catalyst free condition.
In another work [10] information about the synthesis of 2,4,6-threearyl pyridines (with 34-76% yield) by using three-component reaction of chalcones, ketones and ammonia in the presence of magnezium metoxide was presented.
Important information about the synthesis of substituted pyridines in water, ethanol,
methanol, dichloromethane and on the basis of aldehydes, malononitrile, aromatic amines, ena-mines, dimethylacetylenedicarboxylate, ketones, benzoyl acetonitrile etc. are presented in references [11-18].
Results and discussions
In the present work one-pot, catalyst free, three-component reaction of benzylidenemalononitriles, malononitrile and furfurilamine (or 2-thiophenemethylamine) in methanol solution, at room temperature, at 48-72 hours reaction time and formation of corresponding dihydropyri-dine derivatives (IV-VI) are demonstrated (Scheme 1).
Structures of synthesized compounds confirmed by NMR and X-Ray spectrometry (X-Ray structure of compound 6 was presented in Figure).
C=N
X"A rCH=C\
C=N
C=N /
C=N II
Y III
NH
N
2 CH3OH
NH2 -Y
HN^>
N
X= H, Y=O (IV); X=F, Y=S (V); X=CH3 Y=S (VI).
IV, V
VI
Scheme 1. Three-component one-pot synthesis of benzylidenemalononitrile, malononitrile and furfurilamine (or 2-thiophenemethylamine).
X
X
+
+
r.t., 48-72 h
2
I
X-ray structure of compound VI.
As seen in the Figure, hydrogen bond was formed between the nitrogen atom of nitrile group of one molecule and hydrogen atom of NH2-group of another molecule of compound VI and so as thiophene and aromatic ring located perpendicular to dihydropyridine ring.
There was revealed the formation of corresponding tetrahydroimidazopyridine derivatives (X-XII) by using three component, one-pot reaction of different benzylidenemalo-nonitriles with the malononitrile and ethylen-diamine (Scheme 2).
N—. C=N C=N
Y4 rCH=C(
+
^_/J
Z
+ HN,
NH,
VII
VIII
IX
N.
r.t., 48-72 h
C^.N:
N
N Y "NH2 hn N ^NH2
X XI. XII
X=H, Y=OH, Z= OCH3 (X); X= H. Y=CF3, Z=H (XI); X=Br, Y=H, Z=Br (XII).
Scheme 2. Three-component one-pot reaction of corresponding benzylidenemalononitriles (VII), malononitrile and ethylendiamine.
If process occurs in MW, reaction time decreases up to 170-175 minutes.
Experimental part. General remarks
All commercially available chemicals were obtained from Merck and Fluka (sigma aldrich) companies and used without further purification. Melting points were measured on a Stuart SMP30
1 13
apparatus without correction. Spectra 1H/13C NMR were recorded on Bruker Avance 300-MHz spectrometer at 300 and 75 MHz, respectively. X-Ray analyses were performed on Bruker APEX X-Ray equipment. Thin-layer chromatography (TLC) on commercial aluminum-backed plates
of silica gel (60 F254) was used to monitor the progress of reactions.
General experimental procedure
2,6-Diamino-1-(furan-2-ylmethyl)-4-phe-nyl-1,4-dihydropyridine-3,5-dicarbonitrile (IV).
Benzylidenemalononitrile (5.2 mmol) and malononitrile (5.3 mmol) stirred in 30 ml of methyl alcohol. Furfurilamine (5.3 mmol) (or 2-thiophenemethylamine) also added to reaction mixture stirred 72 hours at room temperature. The progress of the reaction was monitored by TLC (EtOAc/«-hexane, 3:1). Crystals were precipitated after evaporation of solvent, filtered by
Y
Y
Z
X
F.N.NAGHIYEV et al.
13
paper, recrystallized from ethanol-water mixture and obtained in pure form (yield 1.15 g, 70.12%).
White powder; m.p. - 1770C; 1H NMR (300 MHz, DMSO-J6): 7.65 (s, 1H, OCH=); 7.19 (m, 3H, 3CHarom); 6.83 (d, 2H, NH2); 6.45 (t, 1H, CH=); 6.34 (m, 5H, 2CHarom + CH= + NH2); 5.01 (s, 2H, CH2N); 3.92 (s, 1H, CH). 13C NMR (75 MHz, DMSO-J6): 152.90, 150.09, 145.67, 143.39, 128.78, 126.93, 121.83, 110.98, 109.91, 62.50, 41.37, 40.15.
2,6-Diamino-4-(4-fluorophenyl)-1-(thio-phen-2-ylmethyl)-1,4-dihydropyridine-3,5-di-carbonitrile (V) was synthesized in the same conditions by using 2-(4-fluorobenzylidene)ma-lononitrile (yield - 1.21 g, 84.61%).
Colorless powder; m.p. - 2050C; 1H NMR (300 MHz, DMSO-J6): 7.51 (m, 1H, SCH=); 7.06 (t, 2H, NH2); 6.90 (t, 2H, 2CHarom); 6.68 (t, 2H, 2CHarom); 6.37 (m, 4H, NH2+2CH=); 5.17 (s, 2H, CH2N); 3.96 (s, 1H, CH). 13C NMR (75 MHz, DMSO-J6): 160.98, 152.47, 141.73, 137.63, 128.83, 128.18, 127.22, 121.63, 115.36, 115.08, 63.14, 42.89, 39.34.
