Green preparation method for quinoline compounds

Abstract

Pharmaceutical and chemical intermediates and related chemistry providing a green preparation method for quinoline compounds. N-Substituted arylamine derivatives as raw material react with arylacetylene or arylethylene derivatives for 24 hours at 80 C.-160 C. in the presence of Brnsted acid catalyst and oxidant without solvent, to obtain quinoline compounds. Beneficial characteristics include convenient operation, mild reaction conditions, environmentally friendly property and possibility of realizing industrialization, and provides the quinoline compounds in high yields. The quinoline compounds synthesized by this method can be further functionalized into various compounds which have potential applications in development and research of natural products, functional materials and fine chemicals.

Claims

1. A green preparation method for quinoline compounds, wherein N-Substituted arylamine derivatives as raw material reacting with arylacetylene or arylethylene derivative for 24 hours at 80 C.160 C. in the presence of Brnsted acid catalyst and oxidant without solvent, to obtain quinoline compounds, wherein a synthetic route as follows: ##STR00010## R.sup.1 is selected from H, alkyl and halogens; R.sup.2 is selected from H, alkyl, ester, substituted phenyl and thiophenyl; R.sup.3 is selected from H, alkyl, ester, halides, OMe and carbomethoxy; a molar ratio of the N-Substituted arylamine derivative to the catalyst is 1:0.05 to 1:0.2; and a molar ratio of the N-Substituted arylamine derivative to the arylacetylene or arylethylene derivative is 1:1 to 1:20.

2. The preparation method according to claim 1, wherein the catalyst is acetic acid, trifluoroacetic acid, toluene-p-sulfonic acid or trifluoromethanesulfonic acid.

3. The preparation method according to claim 1, wherein the oxidant is air, pure oxygen or peroxide.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a .sup.1H NMR of 2,4-diphenylquinoline in example 1.

(2) FIG. 2 is a .sup.13C NMR of 2,4-diphenylquinoline in example 1.

(3) FIG. 3 is a .sup.1H NMR of 2-(5-bromothiophen-2-yl)-6-methyl-4-phenylquinoline in example 2.

(4) FIG. 4 is a .sup.13C NMR of 2-(5-bromothiophen-2-yl)-6-methyl-4-phenylquinoline in example 2.

(5) FIG. 5 is a .sup.1H NMR of 2-(3, 4-dichlorophenyl)-6-methyl-4-phenylquinoline in example 3.

(6) FIG. 6 is a .sup.13C NMR of 2-(3, 4-dichlorophenyl)-6-methyl-4-phenylquinoline in example 3.

(7) FIG. 7 is a .sup.1H NMR of ethyl 2-(6-methyl-4-phenylquinolin-2-yl)acetate in example 4.

(8) FIG. 8 is a .sup.13C NMR of ethyl 2-(6-methyl-4-phenylquinolin-2-yl)acetate in example 4.

(9) FIG. 9 is a .sup.1H NMR of 6-methyl-2-phenyl-4-(o-tolyl)quinoline in example 5.

(10) FIG. 10 is a .sup.13C NMR of 6-methyl-2-phenyl-4-(o-tolyl)quinoline in example 5.

(11) FIG. 11 is a .sup.1H NMR of 4-(4-fluorophenyl)-6-methyl-2-phenylquinoline in example 6.

(12) FIG. 12 is a .sup.13C NMR of 4-(4-fluorophenyl)-6-methyl-2-phenylquinoline in example 6.

(13) FIG. 13 is a .sup.1H NMR of 4-(4-methoxyphenyl)-6-methyl-2-phenylquinoline in example 7.

(14) FIG. 14 is a .sup.13C NMR of 4-(4-methoxyphenyl)-6-methyl-2-phenylquinoline in example 7.

(15) FIG. 15 is a .sup.1H NMR of 4-(6-methyl-2-phenylquinolin-4-yl)phenyl acetate in example 8.

(16) FIG. 16 is a .sup.13C NMR of 4-(6-methyl-2-phenylquinolin-4-yl)phenyl acetate in example 8.

DETAILED DESCRIPTION

(17) The preparation method for the quinoline compounds in current invention has the advantages of low cost of raw material, fewer reaction steps, mild reaction conditions, environmentally friendly property, convenient operation and high reaction yield.

(18) The current invention is further described below in combination with the specific examples. The examples are only used for illustrating the current invention, not used for limiting the scope of current invention. Simple replacement or improvement made to the current invention by those skilled in the art belongs to the technical solution protected by the current invention.

