* 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 sulfuric acid; hydrogen bromide In water; toluene for 26 h; Reflux; Large scale
In a 50-liter glass reactor equipped with a stirring and thermometer, 4860 g of 40percent hydrobromic acid, 2110 g of concentrated sulfuric acid, 25000 ml of toluene, 2710 g of 1,7-heptanediol were added, stirring was started, and the temperature was increased to reflux for 26 hours.Sampling material without remaining, stop the reaction, stratification, the aqueous layer was extracted once with 5000ml of toluene, the combined organic layers were washed once with 5000ml saturated saline, and then washed with saturated sodium bicarbonate solution to neutrality, separated into aqueous layers, organic The solvent was removed from the layer to obtain 3780 g of crude 7-bromo-1-heptanol, and the crude product of 7-bromo-1-heptanol was subjected to high vacuum distillation. The temperature of the oil bath was 110° C. and the degree of vacuum was 42 Pa.The collection temperature is 74° C. to obtain 3520 g of 7-bromo-1-heptanol.Content 99.4percent, yield 88percent.
62%
With hydrogen bromide In water; benzeneReflux; Dean-Stark apparatus
Example 3 Synthesis of (8Z,14Z)-16-(3-Ethyloxirane-2-yl)hexadeca-8,14-dienoic Acid (3) Heptane-1,7-diol (36.0 g, 272 mmol; Alfa Aesar) and aq. 48percent HBr (38 mL) were heated under reflux in benzene (400 mL) with water removal using a Dean-Stark apparatus. After 12 h, all volatiles were removed in vacuo and the residue was purified by SiO2 column chromatography using a gradient of 10-30percent EtOAc/hexanes as eluent to give 7-bromoheptan-1-ol (26.22 g, 62percent) as colorless oil. TLC: 50percent EtOAc/hexanes, Rf 0.4; 1H NMR (400 MHz, CDCl3) δ 3.61 (t, 2H, J = 7.1 Hz), 3.39 (t, 2H, J = 6.8 Hz), 1.80-1.88 (m, 2H), 1.52-1.58 (m, 2H), 1.30-1.46 (m, 6H).
62%
With hydrogen bromide In water; benzene for 16 h; Reflux
7- bromoheptane-l-ol1 (2): Heptane- 1,7-diol (36.0 g, 272 mmol; Alfa Aesar) and aq. 48percent HBr (38 mL, 0.9 equiv.) were heated under reflux in benzene (400 mL) with water removal using a Dean-Stark apparatus. After 16 h, all volatiles were removed in vacuo and the residue was purified by Si02 column chromatography using a gradient of 10-30percent EtOAc/hexanes as eluent to give 7-bromoheptan-l-ol (26.22 g, 62percent) as a colorless oil. TLC: 50percent EtOAc/hexanes, Rf ~ 0.40; NMR (400 MHz, CDC13) δ 3.61 (t, 2H, J = 7.1 Hz), 3.39 (t, 2H, J= 6.8 Hz), 1.80- 1.88 (m, 2H), 1.52-1.58 (m, 2H), 1.30-1.46 (m, 6H).
