Synthesis and Tautomerism of Novel Quinoxalines (Part I) Quinoxaline ( 1 )

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(1)Journal of the Korean Chemical Society 2003, Vol. 47, No. 3 Printed in the Republic of Korea. Quinoxaline

(2) (1) *. (2003. 3. 11

(3) ) Synthesis and Tautomerism of Novel Quinoxalines (Part I) Ho Sik Kim * and Jin Hee Kim Department of Chemistry, Catholic University of Daegu, Gyongsan 712-702, Korea Received March 11, 2003). .. hydrazine hydrate 3-(1-hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline(9) , 9 !"# $% heteroaryl aldehyde# 2-hydroxyquinoxaline#(10-12) &. $' 9 alkyl (ethoxymethylene)cyanoacetate# $% ethoxymethylenemalononitrile () * + ,- 5-amino-1-[2-(3hydroxyquinoxalin-2-yl)propanoyl]-pyrazole#(13) &. ./0 10-131 dimethyl sulfoxide 23+4 lactam5 lactime5 6!+ 778 9: ;<)=% , !>, 778 ? H NMR@4 AB&. C* ' >+ ' DEF GHFI J6&. : KLGM#, () * , 778 9:, DEF, GHF 3-(1-Ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline(8). 1. ABSTRACT. The reaction of 3-(1-ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline (8) with hydrazine hydrate gave 3-(1-hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline (9). The reaction of compound 9 with substituted benzaldehydes and heteroaryl aldehydes afforded 2-hydroxyquinoxalines (10-12), respectively. The reaction of compound 9 with alkyl (ethoxymethylene)cyanoacetates and ethoxymethylenemalononitrile resulted in the intramolecular cyclization to give the 5-amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-pyrazoles (13), respectively. Compounds 10-13 showed the tautomerism between the lactam and lactim forms in dimethyl sulfoxide solution. The tautomer ratios were determined by the 1H NMR. The herbicidal and fungicidal activities of the synthesized compounds were investigated. Keywords: Quinoxalines, Intramolecular Cyclization, Tautomerism, Herbicidal Activity, Fungicidal Activity. . 4. NO P QRS TU@* V quinoxaline WIX>1 YZ[\] ^! _/ `ab, !> W IX% cd e ]% f! ^& g_/ `/4 Wh >, ij, :! _/k&. l >m, 5,6-dichloro-3-trifluoromethyl-2-quinoxalinone (1) 1 nH ;<)b, 2,3-diphenylbenzoquinoxaline# (2)% nop, 3-(2-thienyl)-2-chloroquinoxaline(3)1 1. 2. 3. DE, 3-amino-2-quinoxalinecarbohydrazide imide 4oxide(4)% qrs, 2-alkylthio-3-methylquinoxaline #(5)% ntu, C* chloroquinoxaline sulfonamide (NCS 339004, 6)% nv ! `& ww g_/ ` &(Chart 1). xV>1 quinoxaline WIX>! y z1 -{ ] c*e 0&% 6|+ ij } quinoxaline WIX> - nH J6' ~ `&. x +4% o-phenylenediamine(7) diethyl oxalpro5. 6. 7. 8-13. 241.

