Esquema 6.4 Síntese MCR do núcleo (SQXO )
5. CONCLUSÕES
6.1 MATERIAIS E REAGENTES
6.1.5 Procedimento geral para a síntese multicomponente de derivados de (E)-3-
Esquema 6.4- Síntese MCR do núcleo (SQXO)
Fonte: Autoria própria, 2019
Inicialmente, em um balão de fundo redondo de 250 ml contendo uma solução aquosa com 25 ml de AcOH (20%), foram adicionados O-Phenilenodiamina 0,2g (1,85 mmol), piruvato de sódio 0,21g(1,90 mmol), a solução ficou sob agitação durante 5 minutos, logo em seguida foi adicionado 1,2 equivalentes do aldeído aromático apropriado (2,22 mmol) juntamente com 5 equivalentes de acetato de sódio 0,75g (9,25 mmol). O meio reacional ficou sob agitação em refluxo a 120°C durante 8-14h. Após o término da reação o meio reacional foi resfriado a temperatura ambiente e foi adicionado 20 ml de água gelada, o produto precipitado foi filtrado por gravidade. Gerando os derivados de estirilquinoxalina com rendimento de 65-92%.
57 (E)-3-estiril-1H-quinoxalin-2-ona (SQXO) 50
Figura 6.1- Estrutura química de SQXO
Fonte: Autoria própria, 2019
(E)-3-estiril-1H-quinoxalin-2-ona: pf 256-258°C. IV (ATR, υmax/cm-1): 3300, 2990, 1660, 1600, 1565. 1H NMR (400 MHz, DMSO-d6): δ(ppm) 7,31 (t, 2H, CH-Ar), 7,39
(d,1H, Ar-H); 7,44 (t, 2H, Ar-H), 7,50 (t,1H, Ar-H), 7,62 (d,1H, =CH, J = 16 Hz); 7,73 (d, 2H, Ar-H); 7,78 (d,1H, Ar-H), 8,06 (d, 1H, =CH, J = 16 Hz), 12.53 (s,1H, NH). 13C NMR (400 MHz, DMSO-d6): δ(ppm) 115.7, 122.5, 123.9, 128.1, 128.8, 129.5, 129.8,
130.3, 132.2, 132.8, 136.5, 137.6, 153.5, 155.3. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H12N2O2 = 249.1022, encontrado= 249.1021.
(E)-3-(2-hidroxistiril)quinoxalin-2(1H)-ona. ( 2-HSQX) 70
Figura 6.2- Estrutura química de 2-HSQX
Fonte:Autoria própria, 2019
3-[2-(2-Hydroxi-fenil)-vinil]-1H-quinoxalin-2-ona: pf 230-232 °C (column chromatography: silica gel, hexane-ethyl acetate 10:1 v/v). IV (ATR, υmax/cm-1): 3300, 2925, 1655, 1620, 1598, 1460, 1242. 1H NMR (400 MHz, DMSO d6): δ(ppm) 6.86 (t, 1H,
J = 8Hz, Ar-H), 6.92 (d, 1H, J = 8Hz, Ar-H), 7.20 (t, 1H, J = 8Hz, Ar-H), 7.30 (t, 2H, J = 8Hz, Ar-H), 7.47 (t, 1H, J = 8Hz, Ar-H), 7.64 (d, 1H, J = 8Hz, Ar-H); 7.67 (d, 1H, J
= 16Hz, =CH), 7.77 (d, 1H, J = 8Hz, Ar-H), 8.29 (d, 1H, J = 16Hz, =CH), 10.16 (s, 1H, OH), 12.46 (s, 1H, NH). 13C NMR (400 MHz, DMSO-d6): δ(ppm) 115.6, 116.6, 120.0,
121.3, 123.3, 123.9, 128.3, 128.6, 129.9, 130.9, 132.0, 132.9, 133.2, 154.1, 155.3, 156.8. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H12N2O2 = 265.0972, encontrado= 265.0974.
58 (E)-3-(3-hidroxiestiril)quinoxalin-2(1H)-ona (3- HSQX) 71.