Reference:
[1] Angewandte Chemie - International Edition, 2012, vol. 51, # 32, p. 8110 - 8113
[2] Patent: CN107417496, 2017, A, . Location in patent: Paragraph 0012; 0013; 0014
[3] Polish Journal of Chemistry, 2004, vol. 78, # 7, p. 937 - 942
[4] Journal of Natural Products, 2016, vol. 79, # 1, p. 244 - 247
[5] Journal of Heterocyclic Chemistry, 1990, vol. 27, # 5, p. 1233 - 1239
[6] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 12, p. 1648 - 1652
[7] Natural Product Research, 2009, vol. 23, # 11, p. 1029 - 1034
[8] Organic Process Research and Development, 2003, vol. 7, # 3, p. 339 - 340
[9] Synthesis, 1985, # 12, p. 1161 - 1162
[10] Chinese Chemical Letters, 2017, vol. 28, # 3, p. 558 - 562
[11] Bioscience, Biotechnology and Biochemistry, 2005, vol. 69, # 7, p. 1348 - 1352
[12] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 6, p. 537 - 548
[13] Canadian Journal of Chemistry, 1994, vol. 72, # 6, p. 1500 - 1511
[14] Journal of Organic Chemistry, 1980, vol. 45, # 20, p. 3952 - 3957
[15] Tetrahedron, 1992, vol. 48, # 16, p. 3413 - 3428
[16] Patent: EP2208720, 2010, A1, . Location in patent: Page/Page column 22
[17] Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4109 - 4118
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[23] Journal of the American Chemical Society, 1990, vol. 112, # 15, p. 5844 - 5850
[24] Journal of the American Chemical Society, 1987, vol. 109, p. 4976
[25] Synthesis, 1993, # 1, p. 149 - 152
[26] Agricultural and Biological Chemistry, 1985, vol. 49, # 1, p. 141 - 148
[27] Synthesis, 2003, # 8, p. 1187 - 1190
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[29] Chemistry Letters, 1994, # 10, p. 1789 - 1792
[30] Journal of chemical ecology, 2002, vol. 28, # 6, p. 1191 - 1208
[31] Patent: WO2005/19164, 2005, A2, . Location in patent: Page/Page column 16
[32] Bioscience, Biotechnology and Biochemistry, 2009, vol. 73, # 7, p. 1618 - 1622
[33] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 2, p. 605 - 611
[34] Synthesis (Germany), 2013, vol. 45, # 11, p. 1513 - 1518
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[37] Bulletin of the Korean Chemical Society, 2011, vol. 32, p. 3120 - 3122
3
[ 629-30-1 ]
[ 10160-24-4 ]
[ 4549-31-9 ]
Reference:
[1] Journal of Organic Chemistry, 2000, vol. 65, # 18, p. 5837 - 5838
[2] Liebigs Annalen der Chemie, 1991, # 6, p. 569 - 574
4
[ 629-30-1 ]
[ 3710-42-7 ]
Yield
Reaction Conditions
Operation in experiment
76%
With dihydrogen peroxide; sodium hydroxide In water at 79.84℃; for 8 h; Schlenk technique
General procedure: All experiments to test the catalytic activity were performed in a Schlenk tube (50mL vol.) attached to a condenser. The catalytic activity was evaluated for HDO oxidation in basic aqueous media with H2O2 as oxidant to obtain HCA. In a typical reaction procedure, aliphatic diol (0.5mmol) and catalyst (25mg) were weighed and dispersed in deionized water (3.5mL) in a Schenk tube. 30percent H2O2 (0.75mL) and 0.5M NaOH (0.75mL) were added to the above mixture, and then the Schlenk tube was mounted on a preheated oil bath at 353K. The mixture was allowed to react for various time intervals with continuous magnetic stirring (500 rpm). After the reaction, a part of the resultant solution was diluted 20 times with an aqueous H2SO4 (10mM) solution, and the catalyst was filtered off using a 0.20μm filter (Milex®-LG). The obtained filtrate was analyzed by high performance liquid chromatography (HPLC, WATERS 600) using an Aminex HPX-87H column (Bio-Rad Laboratories, Inc.) attached to a refractive index detector. An aqueous 10mM H2SO4 solution (eluent) was run through the column (maintained at 323K) at a flow rate of 0.5mLmin−1. The conversion and yield(s) were determined with a calibration curve method using commercial products.
