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CHEMICAL PROBLEMS 2018 no. 3 (16) ISSN 2221-8688
337
UOT 547.97+535.37
INVESTIGATION OF REACTION OF VARIOUS THIOPHENE BASED KNOEVENAGEL ADDUCTS WITH ACETOACETANILIDE
F.N. Naghiyev, A.M. Maharramov, A.R. Asgarova, A.G. Rahimova, M.A. Akhundova, I.G. Mamedov
Baku State University 23, Z.Khalilov str., AZ-1148 Baku, Azerbaijan; e-mail: [email protected]
Received 15.05.2018
The reaction of Michael addition interaction of 3-phenyl-2-(thiophene-2-carbonyl)acrylonit-rile, 2-(thiophene-2-carbonyl)-3-(p-tolyl)acrylonitrile, 3-(4-methoxyphenyl)-2-(thio-phene-2-carbonyl)acrylonitril, as well as 3-pyridinyl-2-(thiophene-2-carbonyl)acrylonitri-le with acetoacetanilide made it possible to produce substituted hexanones and 3,4-dihyd-ro-2H-pyrane derivatives. Structures of synthesized compounds were acknowledged by NMR and X-Ray structural analysis.
Keywords: thiophene, acrylonitrile, acetoacetanilide, pyran, NMR
INTRODUCTION
Pyranes and cyclic ketones are biologically active compounds to make up a structural part of natural compounds [1-2]. New [4+2] annulations were carried out in the presence of triphenylphosphine catalyst and high yield synthesized functionalized dihydropyranes [3]. A similar reaction of avalin derived phosphine was used as catalyst in another work [4]. Also, new cyclation was carried out for a,P-unsaturated ketones through the use of DABCO-catalyst and synthesized
diastereomeric dihydropyrane derivatives [5]. A cascade reaction of malononitrile and a-substituted calcone allowed to synthesize chiral multi-substituted amino-4H-pyrane derivatives. Alkoloids were checked up as catalyst in pyrane synthesis reactions [6].
The reaction of isatilidenmalononitriles with malononitriles and 2-tiophenmethylamine (or furfuril amine) one-pot three component condensation was carried out for the first time to obtain appropriate spiropiridines [7].
RESULTS AND DISCUSSION
We carried out an experiment through the use of the Michael addition reaction for 2-(thiophene-2-carbonyl)-3-(p-tolyl)acrylonitrile and 3-(4-methoxyphenyl)-2-(thiophene-2-car-bonyl)acrylonitrile with acetoacetanilide at room temperature in methanol media using of 23 drops of methylpiperazine to obtain corresponding hexanone-substituted derivatives. As
follows from the reaction mechanism, at the first stage the Michael addition of methylene active compound to double bond takes place and from the obtained Michael adduct (3) forms CH2-anion by action of base. At the last stage this anion atacks a carbonyl group of anion to synthesize an appropriate reaction products(5).
k>
^-' 1 ^=N
R = a) CH3, b) OCH3
O O
AA.
+ methylpiperazine (2-3 drops) R_fe />-
H3C CH2 NHPh MeOH \ ff
CH-CH^
TCVC
PhHN 3 O
C=N CH-CH^
5 OH
R = a) CH3, b) OCH3
>m
rvC
PhHN 4 O
2
R
1H NMR spectra of 3-cyano-4-hydroxy-6-oxo-N-phenyl-4-(thiophen-2-yl)-2-(p-tolyl)cyclo-
hexane-1-carboxamide (5a)
Subsequently by means of the Michael addition reaction of Knoevenagel adduct obtained as a result of interaction between pyridine aldehyde and 2-thenoylacetonitrile,
with acetoacetanilide in ethanol-water media through the use of 2-3 drops of methylpiperazine to obtain appropriate 3,4-dihydro-2#-pyrane derivatives.
X-Ray structure of 5-cyano-2-hydroxy-2-methyl-N,4-diphenyl-6-(thiophen-2-yl)-3,4-dihydro-2H-
pyran-3-carboxamide (11a)
EXPERIMENTAL PART
It should be noted that all used reagents were bought from Merc and Fluca and used without cleaning. The melting points of compounds were measured at STUART SPM30. Purity of synthesized compounds were checked by TLC, and structures acknowledged on "Bruker 300" NMR apparatus (300 and 75 MHz).
3-Cyano-4-hydroxy-6-oxo-N-phenyl-4-(thiophen-2-yl)-2-(p-tolyl)cyclohexane-1-carboxamide (5a): Mixture of 2-(thiophene-2-carbonyl)-3-(p-tolyl)acrylonitrile (2.9 mmol) and acetoacetanilide (3 mmol) dissolved in 35 ml of methanol was stirrered for 5-7 minutes and a 2-3 drop methylpiperazine was added, so the stirring was continued. The reaction progress was tracked by TLC (EtOAc/n-hexane, 2:1) and the mixture kept quietly for
24-48 hours. Through evaporating of solvent it became possible to precipitate crystals. Note that crystals were separated by filter paper and recrystalliized from ethanol (95%) - water mixture, yield 0.89 g, 71.60%. mp. 210°C.