(4) . 242. 3-(1-Ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline. . #wh S 250 mL ¡¢+. (8). o-phenylenediamine 7(5.0 g, 46.24 mmol), diethyl oxalp-. C* +£¤ 150 mL ¥ ¦+4 2§ #¨&. |© a@ wª « cS X ¬r- n-® a@ ¯°- ±² tBV 8(6.10 g, ³´ 54%) .=&. mp: 161-162 C(N,N-µ¶Q·¸¹" /+£¤, Lit., 161-163 C); IR(KBr, cm ): 1731, 1662; ropionate(11.22 g, 55.48 mmol),. o. 15. −1. o. MS(m/z): 246(M+); 1H NMR(DMSO-d6, δ): 12.48(s, 1H,. NH), 7.82-7.26(m, 4H, aromatic H), 4.21-3.95(m, 3H, CH and OCH2), 1.45(d, J=7.2 Hz, 3H, CH3), 1.13(t, J=7.0 Hz, 3H, CH3). 3-(1-Hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline. . #wh S 250 mL ¡¢+. 8(5.0 g, 20.33 mmol), hydrazine hydrate(41.05 g, 813.2 mmol), C* +£¤ 150 mL ¥ ¦+ 4 3§ #¨&. |©a@ wª « + º» ¼- cS X ¬r- n-®a@ ¯°- ±² ½: tBV 9(4.92 g, ³´ 98%) .=&. mp: 286 C(N,N-µ¶Q· ¸¹"/+£¤, dec.); IR (KBr, cm ): 3433, 3264, 1667, (9). Chart 1. .1 3-(1-ethoxycarbonyl)ethyl-1,2 N@ - ! f hydrazinolysis 3-(1-hydrazinocarbonyl)ethyl2-hydroxyquinoxaline(9) &. C* 9 -{ ] cd e N fa@ l:_% @ 2-hydroxyquinoxaline# ab, 778@ % >+ 4% C>, 778 9: H NMR !@ 4 &. $' ' >+ - DEF GHFI J6&. pionate. dihydro-2-oxoquinoxaline(8)14-16. 1. o. −1. 1639; MS(m/z); 232(M ); H NMR(DMSO-d6, δ): 12.36 +. 1. (brs, 1H, OH), 9.10(s, 1H, NH), 7.82-7.22(m, 4H, aromatic H), 4.17(brs, 2H, NH2), 4.06(q, J=7.0 Hz, 1H, CH), 1.40(d, J=7.0 Hz, 3H, CH 3). 3-[1-(Substitute benzylidene)hydrazinocarbonyl]ethyl-2-. (10) . #wh S 100 mL ¡¢+ 9(1.0 g, 4.31 mmol), !"(0.69 g, 6.47 mmol), C* N,N-µ¶Q ·¸¹" 30 mL ¥ h·¦+4 2§ #¨ &. |©a@ wª « 2 pD¾ cS tB+ O¿, +£¤ - ¬r- ' « n-®a@ ¯°- ±² tBV 3-[1-(benzylidene)hydroxyquinoxaline. . x |+4 62' methyl (ethoxymethylene)C , cyanoacetate% - 62ab, 1 BD] C@ 62 2 % EP @ 62&. L%1 Haake Buchler 6, ] L% AB 62- ABa b gB1 ] &. IR 1 Mattson Genesis II FT-IR (I 62- .=ab, H NMR 1 Varian Gemini-200(200 MHz) ( 62 - .=&. C* Mass 1 Shimadzu GC/ MS QP-5000 ( 62- .=&. 17-20. 1. hydrazinocarbonyl]ethyl-2-hydroxyquinoxaline (10a). ³´ 54%) .=&. mp: 260-262 C(N,N- µ¶Q·¸¹"/+£¤); IR(KBr, cm ): 3210, 1659, o. 0.74 g(. −1. 756, 672; MS(m/z): 320(M+); 1H NMR(DMSO-d6, δ):. (lactam form A) 11.62(s, NH), 8.21(s, hydrazone CH), 4.17(q, J=7.2 Hz, CH), 1.48(d, J=7.2 Hz, CH3); (lactim form B) 11.35(s, NH), 7.87(s, hydrazone CH), 4.85(q, Journal of the Korean Chemical Society.

(5) Quinoxaline .

