* 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.
With thionyl chloride In dichloromethane; N,N-dimethyl-formamide
In a 500 ml eggplant type bottle, 1,9-nonanediol (5.0 g, 31.2 mmol) was added.Dichloromethane (100 ml) and DMF (3 drops).Thionyl chloride (11.7 g, 98.3 mmol) was dissolved in dichloromethane (155 ml).In an ice bath, the solution of thionyl chloride is added dropwise into the eggplant type bottle.The reaction was overnight.The reaction mixture was washed with saturated sodium bicarbonate solution and then washed with saturated sodium chloride solution.The organic phase is dried over anhydrous sodium sulfate.Evaporation gave 4.0 g of 1,9-dichlorononane (light yellow oil, yield 65percent).
Reference:
[1] Journal of Organic Chemistry USSR (English Translation), 1989, vol. 25, # 4.1, p. 642 - 646[2] Zhurnal Organicheskoi Khimii, 1989, vol. 25, # 4, p. 716 - 721
[3] Patent: CN107721925, 2018, A, . Location in patent: Paragraph 0096; 0097
[4] Journal of the American Chemical Society, 1948, vol. 70, p. 3393
[5] Pharmaceutical Chemistry Journal, 1972, vol. 6, # 5, p. 283 - 286[6] Khimiko-Farmatsevticheskii Zhurnal, 1972, vol. 6, # 5, p. 11 - 14
2
[ 3937-56-2 ]
[ 55362-80-6 ]
Yield
Reaction Conditions
Operation in experiment
94%
With hydrogen bromide In toluene for 30 h; Dean-Stark; Reflux
In a 500 mL round bottom flask fitted with a Dean-Stark apparatus 1 ,9-nonanediol (Sigma- Aldrich) (20 g, 0.125 mol) was dissolved in toluene (500 ml). To this solution was added 21 mL hydrobromic acid (48 percent, 188 mmol) and the mixture was heated for 30 h at reflux. The water formed during the reaction was removed using a Dean—Stark trap. The progress of the reaction monitored by thin layer chromatography (TLC) indicated that all starting materials reacted withHBr. After cooling to room temperature, the mixture was washed with 1 M HCI (100 mL), 1M NaOH (100 ml), 100 mL water and finally with 100 mL brine. The organic layer was dried over anhydrous magnesium sulfate, and concentrated in vacuo. The crude oil obtained was fractionally distilled to give 9-bromononanol in 94 percent yield. B.p.:124-128 ° C/2 mmHg (lit: 125- 126 °C/2 mmHg).
87%
With hydrogen bromide In toluene at 110℃; for 24 h;
General procedure: To a stirred solution of 1,6-hexanodiol 1a (1.00 equiv.), 1,9-nonanediol 1b (1.00 equiv.), or 1,12-dodecanediol 1c (1.00 equiv.), in 30 mL of toluene was added HBr 48 percent (2.00 equiv.). The reaction was stirred at 110 °C for 24 h. The solvent was removed under reduced pressure, and the residue was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield pure haloalcohol 2a–c. These compounds were transformed into their corresponding azido alcohols 3a–c by SN2 substitution (Scheme 1). A stock solution of 0.5 M NaN3 in DMSO was prepared by stirring the solution for 24 h at room temperature. To a 100-mL round-bottom flask equipped with a magnetic stir bar was added a 0.5 M solution of NaN3 in DMSO at room temperature. To this solution was added the bromo alcohol 2a (1.00 equiv.), 2b (1.00 equiv.), or 2c (1.00 equiv.), and the mixture was stirred for 24 h at room temperature.The reaction was quenched with H2O (50 mL) and stirred until it cooled to room temperature. The mixture was extracted with Et2O (3 9 30 mL), and the resulting extracts were washed with H2O (3 x 50 mL) and brine (50 mL). The organic layer was dried (Na2SO4) and filtered, and the residue obtained was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield pure alkyl azido alcohols 3a–c. A solution of the azido alcohol 3a (1.00 equiv.), 3b (1.00 equiv.), or 3c (1.00 equiv.) in CH2Cl2 (50 mL) was cooled to 0 °C. Et3N (2.00 equiv.) and methanesulfonyl chloride (2.00 equiv.) was added. The reaction mixture was stirred for 24 h and then allowed to reach room temperature. The reaction mixture was poured into crushed ice (70 mL) and was then extracted with methylene chloride (3 9 30 mL). The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure. The residue obtained was purified by column chromatography over silica gel, eluting with hexane/EtOAc 9:1, to yield highly purified halo alcohol pure methanesulfonate alkyl azides compounds 4a, 4b, and 4d.
