Metal free process for allylic oxidation
09745240 · 2017-08-29
Assignee
Inventors
Cpc classification
C07C49/248
CHEMISTRY; METALLURGY
C07C45/64
CHEMISTRY; METALLURGY
C07C45/64
CHEMISTRY; METALLURGY
C07C49/248
CHEMISTRY; METALLURGY
International classification
C07C45/64
CHEMISTRY; METALLURGY
Abstract
The patent discloses a novel metal free process for the preparation of corresponding phenol and ketone via allylic oxidation of substituted cyclohexenes. Air is used as oxidant in the present process and can be used as such or optionally selected from pure oxygen or atmospheric oxygen. Moreover, the process of the present invention utilizes easily available starting materials and is a green eco-friendly, convenient and economical process with high yield of >60% and high selectivity.
Claims
1. A metal free process for the synthesis of a phenol compound of Formula I or a ketone compound of Formula II, ##STR00052## wherein, R is selected from CHO, COR.sub.3, COOR.sub.4, COOH, CN, NO.sub.2, Ts, nitroethene, α,β unsaturated ketone, or α,β-unsaturated ester; R.sub.1 is selected from halides, phenyl or p-F-Ph; R.sub.2 is selected from H or alkyl; R.sub.3 is selected from alkyl, allyl or phenyl; R.sub.4 is selected from alkyl, allyl or benzyl; the process comprising: a. mixing a substituted cyclohexene of formula III ##STR00053## wherein, R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as above and a solvent, with continuous bubbling of molecular oxygen at 50 to 100° C. for 5 to 60 hours; b. extracting the product of step (a); and c. purifying the product of step (b) to obtain the phenol compound of Formula I or ketone compound of Formula II which is substantially purified.
2. The process according to claim 1, wherein the extraction step involves filtering the product of step (a); treating the filtrate with water; extracting with a solvent; washing the organic extract with brine; drying the organic extract with anhydrous Na.sub.2SO.sub.4; filtering the organic extract and removing the solvent in vacuo.
3. The process according to claim 1, wherein the purification is done by column chromatography.
4. The process according to claim 1, wherein the solvent is selected from water, methanol, isopropyl alcohol, methyl cyanide, dimethyl formamide or degassed dimethyl formamide, either alone or in combination with tetrahydrofuran.
5. The process according to claim 1, wherein the step (a) mixing a substituted cyclohexene of formula III and a solvent further comprises a base selected from alkali carbonates including Potassium carbonate and Cesium carbonate, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, 2,6-lutidine, triphenylphosphine, imidazole, triethylamine or pyridine.
6. The process according to claim 1, wherein the molecular oxygen is selected from pure oxygen or atmospheric oxygen.
7. The process according to claim 1, wherein the yield of phenol compound of Formula I or ketone compound of Formula II is greater than 60%.
8. The process according to claim 1, wherein the temperature is in the range of 70 to 90° C.; time is in the range of 20 to 40 hours and yield is greater than 75%.
9. The process according to claim 1, wherein the compound of Formula I is selected from the group consisting of 3-hydroxybenzaldehyde; 3-Hydroxy-5-methylbenzaldehyde; 3-(tert-Butyl)-5-hydroxybenzaldehyde; 6-Hydroxy-[1,1′-biphenyl]-2-carbaldehyde; 4′-Fluoro-6-hydroxy-[1,1′-biphenyl]-2-carbaldehyde; (E)-4-(3-Hydroxyphenyl)but-3-en-2-one; (E)-3-(3-Hydroxyphenyl)-1-phenylprop-2-en-1-one; (E)-3-(3-Hydroxyphenyl)-1-(p-tolyl)prop-2-en-1-one; (E)-3-(3-Hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one; (E)-Ethyl 3-(3-hydroxyphenyl)acrylate; (E)-Ethyl 3-(3-hydroxy-5-methylphenyl)acrylate; and (E)-Ethyl 3-(3-(tert-butyl)-5-hydroxyphenyl)acrylate.
