首页   按字顺浏览 期刊浏览 卷期浏览 Steric factor in reactions of substituted 2-trifluoromethylchromones with ammonia and p...
Steric factor in reactions of substituted 2-trifluoromethylchromones with ammonia and primary amines

 

作者: Vyacheslav Y. Sosnovskikh,  

 

期刊: Mendeleev Communications  (RSC Available online 1999)
卷期: Volume 9, issue 5  

页码: 204-205

 

ISSN:0959-9436

 

年代: 1999

 

出版商: RSC

 

数据来源: RSC

 

摘要:

Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Steric factor in reactions of substituted 2-trifluoromethylchromones with ammonia and primary amines Vyacheslav Ya. Sosnovskikh,* Valentin A. Kutsenko and Danil S. Yachevskii Department of Chemistry, A. M. Gor’ky Urals State University, 620083 Ekaterinburg, Russian Federation. Fax: +7 3432 61 5978; e-mail: Vyacheslav.Sosnovskikh@usu.ru Substituted 2-trifluoromethylchromones react with ammonia and primary amines at the activated double bond to form 3-aminoand 3-alkylamino-4,4,4-trifluoro-1-(2-hydroxyaryl)but-2-en-1-ones or 2-amino- and 2-alkylamino-2-trifluoromethylchroman-4-ones depending on the substituent in the 5-position of the chromone system.Previously,1–3 it was found that condensation of substituted 2-hydroxyacetophenones with trifluoroacetonitrile results in either hydroxy oxo enamines 1a,b or, in the presence of a substituent in the 6-position of the benzene ring, mixtures of hydroxy oxo enamines 1c,d and 2-amino-2-trifluoromethylchromanones 2c,d.Subsequently, compounds 1c,d were found (unpublished data) to undergo irreversible transformation in alcoholic solutions in the presence of ethylenediamine at room temperature with the formation of cyclic species 2c,d.The latter are stable substances and do not exhibit ring–chain tautomerization in solvents such as CDCl3 and [2H6]DMSO at room temperature (1H NMR data). Thus, with a CF3 group at the C(2) atom and R1 � H, the chromanone structure of 2 is energetically more favourable than aminoenone species 1. Hydrolysis of compounds 1a–d under mild conditions1 gives 2-hydroxy-2-trifluoromethylchroman-4-ones 3a–d, which can also be prepared on condensation of corresponding methyl ketones with ethyl trifluoroacetate,4 and boiling of chromanones 2c,d and 3a–d in ethanol with catalytic amounts of HCl results in 2-trifluoromethylchromones 4a–d.4 The aim of this study was to examine the reactions of substituted 2-trifluoromethylchromones 4a–d with ammonia and primary amines. It is well known5–7 that 2-methylchromones undergo ring opening under the action of amines to form corresponding aminoenones with a 2-hydroxyaryl substituent at the carbonyl group.In this connection, taking into account published data,1–3 it is believed that 2-trifluoromethylchromones 4a–d will either exhibit a similar behaviour or, because of high electron-withdrawing capability of the CF3 group (at R1 � H), give products of amine addition to the double bond without opening the pyrone ring.We found that the structure of products strictly depends on the substituent in the 5-position of the chromone system: at R1 � H, reactions of chromones 4 with ammonia and primary amines are arrested at the step of nucleophilic addition and at R1 = H proceed further and are accompanied by opening of the pyrone ring to form corresponding aminoenones.Thus, the reactions of ammonia, methylamine (25% aqueous solutions) and benzylamine with alcoholic solutions of chromones 4a,b proceed at room temperature in 1–3 h and result in yellow hydroxy oxo enamines 1a,b, 5a,b and 6a,b, respectively,† in 58–88% yields.At the same time, chromones 4c,d having substituents in the 5-position (R1 � H) react with the above amines under the same conditions to form chromanones 2c,d, 7c,d and 8c,d (25–76% yields)‡ in 0.5 h (NH3 and MeNH2) or 7 h (PhCH2NH2). To explain the structural difference between the products, it is reasonable to suggest that, regardless of the position of a substituent in the aromatic ring, the reaction proceeds via pyrone ring opening to form intermediate B being in the equilibrium with cyclic intermediate A, the primary product of nucleophilic addition.At R1 � H, intermediate B is destabilised because of steric hindrances that occur between the substituent R1 and vinyl hydrogen of the enamine unit and hinder the formation of a planar conformation. Interactions that are inevitable in the structure of B at R1 � H render the open species energetically less favourable and shift the equilibrium towards intermediate A.The latter intermediate leads to chromanones 2c,d, 7c,d and 8c,d, which are incapable of ring–chain tautomerization. At R1 = H, the equilibrium is shifted towards intermediate B, which forms aminoenones 1a,b, 5a,b and 6a,b upon proton transfer.These aminoenones exhibit planar conformations stabilised by two intramolecular hydrogen bonds and, because of this, are not prone to cyclization.§ Taking into account that aminoenones 1c,d easily convert to chromanones 2c,d, the possibility of intermediate B converting into aminoenones with R1 � H, which undergo irreversible cyclization to chromanones R2 R3 R4 OH R1 O CF3 NH2 R1 R2 R3 R4 O O NH2 CF3 R1 � H R1 R2 R3 R4 O O OH CF3 1a–d 2c,d 3a–d THF HCl R1 R2 R3 R4 O O 4a–d D HCl CF3 HCl D a R1 = R2 = R3 = R4 = H b R1 = R2 = H, R3 + R4 = benzo c R1 = R3 = Me, R2 = R4 = H d R1 + R2 = benzo, R3 = R4 = H R1 R2 R3 R4 O H O H CF3 N H R R1 R2 R3 R4 O O NHR CF3 4a–d 1a,b, 5a,b, 6a,b 2c,d, 7c,d, 8c,d RNH2 R1 = H R1 � H a R1 = R2 = R3 = R4 = H b R1 = R2 = H, R3 + R4 = benzo c R1 = R3 = Me, R2 = R4 = H d R1 + R2 = benzo, R3 = R4 = H 1,2 R = H 5,7 R = Me 6,8 R = CH2PhMendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) 2c,d, 7c,d and 8c,d under the reaction conditions, cannot also be excluded. The appearance of a doublet of quartets of the N–Me group is the characteristic feature of the 1H NMR spectra of aminoenones 5a and 5b, which have the Z-configuration of the double † Compounds 1a,b were described in refs. 1 and 2. 