[ CAS No. 39835-11-5 ]

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2D
Chemical Structure| 39835-11-5
Chemical Structure| 39835-11-5
Structure of 39835-11-5

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SDS

Product Details of [ 39835-11-5 ]

CAS No. :39835-11-5MDL No. :MFCD08567959
Formula :C8H7NO2Boiling Point :330.4°C at 760 mmHg
Linear Structure Formula :-InChI Key :-
M.W :149.15Pubchem ID :11423680
Synonyms :

Computed Properties of [ 39835-11-5 ]

TPSA : 53.2 H-Bond Acceptor Count : 3
XLogP3 : 1.8 H-Bond Donor Count : 1
SP3 : 0.13 Rotatable Bond Count : 1

Safety of [ 39835-11-5 ]

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305 P351 P338UN#:N/A
Hazard Statements:H302-H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 39835-11-5 ]

  • Upstream synthesis route of [ 39835-11-5 ]
  • Downstream synthetic route of [ 39835-11-5 ]

[ 39835-11-5 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 673-22-3 ]
  • [ 39835-11-5 ]
YieldReaction ConditionsOperation in experiment
86% With Nitroethane; sodium acetate In acetic acid for 12.00 h; Heating / reflux A mixture of the 2-hydroxy-4-methoxybenzaldehyde (20 g, 128.8 mmol), sodium acetate (35.05 g, 257.6 mmol) and nitroethane (19 mL, 257.6 mmol) in glacial acetic acid (100 mL) was heated at gentle reflux for 12 h.
The reaction mixture was then poured into ~1000 mL of ice water (1:1 ratio of ice and water).
The product was extracted with ethyl acetate (3*200 mL).
The organic extracts were washed with sodium bicarbonate solution until the aqueous layer had pH ~8.
The organic layers were then dried over anhydrous magnesium sulfate and concentrated in vacuo to afford 2-hydroxy-4-methoxy-benzonitrile as a yellow oil (16.5 g, 86percent).
84% With hydroxylamine hydrochloride; sodium formate In formic acid Example I
2-Hydroxy-4-methoxybenzonitrile
2-Hydroxy-4-methoxybenzaldehyde (55 g; 0.36 mol), hydroxylamine hydrochloride (30 g; 0.43 mol) and sodium formate (34 g; 0.5 mol) were refluxed in formic acid (200 ml; 98-100percent) for 1.25 h.
The solution was then rapidly chilled in an ice bath, with stirring over 30 min.
The resulting precipitate was separated by filtration and washed well with water.
Following drying, in a desicator under vacuum, the title compound was obtained (45 g; 0.3 mol; 84percent yield) as a brick-red solid, mp 169-171° C., rf (EtOAc) 0.43.
Reference: [1] Synthetic Communications, 2004, vol. 34, # 11, p. 2025 - 2029
[2] Patent: US2004/259867, 2004, A1. Location in patent: Page/Page column 7
[3] Patent: US6399657, 2002, B1
[4] Journal of Medicinal Chemistry, 2003, vol. 46, # 8, p. 1470 - 1477
[5] Synlett, 2000, # 8, p. 1169 - 1171
[6] Chemische Berichte, 1934, vol. 67, p. 859,864
[7] Biochemical Journal, 1936, vol. 30, p. 1303,1313
[8] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 18, p. 8419 - 8426
[9] Organic Letters, 2011, vol. 13, # 6, p. 1426 - 1428
[10] Journal of Organic Chemistry, 2015, vol. 80, # 2, p. 1229 - 1234
  • 2
  • [ 17861-16-4 ]
  • [ 39835-11-5 ]
YieldReaction ConditionsOperation in experiment
79% With Nonafluorobutanesulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 0.17 h; General procedure: at room temperature, n-C4F9SO2F (20.0mmol, 2.0equiv.) was slowly dropped via syringe into a solution of substrate 1a (10.0mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 50.0mmol, 5.0equiv.) in CH2Cl2 (20mL). The resulting solution was stirred at this temperature for 10min. Evaporation under vacuum to remove volatile components offered residue which was purified through silica gel column chromatography (eluted with a mixture of petroleum ether and ethyl acetate), generating nitrile 2a in 95percent yield.
Reference: [1] Synthetic Communications, 2013, vol. 43, # 13, p. 1778 - 1786
[2] Chinese Chemical Letters, 2016, vol. 27, # 1, p. 96 - 98
  • 3
  • [ 94610-82-9 ]
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YieldReaction ConditionsOperation in experiment
90%
Stage #1: With 2-(methylsulfonyl)ethyl alcohol; sodium hydride In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 2.00 h;
Stage #2: With hydrogenchloride; water In DMF (N,N-dimethyl-formamide)
