* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Added 2.5 L of water to R.B Flask, 80 gms of NaOH was added and stirred to dissolve. Added 500 gms of Guaiacol, 1.12 Kg of Epichlorohydrine and stirred at 25-350C for 5-6 h. The organic layer was separated. To the Epichlorohydrine layer charged 160 gms NaOH dissolved in 2.5 L of water and stirred at 25-30°C for 3-4 h. The organic layer was separated and washed with 150 gms NaOH dissolved in 1.5 L of water. Excess Epichlorohydrine was recovered by distillation of the product layer at 90°C under vacuum (600-700 mmHg) to give 65 0-680 gms of oil. To the cmde oil was added 3.0 L of Isopropanol and cooled to 0°C and filtered the product to get 1-(2- Methoxy phenoxy)-2,3-epoxy propane (3).Yield: 80percent; purity >98percent.
72.2%
Stage #1: With tetrabutylammomium bromide; sodium hydroxide In water; N,N-dimethyl-formamide at 50℃; for 0.5 h; Inert atmosphere Stage #2: for 1 h;
In a 100 mL three-neck flask, 2-methoxyphenol (1.24 g, 10 mmol) was added in succession.Sodium hydroxide (0.55 g, 13.7 mmol), tetrabutylammonium bromide (100 mg, 1 mmol),30mL DMF and 12mL water, nitrogen protection, stirring at 50 °C for 30min.Epichlorohydrin (2.76 g, 30 mmol) was added dropwise and the reaction was continued for 1 h.TLC showed that the reaction was almost complete and the reaction solution was concentrated.The pH was adjusted to 7 with acetic acid, and the mixture was extracted with ethyl acetate. The organic phase was dried, concentrated, and separated by column chromatography.Concentration under reduced pressure afforded 1.3 g of a colorless oily product in a yield of 72.2percent.
43%
With sodium hydroxide In 1,4-dioxane; water for 3 h; Heating / reflux
2-(2-Methoxy-phenoxymethyl)-oxirane: Epichlorohydrin (8.4 g, 91.3 mmol) was slowly added to a solution of 2-methoxyphenol (8 g, 64.4 mmol) dissolved in water (6 mL) and dioxane (20 mL) containing sodium hydroxide (2.9 g, 72.5 mmol). The resulting mixture was heated at reflux for about 3 hours. Following standard extractive workup with ether, the crude product was purified by flash column chromatography on silica gel (4*20 cm, petroleum ether/ethyl acetate=5/1 elution) to afford the title product (4.95 g, 43percent). 1H NMR (300 MHz, CDCl3) δ 6.99-6.89 (m, 4H), 4.24 (dd, 1H, J=8.4, 3.6 Hz), 4.05 (dd, 1H, J=9.6, 5.4 Hz), 3.88 (s, 3H), 3.43-3.38 (m, 1H), 2.90 (t, 1H, J=4.5 Hz), 2.76-2.74 (m, 1H); LC-MS: m/z=195 (MH)+.
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[4] Tetrahedron, 2006, vol. 62, # 47, p. 10968 - 10979
[5] Angewandte Chemie - International Edition, 2014, vol. 53, # 26, p. 6641 - 6644[6] Angew. Chem., 2014, p. 6759 - 6762,4
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[8] Patent: WO2016/142819, 2016, A2, . Location in patent: Page/Page column 17
[9] Polish Journal of Chemistry, 2009, vol. 83, # 4, p. 595 - 604
[10] Patent: CN107043361, 2017, A, . Location in patent: Sheet 0053; 0054; 0055; 0056
[11] Bioorganic and medicinal chemistry, 2003, vol. 11, # 16, p. 3513 - 3527
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[13] Chemical and Pharmaceutical Bulletin, 2009, vol. 57, # 11, p. 1218 - 1222
[14] Journal of the Chemical Society, Chemical Communications, 1980, # 22, p. 1053 - 1054
[15] Patent: US2008/312247, 2008, A1, . Location in patent: Page/Page column 31
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[22] Patent: WO2010/25370, 2010, A2, . Location in patent: Page/Page column 49
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[25] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5419 - 5423
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2
[ 90-05-1 ]
[ 3132-64-7 ]
[ 2210-74-4 ]
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3
[ 90-05-1 ]
[ 106-89-8 ]
[ 16929-60-5 ]
[ 2210-74-4 ]
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4
[ 90-05-1 ]
[ 106-89-8 ]
[ 25772-81-0 ]
[ 2210-74-4 ]
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[2] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[3] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
5
[ 90-05-1 ]
[ 106-89-8 ]
[ 25772-81-0 ]
[ 16929-60-5 ]
[ 93-14-1 ]
[ 2210-74-4 ]
Reference:
[1] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
6
[ 96-23-1 ]
[ 90-05-1 ]
[ 2210-74-4 ]
Reference:
[1] Chem. Zentralbl., 1910, vol. 81, # I, p. 1134
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1173
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[ 90-05-1 ]
[ 7168-85-6 ]
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[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 3029 - 3036
[2] Tetrahedron, 2015, vol. 71, # 29, p. 4835 - 4841
[3] Organic Letters, 2016, vol. 18, # 21, p. 5624 - 5627
[4] European Journal of Organic Chemistry, 2018, vol. 2018, # 22, p. 2774 - 2779
8
[ 90-05-1 ]
[ 20351-79-5 ]
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[1] Chemische Berichte, 1925, vol. 58, p. 1955
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 4, p. 1022 - 1032
[3] ChemMedChem, 2012, vol. 7, # 3, p. 391 - 395
9
[ 67-66-3 ]
[ 90-05-1 ]
[ 148-53-8 ]
[ 121-33-5 ]
Yield
Reaction Conditions
Operation in experiment
10 %Chromat.
With sodium hydroxide In water at 20℃; for 24 h; Inert atmosphere
To an aqueous solution of NaOH (20 wtpercent, 20 mL) wereadded guaiacol (5 mmol, 0.62 g) and zeolite (5 g) under N2atmosphere at room temperature. Then chloroform(20 mL) was dropped to the mixture. Dodecane (1 mmol,0.224 mL) was added as GC internal standard. The reactionmixture was stirred at room temperature for 24 h. Thereaction was quenched with 3 N aqueous HCl. The mixturewas extracted with ethyl acetate. The yield and selectivityof products was detected by GC.
Stage #1: With copper(I) oxide In trifluoroacetic acid for 5 h; Reflux Stage #2: With hydrogenchloride In water at 20℃; for 1 h;
General procedure: To a solution of substrates (1a–1q, 0.15 mmol) in trifluoroacetic acid (5 ml), hexamethylenetetramine (0.3 mmol) and cuprous oxide (0.15 mmol) were added. The reaction mixture was refluxed for about 5 h, cooled to room temperature, followed by addition of hydrochloric acid (3 N, 5 ml). After stirring for another 1 h, the solution was concentrated under reduced pressure. The products were purified by silica gel column chromatography (200–300 mesh).