Reference:
[1] Journal of Organic Chemistry, 2000, vol. 65, # 18, p. 5837 - 5838
[2] Liebigs Annalen der Chemie, 1991, # 6, p. 569 - 574
6
[ 629-30-1 ]
[ 4549-31-9 ]
Reference:
[1] Journal of the Korean Chemical Society, 2011, vol. 55, # 4, p. 685 - 690
[2] Tetrahedron, 2007, vol. 63, # 6, p. 1360 - 1365
[3] Biochemical Journal, 1947, vol. 41, p. 57
[4] Archiv der Pharmazie (Weinheim, Germany), 1935, p. 326[5] Zhurnal Obshchei Khimii, 1935, vol. 5, p. 1511[6] Chem. Zentralbl., 1936, vol. 107, # II, p. 2371
[7] Monatshefte fuer Chemie, 1927, vol. 48, p. 735[8] Organic Syntheses, 1931, vol. 11, p. 43
[9] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 336 - 343
[10] Asian Journal of Chemistry, 2010, vol. 22, # 9, p. 6945 - 6954
7
[ 629-30-1 ]
[ 54049-24-0 ]
Reference:
[1] Bulletin of the Chemical Society of Japan, 1986, vol. 59, # 11, p. 3535 - 3539
[2] Journal of Natural Products, 2016, vol. 79, # 1, p. 244 - 247
With lithium aluminium tetrahydride; In tetrahydrofuran; at 5 - 20℃; for 2.5h;Large scale;
Add 25000 ml of tetrahydrofuran to a 50-liter glass reactor and start stirring.Add 1500g lithium tetrahydroaluminate when cooling to 5C,Then, a mixture of 5000 g of <strong>[1732-08-7]dimethyl pimelate</strong> and 5000 ml of tetrahydrofuran was transferred to a dropping funnel.When the temperature of the reaction flask dropped to 5C, it began to be added dropwise.Control the temperature at 5 C, after the completion of the drop 1hThe mixture was slowly heated to room temperature and stirred for 1.5 hours. After the sample was taken, no raw material remained. It was qualified. The temperature was lowered to 5 C., and 1500 g of water, 1500 g of 15% sodium hydroxide solution, and 1500 g of water were added dropwise. The filtrate was concentrated to give 3360 g 1, Crude 7-heptanediol, crude 1,7-heptanediol was distilled under reduced pressure by an oil pump, and the oil bath temperature was 105C.The gas-phase collection temperature is 74C, giving 3201 g of 1,7-heptanediol,Content 99.6%, yield 95.3%;
7-(6-chloro-pyridin-2-ylmethoxy)-heptan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-Bromosuccinimide; dibenzoyl peroxide; In tetrahydrofuran; tetrachloromethane; hexane; toluene;
EXAMPLE 36 (2E,4E) N-Isobutyl 11-(6'-chloro-2'-pyridylmethoxy)-3-methylundeca-2,4-dienamide 6-Chloro-2-methylpyridine (20 g), (Ex Aldrich), N-bromosuccinimide (31 g), benzoyl peroxide (570 mg) and tetrachloromethane (250 ml) were heated together under reflux and under irradiation from a powerful lamp for 6 hours. After standard work-up and purification by column chromatography (silica; 5% ether in hexane), 6-chloro-2-bromomethylpyridine (25 g,) was obtained. Sodium hydride (0.109 mol.) was added to 1,7-heptanediol (0.218 mol.) in toluene. After heating under reflux for 3 hours, dry tetrahydrofuran was added, followed by 6-chloro-2-bromomethylpyridine (0.073 mol). After heating under reflux for 4 hours, the cooled mixture was worked-up and purified by column chromatography (silica; 1'1 ether: hexane) to give 7-(6-chloro-2-pyridylmethoxy)-heptan-1-ol (12 g).
B2 (2E/Z, 4E) N-Isobutyl 3-methyl-11-(2-trifluoromethyl-4-quinolinyloxy)undeca-2,4-dienamide Starting from 2-trifluoromethyl-4-chloroquinoline and 1,7-heptanediol. Ethyl trifluoroacetoacetate (3.7 g) and aniline (1.8 ml) were reacted together in polyphosphoric acid according to Joullie et al, J. Med. Chem., 16, 134 (1973), to give 2-trifluoromethyl-4-hydroxyquinoline (1.8 g).
(2E/Z,4E) N-Isobutyl 3-methyl-11-(2-quinolinylmethoxy)-undeca-2,4-dienamide Starting from 1,7-heptanediol and using the following modified Stage a (ii). 1,7-Heptanediol (ex Lancaster) (1.7 g) was reacted with sodium (0.24 g) in toluene (50 ml) as in Stage A(ii). 2-Chloromethylquinoline hydrochloride (ex Aldrich) was added followed by triethylamine (0.7 ml). After heating under reflux for 6 hours, the reaction mixture was partitioned between water and diethyl ether and the organic phase washed with brine and dried. The crude material was purified by chromatography on silica (eluding with ether-hexane) to give 7-(2-quinolinylmethoxy)heptan-1-ol (0.43 g) which was used in Stage b.