(6) (1). 243. J=7.2 Hz, CH), 1.42(d, J=7.2 Hz, CH3). The other proton. A) 11.40(s, NH), 4.86(q, J=7.0 Hz, CH), 1.42(d, J=7.0. signals were observed at 12.46(s, OH), 7.82-7.19(m,. Hz, CH3); (lactim form B) 11.67(s, NH), 4.17(d, J=6.8 Hz,. aromatic H) ppm.. ÀÁ' ¼Âa@ 10b-f ab, !> , *d N Ã (d !% &Ä z&.. CH), 1.48(d, J=6.6 Hz, CH3). The other proton signals. 2 - H y d ro x y -3 - [1 -(p -m et hy l be n z en yl id e n e) -. 2-Hydroxy-3-[1-(m-nitrobenzylidene)-hydrazinocarbonyl]-. 1 0.78 g( ³ ´ 55%, ±² tB) .=&. mp: 271 C(N,N-µ¶ Q·¸¹"/+£¤, dec.); IR(KBr, cm ): 3217, 1658, hydrazinocarbonyl]ethylquinoxaline(10b). o. −1. 810; MS(m/z): 334(M ); H NMR(DMSO-d6, δ): (lactam +. 1. were observed at 12.42(s, OH), 7.99-7.20 (m, aromatic H and hydrazone CH) ppm.. 1 1.35 g( ³´ 86%, ±² tB) .=&. mp: 241-243 C(N,N-µ¶Q·¸¹"/ +£¤); IR(KBr, cm ): 3203, 1659, 759, 677; MS(m/ ethylquinoxaline(10f). o. −1. z): 365(M ); H NMR(DMSO-d6, δ): (lactam form A) +. 1. form A) 11.29(s, NH), 7.84(s, hydrazone CH), 4.82(q,. 11.59(s, NH), 4.90(q, J=7.0 Hz, CH), 1.44(d, J=7.2 Hz,. J=7.0 Hz, CH), 2.29(s, p-CH3), 1.41(d, J=7.0 Hz, CH3);. CH3); (lactim form B) 11.88(s, NH), 4.21(q, J=7.0 Hz,. (lactim form B) 11.55(s, NH), 8.16(s, hydrazone CH),. CH), 1.50(d, J=7.0 Hz, CH3). The other proton signals. 4.16(q, J=7.0 Hz, CH), 2.34(s, p-CH3), 1.48(d, J=7.0 Hz,. were observed at 12.42(s, OH), 8.45-7.20 (m, aromatic. CH 3). The other proton signals were observed at 12.44. H and hydrazone CH) ppm.. (s, OH), 7.78-7.08(m, aromatic H) ppm.. 11.46(s, NH), 8.64(s, hydrazone CH), 4.16(q, J=7.2 Hz, CH),. . #wh S 100 mL ¡¢+ 9(1.0 g, 4.31 mmol), 4-pyridinecarboxaldehyde(0.70 g, 6.47 mmol), C* N,N-µ¶Q·¸¹" 30 mL ¥ h·¦+4 2 § #¨&. 2 pD¾ cS X ¬r- ' « n-®a@ ¯°- ±² tBV 11(0.94 g, ³´ 68%) .=&. mp: 258-259 C (N,N-µ¶Q·¸¹"/+£¤); IR(KBr, cm ): 3213,. 3.80(s, OCH3), 1.48(d, J=7.2 Hz, CH3). The other proton. 1663; MS(m/z): 321(M+);. signals were observed at 12.41 (s, OH), 7.84-6.80(m, aromatic. (lactam form A) 11.65(s, NH), 4.88(q, J=7.0 Hz, CH),. H) ppm.. 1.42(d, J=7.0 Hz, CH3); (lactim form B) 11.90(s, NH),. 2-Hydroxy-3-[1-(p-methoxybenzylidene)hydrazino-. 1 1.35 g( ³´ 89%, ±² tB) .=&. mp; 249-251 C(N,N-µ¶Q·¸ ¹"/+£¤); IR(KBr, cm ): 3206, 1659, 829; MS(m/z): carbonyl]-ethylquinoxaline(10c). o. −1. 350(M+); 1H NMR(DMSO-d6, δ): (lactam form A) 11.20 (s, NH), 8.15(s, hydrazone CH), 4.84(q, J=7.2 Hz, CH), 3.84(s, OCH3), 1.41(d, J=7.2 Hz, CH3); (lactim form B). 3-[1-(p-Fluorobenzylidene)hydrazinocarbonyl]ethyl-2-. 1 1.28 g( ³´ 88%, ±² t B) .=&. mp: 268-270 C(N,N-µ¶Q·¸¹"/ +£¤); IR(KBr, cm ): 3211, 1660, 756; MS(m/z): 338 hydroxyquinoxaline( 10d). o. −1. (M+); 1H NMR(DMSO-d6, δ); (lactam form A) 11.36 (s, NH), 7.88(s, hydrazone CH), 4.86(q, J=7.2 Hz, CH), 1.42(d, J=7.0 Hz, CH3); (lactim form B) 11.63(s, NH), 8.21(s, hydrazone CH), 4.17(q, J=6.6 Hz, CH), 1.48(d, J=6.6 Hz, CH3). The other proton signals were observed at 12.45(s, OH), 7.82-7.10(m, aromatic H) ppm. 3-[1-(p-Chlorobenzylidene)hydrazinocarbonyl]ethyl-. 1 1.21 g( ³´ 79%, ±² tB) .=&. mp: 261-262 C(N,N-µ¶Q·¸¹" /+£¤); IR(KBr, cm ): 3208, 1658, 818; MS(m/z): 354 2-hydroxyquinoxaline(10e). o. −1. (M ), 356(M +2); H NMR(DMSO-d6, δ): (lactam form +. +. 2003, Vol. 47, No. 3. 1. 2-Hydroxy-3-[1-(4-pyridylmethylidene)hydrazino-. carbonyl]ethylquinoxaline(11). o. −1. H NMR(DMSO-d6, δ):. 1. 4.18(q, J=7.0 Hz, CH), 1.49(d, J=7.0 Hz, CH3). The other proton signals were observed at 12.50(s, OH), 8.52 (d, J=5.8 Hz, pyridine C2-H and C6-H), 7.85-7.20(m, aromatic H, hydrazone CH, pyridine C3-H and C5-H) ppm. 3-[1-(Heteroarylmethylidene)hydrazinocarbonyl]ethyl-. . #wh S 100 mL ¡¢+ 9(1.0 g, 4.31 mmol), furfural(0.62 g, 6.47 mmol), C* N,N-µ¶Q·¸ ¹" 30 mL ¥ h·¦+4 2§ #¨&. 2 pD¾ª « cS tB+ O¿, +£¤ - ¬r- n-®a@ ¯°- ±² t BV 3-[1-(2-furylmethylidene)hydrazinocarbonyl]ethyl2-hydroxyquinoxaline(12a) 0.76 g( ³´ 57%) .= &. mp: 300 C(N,N-µ¶Q·¸¹"/+£¤, dec.); IR 2-hydroxyquinoxaline (12). o. −1. (KBr, cm ): 3210, 1658; MS(m/z): 310(M+); 1H NMR.