Reference:
[1] Research on Chemical Intermediates, 2015, vol. 41, # 11, p. 8147 - 8158
11
[ 50-00-0 ]
[ 90-05-1 ]
[ 148-53-8 ]
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[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 6, p. 1939 - 1943
[2] Organic Letters, 2017, vol. 19, # 23, p. 6340 - 6343
[3] Organic Letters, 2018, vol. 20, # 10, p. 2880 - 2883
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[1] Recueil des Travaux Chimiques des Pays-Bas, 1927, vol. 46, p. 147
14
[ 90-05-1 ]
[ 864131-95-3 ]
[ 148-53-8 ]
Reference:
[1] Journal of the Chemical Society, 1924, vol. 125, p. 2406
15
[ 67-66-3 ]
[ 90-05-1 ]
[ 621-59-0 ]
[ 148-53-8 ]
[ 121-33-5 ]
Reference:
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1992, vol. 31, # 8, p. 543 - 546
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1992, vol. 31, # 8, p. 543 - 546
16
[ 54043-60-6 ]
[ 90-05-1 ]
[ 148-53-8 ]
[ 121-33-5 ]
Reference:
[1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 764
17
[ 32752-36-6 ]
[ 90-05-1 ]
[ 148-53-8 ]
[ 121-33-5 ]
Reference:
[1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 764
18
[ 90-05-1 ]
[ 91-78-1 ]
[ 148-53-8 ]
[ 121-33-5 ]
Reference:
[1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 764
19
[ 90-05-1 ]
[ 106-93-4 ]
[ 4463-59-6 ]
Yield
Reaction Conditions
Operation in experiment
62%
With potassium carbonate; potassium iodide In acetone at 60℃;
General procedure: A solution of 1,2-dibromoethane (0.02 mol) in 40 ml ofacetone was added dropwise into the mixture of respective phenol (0.08 mol) andK2CO3 (0.04 mol) in 30 ml of acetone. Subsequently, acatalytic amount of KI (0.3 mmol) was added and the resulting mixture wasstirred at 60°C for 24–72 hours. After the completion of the reaction theinorganic residues were filtrated off and organic mixture was concentrated undervacuum. The obtained crude product was purified on silica gel with AcOEt/hexaneas eluting system.
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[1] Farmaco, Edizione Scientifica, 1986, vol. 41, # 10, p. 794 - 800
[2] Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999), 1997, p. 449 - 462
[3] European Journal of Medicinal Chemistry, 2009, vol. 44, # 2, p. 809 - 817
[4] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 6, p. 527 - 531
[5] European Journal of Medicinal Chemistry, 2016, vol. 108, p. 334 - 346
[6] Journal of Pharmaceutical Sciences, 1984, vol. 73, # 9, p. 1241 - 1244
[7] Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti, 1897, vol. <5> 6 II, p. 33
[8] Chemische Berichte, 1910, vol. 43, p. 2179
[9] Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti, 1897, vol. <5> 6 II, p. 33
[10] Journal of Medicinal Chemistry, 1965, vol. 8, p. 356 - 367
[11] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 719 - 730
[12] Journal of Medicinal Chemistry, 2004, vol. 47, # 8, p. 1900 - 1918
[13] Chinese Chemical Letters, 2010, vol. 21, # 3, p. 287 - 289
[14] Synthetic Communications, 2011, vol. 41, # 1, p. 85 - 93
[15] Chinese Journal of Chemistry, 2013, vol. 31, # 9, p. 1228 - 1233
[16] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5582 - 5591
[17] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 9, p. 931 - 935
20
[ 90-05-1 ]
[ 4463-59-6 ]
Reference:
[1] Patent: US2003/212094, 2003, A1,
21
[ 90-05-1 ]
[ 107-05-1 ]
[ 97-53-0 ]
[ 579-60-2 ]
Reference:
[1] Patent: WO2015/15445, 2015, A2, . Location in patent: Paragraph 0119-0121
[2] Patent: CN105294409, 2016, A, . Location in patent: Paragraph 0042; 0043; 0044; 0045; 0046
22
[ 90-05-1 ]
[ 107-05-1 ]
[ 97-53-0 ]
Reference:
[1] Patent: US4048236, 1977, A,
23
[ 90-05-1 ]
[ 97-53-0 ]
[ 579-60-2 ]
Reference:
[1] Patent: US4048236, 1977, A,
[2] Patent: US4048236, 1977, A,
[3] Patent: US4048236, 1977, A,
[4] Patent: US4048236, 1977, A,
[5] Patent: US4048236, 1977, A,
[6] Patent: US4048236, 1977, A,
[7] Patent: US4048236, 1977, A,
24
[ 4873-09-0 ]
[ 90-05-1 ]
[ 97-53-0 ]
Reference:
[1] Synlett, 2003, # 10, p. 1431 - 1434
25
[ 90-05-1 ]
[ 106-95-6 ]
[ 97-53-0 ]
Reference:
[1] Chemical Communications, 2012, vol. 48, # 56, p. 7019 - 7021
26
[ 90-05-1 ]
[ 97-53-0 ]
Reference:
[1] Zhurnal Obshchei Khimii, 1941, vol. 11, p. 722,725[2] Chem.Abstr., 1942, p. 430
27
[ 105-36-2 ]
[ 90-05-1 ]
[ 13078-21-2 ]
Yield
Reaction Conditions
Operation in experiment
66%
With potassium carbonate In acetonitrile
£'rytftro-l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-l,3-propanediol (2g): (0178) (0179) 2g (0180) Scheme 8. Synthesis of i?? i zro-l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-l,3- propanediol (2g). This compound was prepared according to a literature procedure. (Buendia, J. ; (0181) Mottweiler, J.; Bolm, C. Chem. Eur. J. 2011, 17, 13877.) Spectral data were consistent with those reported in the literature. *H NMR (400 MHz, CDC13) δ 7.07 (ddd, J = 8.2 Hz, 7.2, 1.6, 1.6 Hz, 1H), 7.02-6.84 (M, 5H), 6.82 (D, J = 8.2 Hz, 1H), 4.98 (b t, J = 4.8 Hz, 1 H), 4.16 (ddd, J = 6.0, 4.8, 3.5 Hz, 1 H), 3.95-3.90 (m, 1H), 3.87 (s, 3H), 3.86 (s, 6H), 3.66 (ddd, J = 12.0, 7.2, 3.5 Hz, 1H), 2.87 ppm (b s, 1H). HRMS (EI) calculated for C18H2206Na [M + Na]+ 357.1314, found 357.1311.