Stage #1: 1,7-heptandiol With sodium In toluene at 60 - 100℃; for 1h;
Stage #2: 4-chloro-2,3-dimethylpyridine-N-oxide In toluene at 100℃; for 2h;
7
Under a nitrogen stream and in a silicone oil bath, 24.8 g (0.188 mol, 2.2 eq.) of 1, 7-heptanediol and 100 mL of toluene were introduced, and while stirring, the mixture was dissolved at 60°C. Then, 3.1 g (0.136 mol, 1.6 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, 13.4 g (0.085 mol, 1.0 eq.) of 4-chloro-2,3 -dimethylpyridine-N-oxide was added, then the temperature was elevated to 100°C, and the mixture was allowed to react for 2 hours. The reaction liquor was cooled by standing overnight, and the separated toluene layer was removed by decantation. To the resulting residue, 100 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 45.5 g of 4-(7-hydroxy heptyloxy)-2,3-dimethylpyridine-N-oxide.
With N,N,N,N-tetraethylammonium tetrafluoroborate; In acetonitrile;Electrochemical reaction;
IFO therefore was electrochemically oxidized in acetonitrile in the presence of various alcohols with 5 carbon atoms. The reaction was stopped when all the starting material appeared to be consumed as monitored by TLC. At the end of the reaction, sodium bicarbonate (1 Eq.) was added to the medium to neutralize electrogenerated hydrons. The proportions of the various diastereomers were determined on the crude reaction mixture by 31P-NMR before being isolated by ?flash chromatography?.
Multi-step reaction with 8 steps
1.1: pyridinium p-toluenesulfonate / dichloromethane / 4 h / 20 °C
2.1: pyridinium chlorochromate / dichloromethane / 1 h / 20 °C
3.1: lithium chloride; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.5 h
3.2: 1 h
4.1: lithium aluminium tetrahydride; aluminum (III) chloride / diethyl ether / 0 - 20 °C
5.1: pyridinium chlorochromate / dichloromethane / 1 h / 20 °C
6.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 20 °C
6.2: 1 h / 20 °C
7.1: pyridinium p-toluenesulfonate / ethanol / 80 °C
8.1: pyridine / 3 h / 0 - 20 °C
Multi-step reaction with 4 steps
1.1: NKC-9 ion exchange resin / toluene / 10 h / 75 °C
2.1: pyridinium chlorochromate / dichloromethane / 12 h / 20 °C
3.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 2 h / -5 °C / Inert atmosphere; Cooling with ice
3.2: 10 h
4.1: sodium hexamethyldisilazane / tetrahydrofuran / 2 h / -5 °C / Inert atmosphere
4.2: 10 h / -78 °C
With dihydrogen peroxide; sodium hydroxide; In water; at 79.84℃; for 8h;Schlenk technique;
General procedure: All experiments to test the catalytic activity were performed in a Schlenk tube (50mL vol.) attached to a condenser. The catalytic activity was evaluated for HDO oxidation in basic aqueous media with H2O2 as oxidant to obtain HCA. In a typical reaction procedure, aliphatic diol (0.5mmol) and catalyst (25mg) were weighed and dispersed in deionized water (3.5mL) in a Schenk tube. 30% H2O2 (0.75mL) and 0.5M NaOH (0.75mL) were added to the above mixture, and then the Schlenk tube was mounted on a preheated oil bath at 353K. The mixture was allowed to react for various time intervals with continuous magnetic stirring (500 rpm). After the reaction, a part of the resultant solution was diluted 20 times with an aqueous H2SO4 (10mM) solution, and the catalyst was filtered off using a 0.20mum filter (Milex-LG). The obtained filtrate was analyzed by high performance liquid chromatography (HPLC, WATERS 600) using an Aminex HPX-87H column (Bio-Rad Laboratories, Inc.) attached to a refractive index detector. An aqueous 10mM H2SO4 solution (eluent) was run through the column (maintained at 323K) at a flow rate of 0.5mLmin-1. The conversion and yield(s) were determined with a calibration curve method using commercial products.
With dicarbonylacetylacetonato rhodium (I); carbon monoxide; hydrogen; C14H12N5OPS2 at 45℃; for 5h;
5 Example 5
Use 128.17g (1mol) heptenoic acid to prepare 0.2M dichloromethane solution, according to mass ratio Rh(acac)(CO)2: Ligand M2: Heptenoic acid=1:3:150 is added to the reactor, in CO/H2The mass ratio is 3:15, the pressure is 1.2MPa, the temperature is 45°C, and the reaction is 5 hours. The conversion rate is 98.8% by gas chromatography analysis; the linear product 1,7-heptanediol has a selectivity of 97.0%, 2-methyl-1,6-hexanediol is 1.2%.