10. The process according to claim 1, wherein the compound of Formula II is selected from the group consisting of 2-Chloro-3-oxocyclohex-1-enecarbaldehyde; and 6-Oxo-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbaldehyde.
11. The process according to claim 1, wherein R.sub.2 is methyl, tertiary butyl or phenyl.
12. The process according to claim 2, wherein the extracting solvent is EtOAc.
13. The process according to claim 3, wherein the column chromatography is flash column chromatography.
14. The process according to claim 4, wherein the yield of phenol compound of Formula I or ketone compound of Formula II is greater than 60%.
15. The process according to claim 6, wherein the molecular oxygen is atmospheric oxygen.
Description
DETAILED DESCRIPTION OF THE INVENTION
(1) In accordance with the objectives of the invention, the present invention provides a novel, environment friendly, convenient, economical metal free process for the preparation of corresponding phenol and ketone via allylic oxidation of substituted cyclohexenes with yield >60%.
(2) In an embodiment, the present invention provides a novel metal free process for the preparation of phenol compound of formula I,
(3) ##STR00002##
Wherein, R is selected from CHO, COR.sub.3. COOR.sub.4. COOH, CN, NO.sub.2, Ts, Nitroethene, α,β-unsaturated ketone, α,β-unsaturated ester;
R.sub.1 is selected from halides, particularly Cl, Br or I or phenyl or p-F-Ph;
R.sub.2 is selected from H or alkyl, preferably methyl, tertiary butyl or phenyl;
R.sub.3 is selected from alkyl, allyl or phenyl;
R.sub.4 is selected from alkyl, allyl or benzyl;
, from substituted cyclohexene compound of formula III,
(4) ##STR00003##
(5) Wherein, R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as above;
(6) Comprising: a. Mixing the substrate, solvent and base with continuous bubbling of air at 50 to 100° C. for 5 to 60 hours; and b. Extracting the product of step (a) and c. purifying the product of step (b) to obtain the substantially pure desired product.
(7) Yet another embodiment of the present invention is to provide to a metal free process for the preparation of corresponding phenol via allylic oxidation of substituted cyclohexenes with yield >60%.
(8) The above process is shown below in Scheme 1:
(9) ##STR00004##
(10) In a preferred embodiment, the base for the process of the invention is selected from alkali carbonates, preferably Potassium carbonate and Cesium carbonate, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, 2,6-lutidine, triphenylphosphine, imidazole, triethylamine or pyridine.
(11) In another preferred embodiment, the polar solvent of the invention is selected from water, alcohol-linear or branched selected from methanol or isopropyl alcohol, methyl cyanide or dimethyl formamide or degassed dimethyl formamide, either alone or in combination with tetra hydro furan.
(12) In yet another preferred embodiment, the present invention provides a process wherein air is used as oxidant and can be used as such or optionally selected from pure oxygen or atmospheric oxygen.
(13) In still another preferred embodiment the present invention provides a process wherein the temperature is preferably in the range of 70 to 90° C.; time is preferably in the range of 20 to 40 hours and yield is preferably >75%.
(14) In an embodiment, the present invention provides a novel metal free process for the preparation of ketone compound of formula II,
(15) ##STR00005##
Wherein, R is selected from CHO, COR.sub.3. COOR.sub.4. COOH, CN, NO.sub.2, Ts, Nitroethene, α,β-unsaturated ketone, α,β-unsaturated ester;
R.sub.1 is selected from halides, particularly Cl, Br or I or phenyl or p-F-Ph;
R.sub.2 is selected from H or alkyl, preferably methyl, tertiary butyl or phenyl;
R.sub.3 is selected from alkyl, allyl or phenyl;
R.sub.4 is selected from alkyl, allyl or benzyl;
, from substituted cyclohexene compound of formula III,
(16) ##STR00006##
Wherein, R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as above;
comprising: a. Mixing the substrate and solvent with continuous bubbling of air at 50 to 100° C. for 5 to 60 hours and b. Extracting the product of step (a) and c. purifying the product of step (b) to obtain the substantially pure desired product.