76%
With hydrogen bromide In water; toluene for 6 h; Reflux; Inert atmosphere
According to a known protocol,23 1,9-nonanediol (4) (8.0 g, 50 mmol, 1 eq) was dissolved in toluene (100 mL) and 48percent HBr (66 mL, 400 mmol, 8 eq) was added. Then the reaction mixture was refluxed for 6 h. After completion the reaction mixture was cooled to room temperature and brine (100 mL) was added. The aqueous phase was extracted with hexane (2 100 mL), the combined organic layer was dried over MgSO4 and evaporated. The crude mixture obtained was purified by column chromatography (17 cm 5 cm, cyclohexane/ethyl acetate, 20:1) to give a white solid. Yield: 8.5 g (76percent). M.p.: 42-43 °C. 1H NMR (400 MHz, CDCl3): δ = 1.25 – 1.38 (m, 9H, 4-CH2, 5-CH2, 6-CH2, 7-CH2, OH), 1.43 (quin, 3JH,H = 6.5 Hz, 2H, 3-CH2), 1.56 (quin, 3JH,H = 7.2 Hz, 2H, 8-CH2), 1.85 (p, 3JH,H = 7.2 Hz, 2H, 2-CH2), 3.41 (t, 3JH,H = 6.9 Hz, 2H, 1-CH2), 3.64 (t, 3JH,H = 6.6 Hz, 2H, 9-CH2) ppm. 13C NMR (101 MHz, CDCl3): δ = 25.7 (C-7), 28.1 (C-3), 28.6 (C-4), 29.3 (C-5), 29.3 (C-6), 32.7 (C-2), 32.8 (C-8), 34.0 (C-1), 63.0 (C-9) ppm. HRMS (ESI+): m/z C9H19BrO + Na+: calcd. 245.0517, found 245.0511. The spectroscopic data agree with published ones.23
1.1 kg
With hydrogen bromide In toluene at 90 - 100℃; for 24 h; Large scale
1,9-nonanediol (1 kg) was added to toluene (20 L), hydrobromic acid (40percent, 2.5 L) was added with stirring, heated to reflux (Internal temperature 90-100 ° C) 24 hrs. (4 L) and cold water (4 L) were added and the layers were stirred. The organic phase was washed successively with saturated aqueous sodium bicarbonate and aqueous solution, dried over anhydrous sodium sulfate, dried over anhydrous sodium bicarbonate, Spin dry 1.6 kg crude product, adding n-hexane 4.8 L, stirring and heating dissolved, Crystallization was carried out to give 1.1 kg of 9-bromo-1-nonanol.
1.1 kg
With hydrogen bromide In toluene at 90 - 100℃; for 24 h; Large scale
1. Add 1,9-nonanediol (1 kg) to toluene (20 L). Add hydrobromic acid (40percent, 2.5 L) with stirring and heat to reflux (internal temperature 90-100 ° C) for 24 hrs. The heating was stopped and cooled to 40 ° C. Ethyl acetate (4L) and cold water (4L) were added. The mixture was stirred and layered. The organic phase was washed successively with saturated aqueous sodium bicarbonate solution and water, dried over anhydrous sodium sulfate and spun dry to 1.6 kg The crude product was added with 4.8 L of n-hexane, stirred and heated to dissolve and crystallized by cooling to obtain 1.1 kg of 9-bromo-1-nonanol
1.1 kg
With hydrogen bromide In toluene at 90 - 100℃; for 24 h; Large scale
1,9-Nonanediol (1 kg) was added to toluene (20 L) and hydrobromic acid (40percent, 2.5 L)Heat reflux (internal temperature 90-100 ) 24 hrs. Stop heating, cooled to 40 ,Ethyl acetate (4L) and cold water (4L) were added, the mixture was stirred and layered,The organic phase was washed successively with saturated aqueous sodium bicarbonate solution and aqueous solution, dried over anhydrous sodium sulfate,Spin dried to 1.6 kg of crude product, adding n-hexane 4.8 L, stirring heated to dissolve, cooling crystallization,1.1 kg of 9-bromo-1-nonanol were obtained
Reference:
[1] Patent: WO2017/171674, 2017, A1, . Location in patent: Page/Page column 3; 4
[2] Tetrahedron, 1997, vol. 53, # 21, p. 7255 - 7266
[3] Chemical Research in Toxicology, 2012, vol. 25, # 10, p. 2253 - 2260
[4] Journal of Fluorine Chemistry, 2003, vol. 123, # 2, p. 255 - 259
[5] Molecules, 2013, vol. 18, # 5, p. 5201 - 5208
[6] Journal of Organic Chemistry, 2000, vol. 65, # 25, p. 8582 - 8588
[7] Medicinal Chemistry Research, 2015, vol. 24, # 1, p. 430 - 441
[8] European Journal of Organic Chemistry, 2006, # 5, p. 1285 - 1295
[9] Tetrahedron Letters, 2015, vol. 56, # 39, p. 5353 - 5356
[10] Journal of Heterocyclic Chemistry, 1990, vol. 27, # 5, p. 1233 - 1239
[11] Synthetic Communications, 1981, vol. 11, # 6, p. 497 - 504
[12] Tetrahedron, 1992, vol. 48, # 16, p. 3413 - 3428
[13] Organic Process Research and Development, 2003, vol. 7, # 3, p. 339 - 340
[14] Tetrahedron, 1999, vol. 55, # 12, p. 3595 - 3604
[15] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5048 - 5051
