Synthesi̇s of substi̇tuted pyri̇dine deri̇vati̇ves by the three component reacti̇on based on yli̇dene-cyano-acetami̇des Текст научной статьи по специальности «Химические науки»

CHEMICAL PROBLEMS 2019 no. 1 (17) ISSN 2221-8688

87

UOT 547.327+547.82

SYNTHESiS OF SUBSTITUTED PYRIDINE DERIVATIVES BY THE THREE COMPONENT REACTION BASED ON YLiDENE-CYANO-ACETAMiDES

F.N. Naghiyev, A.M. Maharramov, A.R. Asgarova, S.A. Musayeva, A.G. Rahimova,

M.A. Akhundova, I.G. Mamedov

Baku State University Z. Khalilov 23, AZ1148 Baku, Azerbaijan, e-mail:_farid.orgchemist@gmail.com

Received 16.01.2019

it was established, that by one-pot three component interaction of substituted ylidene-cyanoacetamides (or ylidenemalononitriles)with malononitrile and (S)-(-)-1-phenyl-ethylamine in methanol solution, at room temperature and without catalyst new substituted iminopyridines were formed. The corresponding substituted terpyridine derivative was synthesized by one-pot three component reaction of pyridylidenecyanoacetamide, malononitrile and 2-amino-5-bromopyridine in methanol and heating for 5-7 minutes. Structures of all synthesized compounds confirmed by NMR spectroscopy.

Keywords: ylidenecyanoacetamides, malononitrile, iminopyridines, terpyridine, NMR Doi.org/10.32737/2221-8688-2019-1-87-92

INTRODUCTION

Cyanopyridine fragment is the part of many natural physiologically active compounds. There are much information about antimicrobical and antiviral activity of cyanopyridines in world publications [1-2].

By the multicomponent interaction of

carbonyl compounds, aldehydes and amine derivatives in the presence of various catalytic systems biologically active compounds containing quinazoline, pyridine, pyrimidine, indole, imidazole pyrane fragments had been synthesized [3-13].

RESULTS AND DISCUSSIONS

Corresponding substituted pyridine in methanol, at room temperature for 48 hours.

derivatives were synthesized by one-pot three It was established that, does not dependence

component reaction of p-methyl-, p-metoxy using of benzylidenemalononitriles or

substituted benzylidenecyanoacetamides (or benzylidenecyanoacetamides, the same

thiopheneylidenecyanoacetamide) with reaction product was formed.

malononitrile and (S)-(-)-1-phenylethylamine

NC

R—CH=C// 1 \

CN CN H3C

+ / + CH CN hN

2

L2" 3

CH3OH, r.t., 48 h. _3___m^ ^

CN

R = d) 4-CH3C6H4, b) 4-CH3OC6H4, c) tiofenil,

6H4

X = CONH2 CN

HN^ ^N^ "NH.

H3C 4

R = a) 4"-CH?C6H4, b) 4-CH3OC6H4, c) tiofenil,

6H4

The plausible mechanism of reaction and 1H given (Figure 1): NMR spectra of synthesized compounds are

R

Fig. 1. 1H NMR spectrum of 6-amino-2-imino-1-(1-phenylethyl)-4-(thiophen-2-yl)-1,2-dihydro-pyridine-3,5-dicarbonitrile (4c).

By the one-pot three-component the same reaction conditions the corresponding reaction of pyridylylidenecyanoacetamide with substituted terpyridine derivatives (Figure 2) malononitrile and 2-amino-5-bromopyridine in were synthesized (7).

EXPERIMENTAL PART. GENERAL REMARKS

All commercially available chemicals Avance 300-MHz spectrometer at 300 and 75

were obtained from Merck and Fluka (Sigma MHz, respectively. Thin-layer chromatog-

Aldrich) companies and used without further raphy (TLC) on commercial aluminum-backed

purification. Melting points were measured on plates of silica gel (60 F254) was used to mo-

Stuart SMP30 apparatus without correction. nitor the progress of reactions. 1H, 13C NMR spectra were recorded on Bruker

SYNTHESiS OF SUBSTiTUTED PYRIDINE DERiVATiVES

89

.r 7

Fig. 2. 1H NMR spectrum of 6'-amino-5-bromo-2'-imino-3',4'-dihydro-2'H-[2,1':4',4''-terpyridi-ne]-3',5'-dicarbonitrile (7).

General experimental procedure

6-Amino-2-imino-1-(1-phenylethyl)-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4a): 4-Methylbenzylidenecyanoacetamide, (3 mmol) malononitril (3.1 mmol) and (S)-(-)-1-phenylethylamine (3.1 mmol) stirrered in 35 ml of methyl alcohol. Then the reaction mixture is maintained at room temperature for 2 days. The progress of the reaction was monitored by TLC (EtOAc/n-hexane, 3:2). Crystals were precipitated after evaporation of (CN), 127.16 (3CHarom), 128.61 (2CHarom.), 128.67 (2CHarom.), 129.56 (2CHarom.), 132.67 (Carom.), 140.04 (Carom.),

solvent, filtered by paper, recrystallized from ethanol-water mixture and obtained in pure form (yield 0.94 g, 88.68%). Tmp. = 180°C.