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[1] Organic Letters, 2016, vol. 18, # 19, p. 5166 - 5169
[2] Chemistry - A European Journal, 2011, vol. 17, # 49, p. 13877 - 13882
[3] Green Chemistry, 2017, vol. 19, # 19, p. 4538 - 4543
[4] Journal of Organic Chemistry, 2010, vol. 75, # 19, p. 6549 - 6562
[5] Journal of the American Chemical Society, 2013, vol. 135, # 17, p. 6415 - 6418
[6] Patent: WO2015/138563, 2015, A1, . Location in patent: Page/Page column 24
[7] Patent: US2002/128290, 2002, A1,
[8] Patent: US6514996, 2003, B2,
[9] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 23, p. 10049 - 10060
[10] Journal of the American Chemical Society, 2013, vol. 135, # 17, p. 6415 - 6418
[11] Patent: US2014/235838, 2014, A1, . Location in patent: Paragraph 0068
28
[ 105-39-5 ]
[ 90-05-1 ]
[ 13078-21-2 ]
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[1] Chemische Berichte, 1894, vol. 27, p. 2799
[2] Collection of Czechoslovak Chemical Communications, 1961, vol. 26, p. 902 - 906
[3] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1987, vol. 26, # 1-12, p. 251 - 254
[4] Journal of the Indian Chemical Society, 1986, vol. 63, p. 317 - 319
[5] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 15, p. 4428 - 4433
[6] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 10, p. 2526 - 2530
[7] Biomacromolecules, 2016, vol. 17, # 6, p. 1921 - 1929
[8] Green Chemistry, 2018, vol. 20, # 16, p. 3761 - 3771
29
[ 90-05-1 ]
[ 4136-26-9 ]
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[1] Journal of Heterocyclic Chemistry, 1985, vol. 22, # 2, p. 363 - 368
30
[ 90-05-1 ]
[ 10535-17-8 ]
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[3] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
[4] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
[5] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
[6] Green Chemistry, 2018, vol. 20, # 16, p. 3761 - 3771
31
[ 225793-15-7 ]
[ 292638-84-7 ]
[ 700-44-7 ]
[ 24677-78-9 ]
[ 90-05-1 ]
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[1] Journal of Organic Chemistry, 2000, vol. 65, # 5, p. 1376 - 1389
32
[ 90-05-1 ]
[ 75-36-5 ]
[ 6100-74-9 ]
Reference:
[1] Helvetica Chimica Acta, 1927, vol. 10, p. 389
33
[ 90-05-1 ]
[ 6100-74-9 ]
Reference:
[1] Chemische Berichte, 1922, vol. 55, p. 1896
34
[ 64-19-7 ]
[ 90-05-1 ]
[ 6100-74-9 ]
Reference:
[1] Journal of the Chemical Society, 1930, p. 280,291
35
[ 64-19-7 ]
[ 90-05-1 ]
[ 10025-87-3 ]
[ 6100-74-9 ]
Reference:
[1] Journal of the Chemical Society, 1930, p. 280,291
36
[ 90-05-1 ]
[ 7368-78-7 ]
Yield
Reaction Conditions
Operation in experiment
95%
With tetra-N-butylammonium tribromide In dichloromethane at 23℃; for 2 h;
General procedure: A solution of NBu4Br3 (1.0 eq) in CH2Cl2 (~5 mL per mmol NBu4Br3) was added immediately to a solution of a phenole 1 (1.0 eq) in CH2Cl2 (~ 5 mL per mmol 1). The reaction mixture was stirred at 23 °C for 2 h. The solvent was removed under reduced pressure (12 mbar, 40 °C). Water (5.0 mL) was added to the residue and the aqueous layer was extracted with Et2O (3 * 10 mL). The organic layer was separated and dried (MgSO4). The organic solvent was removed under reduced pressure (14 mbar, 40 °C) to leave an oily residue, which was purified by adsorption chromatography (SiO2, CH2Cl2).
95%
With N-Bromosuccinimide In acetonitrile for 0.5 h;
N-Bromosuccin I self-imide (180 mg, 1 mmol)Add to guaiac acid (124 mg, 1 mmol, Structure 1)In acetonitrile (20 mL);After stirring for 30 minutes, the reaction was quenched with saturated sodium thiosulfate solution,Ethyl acetate extraction three times; the combined organic phase, washed with saturated saline,Drying over anhydrous sodium sulfate and removal of the solvent under reduced pressure give the crude product,Column chromatography (ethyl acetate: petroleum ether, 10: 1),The product 4-bromo-2-methoxyphenol was obtained in a yield of 95percent.
91%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 0.5 h; Inert atmosphere
To a stirred solution of 2-methoxyphenol (5.00 g, 40 mmol) in DMF (25 mL) under an atmosphere of nitrogen at 0 °C, was added a solution of N-bromosuccinimide (7.2 g, 40 mmol) in DMF (25 mL). The resulting mixture was stirred for 30 min. Ice cold water (50 mL) was added and the mixture was warmed to room temperature. The aqueous mixture was extracted with diethyl ether (3 * 30 mL) and the combined organic extracts were washed with water (50 mL), brine (50 mL) and then dried (Na2SO4). The crude product was purified by flash chromatography (3:1 hexanes/ethyl acetate) to give the title product 8 (7.41 g, 91percent) as a yellow oil. 1H NMR (300 MHz; CDCl3) 3.87 (3H, s, 2-OCH3), 5.70 (1H, br s, OH), 6.78 (1H, d, J = 6.2 Hz, 6-H), 6.98 (2H, m, 2 * Ar-H); 13C NMR (75 MHz; CDCl3) 56.2 (OCH3), 111.5 (C-4), 114.1, 115.7 and 124.1 (Ar-CH), 144.8 (C-1), 147.2 (C-2). The 1H and 13C NMR data were in agreement with the literature values
78%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 0.5 h;
A solution of NBS (1 eq.) in DMF (50mL) was added dropwise to a solution of guaiacol (1eq.) in DMF (50mL) at 0°C. After being stirred for 30min, the reaction mixture was quenched with ice water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and then evaporated to dryness under reduced pressure. The residue was further purified by column chromatography over Silica Gel 200–300N (petroleum ether/ethyl acetate 9.5:0.5) to give 10a as an oil (78percent).
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[4] Synlett, 2012, vol. 23, # 7, p. 1082 - 1084
[5] Journal of the Serbian Chemical Society, 2011, vol. 76, # 5, p. 685 - 692
[6] Canadian Journal of Chemistry, 1989, vol. 67, p. 2061 - 2066
[7] Tetrahedron, 2012, vol. 68, # 46, p. 9456 - 9463
[8] Journal of Medicinal Chemistry, 2017, vol. 60, # 17, p. 7300 - 7314
[9] Patent: CN107325031, 2017, A, . Location in patent: Paragraph 0041-0043
[10] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 11, p. 2542 - 2545
[11] European Journal of Medicinal Chemistry, 2013, vol. 60, p. 240 - 248
[12] Bulletin of the Chemical Society of Japan, 1987, vol. 60, # 11, p. 4187 - 4189
[13] Advanced Synthesis and Catalysis, 2004, vol. 346, # 1, p. 77 - 82
[14] Organic and Biomolecular Chemistry, 2017, vol. 15, # 35, p. 7404 - 7410
[15] European Journal of Organic Chemistry, 2016, vol. 2016, # 12, p. 2177 - 2186
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[22] Organic Letters, 2011, vol. 13, # 12, p. 3126 - 3129
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[25] Patent: DE105052, , ,
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[ 28165-49-3 ]