(7) . 244. (DMSO-d6, δ): (lactam form A) 11.29(s, NH), 4.80(q,. OH), 7.76-7.24(m, 7H, aromatic H, pyrazole C3-H and. J=7.0 Hz, CH), 1.41(d, J=7.2 Hz, CH3); (lactim form B). NH2), 5.11(q, J=7.0 Hz, 1H, CH), 4.19(q, J=7.0 Hz, 2H,. 11.53(s, NH), 4.13(q, J=7.4 Hz, CH), 1.47(d, J=7.0 Hz,. CH2CH3), 1.49(d, J=7.0 Hz, 3H, CHCH3), 1.23(t, J=7.0. CH 3). The other proton signals were observed at 12.37. Hz, 3H, CH2CH3).. (s, OH), 8.14-6.51(m, aromatic H, hydrazone CH and furan H) ppm.. C* ! z1 ¼Âa@ 9 furfural Å + 2-thiophenecarboxaldehyde 12b &. 2-Hydroxy-3-[1-(2-thienylmethylidene)hydrazinocarbonyl]-. 1 0.70 g( ³´ 50%, ±² tB) .=&. mp: 253-255 C(N,N-µ¶Q·¸¹"/+£ ¤); IR(KBr, cm ): 3204, 1658; MS(m/z): 326(M ); H ethylquinoxaline(12b). o. −1. +. 1. NMR(DMSO-d6, δ): (lactam form A) 11.33(s, NH), 8.06. 5-Amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-. . #wh S 100 mL ¡¢+ 9(1.0 g, 4.31 mmol), ethoxymethylenemalononitrile(0.80 g, 6.47 mmol), C* +£¤ 30 mL ¥ ¦+4 4§ #¨ &. 23 pD¾ª « cS X+ +£¤ - ¬r- ' « n-®a@ ¯°- ±² ½: tBV 13c(0.76 g, ³´ 57%) .=&. mp: 268-270 C(N,N-µ¶Q·¸¹"/+£¤); IR(KBr, cm ): pyrazole-4-carbonitrile(13c). −1. o. 3410, 3306, 2222, 1732, 1659, 1641, 1562; MS(m/z):. (s, hydrazone CH), 4.75(q, J=7.6 Hz, CH), 1.39(d, J=7.2. 308(M+); 1H NMR(DMSO-d6, δ): (lactam form A) 5.08. Hz, CH3); (lactim form B) 11.58(s, NH), 8.41(s, hydrazone. (q, J=7.0 Hz, CH), 1.47(d, J=7.0 Hz, CH3); (lactim form. CH), 4.13(q, J=7.6 Hz, CH), 1.47(d, J=6.8 Hz, CH3). The. B) 4.05(q, J=7.0 Hz, CH), 1.40(d, J=7.0 Hz, CH3). The. other proton signals were observed at 12.44(s, OH),. other proton signals were observed at 12.49(brs, OH),. 7.83-6.96(m, aromatic H and thiophene H) ppm.. 12.33(brs, NH), 8.08-7.16(m, aromatic H, pyrazole C3-. Alkyl 5-Amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-. pyrazole-4-carboxylate (13a,b) . #wh S 100 mL ¡¢+ 9(1.0 g, 4.31 mmol), methyl (ethoxymethylene)cyanoacetate(0.8 g, 5.17 mmol), + £¤ 30 mL, C* N,N-µ¶Q·¸¹" 10 mL ¥ h·¦+4 5§ #¨&. 2 pD¾ cS tB+ O¿, +£¤ - ¬r- ' « n-®a@ ¯°- ±² tBV methyl 5-amino1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-pyrazole-4-. ³´ 14%) .=&. mp: 280 C(N,N-µ¶Q·¸¹"/+£¤, dec.); IR(KBr,. carboxylate(13a) 0.2 g( o. cm−1): 3436, 3317, 1729, 1675, 1614; MS(m/z): 341(M+);. 1. H NMR(DMSO-d6, δ): 12.50(s, 1H, OH), 7.76-7.20(m,. 7H aromatic H, pyrazole C 3-H and NH2), 5.11(q, J=7.0 Hz, 1H, CH), 3.71(s, 3H, CH3), 1.49(d, J=7.0 Hz, 3H, CHCH3).. ÀÁ' ¼Âa@ 9 ethyl (ethoxymethylene)cyanoacetate 13b &. Ethyl 5-Amino-1-[2-(3-hydroxyquinoxalin-2-yl)propanoyl]-. pyrazole-4-carbxylate(13b)% 0.66 g( ³´ 43%, ±² tB) .=&. mp: 300 C(N,N-µ¶Q·¸¹"/+ £¤, dec.); IR(KBr, cm ): 3435, 3317, 1728, 1673, 1614; o. −1. MS(m/z): 355(M ); H NMR(DMSO-d6, δ): 12.50(s, 1H, +. 1. H and NH2)..