1H NMR (300 MHz, DMSO-J6): 1.54 (d, 3H, CH3, Vh-h = 6,9); 2.38 (s, 3H, CH3); 5.45 (m, 1H, CH); 7.20-7.69 (m, 12H, 9Ar-H+NH+NH2). 13C NMR (DMSO-J6), 5, m.h.: 21.38 (CH3), 21.73 (Ar-CH), 49.88 (Ar-CH), 79.74 (=Cquat.), 80.83 (=CqUat.), 116.88 (CN), 117.03

144.65 (Carom.), 158.57 (=Cquat.), 160.34 (=Cquat.), 161.25 (=Cquat.).

Found, %: 74.74 C; 5.32 H, 19.77 N. C22H19N5. Calculated, %: 74.79 C; 5.38 H, 19.83 N.

6-Amino-2-imino-4-(4-methoxyphenyl)-1-(1-phenylethyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b):

Synthesized by the same way (yield 0.9 g, 82.57%). Tmp. = 192°C.

1H NMR (300 MHz, DMSO-d6), 5, m.h.: 1.54 (d, 3H, CH3, Vh-h = 6,6); 3.82 (s, 3H, OCH3); 5.45 (m, 1H, CH); 7.10-7.81 (m, 12H, 9Ar-H+NH+NH2). 13C NMR (DMSO-d6), 5, m.h.: 21.74 (CH3), 49.89 (Ar-CH), 55.71 (Ar-CH), 79.73 (=Cquat.), 80.82 (=Cquat.), 114.36 (2CHarom.), 117.02 (CN), 117.17 (CN), 117.55 (Carom.), 124.86 (CHarom.), 127.13 (2CHarom.), 127.19 (Carom.), 127.52 (2CHarom.), 130.43 (2CHarom.), 144.65 (Carom.), 158.64 (=Cquat), 160.88 (=Cquat), 161.31

(_Cquat.).

Found, %: 71.60 C; 5.21 H, 18.92 N. C22H19N5O. Calculated, %: 71.54 C; 5.15 H, 18.97 N.

6-Amino-2-imino-1-(1-phenylethyl)-4-(thiophen-2-yl)-1,2-dihydropyridine-3,5-dicarbonitrile (4c): Synthesized by the same way (yield 0.96 g, 93.20%). Tmp. = 187°C.

1H NMR (300 MHz, DMSO-d6): 1.54 (d, 3H, CH3, Vh-h = 6,9); 5.44 (m, 1H, CHAr); 7.20-7.87 (m, 11H, 5Ar-H+3CHthiophen.+NH2+NH=). 13C NMR (75 MHz, DMSO-d6): 21.70 (CH3), 50.00 (CHAr), 79.76 (=Cquat), 80.91 (=Cquat.), 116.84 (CN), 116.96 (CN), 127.13 (2CHarom.), 127.21 (CHarom.), 128.10 (CHthiophen.), 128.62 (2CHarom.), 130.13 (CHtiophen.), 130.76 (CHtiophen.), 134.52 (Carom.), 144.52 (Ctiophen.), 152.29 (=Cquat.), 158.69 (N=Cquat.), 161.37

(_Cquat.).

Found, %: 66.04 C; 4.29 H, 20.35 N. C19H15N5S. Calculated, %: 66.09 C; 4.35 H, 20.29 N.

6-Amino-4-(4-fluorophenyl)-2-imino-1-(1-phenylethyl)-1,2-dihydropyridine-3,5-

dicarbonitrile (4d): Synthesized by the same way (yield 0.83 g, 77.57%). Tmp. = 241°C.

1H NMR (300 MHz, DMSO-J6): 1.54 (d, 3H, CH3, Vr-h = 7,2); 5.44 (m, 1H, CHAr); 7.20-7.75 (m, 12H, 9Ar-H+NH+NH2). 13C NMR (DMSO-J6), 5, m.h.: 21.70 (CH3), 49.89 (CH-Ar), 79.87 (=CqUat), 80.97 (=CqUat), 115.94-116.24 (CHarom), 116.72 (CN), 116.86 (CN), 127.17 (3 CHarom.), 127.20 (CHarom.), 128.61 (3 CHarom.), 131.21-131.33 (CHarom), 131.96 (Carom.), 144.60 (Carom.), 158.44 (=CqUat.), 159.38 (=Cquat), 161.14 (=Cquat), 161.68-164.95

(F-Carom.).

Found, %: 70.64 C; 4.54 H, 19.66 N. C21H16N5F. Calculated, %: 70.59 C; 4.48 H, 19.61 N.