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[3] Synlett, 1997, vol. 1997, # 11, p. 1241 - 1242
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[5] Tetrahedron, 2010, vol. 66, # 34, p. 6928 - 6935
[6] Tetrahedron, 2012, vol. 68, # 46, p. 9456 - 9463
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[1] Journal of the American Chemical Society, 1946, vol. 68, p. 1913,1916
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 12, p. 2177 - 2186
48
[ 507-40-4 ]
[ 90-05-1 ]
[ 3743-23-5 ]
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[ 90-05-1 ]
[ 3743-23-5 ]
Reference:
[1] Gazzetta Chimica Italiana, 1898, vol. 28 I, p. 226
50
[ 56-23-5 ]
[ 507-40-4 ]
[ 90-05-1 ]
[ 3743-23-5 ]
Reference:
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 2423
51
[ 90-05-1 ]
[ 99-40-1 ]
Reference:
[1] Chemische Berichte, 1913, vol. 46, p. 4019
52
[ 64-17-5 ]
[ 201230-82-2 ]
[ 90-05-1 ]
[ 617-05-0 ]
Reference:
[1] European Journal of Organic Chemistry, 2018, vol. 2018, # 22, p. 2877 - 2881
53
[ 90-05-1 ]
[ 617-05-0 ]
Reference:
[1] Journal of Organic Chemistry, 1972, vol. 37, p. 3160 - 3163
54
[ 92409-34-2 ]
[ 6766-82-1 ]
[ 20736-25-8 ]
[ 90-05-1 ]
Reference:
[1] Green Chemistry, 2017, vol. 19, # 8, p. 1895 - 1903
55
[ 92409-34-2 ]
[ 7429-44-9 ]
[ 20736-25-8 ]
[ 90-05-1 ]
Reference:
[1] Green Chemistry, 2017, vol. 19, # 8, p. 1895 - 1903
56
[ 92409-34-2 ]
[ 6766-82-1 ]
[ 7429-44-9 ]
[ 20736-25-8 ]
[ 90-05-1 ]
Reference:
[1] Green Chemistry, 2017, vol. 19, # 8, p. 1895 - 1903
57
[ 87199-16-4 ]
[ 90-05-1 ]
[ 66855-92-3 ]
Yield
Reaction Conditions
Operation in experiment
23%
With pyridine; copper diacetate In dichloromethane at 20℃; Molecular sieve
a) 3-(2-methoxyphenoxy)benzaldehyde(3-Formylphenyl)boronic acid (5.0 g, 33 mmol) and guaiacol (2.8 g, 22 mmol) were mixed with Cu(OAc)2 (4.0 g, 22 mmol), 4A molecular sieves and pyridine (9 mL) in dry EPO <DP n="26"/>dichloromethane (150 mL) and the resulting mixture was stirred overnight at room temperature. The reaction mixture was filtered and concentrated. Column cromatography on SiO2 gave the title compound as an oil (1.7 g, 23percent).1R NMR (400 MHz, CDCB) δ 9.95 (s, IH), 7.58-7.54 (m, IH), 7.47 (t, J= 7.S Hz, IH), 7.38-7.34 (m, IH), 7.26-7.19 (m, 2H), 7.08-7.02 (m, 2H), 7.01-6.95 (m, IH), 3.82 (s, 3H)GC-MS m/z: 228.0 [M]
23%
With pyridine; copper diacetate In dichloromethane at 20℃; Molecular sieve
a) 3-(2-methoxyphenoxy)benzaldehyde(3-Formylphenyl)boronic acid (5.0 g, 33 mmol) and guaiacol (2.8 g, 22 mmol) were mixed with Cu(OAc)2 (4.0 g, 22 mmol), 4A molecular sieves and pyridine (9 mL) in dry dichloromethane (150 mL) and the resulting mixture was stirred overnight at room temperature. The reaction mixture was filtered and concentrated. Column cromatography on SiO2 gave the title compound as an oil (1.7 g, 23percent).1H NMR (400 MHz, CDC13) δ 9.95 (s, IH), 7.58-7.54 (m, IH), 7.47 (t, J= 7.8 Hz, IH), 7.38-7.34 (m, IH), 7.26-7.19 (m, 2H), 7.08-7.02 (m, 2H), 7.01-6.95 (m, IH), 3.82 (s, 3H)GC-MS m/z: 228.0 [M]
23%
With pyridine; copper diacetate In dichloromethane at 20℃; Molecular sieve
a) 3-(2-methoxyphenoxy)benzaldehyde(3-Formylphenyl)boronic acid (5.0 g, 33 mmol) and guaiacol (2.8 g, 22 mmol) were mixed with Cu(OAc)2 (4.0 g, 22 mmol), 4A molecular sieves and pyridine (9 mL) in dry EPO <DP n="26"/>dichloromethane (150 mL) and the resulting mixture was stirred overnight at room temperature. The reaction mixture was filtered and concentrated. Column cromatography on SiO2 gave the title compound as an oil (1.7 g, 23percent).1H NMR (400 MHz, CDCB) δ 9.95 (s, IH), 7.58-7.54 (m, IH), 7.47 (t, J= 7.8 Hz, IH), 7.38-7.34 (m, IH), 7.26-7.19 (m, 2H), 7.08-7.02 (m, 2H), 7.01-6.95 (m, IH), 3.82 (s, 3H)GC-MS m/z: 228.0 [M]
Reference:
[1] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1940, p. 235,237[2] Chem.Abstr., 1942, p. 1032
[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1940, p. 421,423[4] Chem.Abstr., 1941, p. 5101
62
[ 109-72-8 ]
[ 60-29-7 ]
[ 90-05-1 ]
[ 877-22-5 ]
[ 2169-28-0 ]
Reference:
[1] Journal of the American Chemical Society, 1958, vol. 80, p. 4537
63
[ 90-05-1 ]
[ 2632-13-5 ]
[ 19513-80-5 ]
Reference:
[1] Green Chemistry, 2017, vol. 19, # 3, p. 702 - 706
[2] Green Chemistry, 2016, vol. 18, # 24, p. 6545 - 6555
[3] Journal of the American Chemical Society, 2014, vol. 136, # 4, p. 1218 - 1221
[4] Journal of Organic Chemistry, 2014, vol. 79, # 22, p. 11091 - 11100
[5] Organic Letters, 2016, vol. 18, # 19, p. 5166 - 5169
[6] Green Chemistry, 2016, vol. 18, # 7, p. 2029 - 2036
[7] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
[8] Journal of Catalysis, 2017, vol. 346, p. 170 - 179
[9] Green Chemistry, 2017, vol. 19, # 19, p. 4538 - 4543
64
[ 90-05-1 ]
[ 19513-80-5 ]
Reference:
[1] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
[2] Green Chemistry, 2016, vol. 18, # 23, p. 6229 - 6235
65
[ 90-05-1 ]
[ 28165-49-3 ]
Reference:
[1] Synthesis, 2001, # 5, p. 741 - 744
[2] Journal of Organic Chemistry, 1993, vol. 58, # 15, p. 3877 - 3885
[3] Synlett, 2012, vol. 23, # 8, p. 1230 - 1234
[4] Organic Letters, 2011, vol. 13, # 5, p. 960 - 963
[5] Synthesis, 1999, # 7, p. 1127 - 1134
[6] Angewandte Chemie - International Edition, 2017, vol. 56, # 38, p. 11450 - 11455[7] Angew. Chem., 2017, vol. 129, p. 11608 - 11613,6
[8] Tetrahedron, 1996, vol. 52, # 33, p. 10935 - 10944
[9] Australian Journal of Chemistry, 2010, vol. 63, # 10, p. 1437 - 1447
66
[ 90-05-1 ]
[ 7368-78-7 ]
[ 28165-49-3 ]
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 15, p. 1877 - 1878
[2] Synlett, 1997, vol. 1997, # 11, p. 1241 - 1242
[3] Synlett, 1997, vol. 1997, # 11, p. 1241 - 1242
[4] Tetrahedron Letters, 2007, vol. 48, # 36, p. 6401 - 6404
[5] Tetrahedron, 2010, vol. 66, # 34, p. 6928 - 6935
[6] Tetrahedron, 2012, vol. 68, # 46, p. 9456 - 9463
Reference:
[1] Chemische Berichte, 1906, vol. 39, p. 2725
[2] Journal of Medicinal Chemistry, 1986, vol. 29, # 4, p. 538 - 549
[3] Patent: US4965261, 1990, A,
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 9, p. 2928 - 2932
[5] Patent: US2007/10670, 2007, A1, . Location in patent: Page/Page column 104
[6] Patent: US2008/64871, 2008, A1, . Location in patent: Page/Page column 67
70
[ 90-05-1 ]
[ 20734-71-8 ]
[ 15969-08-1 ]
Yield
Reaction Conditions
Operation in experiment
29%
With nitric acid In dichloromethane at -20 - 20℃; for 2 h;
Fuming HNO3 (0.34 mL, 0.008 mmol) was carefully added to a mixture of 2-methoxyphenol (0.886 mL, 0.008 mmol) in anhydrous DCM (10 mL) at -20° C. After stirring for 2 h at RT, the mixture was concentrated under vacuum. Chromatography (10-30percent EtOAc/hexanes) provided 9A12 (400 mg, 29percent) and 2-methoxy-3-nitrophenol (400 mg, 29percent).