(8) x +4% cd e! h_% @ quinoxaline#, I% , !>, Æ@% &Ä z&. o-phenylenediamine(7) diethyl oxalpropionate +£¤ 23+4 3-(1-ethoxycarbonyl)ethyl-1,2-dihydro-2-oxoquinoxaline(8) ,. 8 +£¤ 23+4 z1 Ç¿, hydrazine hydrate ÈÉ ! Á/;] ¸4 ¿, hydrazine hydrate 3-(1-hydrazinocarbonyl)ethyl-2-hydroxyquinoxaline(9) &(Scheme 1).. 8, 9 z1 J 0 1 &Ä z 1 Ê] 778, Ë *+ carbonyl-imidoh 0 lactam5 (A) *+ enolich 0 lactim5 (B), 778@ ww Ì `&(Scheme 2).. 8 KBr pelleta@ IR .= Í 1731, 1662 cm +4 ÎÏgÐh, Ñ Ò 2Ó ;< Ô% , dimethyl sulfoxide(DMSO) 23+4% ÎÏg Ðh, Ñ Ò Õ Ó ;<;% hy- 8 DMSO 23+ LV « 1 mm spacer 0 AgCl plate 62- IR ./gÉ ÎÏgÐh 14-16. 21-24. −1. Journal of the Korean Chemical Society.

(9) Quinoxaline .

(10) (1). 245. Scheme 1.. h &·+ Û¡ cd e+I Ü! ` fa@ lA_/ 9 key intermediate@ 6 2- quinoxaline *, C y+ -{ ] h> ! S quinoxaline# &. Ë 9 N,N-µ¶Q·¸¹" 23+4 ! "# hydrazone#V 3-[1-(substituted 3. Scheme 2.. , Ñ Ò 1736, 1672 cm +4 ww ;<Ô&. C{ Ö@ 81 deuteriodimethyl sulfoxide(DMSO-d ) 23+4 ÎÏgÐh 2Ó `% lactam5 (A)a@× R `=% , !f1 Campaigne Ø! D ' J Á&. CÙ 9% IR +4 1667 cm +4 ÎÏgÐh, Ñ Ò 1Ó ; <Ô, DMSO 23+ L-4 .1 IR +4 I 1669 cm +4 ÎÏgÐh, Ñ Ò 1Ó× ;< Ú fa@ g¸ DMSO-d 23+4 ÎÏgÐh 1Ó `% lactim5 (B)a@× '&% f `= &(Scheme 3). −1. 6. 16. −1. −1. 6. benzylidene)hydrazinocarbonyl]ethyl-2-hydroxy-. quinoxaline#(10) &. C* 9 T U@* 0 Ý"#I 2-hydroxy3-[1-(4-pyridylmethylidene)hydrazinocarbonyl]ethylquinoxaline(11). &(Scheme 4). !> 1 IR +4 1663-1658 cm +4 ;<Ú ÎÏgÐh, Ñ Ò H NMR Ã MS Øa@ ÞV&.. 10-12 z1 J 0 I lactam5. Scheme 3. 2003, Vol. 47, No. 3. Ã 3-[1-(heteroarylmethylidene)hydrazino ww . carbonyl]ethyl-2-hydroxyquinoxaline(12). −1. 1.