[16] Synthesis, 1985, # 12, p. 1161 - 1162
[17] Canadian Journal of Chemistry, 1994, vol. 72, # 6, p. 1500 - 1511
[18] Synthesis, 1994, # SPEC. ISS., p. 1257 - 1261
[19] Canadian Journal of Chemistry, 1992, vol. 70, # 5, p. 1427 - 1445
[20] Justus Liebigs Annalen der Chemie, 1962, vol. 658, p. 39 - 64
[21] Chemistry Letters, 1975, p. 103 - 106
[22] Journal of the American Chemical Society, 1990, vol. 112, # 15, p. 5844 - 5850
[23] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1989, vol. 28, # 1-11, p. 579 - 580
[24] Journal of the American Chemical Society, 2002, vol. 124, # 16, p. 4363 - 4370
[25] Journal of Organic Chemistry, 1986, vol. 51, # 14, p. 2751 - 2756
[26] Agricultural and Biological Chemistry, 1987, vol. 51, # 2, p. 309 - 314
[27] Chemistry Letters, 1994, # 10, p. 1789 - 1792
[28] Synthesis, 2002, # 1, p. 111 - 115
[29] Journal of Medicinal Chemistry, 2004, vol. 47, # 25, p. 6270 - 6282
[30] Bioscience, Biotechnology and Biochemistry, 2006, vol. 70, # 2, p. 508 - 516
[31] Organic Process Research and Development, 2010, vol. 14, # 3, p. 544 - 552
[32] Chemical Biology and Drug Design, 2011, vol. 78, # 3, p. 477 - 482
[33] Synlett, 2012, vol. 23, # 12, p. 1843 - 1846
[34] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 24 - 33
[35] Patent: CN103965280, 2016, B, . Location in patent: Paragraph 0069; 0070
[36] Journal of Labelled Compounds and Radiopharmaceuticals, 2017, vol. 60, # 7, p. 316 - 330
[37] Patent: CN104387435, 2017, B, . Location in patent: Paragraph 0042
[38] Patent: CN103980336, 2016, B, . Location in patent: Paragraph 0044; 0046
[39] Bulletin of the Korean Chemical Society, 2011, vol. 32, p. 3120 - 3122
Reference:
[1] Biomacromolecules, 2010, vol. 11, # 4, p. 911 - 918
[2] Synthetic Communications, 2000, vol. 30, # 23, p. 4387 - 4395
[3] Organic Letters, 2012, vol. 14, # 3, p. 840 - 843
[4] Polymer, 2011, vol. 52, # 20, p. 4503 - 4516
[5] Synthetic Communications, 2000, vol. 30, # 5, p. 941 - 946
[6] Bulletin of the Chemical Society of Japan, 1992, vol. 65, # 11, p. 3049 - 3054
[7] Justus Liebigs Annalen der Chemie, 1965, vol. 689, p. 40 - 64
[8] Journal of the Chemical Society, 1965, p. 2067 - 2072
[9] Monatshefte fuer Chemie, 1922, vol. 43, p. 590
[10] Helvetica Chimica Acta, 1926, vol. 9, p. 265
5
[ 624-17-9 ]
[ 3937-56-2 ]
Reference:
[1] Journal of the Chemical Society, 1931, p. 1699
[2] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 328[3] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1513[4] Chem. Zentralbl., 1936, vol. 107, # II, p. 2371
[5] Journal of the Chemical Society, 1948, p. 46
[6] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 951
[7] Annales de Chimie (Cachan, France), 1933, vol. <10> 20, p. 304,367
[8] Journal of the American Chemical Society, 1948, vol. 70, p. 3393
[9] Patent: US2079414, 1932, ,
[10] Patent: US2137407, 1934, ,
[11] Monatshefte fuer Chemie, 1922, vol. 43, p. 590
[12] Helvetica Chimica Acta, 1926, vol. 9, p. 265
[13] Journal of the Chemical Society, 1931, p. 1699
[14] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 328[15] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1513[16] Chem. Zentralbl., 1936, vol. 107, # II, p. 2371
[17] Orgh.Synth., 1934, vol. 14, p. 22
[18] Journal of the Chemical Society, 1948, p. 46
[19] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 951
[20] Annales de Chimie (Cachan, France), 1933, vol. <10> 20, p. 304,367
[21] Journal of the American Chemical Society, 1951, vol. 73, p. 2730,2731
[22] Monatshefte fuer Chemie, 1922, vol. 43, p. 590
[23] Helvetica Chimica Acta, 1926, vol. 9, p. 265
[24] Orgh.Synth., 1934, vol. 14, p. 22
[25] Bulletin de la Societe Chimique de France, 1964, p. 3155 - 3158
[26] Chemistry of Natural Compounds, 1990, vol. 26, # 4, p. 486 - 487[27] Khimiya Prirodnykh Soedinenii, 1990, # 4, p. 568 - 569
[28] Patent: US2079414, 1932, ,
[29] Patent: US2137407, 1934, ,
6
[ 98847-00-8 ]
[ 3937-56-2 ]
Reference:
[1] Synthetic Communications, 2000, vol. 30, # 13, p. 2301 - 2308
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 2000, vol. 39, # 11, p. 860 - 862
7
[ 82777-72-8 ]
[ 3937-56-2 ]
Reference:
[1] Synthesis, 2003, # 14, p. 2179 - 2184
8
[ 634902-05-9 ]