Reference:
[1] Chemische Berichte, 1906, vol. 39, p. 2725
77
[ 7697-37-2 ]
[ 64-19-7 ]
[ 90-05-1 ]
[ 4097-63-6 ]
[ 15969-08-1 ]
Reference:
[1] Chem. Zentralbl., 1898, vol. 69, # II, p. 1169
[2] Monatshefte fuer Chemie, 1912, vol. 33, p. 706
78
[ 60-29-7 ]
[ 7697-37-2 ]
[ 90-05-1 ]
[ 3251-56-7 ]
[ 4097-63-6 ]
[ 15969-08-1 ]
Reference:
[1] Monatshefte fuer Chemie, 1912, vol. 33, p. 706
79
[ 90-05-1 ]
[ 92409-34-2 ]
Reference:
[1] Journal of the American Chemical Society, 2013, vol. 135, # 17, p. 6415 - 6418
[2] Green Chemistry, 2018, vol. 20, # 16, p. 3761 - 3771
80
[ 90-05-1 ]
[ 52200-90-5 ]
Reference:
[1] Chem. Zentralbl., 1907, vol. 78, # II, p. 2044
[2] Journal of the American Chemical Society, 1919, vol. 41, p. 460
81
[ 90-05-1 ]
[ 121-57-3 ]
[ 52200-90-5 ]
Reference:
[1] Chemische Berichte, 1897, vol. 30, p. 2444
82
[ 90-05-1 ]
[ 96-24-2 ]
[ 93-14-1 ]
Reference:
[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 5071 - 5078
[2] Tetrahedron Asymmetry, 2006, vol. 17, # 21, p. 3015 - 3020
[3] Journal of the Chemical Society, 1912, vol. 101, p. 309
[4] Chimica Therapeutica, 1969, vol. 4, p. 200 - 206
[5] Journal of Medicinal Chemistry, 1995, vol. 38, # 3, p. 508 - 525
[6] Patent: WO2013/167988, 2013, A1, . Location in patent: Paragraph 0093; 0094; 0099
[7] Patent: US2015/133533, 2015, A1, . Location in patent: Paragraph 0113
83
[ 616-30-8 ]
[ 90-05-1 ]
[ 93-14-1 ]
Yield
Reaction Conditions
Operation in experiment
72%
Stage #1: at 50℃; for 3 h; Reflux Stage #2: at 90℃; for 5 h;
Equipped with a stirrer, a thermometer, a reflux condenser, a reaction vessel, 1.5mol sodium sulfite was added, the mass fraction of 20percent potassium chloride solution 300ml, controlling the stirring speed of 160 rpm, was slowly added guaiacol (2) 1.3mol, solution temperature rises to 50 , holding 3h, was added 3-amine 1,2-propanediol (3) 1.7mol, increasing the solution temperature 90 , maintained under stirring 5h, the temperature of the solution is reduced to 15 , allowed to stand for 25h after removing the aqueous layer delamination, the mass fraction of oil was added 200ml of 25percent solution of sodium bromide, mass fraction of 35percent oxalic acid solution was adjusted to maintain the pH at 7, after cooling the precipitated solid was suction filtered, washed with a solution of potassium nitrate, mass fraction washed with 70percent nitro methane in the mass fraction of 98percent propylene eye recrystallized to give crystals of 3- (o-methoxyphenoxy) -1,2-propanediol 185.33g, yield 72percent.
Reference:
[1] Patent: CN105566073, 2016, A, . Location in patent: Paragraph 0013; 0014
84
[ 556-52-5 ]
[ 90-05-1 ]
[ 14007-09-1 ]
[ 93-14-1 ]
Yield
Reaction Conditions
Operation in experiment
95%
With calcined hydrotalcite In tetrahydrofuran at 120℃; for 4 h; Autoclave
In a typical reaction, autoclave reactor (details included in sup-porting information) was charged with guaiacol (0.0081 mol), gly-cidol (0.020 mol), tetrahydrofuran (THF) (10 mL) and 0.03 g mL−1(0.9 g) of the catalyst. The total organic phase volume was made to30 mL with THF. An initial sample was taken at the desired temperature. The reaction mixture was stirred with mechanical stirrer atthe desired speed, and samples were collected periodically. For control reaction, speed of agitation was 1000 rpm and temperature was 120°C at self-generated pressure. Reaction samples were analyzed by HPLC (details included in supporting information). Synthesis of guaifenesin (3-(2-methoxyphenoxy)propane-1,2-diol) andbyproduct (2-(2-methoxyphenoxy)propane-1,3-diol) from condensation reaction of guaiacol and glycidol is shown in Scheme 1.