1H NMR (300 MHz, DMSO-J6), 5, m.h.: 2.23 (s, 3H, CH3); 2.79 (d, 1H, CH, 3Vh-h = 14.1); 3.50 (d, 1H, CH, Vh-h = 13.8); 4.06 (s, 2H, CH2); 4.28 (d, 1H, CH, 3Vh-h = 9.9); 6.97-7.48 (m, 12H, 9Ar-H+3CHthiophenyl); 9.94 (s, 1H, NH). 13C NMR spektr (DMSO-J6), 5, m.h.: 21.14 (CH3-Ar), 44.26 (CH), 47.40 (CH), 54.07 (CH2), 62.64 (CH), 75.29 (Cquat), 119.02 (CN), 119.49 (2CHarom), 123.87 (CHthiophenyl), 124.45 (CHarom), 125.71 (CHthiophenyl), 127.63 (CHthiophenyl), 128.75 (2CHarom), 129.14 (2CHarom),129.54 (2CHarom), 137.06 (Car),
137.17 (Car), 139.14 (Car), 150.57 (Cthioph), 165.85 (CONH), 203.12 (C=O).
Found, %: 69.70 C; 5.07 H. C25H22N2O3S. Calculated, %: 69.77 C; 5.12 H. 3-Cyano-4-hydroxy-2-(4-methoxy- phenyl)-6-oxo-N-phenyl-4-(thiophen-2-yl)- cyclohe-xane-1-carboxamide (5b): it was synthesized in the same condition (yield 1.1 g, 85.61%). mp.208°C.
1H NMR (300 MHz, DMSO-d6), Ô, m.h.: 2.77 (d, 1H, CH, Vh-h = 14.1); 3.48 (d, 1H, CH, 3Vh-h = 15.3); 3.69 (s, 3H, CH3O); 4.03 (s, 2H, CH2); 4.27 (d, 1H, CH, Vh-h = 9.6); 6.89-7.47 (m, 12H, 9Ar-H+3CHthiophenyl); 9.93 (s, 1H, NH). 13C NMR spektr (DMSO-d6), Ô, m.h.: 43.88 (CH), 47.51 (CH), 54.06 (CH2), 55.37 (CH3O), 62.79 (CH), 75.22 (Cquat.), 114.23 (2CHarom), 119.07 (CN), 119.52 (2CHarom), 123.87 (CHthiophenyl), 124.42 (CHarom), 125.70 (CHthiophenyl), 127.62 (CHthiophenyl), 129.14 (2CHarom), 129.98 (2CHarom), 131.96 (Car), 139.13 (Car), 150.59 (Cthioph), 158.90 (O-Car), 165.90 (CONH), 203.14 (C=O).
Found, %: 67.50 C; 4.45 H. C25H20N2O4S. Calculated, %: 67.57 C; 4.50 H.
5-Cyano-2-hydroxy-2-methyl-N,4-diphenyl-
6-(thiophen-2-yl)-3,4-dihydro-2H-pyran-3-carboxamide (11a):
Mixture of 3-phenyl-2-(thiophene-2-carbonyl)acrylonitrile (2.9 mmol) and aceto-acetanilide (3 mmol) dissolved in 35 ml of methanol was stirrered for 5-7 minutes and a 2-3 drop methylpiperazine was added, so the stirring was continued. Reaction progress was tracked by TLC (EtOAc/n-hexane, 2:1), and the mixture was kept quietly for 24-48 hours. By evaporating of solvent crystals were precipitated. Crystals were separated by filter paper and recrystalliized from ethanol (95%) -water mixture. yield 0.9 g, 75%. mp.174°C.
1H NMR (300 MHz, DMSO-d6), Ô, m.h.: 1.72 (s, 3H, CH3); 3.07 (d, 1H, CH, 3Jh-h = 11.7); 4.38 (d, 1H, CH, 3Jh-h = 11.7); 7.007.89 (m, 13H, 10Ar-H+3CHthiophenyl); 9.86 (s, 1H, NH). 13C NMR spektr (DMSO-d6), Ô,
m.h.: 26.38 (CH3), 40.62 (CH), 55.87 (CH), 86.25 (=Cquat.), 99.73 (O-Cquat.), 119.58 (CN), 119.66 (2CHarom), 124.15 (CHarom), 128.03 (CHarom), 128.47 (CHthiophenyl), 128.60 (CHarom), 128.87 (2CHarom), 129.05 (3CHarom), 129.78 (CHthiophenyl), 130.63 (CHthiophenyl), 135.99 (Car), 138.87 (Cthioph), 140.12 (Car), 166.77 (CONH), 167.63 (O-Cquat=).