(17) Yet another embodiment of the present invention is to provide to a metal free process for the preparation of corresponding ketone via allylic oxidation of substituted cyclohexenes with yield >60%. The yield can sometimes go upto as high as or more than 89%.
(18) The above process is shown below in Scheme 2:
(19) ##STR00007##
(20) In yet another important embodiment, the extraction step involves filtering the product of step (a), as mentioned above; treating the filtrate with water; extracting with solvents such as EtOAc; washing the organic extracts with brine, dried (anhydrous Na.sub.2SO.sub.4), filtering the organic extract and removing the solvent in vacuo.
(21) In yet another important embodiment, the purification is done preferably by column chromatography; most preferably flash column chromatography, although other alternates can also be used for purification.
(22) In a preferred embodiment, the polar solvent of the invention is selected from water, alcohol-linear or branched selected from methanol or isopropyl alcohol, methyl cyanide or dimethyl formamide or degassed dimethyl formamide, either alone or in combination with tetra hydro furan.
(23) In another preferred embodiment, the present invention provides a process wherein air is used as oxidant and can be used as such or optionally selected from pure oxygen or atmospheric oxygen.
(24) In yet another preferred embodiment, the present invention provides a process wherein the temperature is preferably in the range of 70 to 90° C.; time is preferably in the range of 20 to 40 hours and yield is preferably >75%.
(25) In an aspect the present invention provides a process for the synthesis of compound of formula I selected from the group comprising 3-hydroxybenzaldehyde; 3-Hydroxy-5-methylbenzaldehyde; 3-(tert-Butyl)-5-hydroxybenzaldehyde; 6-Hydroxy-[1,1′-biphenyl]-2-carbaldehyde; 4′-Fluoro-6-hydroxy-[1,1′-biphenyl]-2-carbaldehyde; (E)-4-(3-Hydroxyphenyl)but-3-en-2-one; (E)-3-(3-Hydroxyphenyl)-1-phenylprop-2-en-1-one; (E)-3-(3-Hydroxyphenyl)-1-(p-tolyl)prop-2-en-1-one; (E)-3-(3-Hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one; (E)-Ethyl 3-(3-hydroxyphenyl)acrylate; (E)-Ethyl 3-(3-hydroxy-5-methylphenyl)acrylate; (E)-Ethyl 3-(3-(tert-butyl)-5-hydroxyphenyl)acrylate. (Table: 1)
(26) In another aspect the present invention provides a process for the synthesis of compound of formula II selected from the group comprising 2-Chloro-3-oxocyclohex-1-enecarbaldehyde, 6-Oxo-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbaldehyde. (Table: 1)
(27) Table: 1 enlists the various exemplary embodiments of the process of the invention, wherein the starting substrates are prepared by well-known processes or reactions, and these starting material are readily available.
(28) The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
EXAMPLES
(29) General Procedure
(30) A mixture of cyclohexene (1 molar equiv) and K.sub.2CO.sub.3 (2 molar equiv) in DMF was placed in a two necked RB flask with continuous bubbling of air at 80° C. until the completion of reaction (TLC). The reaction mixture was filtered; the filtrate was then treated with water, extracted by EtOAc. The organic extracts were washed with brine, dried (anhydrous Na.sub.2SO.sub.4), filtered and the solvent removed in vacuo. The residue was purified by column chromatography (silica gel) using pet. ether/ethyl acetate as eluent. The yield was calculated, melting point determined and characterized by NMR.
Example 1
3-hydroxybenzaldehyde (2)
(31) ##STR00008##
(32) Cyclohexene 1 (200 mg, 1.39 mmol), and K.sub.2CO.sub.3 (383 mg, 2.78 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 12 h. Purification by flash column chromatography (silica gel, 9:1 pet. ether/ethyl acetate) afforded the brown solid compound 2 (mp.=100-103° C., 156 mg, 92% yield). R.sub.f 0.5 (20% Ethyl acetate/pet. ether).