Reference:
[1] Chirality, 2016, vol. 28, # 4, p. 313 - 318
[2] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[3] Chemical Communications, 2013, vol. 49, # 52, p. 5886 - 5888
[4] Physical Chemistry Chemical Physics, 2017, vol. 19, # 41, p. 28302 - 28312
86
[ 90-05-1 ]
[ 93-14-1 ]
Reference:
[1] Journal of the Chemical Society, Chemical Communications, 1980, # 22, p. 1053 - 1054
[2] Journal of the American Chemical Society, 1983, vol. 105, # 3, p. 586 - 593
[3] Patent: US4390732, 1983, A,
87
[ 90-05-1 ]
[ 106-89-8 ]
[ 25772-81-0 ]
[ 16929-60-5 ]
[ 93-14-1 ]
[ 2210-74-4 ]
Reference:
[1] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
88
[ 90-05-1 ]
[ 56-81-5 ]
[ 93-14-1 ]
Reference:
[1] Green Chemistry, 2013, vol. 15, # 3, p. 625 - 628
89
[ 90-05-1 ]
[ 95041-90-0 ]
Reference:
[1] Synthesis, 2011, # 22, p. 3711 - 3715
90
[ 90-05-1 ]
[ 95041-90-0 ]
[ 117048-62-1 ]
Reference:
[1] Synthesis, 2011, # 22, p. 3711 - 3715
[2] Synthesis, 2011, # 22, p. 3711 - 3715
Reference:
[1] Organic Preparations and Procedures International, 2016, vol. 48, # 6, p. 481 - 491
97
[ 90-05-1 ]
[ 150728-13-5 ]
Reference:
[1] Patent: WO2011/24056, 2011, A2,
[2] European Journal of Medicinal Chemistry, 2016, vol. 121, p. 658 - 670
[3] Organic Preparations and Procedures International, 2016, vol. 48, # 6, p. 481 - 491
98
[ 90-05-1 ]
[ 160969-03-9 ]
Reference:
[1] Patent: WO2011/101864, 2011, A1,
99
[ 1427177-23-8 ]
[ 90-05-1 ]
[ 95635-55-5 ]
Reference:
[1] Green Chemistry, 2013, vol. 15, # 3, p. 756 - 767
[2] RSC Advances, 2016, vol. 6, # 54, p. 49150 - 49157
100
[ 90-05-1 ]
[ 95635-55-5 ]
Reference:
[1] Organic Process Research and Development, 2012, vol. 16, # 5, p. 748 - 754
[2] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[3] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[4] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[5] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[6] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[7] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[8] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[9] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1660 - 1664
[10] Patent: US2013/90475, 2013, A1,
[11] Patent: US2013/90475, 2013, A1,
[12] Patent: WO2016/142819, 2016, A2,
101
[ 90-05-1 ]
[ 151541-15-0 ]
Reference:
[1] Journal of the American Chemical Society, 2013, vol. 135, # 17, p. 6415 - 6418
102
[ 28868-76-0 ]
[ 90-05-1 ]
[ 150726-89-9 ]
Yield
Reaction Conditions
Operation in experiment
78.7%
With sodium methylate In methanol at 45℃; for 1 h;
A sodiummethoxide solution in methanol (2.3 g of Na, 0.10 mol, 1.0 eq in75 ml of MeOH) was slowly added to a stirred mixture of guaiacole(12.5 g, 0.100 mol, 10 eq) and dimethyl 2-chloromalonate (19.0 g,0.114 mol, 1.14 eq). After having reacted for 1 h at 45 °C, the volatilematerial were evaporated and the residue was taken up in toluene,washed with water and NaHCO3 (1percent aqueous solution). Theconcentrated organic phase afforded 20.0 g (yield 78.7percent) of aviscous oil that was characterized as follows: bp 131 °C (lit. [38] bp128 °C); 1H NMR (CDCl3) δ 7.12-7.00 (m, 2H), 6.98-6.90 (m, 1H),6.90-6.82 (m, 1H), 5.27 (s, 1H), 3.85 (s, 3H), 3.84 (s, 6H); 13C NMR(CDCl3) δ 166.2 (2C), 150.4, 146.0, 124.4, 120.8, 119.0, 112.5, 78.4,55.8, 53.0 (2C); HRMS calcd for C12H14O6 255.0869 (M+H+), found255.0870 (M+H+).
65%
Stage #1: With sodium hydroxide In toluene for 2 h; Reflux; Dean-Stark; Large scale Stage #2: for 3 h; Reflux; Large scale
Sodium hydroxide (28.27 kg, 706.86 mol) was added in one portion to a mixture of 2-methoxyphenol (13, 75 kg, 604.16 mol) and toluene (525 L) at 20–30C under stirring.The reaction mixture was heated to reflux temperature and the water was separated azeotropically using a Dean-Stark trap for 2 h. Then dimethyl chloromalonate (12,110.69 kg, 664.57 mol) was added to the reaction mixture at 60–65C over a period of30 min and heated to reflux and stirred for 3 h. After completion of the reaction, the mixturewas cooled to 20–30C and diluted with de-mineralized water (150 L). The twolayers were separated, and the organic layer was washed with 1percent w/v aqueous sodiumhydroxide (2 £ 150 L). The organic layer was separated and concentrated to give oilymass which was dissolved in methyl tert-butyl ether (225 L) at 20–30C; then n-heptane(60 L) was cautiously added over 45 min at 20–30C. The resulting solution was seededwith crystals of compound 1 (0.075 kg) to induce crystallization, then stirred for 1 h,cooled to 10C and stirred for 2 h at the same temperature. Then the solid formed wascollected and dried at 30C under reduced pressure to afford 99.10 kg (65percent yield) of 1 ascolorless crystals, mp: 38–40C, (purity of 95.13percent a/a). 1H NMR (CDCl3, 300 MHz): d7.02–7.06 (m, 2H), 6.84–6.93 (m, 2H) 5.26 (s, 1H), 3.85 (s, 9H). MS M/z (ESI): 253.0[(MCH)].
Reference:
[1] European Journal of Medicinal Chemistry, 2016, vol. 121, p. 658 - 670
[2] Organic Preparations and Procedures International, 2016, vol. 48, # 6, p. 481 - 491
[3] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 4, p. 897 - 907
[4] Patent: US5292740, 1994, A,
[5] Patent: WO2011/24056, 2011, A2, . Location in patent: Page/Page column 19
103
[ 90-05-1 ]
[ 150727-06-3 ]
Reference:
[1] Patent: WO2011/24056, 2011, A2,
[2] European Journal of Medicinal Chemistry, 2016, vol. 121, p. 658 - 670
[3] Organic Preparations and Procedures International, 2016, vol. 48, # 6, p. 481 - 491
104
[ 90-05-1 ]
[ 94687-10-2 ]
Reference:
[1] Journal of the American Chemical Society, 2013, vol. 135, # 17, p. 6415 - 6418
[2] Patent: WO2015/138563, 2015, A1,
[3] Green Chemistry, 2018, vol. 20, # 16, p. 3761 - 3771
105
[ 90-05-1 ]
[ 92409-15-9 ]
Reference:
[1] Green Chemistry, 2016, vol. 18, # 24, p. 6545 - 6555
[2] Green Chemistry, 2018, vol. 20, # 16, p. 3761 - 3771
106
[ 90-05-1 ]
[ 92409-23-9 ]
Reference:
[1] Organic Letters, 2016, vol. 18, # 19, p. 5166 - 5169
[2] Green Chemistry, 2016, vol. 18, # 24, p. 6545 - 6555
107
[ 90-05-1 ]
[ 2632-13-5 ]
[ 92409-23-9 ]
Reference:
[1] Journal of the American Chemical Society, 2014, vol. 136, # 4, p. 1218 - 1221
EXAMPLE 1 [Synthesis of 6'-methoxybenzoxazinorifamycin] To a stirred mixture of 50 ml of water, 150 ml of ether and 15.0 g of 2-methoxyphenol was added dropwise 12.7 ml of 61% nitric acid, and the mixture was stirred at room temperature for 15 minutes. The ether layer was separated from the aqueous layer and dried over anhydrous sodium sulfate. After the drying agent was filtered off, the solvent was distilled off under reduced pressure. The residue was purified by silica-gel column-chromatography using Wakogel C-200 [eluent: chloroform-n-hexane (1:1)] to give 4.72 g of 2-methoxy-6-nitrophenol.
With nitronium tetrafluoborate; In 1,2-dimethoxyethane; at -50℃;
Step 1 Production of 2-methoxy-6-nitrophenol 1,2-Dimethoxyethane (100 mL) was added to 2-methoxyphenol (6.21 g), and the mixture was cooled to -50 C. Nitronium tetrafluoroborate (6.77 g) was added, and the mixture was stirred at -50 C. After the completion of reaction, the reaction mixture was poured into ice water, and ethyl acetate and ethyl ether were added. The insoluble material was removed by filtration, and the filtrate was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1-3:1) to give the title compound (2.46 g) as a yellow solid.