(11) . 246. Scheme 4.. lactim5 (B), Ê] 778(Scheme 2)@ ww % f IR Ã H NMR a@ `=&. 10-12, Æß DMSO 23+ L -4 .1 IR +4% 10a, Æß 1672 cm +4 ÎÏgÐh, Ñ Ò 1Ó× ;<Ú fa@ g¸ DMSO-d 23+4 ÎÏgÐh 1Ó `% lactim 5 (B)! à ß¯á '&% f `=&. C{; 10b-f, 11, 12, Æß+% DMSO 23 + L-4 .1 IR +4 1739-1737 cm 6! 1672-1667 cm 6!+4 ÎÏgÐh, Ñ Ò 2Ó ; <Ú fa@ g¸ lactam5 (A) lactim5 (B), 778 @ '& cw&(Table 1 and Schemes 5, 6).. 10-12, 778 ?% -CHCH , CH â ã!¢, d(?@4 778, ? ®% ! >, ä Table 2+ ;<)=&.. 10a% lactam5 (A), -CHCH , CH â ã!¢ 4.17 ppm, lactim5 (B), -CHCH , CH â ã!¢% 4.85 ppm+4 ;<Ô, DMSO 23+ L-4 .1 IR +4 ÎÏgÐh, Ñ Ò (A). 1. Table 1. The carbonyl stretching region of compounds in dimethyl sulfoxide solution (window material: AgCl, thickness: 1 mm). −1. 10a 10b 10c 10d 10e 10f 11 12a 12b. 6. −1. −1. 3. 3. 3. Carbonyl Absorption Bands (cm−1). Compound. 1738 1738 1738 1738 1737 1739 1738 1739. 1672 1670 1669 1670 1668 1668 1670 1672 1667. Ó× ;<Ú fa@ g¸ lactam5 (A)g& lactim5 ! à ß¯á ab, !> 778 ?% 36%: 64%&. C* 10b-f, 11 Ã 12a,b% lactam 5 (A), -CHCH , CH â ã!¢% 4.90-4.75 ppm, lactim5 (B), -CHCH , CH â ã!¢% 4.214.13 ppm 6!+4 ;<Ô% , !> 778 ?I 1. (B). 3. 3. Journal of the Korean Chemical Society.

(12) Quinoxaline .

(13) (1). 247. Scheme 5.. Scheme 6.. @4 lactam5 (A)! lactim5 (B)g& à ß åá '&% f `=&(Table 2). CÙ !> 778?% 8.64-7.84 ppm+4 ;<Ú hydrazone CH, â ã!¢@I AB æ]× 8.45-6.51 ppm +4 ;<Ú ¼çè $% TU@*, â ã!¢ é_/ ;<;4 -CHCH , CH â ã!¢@ 778 ? % fg& BÞ! ê/]Ö@ ë &. $' 778 ? -CHCH , CH â ã! ¢@I ABÌ `]× d !Àä! ìí îá 778>, ã!¢ ïð4 ;<Ôh Íñ+ BÞ' d(? ®Ì ò=&. ó !> ã!¢ Þ 4 d(? ® Ì I `a; BÞ+ ñD `hÍñ+ d !Àä! ?d Ü! ;% -CHCH , CH â ã!¢, d(?@4 ® &. C* 10, Æß ô % h $% ô õ% h _/ ` Í h &·+ Û¡ lactam5 (A) lactim5 (B) +4 /ö 778? à ^! % + ' ÷ø1 ù¸ú ò= % , 10+4% hû 778, ?+ ü ýç ] % fa@ cw_=&. !þ+% 9 methyl Ã ethylh 0 alkyl 70%: 30%. Table 2. 1H NMR spectral data for compounds 10-12 Compound. Tautomer Ratio[a] A. B. 10a. 36. 64. 10b. 68. 32. 10c. 65. 35. 10d. 63. 37. 10e. 77. 23. 10f. 71. 29. 11. 74. 26. 12a. 61. 39. 12b. 67. 33. 3. 3. 3. 3. 2003, Vol. 47, No. 3. Chemical shift (δ ppm) CHCH3 4.17(q, 0.36H) 4.85(q, 0.64H) 4.82(q, 0.68H) 4.16(q, 0.32H) 4.84(q, 0.65H) 4.16(q, 0.35H) 4.86(q, 0.63H) 4.17(q, 0.37H) 4.86(q, 0.77H) 4.17(q, 0.23H) 4.90(q, 0.71H) 4.21(q, 0.29H) 4.88(q, 0.74H) 4.18(q, 0.26H) 4.80(q, 0.61H) 4.13(q, 0.39H) 4.75(q, 0.67H) 4.13(q, 0.33H). [a] Calculated from the integral curves of the CH signals of CHCH3..