(33) .sup.1H NMR (200 MHz, CDCl.sub.3): δ 5.91 (s, 1H), 7.14 (dt, J=5.7, 2.8 Hz, 1H), 7.32-7.50 (m, 3H), 9.95 (s, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 115.1, 121.2, 121.9, 129.7, 137.5, 157.9, 191.9; GC-MS (EI): m/z=122 (M).sup.+.
Example 2
3-Hydroxy-5-methylbenzaldehyde (2a)
(34) ##STR00009##
(35) Cyclohexene 1a (0.2 g, 1.26 mmol), and K.sub.2CO.sub.3 (0.34 g, 2.53 mmol) in DMF (7 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 20 h. Purification by flash column chromatography (silica gel, 7:3 pet. ether/ethyl acetate) afforded the brown solid compound 2a (mp.=78-80° C., 0.15 g, 89% yield). R.sub.f 0.5 (30% Ethyl acetate/pet. ether).
(36) .sup.1H NMR (200 MHz, CDCl.sub.3): δ 2.39 (s, 3H), 6.22 (brs, 1H), 6.91-7.00 (m, 1H), 7.15-7.20 (m, 1H), 7.21-7.25 (m, 1H), 9.89 (s, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 20.7, 112.3, 121.6, 122.2, 137.2, 139.5, 157.6, 191.8; GC-MS (EI): m/z=136 (M).sup.+.
Example 3
3-(tert-Butyl)-5-hydroxybenzaldehyde (2b)
(37) ##STR00010##
(38) Cyclohexene 1b (200 mg, 1.00 mmol), and K.sub.2CO.sub.3 (276 mg, 2.00 mmol) in DMF (5 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 24 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the red solid compound 2b (mp.=70-72° C., 137 mg, 77% yield). R.sub.f 0.5 (30% Ethyl acetate/pet. ether).
(39) .sup.1H NMR (200 MHz, CDCl.sub.3): δ 1.36 (s, 9H), 7.17 (s, 1H), 7.21-7.29 (m, 2H), 7.48 (t, J=1.5 Hz, 1H), 9.94 (s, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 31.4 (3C), 35.0, 112.6, 120.0, 120.7, 137.6, 154.4, 156.9, 193.4; GC-MS (EI): m/z=178 (M)+.
Example 4
2-Chloro-3-oxocyclohex-1-enecarbaldehyde (3)
(40) ##STR00011##
(41) Cyclohexene 1 (200 mg, 1.39 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 12 h. Purification by flash column chromatography (silica gel, 9:1 pet. Ether/ethyl acetate) afforded the colorless liquid compound 3 (220 mg, 80% yield). R.sub.f 0.3 (10% Ethyl acetate/pet ether).
(42) .sup.1H NMR (200 MHz, CDCl.sub.3): δ 1.97-2.20 (m, 2H), 2.53-2.77 (m, 4H), 10.44 (s, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4): δ 20.9, 24.1, 38.4, 140.5, 145.6, 191.6, 192.1; GC-MS (EI): m/z=158 (M).sup.+, 130, 102, 95, 73, 65.
Example 5
6-Oxo-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-carbaldehyde (2e)
(43) ##STR00012##
(44) Cyclohexene 1e (200 mg, 1.07 mmol) in DMF (6 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 17 h. Purification by flash column chromatography (silica gel, 9:1 pet. ether/ethyl acetate) afforded the yellow solid compound 2f (mp.=57-59° C., 158 mg, 72% yield). R.sub.f 0.6 (20% Ethyl acetate/pet. ether).