With nitronium tetrafluoborate; In 1,2-dimethoxyethane; at -50℃;
Step 1 Production of 2-methoxy-6-nitrophenol 1,2-Dimethoxyethane (100 mL) was added to 2-methoxyphenol (6.21 g), and the mixture was cooled to -50 C. Nitronium tetrafluoroborate (6.77 g) was added, and the mixture was stirred at -50 C. After the completion of reaction, the reaction mixture was poured into ice water, and ethyl acetate and ethyl ether were added. The insoluble material was removed by filtration, and the filtrate was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1-3:1) to give the title compound (2.46 g) as a yellow solid.
Trans-4-(2-methoxyphenoxy)-1-phenylmethyl-3-pyrrolidinol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
27%
In dichloromethane; benzene;
EXAMPLE 26 Trans-4-(2-methoxyphenoxy)-1-phenylmethyl-3-pyrrolidinol A mixture of 40 g. of crude <strong>[75390-09-9]1-benzyl-3,4-epoxypyrrolidine</strong> and 70 g. of guaiacol was heated at 120 C. for 20 hr. Aspirator vacuum was then used to distill off the excess guaiacol. The residue was dissolved in methylene chloride and extracted with dilute sodium hydroxide. The methylene chloride solution was dried over anhydrous sodium sulfate and the solvent was evaporated. The residue weighed 54 g., was chromatographed on 1 kg. of silica gel. The product was eluted with 50% ethyl acetate in benzene and crystallized from cyclohexane. The m.p. was 115-117 C. and the yield was 27%. Analysis: Calculated for C18 H21 NO3: C,72.22; H,7.07; N,4.68. Found: C,72.30; H,7.04; N,4.70.
27%
In dichloromethane; benzene;
EXAMPLE 26 Trans-4-(2-methoxyphenoxy)-1-phenylmethyl-3-pyrrolidinol A mixture of 40 g. of crude <strong>[75390-09-9]1-benzyl-3,4-epoxypyrrolidine</strong> and 70 g. of guaiacol was heated at 120 C. for 20 hr. Aspirator vacuum was then used to distill off the excess guaiacol. The residue was dissolved in methylene chloride and extracted with dilute sodium hydroxide. The methylene chloride solution was dried over anhydrous sodium sulfate and the solvent was evaporated. The residue weighed 54 g., was chromatographed on 1 kg. of silica gel. The product was eluted with 50% ethyl acetate in benzene and crystallized from cyclohexane. The m.p. was 115-117 C. and the yield was 27%. Analysis: Calculated for C18 H21 NO3: C, 72.22; H, 7.07; N, 4.68. Found: C, 72.30; H, 7.04; N, 4.70.
With nitric acid; In dichloromethane; at -20 - 20℃; for 2.0h;
Fuming HNO3 (0.34 mL, 0.008 mmol) was carefully added to a mixture of 2-methoxyphenol (0.886 mL, 0.008 mmol) in anhydrous DCM (10 mL) at -20 C. After stirring for 2 h at RT, the mixture was concentrated under vacuum. Chromatography (10-30% EtOAc/hexanes) provided 9A12 (400 mg, 29%) and 2-methoxy-3-nitrophenol (400 mg, 29%).
Step 1 Production of 2-methoxy-6-nitrophenol 1,2-Dimethoxyethane (100 mL) was added to 2-methoxyphenol (6.21 g), and the mixture was cooled to -50 C. Nitronium tetrafluoroborate (6.77 g) was added, and the mixture was stirred at -50 C. After the completion of reaction, the reaction mixture was poured into ice water, and ethyl acetate and ethyl ether were added. The insoluble material was removed by filtration, and the filtrate was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate=4:1-3:1) to give the title compound (2.46 g) as a yellow solid.
With hydrogen; sodium t-butanolate;bis(1,5-cyclooctadiene)nickel(0); 1,3-bis[(2,6-diisopropyl)phenyl]imidazolinium chloride; In toluene; at 50℃; under 750.075 Torr; for 16h;Inert atmosphere;Product distribution / selectivity;
Full conversion of the model compound for beta-O-4 lignin linkage was observed after16 h and 20-24% guaicol was detected by GC. Other products were not observed in the GC orGC/MS.
With potassium carbonate; In dimethyl sulfoxide; at 50℃; for 18.0h;
To a solution of 2-methoxyphenol (1 16 mg, 0.79 mmol) in DMSO (3 mL) was added potassium carbonate (218 mg, 1 .6 mmol) followed by <strong>[20372-66-1]methyl 2,4,5-trifluorobenzoate</strong> (150 mg, 0.79 mmol) . The resulting mixture was heated to 50 C with stirring for 18 hours. The mixture was then cooled and diluted with water (30 mL) then washed with EtOAc (3 x 30 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford the title compound (121 mg, 52%) as a yellow gum. 1H NMR (400 MHz, CDCI3): delta ppm 3.81 (s, 3H), 3.91 (s, 3H), 6.41 (dd, 1 H), 6.98-7.03 (m, 2H), 7.05 (dd, 1 H), 7.24-7.29 (m, 1 H), 7.75 (dd, 1 H). LCMS Rt = 1 .72 minutes MS m/z 295 [MH]+
With Trametes hirsuta laccase; In methanol; ethyl acetate; acetonitrile; at 35℃; for 1h;pH 6.4;Enzymatic reaction;
General procedure: Prior to monitoring oxygen consumption the effect of pH on the maximum absorbance value was studied as described below. Buffer solutions were prepared using 20 mM ammonium acetate buffer for pH 4.5-5 and 20 mM phosphate buffer for pH 6.9. The effect of pH on absorbance maxima was studied by dissolving solubilized <strong>[480-41-1]naringenin</strong> in 98% acetone in the various pH values as above and recording the wavelength scans (900-200 nm) after 30 min incubations using a Hitachi U-2001UV-vis spectrophotometer. The reaction mixture contained <strong>[480-41-1]naringenin</strong> (0.5 mM)and one of the polyhydroxylated monoaromatics compound (2 mM) in the molar ratio of 1:4 (in order to increase the probability of coupling), 40% (v/v) of organic solvent (methanol, acetonitrile and ethyl acetate), and 0.67 nkat ml-1 final laccase activity in 20 mM ammonium acetate buffer for pH 6.4. Reactions were carriedout at 35 C while shaking at 600 rpm using a rotary shaker for 1 h. To the incubation mixtures an equal volume of methanol was added and the mixture was centrifuged for 15 min at 14,000 x g and 600 mul aliquots were transferred into cleanvials.
1,1-dimethylethyl (R)-2,2-dimethyl-4-[[2-(methoxy)phenoxy]methyl]-3-oxazolidinecarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
45%
With di-isopropyl azodicarboxylate; triphenylphosphine; In toluene; at 80℃; for 3h;
General procedure: To a stirred solution of 6 (0.100 g, 0.433 mmol), appropriate substituted phenol (0.649 mmol) and PPh3 (0.182 g,0.693 mmol) in anhydrous toluene (5 mL) was added DIAD(0.14 mL, 0.693 mmol) at 80 C. After 3 h, EtOAc (40 mL)was added to the resulting solution. The organic layer was washed with 0.5 M aqueous NaOH (40 mL) and water (2 X40 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash silica gel column chromatography eluting with Hexanes/EtOAc (9:1) or (95:5) to afford compounds 7a-s.