Figura 6.3- Estrutura química de 3-HSQX
Fonte: Autoria própria, 2019
3-[2-(3-Hidroxi-fenil)-vinil]-1H-quinoxalin-2-ona: pf 248-250 °C. IR (ATR, υmax/cm-1): 3400, 2950, 1660, 1620, 1580. 1H NMR (500 MHz, DMSO-d
6): δ(ppm) 6.79 (d, 1H, j =
5Hz, Ar-H), 7.08 (s,1H,Ar-H), 7.13 (d,1H, J = 5Hz, Ar-H), 7.23 (t, 1H, J = 5Hz, Ar-H), 7.30 (t, 2H, J = 5Hz, Ar-H), 7.48 (d, 1H, J = 10Hz, Ar-H), 7.52 (d, 1H, J = 16Hz, =CH), 7.77 (d, 1H, j =10Hz, Ar-H), 7.95 (d, 1H, J = 16Hz, =CH), 9,66 (s, 1H, OH), 12,49 (s, 1H, NH) . 13C NMR (125 MHz, DMSO-d6): δ(ppm) 114.1, 115.7, 117.2, 119.4, 122.1,
123.9, 128.8, 130.2, 130.5, 132.1, 132.8, 137.6, 137.7, 153.4, 155.3, 158.2. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H12N2O2 = 265.0972, encontrado= 265.0970.
(E)-3-(4-hidroxiestirilquinoxalin)-2(1H)-ona (4- HSQX) 72
Figura 6.4- Estrutura química de 4-HSQXO
onte: Autoria própria, 2019
3-[2-(4-Hidroxi-fenil)-vinil]-1H-quinoxalin-2-ona: pf 240-242°C (coluna cromatográfica: silica gel, hexano- acetato de etila 10:1 v/v). IV (ATR, υmax/cm-1): 3420, 2925, 1660, 1600, 1515, 1250, 755. 1H NMR (400 MHz DMSO-d6): δppm = 6.83 (d, 2H,
J = 8Hz, Ar-H), 7.28 (m, 2H, Ar-H), 7.43 (d, 1H, J = 16Hz, =CH), 7.44 (d, 1H, J = 8Hz,
Ar-H), 7.57 (d ,2H, J = 8Hz, Ar-H), 7.74 (d, 1H, J = 8Hz, Ar-H), 7.74 (d, 1H, J = 8Hz, Ar-H), 7.98 (d, 1H, J = 16Hz, =CH), 9.95 (s, 1H, OH), 12.45 (s, 1H, NH), 13C NMR (500
MHz, DMSO-d6): δ(ppm) 115.6, 116.4, 118.8, 123.9, 127.6, 128.5, 129.7, 129.9, 131.9,
132.9, 137.8, 153.8, 155.3, 159.5. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H12N2O2 = 265.0972, encontrado= 265.0973.4.2.4.4
59
(E)-3-(3-nitroestirilquinoxalin)-2(1H)-ona (3- NSQX) 73
Figura 6.5- Estrutura química de 3-NSQX
Fonte: Autoria própria, 2019
3-[2-(3-Nitro-fenil)-vinil]-1H-quinoxalin-2-ona: pf 285-286°C. IV (ATR, υmax/cm-1): 3300, 2920, 1660, 1620, 1518, 1348. 1H NMR (400 MHz, DMSO-d6): δ(ppm) 7.32 (t, 2H,
J = 8Hz, Ar-H), 7.52 (t, 1H, J = 8Hz, Ar-H), 7.70 (d, 1H, J = 8Hz, Ar-H), 7.75 (d, 1H, J
= 16Hz, =CH), 7.78 (d, 1H, Ar-H), 8.15 (d, 1H, J = 16Hz, =CH), 8.20 (m, 2H, Ar-H), 8.51 (s, 1H, Ar-H), 12.59 (s, 1H,NH). 13C NMR (400 MHz, DMSO-d
6) δ(ppm): 115.8,
122.4, 123.9, 124.1, 125.3, 128.9, 130.8, 130.9, 132.4, 132.7, 134.1, 135.0, 138.3, 148.9, 152.9, 155.2. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H11N3O3 = 294.0873, encontrado= 294.0871.
(E)-3-(4-nitroestiril)quinoxalin-2(1H)-ona ( 4-NSQX)74
Figura 6.6- Estrutura química de 4-NSQX
Fonte: Autoria própria, 2019
3-[2-(4-Nitro-fenil)-vinil]-1H-quinoxalin-2-ona: pf 288-290 °C. IV (ATR, υmax/cm-1): 3300, 2990, 1690, 1590, 1545, 1360. 1H NMR (400 MHz, DMSO-d6): δ(ppm) 7.32 (m,
2H, Ar-H), 7.53 (t, 1H, J = 8Hz, Ar-H), 7.78 (d, 1H, J = 16Hz, =CH), 7.79 (d, 1H, Ar- H), 8.01 (d, 2H, J = 8Hz, Ar-H), 8.14 (d, 1H, J = 16Hz, =CH), 8.24 (d, 2H, J = 8Hz, Ar- H), 12.6 (S, 1H, NH). 13C NMR (500 MHz, DMSO-d6): δ(ppm) 115.8, 124.1, 124.5,
126.9, 129.1, 129.1, 130.9, 132.4, 132.8, 134.9, 143.0, 147.6, 152.9, 155.2. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H11N3O3 = 294.0873, encontrado = 294.0875.