[ 3937-56-2 ]
Reference:
[1] Synthesis, 2003, # 14, p. 2179 - 2184
Reference:
[1] Journal of the Chemical Society, 1931, p. 1699
[2] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 328[3] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1513[4] Chem. Zentralbl., 1936, vol. 107, # II, p. 2371
[5] Journal of the Chemical Society, 1948, p. 46
[6] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 951
[7] Annales de Chimie (Cachan, France), 1933, vol. <10> 20, p. 304,367
[8] Monatshefte fuer Chemie, 1922, vol. 43, p. 590
[9] Helvetica Chimica Acta, 1926, vol. 9, p. 265
[10] Orgh.Synth., 1934, vol. 14, p. 22
[11] Monatshefte fuer Chemie, 1922, vol. 43, p. 590
[12] Helvetica Chimica Acta, 1926, vol. 9, p. 265
[13] Journal of the Chemical Society, 1931, p. 1699
[14] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 328[15] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1513[16] Chem. Zentralbl., 1936, vol. 107, # II, p. 2371
[17] Orgh.Synth., 1934, vol. 14, p. 22
[18] Journal of the Chemical Society, 1948, p. 46
[19] Recueil des Travaux Chimiques des Pays-Bas, 1938, vol. 57, p. 951
[20] Annales de Chimie (Cachan, France), 1933, vol. <10> 20, p. 304,367
[21] Synthesis, 1981, # 7, p. 558 - 559
15
[ 143-08-8 ]
[ 3937-56-2 ]
Reference:
[1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 19, p. 6727 - 6733
Reference:
[1] Helvetica Chimica Acta, 1929, vol. 12, p. 478
30
[ 111-84-2 ]
[ 3937-56-2 ]
[ 143-08-8 ]
Reference:
[1] Chemical Communications, 2012, vol. 48, # 42, p. 5115 - 5117
31
[ 4900-30-5 ]
[ 13686-96-9 ]
[ 3937-56-2 ]
Reference:
[1] Journal of Organic Chemistry, 1984, vol. 49, # 6, p. 1072 - 1078
32
[ 143-28-2 ]
[ 3937-56-2 ]
Reference:
[1] Journal of the Chemical Society [Section] C: Organic, 1968, p. 2480 - 2481
33
[ 3937-56-2 ]
[ 4549-33-1 ]
Yield
Reaction Conditions
Operation in experiment
99%
With carbon tetrabromide; Cu(tmp)(BINAP)BF4; sodium bromide In N,N-dimethyl-formamide for 24 h; UV-irradiation; Inert atmosphere
General procedure: To an open oven-dried reaction vial charged with a stir bar was added copper catalyst (2 mg,0.002 mmol, 0.01 equiv), the alcohol (0.20 mmol, 1.0 equiv), carbon tetrabromide (131.6 mg, 0.4mmol, 2.0 equiv) and sodium bromide (41 mg, 0.40 mmol, 2.0 equiv). The flask vial was capped,purged with a stream of nitrogen and dry DMF (1.5 mL) was added via syringe. The reactionmixture was stirred under purple LEDs (394 nm) for 24 h. The vessel was opened and the mixturewas poured into a separatory funnel containing Et2O (10 mL) and H2O (10 mL). The layers wereseparated, and the aqueous layer was extracted with Et2O (2 × 10 mL). The combined organiclayers were washed with sat. Na2S2O3 solution, brine, dried over Na2SO4 and concentrated invacuo. The residue was purified by chromatography (100 percent hexanes)
Reference:
[1] Beilstein Journal of Organic Chemistry, 2018, vol. 14, p. 2730 - 2736
[2] Nippon Kagaku Zasshi, 1957, vol. 78, p. 1504[3] Chem.Abstr., 1960, p. 1540
[4] Bulletin de la Societe Chimique de France, 1957, p. 1463,1467
[5] Biochemical Journal, 1947, vol. 41, p. 57
[6] Org.Synth.Coll. Vol.III<1955>228,
[7] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1512[8] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 328
[9] Chemische Berichte, 1944, vol. 77/79, p. 669,673[10] Monatshefte fuer Chemie, 1947, vol. 77, p. 259,262
[11] Helvetica Chimica Acta, 1926, vol. 9, p. 265
[12] Bulletin de la Societe Chimique de France, 1964, p. 3155 - 3158
[13] Journal of the Chemical Society, 1965, p. 2067 - 2072
With thionyl chloride; In dichloromethane; N,N-dimethyl-formamide;
In a 500 ml eggplant type bottle, 1,9-nonanediol (5.0 g, 31.2 mmol) was added.Dichloromethane (100 ml) and DMF (3 drops).Thionyl chloride (11.7 g, 98.3 mmol) was dissolved in dichloromethane (155 ml).In an ice bath, the solution of thionyl chloride is added dropwise into the eggplant type bottle.The reaction was overnight.The reaction mixture was washed with saturated sodium bicarbonate solution and then washed with saturated sodium chloride solution.The organic phase is dried over anhydrous sodium sulfate.Evaporation gave 4.0 g of 1,9-dichlorononane (light yellow oil, yield 65%).