Reductive cleavage of oxidized lignin model compound: (0251) In this Example, model compounds bearing a benzylic ketone group and a primary alcohol (Scheme 14) or a benzylic ketone group and aldehyde (Scheme 13) were subjected to cleavage using formic acid in water and in the presence of various metals, as well as in the absence of metals. The amount of metal catalyst and the acidity of the reaction medium were varied as shown in Scheme 12. Scheme 13 depicts the reaction and product yield under specific conditions that resulted in optimum yield. (0252) 0. (0253) 1.5 equiv 10:1 Conv. 100% 64.5% 67% 27% (0254) (1.1 mL total) (0255) S tive cleavage of model compound with primary alcohol group. (0256) + Zn (powder) + HC02H : H20 (0257) (0258) 0.13 mrnol = 48 mg 1.5 equiv 10:1 Conv. 91% 53% 85%
C-O cleavage of oxidized sample without metal: (0267) Further testing revealed that selective cleavage of bond in the beta-Omicron-4 linkage could be accomplished using an acid and without a metal catalyst. An exemplary reaction using model compound 1 (which includes a benzyl-position ketone) and aqueous formic acid is depicted in Scheme 15
C-O cleavage of different oxidized lignin model compounds: (0279) Schemes 17 and 18 show that the approach described herein also function for other oxidized, lignin model compounds. Of particular note here is that all of the model compounds include a ketone in the benzyl position (i.e., the a-position) of the beta-Omicron-4 linkage. (0280) (0281) 0.2 mmol = 67 mg 3 equiv. (2 iota·etaIota.: 100 mu1_) Conversion - 100% 92% (0282) (0283) 3: R=R"= H, R'= OH p-Hydroxyphenyl units (H) 89% 73% (0284) 4: R=H, R'= OH, R"= OMe guaiacyl units (G) 90% 84% (0285) 5: R=R"= OMe, R'= OH syringyl units (S) 940/,, 88% (0286) Scheme 18. C-0 Cleavage of various model compounds. (0287) As shown in Scheme 18, the specific yield of small, aromatic compounds was quite high. C-O cleavage of oxidized lignin to simple chemicals: (0288) Here, an authentic lignin sample was oxidized to introduce a benzylic-position ketone in at least a portion of the beta-Omicron-4 linkages, and then subjected to depolymerization via C-0 cleavage of the ether bond in the beta-Omicron-4 linkages. The resulting product mixture is shown in Fig. 8.
With C32H25Cl2N6O2Rh2(1+)*Cl(1-); sodium hydroxide; In water; at 110℃; for 18.0h;Inert atmosphere;
The 152 mg type g shown in lignin of beta - O - 4 model compound, 8 mg double rhodium catalyst, 80 mg NaOH added 1 ml distilled water, under protection of argon 110 C reaction 18 hours, to complete the lignin complete degradation, wherein the degradation product to the methoxy acetophenone of yield is 24%, P-acetone to yield 34%, O-methoxyphenol of yield is 62%.
With C32H25Cl2N6O2Rh2(1+)*Cl(1-); sodium hydroxide; In water; at 110℃; for 18h;Inert atmosphere;
The 152 mg type g shown in lignin of beta - O - 4 model compound, 8 mg double rhodium catalyst, 80 mg NaOH added 1 ml distilled water, under protection of argon 110 C reaction 18 hours, to complete the lignin complete degradation, wherein the degradation product to the methoxy acetophenone of yield is 24%, P-acetone to yield 34%, O-methoxyphenol of yield is 62%.
With hydrogen; In tetrahydrofuran; water; at 240℃; under 7500.75 Torr; for 12.0h;Autoclave;
General procedure: The catalytic hydrogenolysis of lignin model compounds was performedusing a 50 mL Zr-alloy autoclave provided by Anhui KemiMachinery Technology Co., Ltd. For a typical procedure, lignin modelcompounds (0.5 mmol or 1 mmol) or organosolv lignin (35 mg), heterogeneousFe catalyst (100 mg), and solvent (20 mL) were added intothe autoclave with a quartz lining. After purging the reactor with H2,the reaction was conducted with 1 MPa H2 (at room temperature) at240 C for 12 h with a stirring speed of 800 rpm. After reaction, internalstandards are added to the product solution, and then the liquid productswere analyzed by using both GC and GC-MS. For the conversionof alpha-O-4 lignin model compound, 2-phenylethanol is used as internalstandard to determine the yields of benzyl alcohol and phenol, anddodecane is used to determine the yield of toluene. For the conversionof beta-O-4 lignin model compounds, benzyl alcohol and dodecane areused as internal standards to determine the yields of phenolic fragmentsand aromatic fragments, respectively. A representative GC spectrumcan be seen in Fig. S11 in supporting information. GC-MS analyses wereperformed on an Agilent 7890 Gas Chromatograph equipped with a DBWAXETR30m×0.25 mm×0.25mm capillary column (Agilent) or aHP-5MS 30m×0.25 mm×0.25mm capillary column (Agilent).Although HP-5MS column is unsuitable for the determination of productsyields due to the low polarity, it can be used to confirm whethersome complex lignin model compounds were completely converted.The GC was directly interfaced to an Agilent 5977 mass selective detector(EI, 70 eV). The following GC oven temperature programs wereused: 40 C hold for 1 min, ramp 5 C min-1 to a temperature of 120 C,and then ramp 10 C min-1 to 300 C and hold for 5 min. To get the representative GC spectrum of gaseous products, the gaseous phase wascollected and injected into a Fuli 9790II Gas Chromatograph equippedwith a TDX-01 packed column and a thermal conductivity detector(TCD) through a six-way valve to analyze the composition.
(trans)-methyl 3-(2-methoxyphenoxy)cyclobutanecarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 72h;
Triphenylphosphine (504 mg, 1 .92 mmol) was added to a solution of 2-methoxyphenol (0.18 mL, 1 .6 mmol) in tetrahydrofuran (5 mL). The reaction mixture was cooled to 0 C, and (c/s)-methyl 3-hydroxycyclobutanecarboxylate (250 mg, 1 .92 mmol) was added, followed by DIAD (0.37 mL, 1 .9 mmol). After 10 min, the reaction mixture was warmed to room temperature, stirred for 3 days and diluted with water and EtOAc. The mixture was partitioned, and the aqueous layer was extracted with EtOAc (2X). The organic layer was washed with water, dried over sodium sulfate, filtered, and concentrated. The residue was purified on silica gel eluting with a 0%-100% EtOAc-hexanes gradient to give the title compound (206 mg, 54%). 1H NMR (400 MHz, CD3SOCD3) delta 2.30-2.40 (m, 2 H), 2.58-2.67 (m, 2 H), 3.10-3.20 (m, 1 H), 3.63 (s, 3 H), 3.73 (s, 3 H), 4.71 -4.79 (m, 1 H), 6.68-6.81 (m, 1 H), 6.78-6.89 (m, 2 H), 6.91 -6.95 (m, 1 H); LC-MS (LC-ES) M+H-OMe = 205.
In 5 ml of quartz optical reaction tube, adding 0.05 mmol <strong>[92409-15-9]2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)-1,3-propanediol</strong>, 5 mg mpg-C3N4Catalyst, magneton, and add 1 ml solvent acetonitrile (substrate concentration is 0.05 mol/L). Air above the oxygen displacement reaction tube, and the opening is sealed, is arranged in the integrated light in the reaction device, the rotating speed of 500 r/min, the illumination wavelength is 405 nm (the power of 6 W), temperature constant at 40C, reaction 8 h. After the reaction, gas chromatography - mass spectrum detecting the product, and for high performance liquid chromatography quantitative, substrate conversion and product yield is shown in table 1.