4,4,4-Trifluoro-1-(2-hydroxyphenyl)-3-methylaminobut-2-en-1-one 5a: yield 78%, mp 118–119 °C. 1H NMR (100 MHz, CDCl3) d: 3.15 (dq, 3H, MeN, J 5.8, 1.4 Hz), 6.22 (s, 1H, =CH), 6.85 [td, 1H, H(5), J 8.0, 1.4 Hz], 6.95 [dd, 1H, H(3)], 7.40 [td, 1H, H(4)], 7.66 [dd, 1H, H(6)], 10.4 (br.s, 1H, NH), 12.69 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3190 (br., NH), 1625 (C=O), 1580, 1570 (C=C, NH). Found (%): C, 53.87; H, 4.22; N, 5.76. Calc. for C11H10F3NO2 (%): C, 53.88; H, 4.11; N, 5.71. 4,4,4-Trifluoro-1-(1-hydroxynaphth-2-yl)-3-methylaminobut-2-en-1-one 5b: yield 88%, mp 138–139 °C. 1H NMR (100 MHz, CDCl3) d: 3.13 (dq, 3H, MeN, J 5.8, 1.3 Hz), 6.27 (s, 1H, =CH), 7.15–7.78 (m, 5H, Harom), 8.36–8.48 (m, 1H, peri-H), 10.3 (br.s, 1H, NH), 14.37 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3180 (br., NH), 1620 (C=O), 1600, 1575, 1500 (C=C, NH). Found (%): C, 61.13; H, 4.24; N, 4.82. Calc. for C15H12F3NO2 (%): C, 61.02; H, 4.10; N, 4.74. 3-Benzylamino-4,4,4-trifluoro-1-(2-hydroxyphenyl)but-2-en-1-one 6a: yield 58%, mp 98–99 °C. 1H NMR (100 MHz, CDCl3) d: 4.60 (d, 2H, CH2, J 6.3 Hz), 6.28 (s, 1H, =CH), 6.75–6.96 [m, 2H, H(5), H(3)], 7.30– 7.47 [m, 6H, H(4), Ph], 7.66 [dd, 1H, H(6), J 8.0, 1.4 Hz], 10.6 (br. s, 1H, NH), 12.61 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3190 (br., NH), 3080, 3050 (=CH arom.), 1630 (C=O), 1580, 1530 (C=C, NH). Found (%): C, 63.47; H, 4.52; N, 4.36.Calc. for C17H14F3NO2 (%): C, 63.55; H, 4.39; N, 4.36. 3-Benzylamino-4,4,4-trifluoro-1-(1-hydroxynaphth-2-yl)but-2-en-1-one 6b: yield 65%, mp 84–85 °C. 1H NMR (100 MHz, CDCl3) d: 4.63 (d, 2H, CH2, J 6.5 Hz), 6.34 (s, 1H, =CH), 7.17–7.86 (m, 10H, Harom), 8.36–8.48 (m, 1H, peri-H), 10.6 (br. s, 1H, NH), 14.31 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3180 (br., NH), 1620 (C=O), 1575, 1500 (C=C, NH).Found (%): C, 67.74; H, 4.57; N, 3.80. Calc. for C21H16F3NO2 (%): C, 67.92; H, 4.34; N, 3.77. ‡ Compounds 2c,d were described in refs. 2 and 3. 2-Trifluoromethyl-2-methylamino-5,7-dimethylchroman-4-one 7c: yield 60%, mp 119–120 °C. 1H NMR (100 MHz, CDCl3) d: 2.1 (br. s, 1H, NH), 2.32 (s, 3H, Me), 2.43 (s, 3H, MeN), 2.59 (s, 3H, Me), 2.95 (AB system, Dd 0.34 ppm, 2H, CH2, J 16.4 Hz), 6.69 (s, 1H, Harom), 6.75 (s, 1H, Harom).IR (Vaseline oil, n/cm–1): 3350 (br., NH), 1680 (C=O), 1620, 1570, 1520 (NH, arom.). Found (%): C, 57.25; H, 5.32; N, 4.99. Calc. for , 57.14; H, 5.16; N, 5.13. 2-Trifluoromethyl-2-methylaminobenzo[f]chroman-4-one 7d: yield 76%, mp 103–104 °C. 1H NMR (100 MHz, CDCl3) d: 2.3 (br. s, 1H, NH), 2.45 (s, 3H, MeN), 3.13 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.4 Hz), 7.14–8.06 (m, 5H, Harom), 9.38 (d, 1H, peri-H).IR (Vaseline oil, n/cm–1): 3400 (br., NH), 1660 (C=O), 1625, 1600, 1575, 1515 (NH, arom.). Found (%): C, 60.90; H, 3.98; N, 4.61. Calc. for C15H12F3NO2 (%): C, 61.02; H, 4.10; N, 4.74. 2-Benzylamino-2-trifluoromethyl-5,7-dimethylchroman-4-one 8c: yield 57%, mp 93–94 °C. 1H NMR (100 MHz, CDCl3) d: 2.3 (br. s, 1H, NH), 2.32 (s, 3H, Me), 2.59 (s, 3H, Me), 2.97 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.4 Hz), 3.92 (m, 2H, CH2Ph), 6.72 (s, 2H, Harom), 7.0–7.3 (m, 5H, Ph). IR (Vaseline oil, n/cm–1): 3330 (br., NH), 3080, 3040 (=CH arom.), 1680 (C=O), 1620, 1575, 1515, 1500 (NH, arom.). Found (%): C, 65.38; H, 5.04; N, 4.01. Calc. for C19H18F3NO2 (%): C, 65.32; H, 5.19; N, 4.01. 