To a solution of 2-fluoro-4-hydroxybenzonitrile g (1 g, 7.2 mmol) in acetone (50 ml) was added methyliodide (2 g, 14.4 mmol, 2 equiv. ) and potassium carbonate (2 g, 14 mmol, 2 equiv. ). The mixture was heated under reflux for 2 h, cooled to room temperature, filtered and concentrated. The residue was dissolved in ethyl acetate, washed with water and brine, dried with MgS04, filtered and concentrated to give 1.1 g of the product h as yellow crystals. To a mixture of 2-fluoro-4-methoxybenzonitrile h (1 g, 7 mmol) and 2-methane- sulfonylethanol (1 g, 11 mmol, 1.5 equiv. ), in dry DMF, at 0°C, was added sodium hydride (3 equiv. , 20 mmol, 0.8 g of a dispersion of 60percent NaH in mineral oil). The reaction mixture was allowed to warm to room temperature and, after 2h, was quenched by addition of a IN hydrochloric acid. The resulting solution was diluted with water and extracted with ethyl acetate (2x). The organic layers were combined, washed with brine, dried with MgS04, filtered and concentrated to afford 1 g (90percent) of product i as a yellow solid. Phenol i (1 g, 7 mmol), chloroacetone (0.7 g, 8.4 mmol, 1.2 equiv. ), potassium iodide (1 g, 8.4 mmos, 1.2 equiv. ) and potassium carbonate (2 g, 14 mmol, 2 equiv. ) were mixed in acetone and refluxed for 1 h. The reaction mixture was filtered and concentrated. The residue was dissolved in ethyl acetate, washed with water and brine, dried with MgS04, filtered and concentrated to give 1.6 g (100percent) of product j as a white/brown solid To a solution of compound j (0.2 g, 1 mmol) in methanol (10 ml) was added sodium methoxide (0.06 g, 1.1 mmol, 1.1 equiv.). After stirring at room temperature for 1 h, the reaction mixture was diluted with water, most methanol was stripped off by evaporation under reduced pressure, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried with MgS04, filtered and concentrated to give 175 mg (90percent) of the product k as a yellow powder. To a solution of compound k (0.500 g, 2.4 mmol) in dichloromethane (20 ml) were successively added cyanoacetic acid (1.2 equiv. , 2.92 mmol, 249 mg), 1-(3-dimethyl- aminopropyl) -3-ethylcarbodiimide hydrochloride (1.1 equiv, 2.68 mmol, 514 mg) and catalytic amount of 1-hydroxybenzotriazole. The reaction mixture was stirred at room temperature during 16 h. More dichlormethane was added and the resulting solution was washed with water, a saturated aqueous solution of sodium bicarbonate and brine, The organic layer was dried with MgS04, filtered and concentrated to give 700 mg (100percent) of compound I as an orange powder. Intermediate 1 (0.660 g, 2.42 mmol) and triethylamine (0.368 g, 3.64 mmol, 1.5 equiv.) were heated to reflux in ethanol during 24 h. The reaction mixture was concentrated to give 0.580 g (yield = 94percent) of the product m as a yellow solid. The crude material was used as such in the next step. To a suspension of intermediate m (0.23 g, 0.9 mmol) in dichloromethane were added successively powdered molecular sieves, 4-nitrophenylboronic acid (0.31 g, 1.8 mmol, 2 equiv. ), pyridine (0.145 g, 1.8 mmol, 2 equiv. ), copper acetate (0.33 g, 1.8 mmole, 2 equiv. ) and triethylamine (0.185 g, 1.8 mmole, 2 equiv. ). The reaction mixture was stirred at room temperature with a CaCl2 tube during 22 h. The mixture was filtered over decalite and rinsed thoroughly with multiple portions of dichloromethane. The combined filtrates were washed with a saturated solution of sodium bicarbonate and brine, dried with MgS04, filtered and concentrated. Purification by flash chromatography on silica gel (eluent: 5percent methanol in dichloromethane) followed by purification by preparative TLC (eluent: 5percent methanol in dichloromethane) gave 10 mg of product 5 as a yellow powder. Compound 5 (170 mg, 0.45 mmol) was dissolved in dichloromethane (10 ml) under N2-atmosphere, and the reaction mixture was cooled to 0°C. A solution of boron tribromide (20 equiv. , 9 mmol, 9 ml of a solution of 1M BBr3 in dichloromethane) was added and the reaction mixture was allowed to warm to room temperature. After 4 h, the reaction contents was poured into a mixture of ice and a saturated solution of sodium bicarbonate under vigorous stirring. The precipitate was isolated by filtration, washed with water, isopropanol and diisopropyl ether to give 46 mg (yield = 28percent, purity = 90percent) of the desired phenol 6 as an orange powder.