Example 1: Synthesis of 2,4-diphenylquinoline

(19) In a 25 mL reactor N-benzyl aniline (0.037 g, 0.2 mmol) and arylacetylene (0.102 g, 1.0 mmol) are added; trifluoroacetic acid (0.003 g, 0.03 mmol) is then added while stirred. The reaction mixtures materials are stirred for 24 h under an oxygen atmosphere at 80 C. Column chromatography separation (silica gel with 200-300 meshes; eluent, petroleum ether/dichloromethane=4/1) is conducted to obtain 0.047 g of 2,4-diphenylquinoline with a yield of 83%.

(20) ##STR00002##

(21) Pale yellow oil; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.23 (d, J=8.4 Hz, 1H), 8.19 (d, J=8.4 Hz, 2H), 7.91 (d, J=8.3 Hz, 1H), 7.82 (s, 1H), 7.75-7.71 (m, 1H), 7.57-7.46 (m, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3): 156.8, 149.1, 148.8, 139.6, 138.4, 130.1, 129.5, 129.5, 129.3, 128.8, 128.6, 128.4, 127.5, 126.3, 125.7, 125.6, 119.3.

Example 2: synthesis of 2-(5-bromothiophen-2-yl)-6-methyl-4-phenylquinoline

(22) Operation is the same as that in example 1. N((5-bromothiophen-2-yl)methyl)-4-methylaniline reacts with arylacetylene to produce 0.059 g of 2-(5-bromothiophen-2-yl)-6-methyl-4-phenylquinoline with a Yield of 78%.

(23) ##STR00003##

(24) Brown solid; melting point of 181.1-182.0 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.01 (d, J=8.6 Hz, 1H), 7.56-7.50 (m, 8H), 7.42 (d, J=4.0 Hz, 1H), 7.06 (d, J=4.0 Hz, 1H), 2.43 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3): 149.8, 148.9, 146.6, 138.0, 136.5, 132.2, 131.0, 129.4, 128.9, 128.6, 128.5, 125.8, 125.7, 124.5, 117.1, 116.0, 21.8; HRMS (ESI, m/z) calcd for C.sub.20H.sub.15NBrS.sup.+: 380.0103 [M+H].sup.+; found: 380.0109; IR (neat) 3046, 2959, 2825, 1608, 1563, 1442, 1021, 850, 790, 732, 574 cm.sup.1.

Example 3: Synthesis of 2-(3, 4-dichlorophenyl)-6-methyl-4-phenylquinoline

(25) Operation is the same as that in example 1. N-(3,4-dichlorobenzyl)-4-methylaniline reacts with arylacetylene to produce 0.067 g of 2-(3, 4-dichlorophenyl)-6-methyl-4-phenylquinoline with a yield of 92%.

(26) ##STR00004##
White solid; melting point of 143.0-143.6 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.11 (d, J=8.5 Hz, 1H), 7.71-7.68 (m, 2H), 7.62 (s, 1H), 7.58-7.48 (m, 7H), 7.37 (dd, J=8.5, 2.1 Hz, 1H), 2.47 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3): 154.8, 147.5, 147.2, 138.1, 138.1, 137.0, 135.0, 133.1, 132.6, 131.8, 129.8, 129.7, 129.5, 128.5, 128.3, 127.4, 125.6, 124.4, 122.7, 21.8.

Example 4: Synthesis of ethyl 2-(6-methyl-4-phenylquinolin-2-yl)acetate

(27) Operation is the same as that in example 1. Ethyl p-tolylglycinate reacts with arylacetylene to produce 0.051 g of ethyl 2-(6-methyl-4-phenylquinolin-2-yl)acetate with a yield of 87%.

(28) ##STR00005##

(29) Brown solid; melting point of 115.4-116.1 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 58.27 (d, J=8.7 Hz, 1H), 8.10 (s, 1H), 7.70 (s, 1H), 7.61 (dd, J=8.7, 1.8 Hz, 1H), 7.56-7.51 (m, 5H), 4.56 (q, J=7.1 Hz, 2H), 2.49 (s, 3H), 1.49 (t, J=7.1 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3): 165.5, 148.9, 146.8, 146.7, 138.9, 137.7, 132.3, 130.8, 129.5, 128.6, 128.5, 127.7, 124.3, 121.3, 62.1, 21.9, 14.3.