(14) . 248. Scheme 7.. # ethoxymethylenema. lononitrile () * + , 13&.Ë 9 alkyl (ethoxymethylene)cyanoacetate# ÿ1 ethoxymethylenemalononitrile - +£¤ ' ( !_m4 §X C c _, NO P, ?Wô Éh, £O P - () * a@ §X D ¾ð. 13! cS fa@ cw'&(Scheme 7).. 13a,b, JÞV1 IR +4 34363317 cm 4 ;<Ú ¸¹h, Ñ Ò 1729-1673 cm +4 ;<Ú ÎÏgÐh, Ñ Ò, C* H NMR Ã MS Øa@ ÞV&. C* 13c , JÞV1 IR +4 3410, 3306 cm +4 ;<Ú ¸¹h, Ñ Ò, 2222 cm +4 ;<Ú ¸h, Ñ Ò, C* H NMR Ã MS Ø a@ ÞV&. (ethoxymethylene)cyanoacetate. 25,26. −1. −1. 1. −1. −1. 1. 13a, Æß DMSO 23+ L-4 .1 IR +4 1719, 1672 cm +4 ÎÏgÐh, Ñ Ò 2Ó ;<Ôab, 13b, Æß% 1723, 1669 cm +4 ÎÏgÐh, Ñ Ò 2Ó ;<Ô% , ! > Ñ Ò +4 1719, 1723 cm , Ñ Ò% pyrazole *, 4þ £O P+ tS ÎÏgÐh, Ñ Ò !b, 1672, 1669 cm , Ñ Ò% pyrazole *, 1 þ NO P+ tS ÎÏgÐh, Ñ Ò!h Íñ + 13a,b% 9 z! lactim5 (B)a@ × '& cw&(Scheme 8). C{; 13c% DMSO 23+ L-4 .1 IR +4 1737, 1667 cm +4 ÎÏgÐh, Ñ Ò 2Ó ;<Ú f a@ g¸ lactam5 (A) lactim5 (B), 778@ '& cw&. C* lactam5 (A), -CHCH , CH â ã!¢% 5.08 ppm, lactim5 (B), -CHCH , CH â ã!¢% 4.05 ppm+4 ;<Ô −1. −1. −1. −1. −1. 3. 3. Scheme 8. Journal of the Korean Chemical Society.

(15) Quinoxaline .

(16) (1). ab, !> 778 ?% 65%:35%@4 lactam5 (A) ! à ßåá '&% f `=&(Scheme 8). ' quinoxaline# ã(Echinochloa crus-galli), ~!(Eleusine indica), ¯(Alopecurus aegualis), / (Abutilon avicennae), (Aeschynomene indica) Ã W E(Ipomoea spp.) Ø z1 6Ó

(17) E+ , â+ Û¡ 500 g/ha $% 250 g/ha, ÁI*- Post(¸«*)+4 in vivo primary ¢* ' t DEF ;<)% 1 ò=&. C* ' quinoxaline# I(Pyricularia oryzae), í·(Rhizoctonia solani), Y! !(Botrytis cinerea), 77 (Pyhophthora infestans), L(Puccinia recondita) Ã g* ± (Erysiphe graminis) Ø z1 6Ó