Found, %: 69.17 C; 4.76 H. C24H20N2O3S. Calculated, %: 69.23 C; 4.81 H. 5-Cyano-2-hydroxy-2-methyl-N-phenyl-4-(pyridin-4-yl)-6-(thiophen-2-yl)-3,4-dihyd-ro-2H-pyran-3-carboxamide (11b): Mixture 4-pyridinecarboxaldehyde or (2.9 mmol) and 2-thenoylacetonitrile (3 mmol) dissolved in 50 ml of ethanol-water (4:1) was stirrered 5 minutes, reaction mixture was kept quietly for 36 hours. Then acetoacetanilide (3 mmol) was added to reaction mixture, stirred for 5 minutes and after 2-3 drop methylpipe-razine was added and stirring was continued. Reaction progress was tracked by TLC (EtOAc/n-hexane, 2:1). Reaction mixture was kept quietly for 36 hours. Through evaporating of solvent it became possible to precipitate crystals. Crystals were separated by filter paper and recrystalliized from ethanol (95%) -water mixture. yield 0.97 g, 79.51%. mp.165°C.
1H NMR (300 MHz, DMSO-J6), 5, m.h.: 13C NMR spektr (DMSO-J6), 5, m.h.:
I.70 (s, 3H, CH3); 3.05 (d, 1H, CH, 3Jh-h =
II.4); 4.39 (d, 1H, CH, 3Jh-h = 11.4); 7.03-8.56 (m, 12H, 9Ar-H+3CHthiophenyl); 9.88 (s, 1H, NH). 13C NMR spektr (DMSO-J6), 5, m.h.: 26.31 (CH3), 40.21 (CH), 55.04 (CH), 84.45 (=Cquat.), 99.72 (O-Cquat.), 119.71 (CN), 120.02 (2CHarom), 124.29 (CHarom), 124.44 (CHarom), 128.52 (CHthiophenyl), 129.21 (3CHarom), 130.11 (CHthiophenyl), 130.97 (CHthiophenyl), 135.67 (Car), 138.68 (Cthioph), 149.17 (Car), 150.38 (2CHarom), 166.68 (CONH), 167.23 (O-
Cquat.=).
Found, %: 66.12 C; 4.51 H. C23H19N3O3S. Calculated, %: 66.19 C; 4.56 H.
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TiOFEN OSASLI BdZi KNOEVENAGEL ADDUKTLARININ ASETOASETANiLiDLd
REAKSiYASININ TdDQiQi
F.N. Nagiyev, A.M.Maharramov, A.R. dsgarova, A.G. Rahimova, M.A. Axundova, I.G. Mamedov
Baki Dövlat Universiteti AZ 1148 Baki, Z.Xalilov kûç., 23; e-mail: [email protected]
3-Fenil-2-(tiofen-2-karbonil)akrilonitril, 2-(tiofen-2-karbonil)-3-(p-tolil)akrilonitril vd 3-(4-metok-sifenil)-2-(tiofen-2-karbonil)akrilonitril, elaca ds 3-piridinil-2-(tiofen-2-karbonil)akrilonitrilin aseto-asetanilid ils Mixael birld^md reaksiyasiyasindan avazlanmiç heksanon vs 3,4-dihidro-2H-piran töramalarinin alinmasi müsyysn edirilmiçdir. Sintez edilsn birls^mslsin quruluçu NMR va RQA analiz metodlarinin kömsyils tasdiq olunmuçdur. Açar sözlar: tiofen, akrilonitril, asetoasetanilid, piran, NMR
ИССЛЕДОВАНИЕ РЕАКЦИИ ВЗАИМОДЕЙСТВИЯ НЕКОТОРЫХ АДДУКТОВ КНЕВЕНАГЕЛЯ НА ОСНОВЕ ТИОФЕНА С АЦЕТОАЦЕТАНИЛИДОМ
Ф.Н. Нагиев, А.М. Магеррамов, А.Р. Аскерова, А.Г. Рагимова, М.А. Ахундова, И.Г. Мамедов
Бакинский государственный университет AZ1148 Баку, ул. З.Халилова, 23; e-mail: farid. orgchemist@gmail. com
Путем реакции присоединения по Михаэлю взаимодействием 3-фенил-2-(тиофен-2-карбонил) акрилонитрила, 2-(тиофен-2-карбонил)-3-(п-толил)акрилонитрила и 3-(4-метоксифенил)-2-(тиофен-2-карбонил)акрилонитрила, а также 3-пиридинил-2-(тиофен-2-карбонил)акрилонитрила с ацетоацетанилидом были получены соответствующие замещенные гексаноны и 3,4-дигидро-2Н-пиран-производные. Структуры синтезированных соединений были подтверждены методами ЯМР и рентгено-структурного анализа.
Ключевые слова: тиофен, акрилонитрил, ацетоацетанилид, пиран, ЯМР