6'-Amino-5-bromo-2'-imino-3',4'-dihydro-2'H-[2,1,:4,,4M-terpyridine]-3,,5'-dicarbonitrile (7):

4-Pyridylidenecyanoacetamide (3 mmol), malononitril (3.1 mmol) and 2-amino-5-bromopyridine (3.1 mmol) stirrered in 35 ml of methyl alcohol. The reaction mixture is mixed with heating for 5-7 minutes. Then the reaction mixture is maintained at room temperature for 2 days. The progress of the reaction was monitored by TLC (EtOAc/n-hexane, 3:2). Crystals were precipitated after evaporation of solvent, filtered by paper, recrystallized from ethanol-water mixture and obtained in pure form (yield 0.85 g, 72.03%).Tmp. = 236°C.

fH NMR (300 MHz, DMSO-J6): 4.61 (s, 1H, CH); 4.91 (s, 1H, CH); 7.82 (s, 1H, =NH); 7.97 (s, 2H, NH2); 7.32-8.78 (m, 7H, 7Ar-H). 13C NMR (DMSO-J6), 5, m.h.: 40.95 (CH), 47.12 (CH), 47.35 (=Cquat.), 75.34 (=Cquat), 110.96 (Cpyrd.), 112.38 (Br-Cpyrd.), 116.00 (CN), 117.30 (CN), 124.88 (CHpyrd.), 124.98 (CHpyrd), 140.61 (CHpyrd), 143.93 (CHpyrd.), 146.74 (CHpyrd.), 150.40 (CHpyrd), 150.89 (CHpyrd.), 163.56 (N=Cquat.), 163.56 (N-

Cpyrd.).

Found, %: 51.72 C; 2.99 H, 24.83 N.

C17H12NyBr. Calculated, %: 51.78 C; 3.04 H, 24.87 N.

SYNTHESiS OF SUBSTiTUTED PYRiDINE DERiVATiVES

91

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iLiDENSiANOASETAMiDLOR OSASINDA UQKOMPONENTLi REAKSiYADAN д VOZLONMig PiRiDiN TOROMOLORiMN SiNTEZi

F.N. Nagiyev, A.M. M9h9rr9mov, A.R. Osgdrova, S.A. Musayeva, A.Q. Rdhimova,

M.A. Axundova, i.Q. M9mmzdov

Baki Dovlat Universiteti AZ-1148 Baki, Z.Xalilov kug, 23; e-mail: _ farid.orgchemist agmail.com

dvazlanmi§ ilidensianoasetamidlar (va ya ilidenmalononitrillar) ila malononitril va (S)-(-)-1-fenil-etilaminin bir-marhalali, ug-komponentli reaksiyasi metanol muhitinda, katalizatorsuz §araitda, ot-aq temperaturunda aparilmi§ va reaksiyadan yeni avazlanmi§ iminopiridinlarin amala galdiyi muayyan edilmi§dir. Metanol muhitinda, katalizatorsuz §araitda, 5-7 daqiqa isidilmakla piridili-densianoasetamidin malononitril va 2-amino-5-bromopyridin ila birmarhalali, ugkomponentli reaksiyasindan uygun avazlanmi§ terpiridin toramasi sintez edilmi§dir. Alinan birla§malarin qurulu§u NMR spektroskopiyasinin komayila tasdiqlanmi§dir.

Agar sozlw. ilidensianoasetamidlar, malononitril, iminopiridinlar, terpiridin, NMR

СИНТЕЗ ЗАМЕЩЕННЫХ ПИРИДИНПРОИЗВОДНЫХ ПУТЕМ ТРЕХКОМПОНЕНТНОЙ РЕАКЦИИ НА ОСНОВЕ ИЛИДЕНЦИАНОАЦЕТАМИДОВ

Ф.Н. Нагиев, А.М. Магеррамов, А.Р. Аскерова, С.А. Мусаева, А.Г. Рагимова,

М.А. Ахундова, И.Г. Мамедов

Бакинский государственный университет AZ-1148 Баку, ул. З.Халилова, 23, e-mail: _ farid. orgchemistagmail. com

Установлено, что путем одностадийной трехкомпонентной реакцией замещенных илиденцианоацетамидов (или илиденмалононитрилов) с малононитрилом и (S)-(-)-1-фенилэтиламином в среде метанола, при комнатной температуре без катализатора образуются новые замещенные иминопиридины. А соответствующие замещенные терпиридин производные синтезированы одностадийной, трехкомпонентной реакцией пиридилиденцианоацетамида, малононитрила и 2-амино-5-бромопиридина в метаноле при нагревании в течение 5-7 минут. Структуры всех синтезированных соединений подтверждены ЯМР-спектроскопией.

Ключевые слова: илиденцианоацетамиды, малононитрил, иминопиридины, терпиридин, ЯМР