(18) !PX + 250 ppm, ÁI@ *- in vivo primary ¢* ' t 10b, 12a, 12b% I + ¼D 56%, 63%, 56%, e "a b, 13a% Y!!+ ¼D 64% @4 GHF ;<)=&. !:, t z! @ quinoxaline# ab, 778@ % >+ ' 778. 9: &. C* ' >+ ' c d e+ ' , Áa@ DEF J6 % DEF ;<)% 1 ò=, Õ]. 1 GHF ;<)=&. x % 2003#I ? ] P+ ,- _=ab, DEF GHF+ ' screening test% LG c$ h% P O+ , _=h+ ¬6, &' "(É&.. 1. (a) Cheeseman, C. W. H.; Cookson, R. F. The Chemistry of Heterocyclic Compounds, Condensed Pyrazines; Weissberger, A., Taylor, E. C., Eds.; John Wiley & Sons: New York, 1979; pp 1-290. (b) Sato, N. Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F., Eds.; Pergamon Press : Oxfod, U. K., 1996; Vol. 6, pp 234-278. 2. Carta, A.; Sanna, P.; Loriga, M.; Setzu, M. G.; Colla, P.. 2003, Vol. 47, No. 3. 249. L.; Loddo, R. Farmaco 2002, 57, 19. 3. Yanoshita, R.; Okamoto, K.; Yomo, Y; Suwabe, Y.; Oota, A. Japan Kokai Tokkyo Koho JP 0374372; Chem. Abstr. 1991, 115, 183362e. 4. Makino, K.; Yoshioka, H. Heterocycles 1987, 26, 1215. 5. Monge, A.; Palop, J. A.; Urbasos. I.; Fernández-Alvarez, E. J. Heterocyclic Chem. 1989, 26, 1623. 6. Kunes, J.; Spulak M.; Waisser, K.; Slosarek, M.; Janota, J. Pharmazie 2000, 55, 858. 7. Gao, H.; Yamasaki, E. F.; Chan, K. K.; Shen, L. L.; Snapka, R. M. Cancer Res. 2000, 60, 5937. 8. Kim, H, S.; Kurasawa, Y.; Takada, A. J. Heterocyclic Chem. 1989, 26, 1129. 9. Kim, H. S.; Chung, J. Y.; Kim, E. K.; Park, Y. T.; Hong, Y. S.; Lee, M. K.; Kurasawa, Y.; Takada, A. J. Heterocyclic Chem. 1996, 33, 1855. 10. Kim, H. S.; Kim, E. K.; Kim, S. S.; Park, Y. T.; Hong, Y. S.; Kurasawa, Y. J. Heterocyclic Chem. 1997, 34, 39. 11. Kim, H. S.; Kurasawa, Y. Heterocycles 1998, 49, 557. 12. Kim, H. S.; Jeong, G.; Lee, H. C.; Kim, J. H.; Park, Y. T.; Okamoto, Y.; Kurasawa, Y. J. Heterocyclic Chem. 2000, 37, 1277. 13. Kim, H. S.; Lee, S. U.; Lee, H. C.; Kurasawa, Y. Bull. Korean Chem. Soc. 2002, 23, 511. 14. L’Italien, Y. J.; Banks, C. K. J. Am. Chem. Soc. 1951, 73, 3246. 15. Gore, P. H.; Hughes, G. K. J. Am. Chem. Soc. 1955, 77, 5738. 16. Campaigne, E.; McLaughlin, A. R. J. Heterocycilc Chem. 1983, 20, 623. 17. Fuson, R. C.; Parham, W. E.; Reed, L. J. J. Org. Chem. 1946, 11, 194. 18. Jones, R. G. J. Am. Chem. Soc. 1951, 73, 3684. 19. Jones, R. G. J. Am. Chem. Soc. 1952, 74, 4889. 20. Horning, E. C. Organic Syntheses; Parham, W. E., Reed, L. J., Eds.; John Wiley & Sons: New York, U. S. A., 1995; Collective Vol. 3, pp 395-397. 21. Bensaude, O.; Chevrier, M.; Dubois, J. E. J. Am. Chem. Soc. 1978, 100, 7055. 22. Bensaude, O.; Chevrier, M.; Dubois, J. E. J. Am. Chem. Soc. 1979, 101, 2423. 23. Guillerez, J.; Bensaude, O.; Dubois, J. E. J. Chem. Soc. Perkin Trans. II, 1980, 620. 24. Sayed, M. A.; El-Khamry, A. A.; Soliman, A. Y.; Afify, A. A.; Kassab, E. A. J. Chem. Soc. Pak. 1988, 10, 315. 25. Kim, H. S.; Lee, S. U.; Jeong, W. Y.; Han, S. W.; Kim, D. I.; Kurasawa, Y. J. Korean Chem. Soc. 2001, 45, 318. 26. Kim, H. S.; Jeong, W. Y.; Choi, K. O.; Lee, S. U.; Kwag, S. T.; Lee, M. K. J. Korean Chem. Soc. 2002, 46, 37..

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Synthesis and Tautomerism of Novel Quinoxalines (Part I) Quinoxaline ( 1 )  

Synthesis and Tautomerism of Novel Quinoxalines (Part I) Quinoxaline ( 1 )