6-Amino-2-imino-1-(thiophen-2-ylme-thyl)-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicar-bonitrile (VI) was synthesized in the same conditions by using 2-(4-methylbenzylidene)malo-nonitrile (yield - 0.87 g, 60.41%).
Brown powder; m.p. - 1940C; 1H NMR (300 MHz, DMSO-J6): 8.11 (t, 1H, NH=); 7.45-7.34 (m, 7H, 4CHarom+3CH=); 4.74 (d, 2H, CH2N); 3.40 (s, 2H, NH2); 2.38 (s, 3H, CH3). 13C NMR (75 MHz, DMSO-J6): 161.31, 160.14, 159.09, 142.43, 140.15, 132.57, 129.58, 128.69, 126.94, 126.89, 125.58, 117.02, 116.86, 80.84, 79.87, 39.31, 21.38.
5-Amino-7-(4-hydroxy-3-methoxyphe-nyl)-2,3-dihydroimidazo[1,2-a]pyridine-6,8-di-carbonitrile (X). 2-(4-Hydroxy-3-methoxyben-zylidene)malononitrile (4 mmol) and malono-nitrile (4.1 mmol) stirred for 5-7 min in 30 ml of methyl alcohol. Ethylendiamine (4.1 mmol) also added to reaction mixture stirred 72 hours at room temperature. The progress of the reaction was monitored by TLC (EtOAc/«-he-xane, 3:1). Crystals were precipitated after evaporation of solvent, filtered by paper, recrystallized from ethanol-water mixture and obtained in pure form (yield - 1 g, 81.30%).
Black powder; m.p. - 2790C; 1H NMR (300 MHz, DMSO-J6): 8.17 (s, 2H, NH2); 7.02-6.89 (m, 3H, 3CHarom); 3.91 (s, 4H, 2CH2N); 3.79 (s, 3H, CH3O). 13C NMR (75 MHz, DMSO-J6): 160.00, 154.39, 153.04, 148.75, 147.52, 126.02, 121.72, 117.61, 117.44, 115.71, 112.89, 80.17, 71.97, 56.19, 52.53, 46.72.
5-Amino-7-(4-(trifluoromethyl)phenyl)-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6,8-dicarbonitrile (XI) was synthesized in the same conditions by using 2-(4-(trifluoromethyl)ben-zylidene)malononitrile (yield - 0.77 g, 64.70%).
Brown powder; m.p. - 2340C; 1H NMR (300 MHz, DMSO-J6): 8.20 (s, 1H, NH=); 7.91 (d, 2H, 2CHarom); 7.42 (d, 2H, 2CHarom); 6.43 (s, 2H, NH2); 4.30 (s, 1H, CH-Ar); 3.83 (m, 2H, CH2N); 3.51 (t, 2H, CH2N). 13C NMR (75 MHz, DMSO-J6): 154.11, 151.37, 139.78, 129.45, 128.36, 126.05, 121.96, 121.39, 55.88, 52.91, 45.13, 42.38, 40.84.
5-Amino-7-(3,5-dibromophenyl)-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6,8-dicarbo-nitrile (XII) was synthesized in the same conditions by using 2-(3,5-dibromobenzylidene)-malononitrile (yield - 0.42 g, 77.78%).
Brown powder; m.p. - 2960C; 1H NMR (300 MHz, DMSO-J6): 8.19 (s, 1H, NH=); 7.69 (s, 2H, 2CHarom); 7.40 (s, 1H, CHarom); 6.44 (s, 2H, NH2); 4.27 (s, 1H, CH-Ar); 3.79 (m, 2H, CH2N); 3.51 (t, 2H, CH2N). 13C NMR (75 MHz, DMSO-J6): 154.14, 151.52, 139.44, 135.38, 132.36, 130.31, 129.67, 121.89, 121.33, 55.46, 52.47, 45.13, 42.35, 40.43.
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BOZi BENZiLiDENMALONONiTRlLLOR OSASINDA ÜCKOMPONETLi SiNTEZLOR
F.N.Nagiyev, A.R.Osgarova, LQ.Mammadov, A.M.M3h3rramov
Katalizatorsuz §araitda, metanol mühitinda bazi benzilidenmalononitrillarin malondinitril, elaca da müxtalif aminlarla ardicil ügkomponentli reaksiyasi apanlmi§ va reaksiyadan yeni avazedilmi§ imino- va imidazopiridinlarin amala galmasi müayyan edilmi§dir. Sintez edilan birla§malarin qurulu§u NMR va RQA analiz metodlannin kömayila tasdiq olunmu§dur.
Agar sözlar: 2-tiofenmetilamin, malononitril, benzilidenmalononitril, NMR, X-Ray.
ТРЕХКОМПОНЕНТНЫЕ СИНТЕЗЫ НА ОСНОВЕ НЕКОТОРЫХ БЕНЗИЛИДЕНМАЛОНОНИТРИЛОВ
Ф.Н.Нагиев, А.Р.Аскерова, И.Г.Мамедов, А.М.Магеррамов
Установлено, что в результате одностадийной трехкомпонентной безкатализаторной реакции некоторых бензилиденмалононитрилов с малононитрилом, а также различными аминами образуются новые замещенные имино- и имидазопиридины. Структуры синтезированных соединений подтверждены методами ЯМР и рентгеноструктурного анализа.
Ключевые слова: 2-тиофенметиламин, малононитрил, бензилиденмалононитрил, ЯМР, рентгеноструктурный анализ.