With carbon tetrabromide; Cu(tmp)(BINAP)BF4; sodium bromide; In N,N-dimethyl-formamide; for 24h;UV-irradiation; Inert atmosphere;
General procedure: To an open oven-dried reaction vial charged with a stir bar was added copper catalyst (2 mg,0.002 mmol, 0.01 equiv), the alcohol (0.20 mmol, 1.0 equiv), carbon tetrabromide (131.6 mg, 0.4mmol, 2.0 equiv) and sodium bromide (41 mg, 0.40 mmol, 2.0 equiv). The flask vial was capped,purged with a stream of nitrogen and dry DMF (1.5 mL) was added via syringe. The reactionmixture was stirred under purple LEDs (394 nm) for 24 h. The vessel was opened and the mixturewas poured into a separatory funnel containing Et2O (10 mL) and H2O (10 mL). The layers wereseparated, and the aqueous layer was extracted with Et2O (2 × 10 mL). The combined organiclayers were washed with sat. Na2S2O3 solution, brine, dried over Na2SO4 and concentrated invacuo. The residue was purified by chromatography (100 percent hexanes)
Stage #1: 1,9-Nonanediol With sodium In toluene at 67 - 100℃; for 1h;
Stage #2: 4-chloro-2,3-dimethylpyridine-N-oxide In toluene at 109℃; for 5h;
13
Under a nitrogen stream and in a silicone oil bath, 50.0 g (0.312 mol, 4.0 eq.) of 1, 9-nonanediol and 86.7 mL of toluene were introduced, and while stirring under a nitrogen stream, the mixture was heated to 67°C. Then, 3.6 g (0.156 mol, 2.0 eq.) of metallic Na was added. Subsequently, the silicone oil bath was heated, and the mixture was allowed to react at 100°C for 1 hour. To the obtained reaction liquor, 12.3 g (0.078 mol, 1.0 eq.) of 4-chloro-2,3-dimethylpyridine-N-oxide was added, then the temperature was elevated to 109°C, and the mixture was allowed to react for 5 hours. The reaction liquor was cooled by standing overnight, and the separated toluene layer was removed by decantation. To the resulting residue, 130 mL of methanol was added, and the mixture was stirred. The insoluble was removed by filtration, and then the obtained filtrate was concentrated under reduced pressure and dried to solid, to obtain 56.4 g of 4-(9-hydroxynonyloxy)-2,3-dimethylpyridine-N-oxide as an oily matter.
With (2-hydroxyethyl)(methyl)amine; potassium phosphate; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] In acetone at 25℃; for 24h; Inert atmosphere;
With ammonia;chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); In tetrahydrofuran; at 150℃; under 11251.1 Torr; for 24h;Autoclave; Inert atmosphere;
Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.
With ammonia;(carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); 1,1,1-tris(diethylphosphinomethyl)ethane; In 1,3,5-trimethyl-benzene; at 155℃; under 10501.1 Torr; for 24h;Autoclave;Product distribution / selectivity;
EXAMPLE; General method for the catalytic amination of alcohols by means of ammonia according to the inventionLigand L, metal salt M or catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent and the alcohol to be reacted were placed under an Ar atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 mum). The results for the amination of 1,4-butanediol (tables 1a, 1b and 2), diethylene glycol (tables 3a, 3b and 4), monoethylene glycol (table 5) and diethanolamine (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol (table 7) and 2,5-(dimethanol)-furan (table 8) are given below.