Example 5: Synthesis of 6-methyl-2-phenyl-4-(o-tolyl)quinoline

(30) In a 25 mL reactor N-benzyl-4-methylaniline (0.039 g, 0.2 mmol) and 1-methyl-2-vinylbenzene (0.236 g, 2.0 mmol) are added; toluene-p-sulfonic acid (0.003 g, 0.02 mmol) is then added while stirred. The reaction mixtures are stirred for 24 h under air at 130 C. Column chromatography separation (silica gel with 200-300 meshes; eluent, petroleum ether/dichloromethane=2:1) is conducted to obtain 0.048 g of 6-methyl-2-phenyl-4-(o-tolyl)quinoline with a yield of 78%.

(31) ##STR00006##

(32) Brown solid; melting point of 122.1-123.0 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.18-8.12 (m, 3H), 7.71 (s, 1H), 7.53-7.22 (m, 9H), 2.39 (s, 3H), 2.07 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3): 155.9, 148.3, 147.1, 139.6, 138.0, 136.2, 136.0, 131.7, 130.1, 129.7, 129.6, 129.1, 128.7, 128.2, 127.4, 126.1, 125.7, 124.4, 119.3, 21.6, 20.0.

Example 6: 4-(4-fluorophenyl)-6-methyl-2-phenylquinoline

(33) Operation is the same as that in example 5. N-benzyl-4-methylaniline reacts with 1-fluoro-4-vinylbenzene to produce 0.044 g of 4-(4-Fluorophenyl)-6-methyl-2-phenylquinoline with a yield of 71%.

(34) ##STR00007##

(35) Yellow solid; melting point of 112.9-113.5 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.17-8.12 (m, 3H), 7.72 (s, 1H), 7.58-7.43 (m, 7H), 7.25-7.20 (m, 2H), 2.46 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3): 163.7 (d, .sup.1JC-F=248.0), 154.8, 148.6, 147.3, 138.5, 136.3, 135.9 (d, .sup.4JC-F=3.0 Hz), 131.8, 129.7, 129.5, 129.2 (d, .sup.3J.sub.C-F=8.4 Hz), 128.6, 128.3, 125.6, 124.4, 119.0, 115.7 (d, .sup.2J.sub.C-F=21.5 Hz), 113.0, 21.8.

Example 7: Synthesis of 4-(4-methoxyphenyl)-6-methyl-2-phenylquinoline

(36) In a 25 mL reactor N-benzyl-4-methylaniline (0.039 g, 0.2 mmol) and 1-ethynyl-4-methoxybenzene (0.198 g, 1.5 mmol) are added; trifluoromethanesulfonic acid (0.005 g, 0.03 mmol) is then added while stirred. The reaction mixtures are stirred for 24 h under an oxygen atmosphere at 110 C. Column chromatography separation (silica gel with 200-300 meshes; eluent, petroleum ether/ethyl acetate=5:1) is conducted to obtain 0.056 g of 4-(4-methoxyphenyl)-6-methyl-2-phenylquinoline with a yield of 86%.

(37) ##STR00008##
Yellow solid; melting point of 104.7-105.8 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.17-8.11 (m, 3H), 7.73 (s, 1H), 7.67 (s, 1H), 7.54-7.41 (m, 6H), 7.07-7.03 (m, 2H), 3.86 (s, 3H), 2.44 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3): 159.7, 155.9, 148.1, 147.4, 139.8, 136.0, 131.6, 130.8, 130.7, 129.8, 129.0, 128.7, 127.4, 125.8, 124.4, 119.3, 114.0, 55.3, 21.8.

Example 8: Synthesis of 4-(6-methyl-2-phenylquinolin-4-yl)phenyl acetate

(38) Operation is the same as that in example 7. N-benzyl-4-methylaniline reacts with 4-ethynylphenyl acetate to produce 0.048 g of 4-(6-methyl-2-phenylquinolin-4-yl)phenyl acetate with a yield of 68%.

(39) ##STR00009##

(40) Brown solid; melting point of 126.5-127.3 C.; .sup.1H NMR (400 MHz, CDCl.sub.3): 8.16-8.13 (m, 3H), 7.75 (s, 1H), 7.64 (s, 1H), 7.57-7.43 (m, 6H), 7.27 (d, J=8.5 Hz, 2H), 2.47 (s, 3H), 2.36 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3): 169.4, 156.0, 150.7, 147.5, 147.3, 139.6, 136.4, 136.1, 131.8, 130.6, 129.8, 129.2, 128.8, 127.4, 125.6, 124.2, 121.8, 119.5, 21.8, 21.2.