60 (E)-3-(2,4-dinitroestiril)quinoxalin-2(1H)-ona (DNSQX) 80
Figura 6.7- Estrutura química de DNSQX
Fonte: Autoria própria, 2019
3-[2-(2,4-Dinitro-fenil)-vinil]-1H-quinoxalin-2-ona: pf 288-290°C IV (ATR, υmax/cm-1): 3300, 2920, 1660, 1620, 1590, 1514, 1348. 1H NMR (200 MHz, DMSO-d6): δppm = 7.77
(m, 2H, j= 6Hz,Ar-H), 8.17 (d, 1H, jtrans = 15Hz, =CH), 8.20 (d, 1H, Ar-H), 8.75 (d, 2H, Ar-H), 8.88 (d, 1H, jtrans = 15Hz, =CH), 9.21 (s, 1H,Ar-H), 13.08. (s, 1H,NH). Falta RMN de 13C.
(E)-3-(4-fluoroestiril)quinoxalin-2(1H)-ona ( FSQX)76
Figura 6.8- Estrutura química de FSQX
Fonte: Autoria própria, 2019
3-[2-(4-Fluoro-fenil)-vinil]-1H-quinoxalin-2-ona: pf 168-170°C (recrystallized from
chloroform/hexane 1:1 v/v). IV (ATR, υmax/cm-1): 3300, 2925, 1658, 1620, 1590, 1510, 1228. 1H NMR (400 MHz, CDCl3-d6): δ(ppm) 7,03 (t, 2H, J = 8Hz, Ar-H), 7.25 (m, 2H, J = 8Hz, Ar-H), 7.37 (d, 1H, J = 8Hz, Ar-H), 7.60 (d, 1H, J = 16Hz, =CH), 7.62 (m, 2H, J = 8Hz, Ar-H), 7.83 (d, 1H, J = 8Hz, Ar-H), 8.17 (d, 1H, J = 16Hz, =CH), 12.06 (s, 1H,
NH). 13C NMR (400 MHz, DMSO- d6): δ(ppm) 115.6; 115.8; 115.9; 120.9, 124.1, 127.9,
129.8, 129.9, 130.0, 131.4, 132.6, 152.7, 155.7, 162.3. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H11FN2O = 267.0928, encontrado= 267.0926.
61 (E)-3-(bromoestiril)quinoxalin-2(1H)-ona ( BSQX) 77
Figura 6.9- Estrutura química de BSQX
Fonte:Autoria própria, 2019
3-[2-(4-Bromo-fenil)-vinil]-1H-quinoxalin-2-ona (2e): pf 235-237 °C (recrystallized
from chloroform/hexane 1:1 v/v). IV (ATR, υmax/cm-1): 3300, 2925, 1658, 1620, 1590, 1510, 1228. 1H NMR (300 MHz, DMSO-d6): δ(ppm) 7,31 (d, 2H, J = 6Hz, Ar-H), 7.51 (t, 1H, J = 6Hz, Ar-H), 7.64 (m, 4H, Ar-H), 7.66 (d, 1H, J = 15Hz, =CH), 7.78 (d, 1H, J = 6Hz, Ar-H), 8.02 (d, 1H, J = 15Hz, =CH), 12,5 (s, 1H, NH). 13C NMR (300 MHz, DMSO- d6): δ(ppm) 115.8; 123.0; 123.2; 124.1, 128.8, 130.1, 130.5, 132.1, 132.4, 135.7, 136.2,
137.3, 153.2.2; 155.2. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C16H11BrN2O = 327.0128, encontrado= 279.0131.
(E)-3-(2,4-dicloroestiril)quinoxalin-2(1H)-ona ( DCSQX) 78
Figura 6.10- Estrutura química de DCSQX
Fonte: Autoria própria, 2019
3-[2-(2,4-Dicloro-fenil)-vinil]-1H-quinoxalin-2-ona: pf 300°C IV (ATR, υmax/cm-1): 3300, 2900, 1655, 1620, 1577, 1100. 1H NMR (200 MHz, DMSO-d6): δppm = 6.70 (m,
3H, Ar-H), 6.84 (s, 1H, Ar-H), 6.99 (d, 1H, jtrans = 15Hz, =CH), 7.15 (d, 2H, Ar-H), 7.75 (d, 1H, jtrans = 15Hz, =CH), 11.80. (s, 1H,NH). Falta RMN de 13C.