With ammonia;(carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In 1,3,5-trimethyl-benzene; at 155℃; under 10501.1 Torr; for 24h;Inert atmosphere;Product distribution / selectivity;
Ligand L, metal salt M, solvent and the stated alcohol were introduced as initial charge under an Ar atmosphere in a 160 ml Parr autoclave (hte, (stainless steel V4A)) with magnetically coupled slanted-blade stirrer (stirring speed: 200-500 revolutions/minute). The stated amount of ammonia was either precondensed at room temperature or directly metered in from the NH3 pressurized-gas bottle. If hydrogen was used, this was carried out by means of iterative differential pressure metering. The steel autoclave was heated electrically up to the stated temperature and heated (internal temperature measurement) for the stated time with stirring (500 revolutions/minute). After cooling to room temperature, decompressing the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by means of GC (30 m RTX5 amine 0.32 mm 1.5 mum). Purification of the particular product can be carried out, for example, by distillation. The results for the amination of octanol (Table 1a and 1b), 1,4-butanediol (Table 2), diethylene glycol (Table 3), 1,9-nonanediol, 1,6-hexanediol, 1,10-decandiol (Table 4) and 1,2-dimethanolfuran (Table 5) are given below:
With chlorocarbonylhydrido[4,5-bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia; In tetrahydrofuran; at 150℃; under 11251.1 Torr; for 24h;Autoclave; Inert atmosphere;
General procedure: Example General Rules on the catalyst amination of alcohol with ammoniaaccording to the present invention (See below for manufacturing, initialweighed under an inert atmosphere) catalyst complex XIVb and, with the solvent(amount of up to solvent total amount reaches the 50ml), and the alcohol thatthe reaction is, under an argon atmosphere, magnetic coupling type tilt wingsParr autoclave of 160ml equipped with a stirrer (made of special steel V4A)(stirring speed: 200 to 500 rev / min) were charged in. At described the amountof ammonia at room temperature, it has been directly metered from thepreliminary condensed with or NH 3 gas cylinder. If hydrogen is used, this wasdone by repeated differential-pressure volume. Steel autoclave is electricheating heated to the temperature indicated, for a period of time described, ithas been heated under stirring (500 rev / min) (internal temperaturemeasurement). The autoclave was cooled to room temperature, depressurized,after performing outgassing of ammonia at atmospheric pressure, the reactionmixture was analyzed by GC (30m RTX5 Amin 0.32mm, 1.5mum). The desired product,for example, can be isolated by distillation
With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In 1,3,5-trimethyl-benzene; at 155℃; under 10501.1 Torr; for 24h;Inert atmosphere; Autoclave;
General procedure: Ligand L, see below for the metal salt M or catalyst complex XIVb (manufacturing, inert atmosphere initial mass below), solvent and an alcohol of the reaction, under an argon atmosphere, a magnetic coupling type Parr autoclave of 160ml equipped with atilt wing stirrer (made of special steel V4A) (Stirring speed: were charged to the 200 to 500 rev / min) in. It described theamount of ammonia at room temperature, It is directly metered from the preliminarycondensed with or NH3 gas cylinder. Hydrogenis used Case, this was done by an iterative difference-pressure amount. Power to the temperature indicated the steel autoclave is NetsuNoboru temperature, for a period of time described, has been heated under stirring (500 rev / min) (internal temperature Measurement). The autoclave was cooled to room temperature, depressurized, row outgassing of ammonia at atmospheric pressure after becoming, the reaction mixture was analyzed by GC (30m RTX5 Amin 0.32mm,1.5mum). The amination of 1,4-butanediol result (the first 1a, 1b and the second table), diethylene glycol of the same result (the first 3a, 3b and Table 4), the resultof monoethylene glycol (Table 5), diethanolamine same result (table 6), 1,5-pentanediol, 1,9-nonanediol, 1,6-hexanediol and 1,10-decanediol same result of (table 7), as well as furan-2,5-dimethanol same result (table 8) are as described below.
With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); ammonia; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine]; In toluene; at 155℃; under 10501.1 Torr; for 24h;Autoclave; Inert atmosphere;
General procedure: The ligand L, the metal salt M, the solvent and the alcohol were introduced as an initial feed into a 160 ml Parr autoclave (hte) having a magnetically coupled tilt blade stirrer (stirring rate: 200 to 500 rpm) in an Ar atmosphere , (Stainless steel V4A)). The amount of ammonia is pre-concentrated at room temperature or directly from a cylinder pressurized with NH3. If hydrogen is used, this is done by adding a repeated differential pressure differential. The steel autoclave was electrically heated to the temperature and heated for the time (internal temperature measurement) with stirring (500 revolutions per minute). After cooling to room temperature, the autoclave was decompressed and ammonia was withdrawn at atmospheric pressure, and the reaction mixture (30 m RTX5 amine 0.32 mml. 5 [mu] [pi]) was analyzed by GC. Purification of a specific product can be carried out, for example, by distillation. Octyl alcohol (Table 1), 1,9-nonanediol, 1,6-hexanediol, 1,10_ The amination results of diols (Table 4) and 2,5-dimethanolfuran (Table 5) are given below.