(45) .sup.1H NMR (400 MHz, CDCl.sub.3): δ 2.08-2.23 (m, 2H), 2.67 (q, J=5.9 Hz, 4H), 7.18 (dd, J=6.7, 2.9 Hz, 2H), 7.42 (dd, J=4.9, 1.9 Hz, 3H), 9.69 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3+CCl.sub.4): δ 21.6, 23.2, 39.0, 128.2 (2C), 129.3, 131.0, 131.1 (2C), 147.9, 148.1, 195.2, 200.2; HRMS (ESI) calculated for C.sub.13H.sub.13O.sub.2, 201.0910 (M+H).sup.+. Found, 201.0908.
Example 6
6-Hydroxy-[1,1′-biphenyl]-2-carbaldehyde (2f)
(46) ##STR00013##
(47) Cyclohexene 1e (200 mg, 1.07 mmol), and K.sub.2CO.sub.3 (296 mg, 2.15 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 22 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the green solid compound 2f (mp.=127-129° C., 159 mg, 75% yield). R.sub.f 0.4 (20% Ethyl acetate/pet. ether).
(48) .sup.1H NMR (200 MHz, CDCl.sub.3+CCl.sub.4): δ 5.21 (brs, 1H), 7.23 (dd, J=8.1, 1.3 Hz, 1H), 7.35-7.44 (m, 3H), 7.47-7.62 (m, 4H), 9.70 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3+CCl.sub.4): δ 120.1, 121.1, 129.3, 129.4, 129.7 (2C), 131.0 (2C), 131.2, 131.8, 135.0, 153.5, 191.6; HRMS (ESI) calculated for C.sub.13H.sub.11O.sub.2, 199.0754 (M+H).sup.+. Found, 199.0754.
Example 7
4′-Fluoro-6-hydroxy-[1,1′-biphenyl]-2-carbaldehyde (2g)
(49) ##STR00014##
(50) Cyclohexene 1g (200 mg, 1.02 mmol), and K.sub.2CO.sub.3 (281 mg, 2.04 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 24 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the orange solid compound 2g (mp.=128-130° C., 155 mg, 73% yield). R.sub.f 0.3 (20% ethyl acetate/pet. ether).
(51) .sup.1H NMR (500 MHz, CDCl.sub.3+CCl.sub.4): δ 7.24-7.31 (m, 4H), 7.37-7.42 (m, 2H), 7.43-7.46 (m, 1H), 7.61 (dd, J=7.7, 1.2 Hz, 1H), 9.74 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3+CCl.sub.4): 116.6 (d, Ar—C, J.sub.C-F=21.9 Hz, 2C), 120.4, 121.1, 127.5 (d, Ar—C, J.sub.C-F=3.4 Hz), 129.4, 129.9, 132.6 (d, Ar—C, J.sub.C-F=8.1 Hz, 2C), 135.1, 153.4, 163.7 (d, Ar—C, J.sub.C-F=249.7 Hz), 191.3; HRMS (ESI) calculated for C.sub.13H.sub.10O.sub.2F, 217.0659 (M+H).sup.+. Found, 217.1044.
Example 8
(E)-4-(3-Hydroxyphenyl)but-3-en-2-one (2h)
(52) ##STR00015##
(53) Cyclohexene 1h (200 mg, 1.08 mmol), and K.sub.2CO.sub.3 (298 mg, 2.16 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 32 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the white solid compound 2h (mp.=91-93° C., 144 mg, 82% yield). R.sub.f 0.3 (20% ethyl acetate/pet. ether).
(54) .sup.1H NMR (200 MHz, DMSO-d.sub.6): δ 2.32 (s, 3H), 6.68 (d, J=16.4 Hz, 1H), 6.78-6.91 (m, 1H), 6.98-7.30 (m, 3H), 7.52 (d, J=16.4 Hz, 1H), 9.68 (s, 1H); .sup.13C NMR (50 MHz, DMSO): δ 27.4, 114.7, 117.8, 119.5, 127.1, 130.0, 135.7, 143.5, 157.8, 198.2.