2-Benzylamino-2-trifluoromethylbenzo[f]chroman-4-one 8d: yield 25%, mp 122–123 °C. 1H NMR (100 MHz, CDCl3) d: 2.5 (br. s, 1H, NH), 3.17 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.5 Hz), 3.96 (m, 2H, CH2Ph), 7.05–8.07 (m, 10H, Harom), 9.38 (d, 1H, peri-H). IR (Vaseline oil, n/cm–1): 3425 (br., NH), 1680 (C=O), 1620, 1600, 1575, 1515, 1500 (NH, arom.). Found (%): C, 67.81; H, 4.28; N, 3.71.Calc. for C21H16F3NO2 (%): C, 67.92; H, 4.34; N, 3.77. § Judging from the IR spectra in Vaseline oil, in which the absorption band due to the C=O group at 1660–1680 cm–1 is absent, aminoenones 1a,b, 5a,b and 6a,b with R1 = H occur only in the open form both in the solid state and in CDCl3 solutions (1H NMR spectroscopy data). We assume the possibility of their cyclization to corresponding amino chromanones; however, the conditions for this transformation, which can be considered as a new example of reversible ring–chain tautomerization, remain to be found.bond.2 This is due to the splitting at the NH proton (J 5.8 Hz), which participates in the formation of the intramolecular hydrogen bond, and the spin–spin interaction (J 1.3–1.4 Hz), which is typical of 1H and 19F nuclei and results from the spatial proximity of the methyl and trifluoromethyl groups.8 For chromanones 8c and 8d, in addition to the AB system of the CH2(3) group, we observed a multiplet due to the benzyl methylene group whose diastereotopic protons are split because of the spin–spin interaction with the NH proton.Thus, depending on the substituent in the 5-position of the chromone system, the interaction of 2-trifluoromethylchromones 4a–d with ammonia and primary amines results in either the products of addition at the C(2) atom or the pyrone ring opening to form an aminoenone system.This fact is of interest with respect to both a new approach to the preparation of 2- amino- and 2-alkylamino-2-trifluoromethylchromanones and the synthesis of fluorine-containing N-substituted hydroxy oxo enamines, which cannot be obtained by direct condensation of nitriles with ketones.1–3 This work was supported by the Russian Foundation for Basic Research (grant no. 96-03-33373). References 1 V. Ya. Sosnovskikh and I. S. Ovsyannikov, Zh. Org. Khim., 1993, 29, 89 (Russ. J. Org. Chem., 1993, 29, 74). 2 V. Ya. Sosnovskikh, Mendeleev Commun., 1996, 189. 3 V. Ya. Sosnovskikh, Izv. Akad. Nauk, Ser. Khim., 1998, 362 (Russ. Chem. Bull., 1998, 47, 354). 4 W. B. Whalley, J. Chem. Soc., 1951, 3235. 5 G. Wittig and H. Blumenthal, Ber., 1927, 60, 1085. 6 W. Baker and V. S. Butt, J. Chem. Soc., 1949, 2142. 7 A. E. A. Sammour, J. Org. Chem., 1958, 23, 1222. 8 H.Günther, NMR Spectroscopy, George Thieme Verlag, Stuttgart, 1973 (in German). R1 R2 R3 R4 O O H CF3 NH2R R1 R2 R3 R4 O O NH2R CF3 4a–d 1a–d, 5a–d, 6a–d 2c,d, 7c,d, 8c,d RNH2 R1 � H A B R1 � H Received: 14th October 1998; Com. 98/

 



返 回