62 (E)-3-(3-metoxiestirilquinoxalin)-2(1H)-ona (3- NSQX)79
Figura 6.11- Estrutura química de 3-NSQX
Fonte: Autoria própria, 2019
3-[2-(2-Metoxi-fenil)-vinil]-1H-quinoxalin-2-ona: pf 232-234 °C. IR (ATR, υmax/cm-1): 3300, 2925, 1615, 1590, 1460, 1242. 1H NMR (300 MHz, DMSO-d6): δ(ppm) 3.9 (s, 3H,
OCH3) 7.05 (m, 2H, Ar-H), 7.32 (m, 3H, Ar-H), 7.47 (d, 1H, j = 8Hz, Ar-H), 7.64 (d, 1H, J = 16Hz, =CH), 7.76 (t, 2H, J = 8Hz, Ar-H), 8.32 (d, 1H, J = 16Hz, =CH); 12.46 (s, 1H, NH). 13C NMR (400 MHz, DMSO-d6): δ(ppm) = 56.06, 112.1, 115.6, 121.3, 122.4,
123.9, 124.9, 127.8, 128.7, 130.1, 131.2, 132.1, 132.3, 132.8, 153.8, 155.2, 158.2. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C17H14N2O2 = 229.1128, encontrado=
279.1130.
(E)-3-(4-metoxiestiril)quinoxalin-2(1H)-ona ( 4-MTSQX) 80
Figura 6.12- Estrutura química de 4-MTSQX
Fonte:Autoria própria, 2019
63 (E)-3-(4-hidroxi-3-methoxiestiril)quinoxalin-2(1H)-ona ( HMSQX) 81
Figura 6.13- Estrutura química de HMSQX
Fonte: Autoria própria, 2019
3-[2-(4-Hidroxi-3-metoxi-fenil)-vinil]-1H-quinoxalin-2-ona: mp: 243-245 °C. IR (ATR,
υmax/cm-1): 3400, 2990, 1660, 1590, 1515, 1265. 1H NMR (500 MHz, DMSO-d
6): δ(ppm)
3.86 (s, 3H, OCH3), 6.83 (d, 1H, J = 5Hz, Ar-H),7.15 (d, 1H, J = 10Hz, Ar-H), 7.30(m, 3H, Ar-H),7.45 (d, 1H, J = 15Hz, =CH), 7.44 (d, 1H, j = 5Hz, Ar-H), 7.73 (d, 1H, J = 10Hz, Ar-H); 8.0 (d, 1H, J =15Hz, =CH); 9.51(s, 1H,OH), 12.43(s, 1H, NH). 13C NMR
(125 MHz, DMSO-d6): δ(ppm) 56.1, 111.2, 115.4, 116.4, 119.1, 122.5, 124.0, 128.1,
129.7, 131.7, 133.1, 138.2, 148.4, 149.1, 153.6, 155.4. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C17H14N2O3 = 295.1077, encontrado= 295.1078.
(E)-3-(3-methoxy-4-(octiloxi)estiril)quinoxalin-2(1H)-ona (OCMSQX)82 Figura 6.14- Estrutura química de OCMSQX
Fonte: Autoria própria, 2019
3-[2-(3-Metoxi-4-octiloxi-fenil)-vinil]-1H-quinoxalin-2-ona: mp 175-177 °C. IR (ATR,
υmax/cm-1): 3400, 2990, 1660, 1590, 1515, 1265, 1140. 1H NMR (500 MHz, DMSO- d
6):
δ(ppm) 0.85 (t, 3H, CH3), 1.26 (m, 8H, CH2), 1.29 (m, 2H, CH2,), 1.72 (m, 2H, CH2), 3.85(s, 3H, OCH3), 3.98 (t, 2H,OCH2), 6.99 (d, 1H, J = 10Hz, Ar-H), 7.23 (d, 1H, J = 10Hz, Ar-H), 7.28 (s, 1H, Ar-H), 7.30 (t, 2H, J = 10Hz, Ar-H); 7.46 (d, 1H, j = 10Hz, ArH); 7.50 (d,1H, J = 15Hz, =CH), 7.74 (d, 1H, J = 10Hz, Ar-H); 8.02 (d, 1H, J = 15Hz, =CH), 12.45 (s, 1H,NH). 13C NMR (125 MHz, DMSO-d6): δ(ppm) 14.4, 22.5, 25.9, 29.1,
29.2, 31.7, 56.1, 68.7, 110.7, 113.4, 115.6, 120.1, 122.2, 123.9, 128.5, 129.3, 129.8, 131.9,132.9, 137.9, 149.7, 150.2, 153.7, 155.3. HRMS (ESI/TOF-Q) m/z: [M+H]+ Calculado para C25H30N2O3 = 407.2329, encontrado= 407.2333.
64
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