Example 9
(E)-3-(3-Hydroxyphenyl)-1-phenylprop-2-en-1-one (2i)
(55) ##STR00016##
(56) Cyclohexene 1i (200 mg, 0.81 mmol), and K.sub.2CO.sub.3 (223 mg, 1.62 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 23 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the light green solid compound 2i (mp.=150-152° C., 129 mg, 71% yield). R.sub.f 0.3 (20% ethyl acetate/pet. ether).
(57) .sup.1H NMR (400 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 6.87-6.99 (m, 1H), 7.09-7.19 (m, 2H), 7.23 (d, J=7.9 Hz, 1H), 7.46-7.64 (m, 4H), 7.70 (d, J=15.6 Hz, 1H), 7.97-8.08 (m, 2H), 9.31 (s, 1H); .sup.13C NMR (100 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 114.2, 117.3, 118.9, 120.9, 127.5 (2C), 127.8 (2C), 129.0, 131.9, 135.1, 137.2, 144.1, 157.0, 189.2; HRMS (ESI) calculated for C.sub.15H.sub.13O.sub.2, 225.0910 (M+H).sup.+. Found, 225.0907.
Example 10
(E)-3-(3-Hydroxyphenyl)-1-(p-tolyl)prop-2-en-1-one (2j)
(58) ##STR00017##
(59) Cyclohexene 1j (200 mg, 0.76 mmol), and K.sub.2CO.sub.3 (212 mg, 1.53 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 30 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the yellow solid compound 2j (mp.=137-139° C., 120 mg, 66% yield). R.sub.f 0.3 (10% ethyl acetate/pet. ether).
(60) .sup.1H NMR (200 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 2.24 (s, 3H), 6.56-6.78 (m, 1H), 6.86-6.94 (m, 2H), 6.96-7.14 (m, 3H), 7.27 (d, J=15.7 Hz, 1H), 7.48 (d, J=15.7 Hz, 1H), 7.60-7.82 (m, 2H), 8.87 (s, 1H); .sup.13C NMR (125 MHz, CDCl.sub.3+CCl.sub.4+DMSO): δ 21.2, 114.5, 117.6, 119.3, 121.4, 128.1 (2C), 128.8 (2C), 129.4, 135.2, 135.6, 143.0, 144.2, 157.4, 189.2.
Example 11
(E)-3-(3-Hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (2k)
(61) ##STR00018##
(62) Cyclohexene 1k (200 mg, 0.72 mmol), and K.sub.2CO.sub.3 (200 mg, 1.45 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 32 h. Purification by flash column chromatography (silica gel, 8:2 pet. ether/ethyl acetate) afforded the yellow solid compound 2k (mp.=160-162° C., 112 mg, 61% yield). R.sub.f 0.3 (20% ethyl acetate/pet. ether).
(63) .sup.1H NMR (500 MHz, DMSO): δ 3.86 (s, 3H), 6.80-6.90 (m, 1H), 7.08 (d, J=8.9 Hz, 2H), 7.19-7.22 (m, 1H), 7.25 (t, J=7.7 Hz, 1H), 7.27-7.31 (m, 1H), 7.60 (d, J=15.6 Hz, 1H), 7.82 (d, J=15.6 Hz, 1H), 8.14 (d, J=8.9 Hz, 2H), 9.64 (s, 1H); .sup.13C NMR (125 MHz, DMSO): δ 55.6, 114.1 (2C), 115.2, 117.7, 119.8, 121.9, 129.9, 130.5 (2C), 130.9, 136.1, 143.4, 157.7, 163.2, 187.5.
Example 12
(E)-Ethyl 3-(3-hydroxyphenyl)acrylate (2l)
(64) ##STR00019##
(65) Cyclohexene 11 (200 mg, 0.93 mmol), and K.sub.2CO.sub.3 (200 mg, 1.87 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 36 h. Purification by flash column chromatography (silica gel, 9:1 pet. ether/ethyl acetate) afforded the yellow solid compound 2l (mp.=66-68° C., 145 mg, 81% yield). R.sub.f 0.4 (20% ethyl acetate/pet. ether).