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
6
A solution of nonan-1,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2-hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution was stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed tocrystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel column (75 g) using 0-12% ethyl acetate/hexane as the eluent, yielding 9-(2’-hexyldecanoyloxy)nonan-l-ol (9.5 g) as anoil.
9.5 g
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
7
A solution of nonan-1,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2-hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solutionwas stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed to crystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passeddown a silica gel column (75 g) using 0-12% ethyl acetate/hexane as the eluent, yielding9-(2’-hexyldecanoyloxy)nonan-l-ol (9.5 g) as an oil.
9.5 g
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
7 EXAMPLE 7: (0739) SYNTHESIS OF COMPOUND 1-6
Compound 1-6 was prepared according to method B as follows: A solution of nonan-l,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2- hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution was stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed to crystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel column (75 g) using 0-12%) ethyl acetate/hexane as the eluent, yielding 9-(2'- hexyldecanoyloxy)nonan-l-ol (9.5 g) as an oil. (0741) The product was dissolved in methylene chloride (60 mL) and treated with pyridinum chlorochromate (6.4 g) for two hours. Diethyl ether (200 mL) was added and the supernatant filtered through a silica gel bed. The solvent was removed from the filtrate and resultant oil passed down a silica gel (75 g) column using a ethyl acetate/hexane (0- 12%)) gradient, yielding 9-(2'-ethylhexanoyloxy)nonanal (6.1 g) as an oil. (0742) A solution of the crude product (6.1 g), acetic acid (0.34 g) and 2-N,N- dimethylaminoethylamine (0.46 g) in methylene chloride (20 mL) was treated with sodium triacetoxyborohydride (2.9 g) for two hours. The solution was diluted with methylene chloride washed with aqueous sodium hydroxide, followed by water. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel (75 g) column using a methanol/methylene chloride (0-8%) gradient, followed by a second column (20 g) using a methylene chloride/acetic acid/methanol gradient. The purified fractions were dissolved in methylene chloride, washed with dilute aqueous sodium hydroxide solution, dried over anhydrous magnesium sulfate, filtered and the solvent removed, to yield the desired product (1.6g) as a colorless oil.
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
10 EXAMPLE 10 (0650) SYNTHESIS OF COMPOUND I-6
Compound I-6 was prepared according to method B as follows: (0652) Compound I-6 was prepared according to method B as follows: A solution of nonan-1,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2- hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution was stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed to crystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel column (75 g) using 0-12% ethyl acetate/hexane as the eluent, yielding 9-(2′- hexyldecanoyloxy)nonan-1-ol (9.5 g) as an oil. (0653) The product was dissolved in methylene chloride (60 mL) and treated with pyridinum chlorochromate (6.4 g) for two hours. Diethyl ether (200 mL) was added and the supernatant filtered through a silica gel bed. The solvent was removed from the filtrate and resultant oil passed down a silica gel (75 g) column using a ethyl acetate/hexane (0- 12%) gradient, yielding 9-(2′-ethylhexanoyloxy)nonanal (6.1 g) as an oil. A solution of the crude product (6.1 g), acetic acid (0.34 g) and 2-N,N- dimethylaminoethylamine (0.46 g) in methylene chloride (20 mL) was treated with sodium triacetoxyborohydride (2.9 g) for two hours. The solution was diluted with methylene chloride washed with aqueous sodium hydroxide, followed by water. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel (75 g) column using a (0654) methanol/methylene chloride (0-8%) gradient, followed by a second column (20 g) using a methylene chloride/acetic acid/methanol gradient. The purified fractions were dissolved in methylene chloride, washed with dilute aqueous sodium hydroxide solution, dried over anhydrous magnesium sulfate, filtered and the solvent removed, to yield the desired product (1.6g) as colorless oil.
9.5 g
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
A solution of nonan-l,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2-hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution was stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed to crystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel column (75 g) using 0-12% ethyl acetate/hexane as the eluent, yielding 9-(2'-hexyldecanoyloxy)nonan-l-ol (9.5 g) as an oil.
9.5 g
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
5
Compound 1-6 was prepared according to method B as follows: A solution of nonan-l,9-diol (12.6 g) in methylene chloride (80 mL) was treated with 2- hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution was stirred for two hours. The reaction mixture was filtered and the solvent removed. The residue was dissolved in warmed hexane (250 mL) and allowed to crystallize. The solution was filtered and the solvent removed. The residue was dissolved in methylene chloride and washed with dilute hydrochloric acid. The organic fraction was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel column (75 g) using 0-12% ethyl acetate/hexane as the eluent, yielding 9-(2'- hexyldecanoyloxy)nonan-l-ol (9.5 g) as an oil.