(66) .sup.1H NMR (200 MHz CDCl.sub.3+CCl.sub.4): δ 1.34 (t, J=7.1 Hz, 3H), 4.27 (q, J=7.1 Hz, 2H), 6.38 (d, J=16.0 Hz, 1H), 6.83-6.95 (m, 1H), 6.97-7.11 (m, 2H), 7.14-7.42 (m, 1H), 7.62 (d, J=16.0 Hz, 1H); .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4): δ 14.4, 61.0, 114.8, 117.9, 118.1, 120.6, 130.2, 135.8, 145.3, 156.7, 167.9.
Example 13
(E)-Ethyl 3-(3-hydroxy-5-methylphenyl)acrylate (2m)
(67) ##STR00020##
(68) Cyclohexene 1m (200 mg, 0.88 mmol), and K.sub.2CO.sub.3 (242 mg, 1.75 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 48 h. Purification by flash column chromatography (silica gel, 9:1 pet. ether/ethyl acetate) afforded the yellow liquid compound 2m (128 mg, 71% yield). R.sub.f 0.5 (20% ethyl acetate/pet. ether).
(69) .sup.1H NMR (200 MHz, DMSO): δ 1.24 (t, J=7.1 Hz, 3H), 2.22 (s, 3H), 4.17 (q, J=7.1 Hz, 2H), 6.46 (d, J=16.0 Hz, 1H), 6.65 (s, 1H), 6.83 (s, 1H), 6.95 (s, 1H), 7.50 (d, J=16.0 Hz, 1H), 9.57 (s, 1H); .sup.13C NMR (101 MHz, DMSO): δ 14.3, 21.0, 60.1, 112.0, 117.7, 118.4, 120.1, 135.0, 139.5, 144.8, 157.7, 166.3. HRMS (ESI) calculated for C.sub.12H.sub.15O.sub.3, 207.1016 (M+H).sup.+. Found, 207.1015.
Example 14
(E)-Ethyl 3-(3-(tert-butyl)-5-hydroxyphenyl)acrylate (2n)
(70) ##STR00021##
(71) Cyclohexene 1n (200 mg, 0.88 mmol), and K.sub.2CO.sub.3 (242 mg, 1.75 mmol) in DMF (8 mL) was placed in a two necked RB flask with continuous bubbling of air at 80° C. for 40 h. Purification by flash column chromatography (silica gel, 9:1 pet. ether/ethyl acetate) afforded the yellow liquid compound 2n (128 mg, 78% yield)..sup.1 R.sub.f 0.4 (20% ethyl acetate/pet. ether).
(72) .sup.1H NMR (200 MHz, CDCl.sub.3+CCl.sub.4) δ 1.28-1.41 (m, 12H), 4.27 (q, J=7.1 Hz, 2H), 6.38 (d, J=15.9 Hz, 1H), 6.82-6.88 (m, 1H), 6.88-6.94 (m, 1H), 7.08 (s, 1H), 7.63 (d, J=16.0 Hz, 1H). .sup.13C NMR (50 MHz, CDCl.sub.3+CCl.sub.4): δ 14.6, 31.4 (3C), 34.9, 60.8, 111.6, 115.3, 118.2, 118.4, 135.6, 145.5, 153.9, 156.2, 167.4; HRMS (ESI) calculated for C.sub.15H.sub.21O.sub.3, 249.1485 (M+H).sup.+. Found, 249.1481.
Advantages of Invention
(73) a. Easily available or easily synthesizable starting materials. b. Green eco-friendly, convenient, economical process. c. Avoids metal catalysts. d. High yield and selectivity.
(74) List of Tables:
(75) TABLE-US-00001 TABLE 1 time yield Entry substrate.sup.a products (h) (%).sup.b 1