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 2h;
6 Synthesis of compound 6
A solution of nonane-1,9-diol (12.6 g) in methylene chloride (80 mL) is treated with 2-hexyldecanoic acid (10.0 g), DCC (8.7 g) and DMAP (5.7 g). The solution is stirred for 2 hours. The reaction mixture is filtered and the solvent is removed. The residue is dissolved in warm hexane (250 mL) and crystallized. The solution is filtered and the solvent is removed. The residue was dissolved in methylene chloride and washed with diluted hydrochloric acid. The organic fraction is dried over anhydrous magnesium sulfate, filtered and the solvent is removed. The residue was passed through a silica gel column (75 g) using 0-12% ethyl acetate/hexane as eluent to give 9-(2'-hexyldecanoyloxy)nonan-1-ol as an oil.The product was dissolved in methylene chloride (60 mL) and treated with pyridinium chlorochromate (6.4 g) for 4 hours. Diethyl ether (200 mL) is added and the supernatant is filtered through a bed of silica gel. The solvent was removed from the filtrate, and the resulting oil was passed through a silica gel (75 g) column using an ethyl acetate/hexane (0-12%) gradient, as an oil. 9-(2'-ethylhexanoyloxy)nonanal is obtained.
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 72h;
38
A solution of nonan-1,9-diol (16 g) in methylene chloride (100 mL) wastreated with 2-butyloctanoic acid (10 g), DCC (10.3 g) and DMAP (6.7 g). The solutionwas stirred for three days. The reaction mixture was filtered and hexane (250 mL) added to the filtrate. The mixture was stirred and the precipitates allowed to settle out. The supernatant was decanted and the solvent removed. The residue was suspended in hexane and allowed to settle. The supernatant was decanted and the solvent removed(repeated twice). The residue was dissolved in hexane, allowed to stand at room temperature and then filtered. The solvent was removed and the residue passed down a silica gel column (18 g) using methylene chloride, yielding crude 9-(2’- butyloctanoyloxy)nonan-1-ol (17.7 g) as an oil.
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 72h;
42 EXAMPLE 42 (0733) Synthesis of Compound I-38
Compound I-38 was prepared according to method B as follows: (0735) A solution of nonan-1,9-diol (16 g) in methylene chloride (100 mL) was treated with 2-butyloctanoic acid (10 g), DCC (10.3 g) and DMAP (6.7 g). The solution was stirred for three days. The reaction mixture was filtered and hexane (250 mL) added to the filtrate. The mixture was stirred and the precipitates allowed to settle out. The supernatant was decanted and the solvent removed. The residue was suspended in hexane and allowed to settle. The supernatant was decanted and the solvent removed (repeated twice). The residue was dissolved in hexane, allowed to stand at room temperature and then filtered. The solvent was removed and the residue passed down a silica gel column (18 g) using methylene chloride, yielding crude 9-(2’-butyloctanoyloxy)nonan-1-ol (17.7 g) as an oil. (0736) The crude product was dissolved in methylene chloride (250 mL) and treated with pyridinium chlorochromate (11.2 g) overnight. Diethyl ether (750 mL) was added and the supernatant filtered through a silica gel bed. The solvent was removed from the filtrate and resultant oil dissolved in hexane (150 mL). The suspension was filtered through a silica gel plug and the solvent removed. The crude product was passed down a silica gel (80 g) column using a 0-6% ethyl acetate/hexane gradient, yielding 9-(2’- butyloctanoyloxy)nonanal (5.3 g) as an oil. A solution of the product (5.3 g), acetic acid (0.37 g) and 2-N,N- dimethylaminoethylamine (0.47 g) in methylene chloride (50 mL) was treated with sodium triacetoxyborohydride (3.35 g) overnight. The solution was washed with aqueous sodium hydroxide solution. The organic phase was dried over anhydrous magnesium sulfate, filtered and the solvent removed. The residue was passed down a silica gel (60 g) column using an acetic acid/methanol/methylene chloride (2-0%/0-12%/98-88%) gradient. The purified fractions were washed with aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and the solvent removed, yielding compound I-38 as an oil (2.3 g).
6 g
With dmap; dicyclohexyl-carbodiimide In dichloromethane
A solution of nonan-l,9-diol (12.0 g) in methylene chloride (150 mL) was treated with 2-butyloctanoic acid (5.0 g), DCC (7.7 g) and DMAP (4.5 g). The solution was stirred overnight. The reaction mixture was filtered and the solvent removed. The residue was suspended in hexane and filtered. The filtrate was washed with dilute hydrochloric acid. The organic phase was dried over anhydrous magnesium sulfate, filtered through a silica gel bed, and the solvent removed. The crude product was passed down a silica gel column using a methanol/methylene chloride (0-4%) gradient, to produce 9-(2'-butyloctanoyloxy)nonan-l-ol (6 g) as an oil.