Reference: [1] Patent: WO2005/111044, 2005, A1. Location in patent: Page/Page column 71-73
  • 4
  • [ 4107-65-7 ]
  • [ 39835-11-5 ]
YieldReaction ConditionsOperation in experiment
96%
Stage #1: With decylthiol; potassium tert-butylate In N,N-dimethyl-formamide at 110℃; for 1.00 h; Inert atmosphere
Stage #2: With hydrogenchloride In waterCooling with ice
A mixture of 1-decanethiol (6.41 g, 36.77 mmol) in N,N-dimethylformamide (50 mL) was cooled to 5-10 °C under nitrogen atmosphere.
When the internal temperature was below 10 °C, solid KOtBu (5.16 g, 45.96 mmol) was added in one portion after 10 min, the reaction mass was allowed to warm to 20-25 °C. After 15 min, 2,4-dimethoxybenzonitrile (5.00 g, 30.64 mmol) was added and the reaction was heated to 110 °C for 60 min. TLC analysis (petroleum ether/ethyl acetate 1:1 as mobile phase) showed complete reaction.
The mixture was allowed to cool to 20-25 °C and then poured into ice water (150 mL).
To the flask was added 1 N HCl dropwise to bring the pH to 1 followed by the addition of water (150 mL).
The aqueous phase was extracted with ethyl acetate (3 * 100 mL), and the combined organic extracts were washed with (2 * 100 mL) saturated brine and dried over Na2SO4.
The solvent was removed under vacuum to give a free flowing solid.
To this solid was added 100 mL heptane and stirred for 60 min.
The solid obtained was filtered off and washed with 50 mL heptane to give 2-hydroxy-4-methoxybenzonitrile (7) as a grey solid (4.39 g, 96percent); mp 174-175 °C (lit.
[8]
: 169-172 °C); IR (KBr) νmax (cm-1): 3213 (OH), 2226 (CN), 1601, 1595, 1514, 1465, 1449, 1435, 1379, 1323, 1277, 1211, 1169, 1103, 1026, 829, 800; 1H NMR (400 MHz, DMSO-d6): δ 11.08 (br s, 1H, OH), 7.51 (d, 1H, J = 8.4 Hz, H-6), 6.56-6.47 (m, 2H, H-3, H-5), 3.77 (s, 3H, OCH3); 13C NMR (100 MHz, DMSO-d6): δ 164.0, 161.9, 134.4, 117.4, 106.7, 101.0, 91.2, 55.5; HRMS m/z calcd for C8H7NO2 149.0477 [M] found 149.0474.
Reference: [1] European Journal of Medicinal Chemistry, 2013, vol. 59, p. 283 - 295
  • 5
  • [ 673-22-3 ]
  • [ 79-24-3 ]
  • [ 39835-11-5 ]
YieldReaction ConditionsOperation in experiment
86% With sodium acetate In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; acetic acid EXAMPLE 18
4,5-bis-(4-Chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole
A mixture of the 2-hydroxy-4-methoxybenzaldehyde (20 g, 128.8 mmol), sodium acetate (35.05 g, 257.6 mmol) and nitroethane (19 mL, 257.6 mmol) in glacial acetic acid (100 mL) was heated at gentle reflux for 12 h.
The reaction mixture was then poured into ~1000 mL of ice water (1:1 ratio of ice and water).
The product was extracted with ethyl acetate (3*200 mL).
The organic extracts were washed with sodium bicarbonate solution until the aqueous layer had pH ~8.
The organic layers were then dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford 2-hydroxy-4-methoxy-benzonitrile as a yellow oil (16.5 g, 86percent).
65% With sodium acetate In acetic acid; ethyl acetate EXAMPLE 9
[4,5-Bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-methanone hydrochloride
A mixture of 2-hydroxy-4-methoxybenzaldehyde (25.0 g, 164 mmol), sodium acetate (26.4 g, 322 mmol), nitroethane (23 g, 307 mmol) in acetic acid (45 mL) was heated at reflux for 6 h.
The mixture was then cooled to room temperature and poured onto ice water.
The solids were filtered off, washed with water and dried.
Recrystallization of the crude solid in ethyl acetate gave 2-hydroxy-4-methoxy-benzonitrile as a brown solid (15.9 g, 65percent).
Reference: [1] Patent: US6617346, 2003, B1
[2] Patent: US2003/153580, 2003, A1
  • 6
  • [ 6745-77-3 ]
  • [ 39835-11-5 ]
Reference: [1] Patent: US2010/75966, 2010, A1. Location in patent: Page/Page column 12
  • 7
  • [ 5446-02-6 ]
  • [ 39835-11-5 ]
Reference: [1] Synthesis, 1998, # 3, p. 329 - 332
  • 8
  • [ 155912-26-8 ]
  • [ 39835-11-5 ]
Reference: [1] Journal of Organic Chemistry, 2015, vol. 80, # 2, p. 1229 - 1234
[2] Synlett, 2000, # 8, p. 1169 - 1171
  • 9
  • [ 673-22-3 ]
  • [ 39835-05-7 ]
  • [ 39835-11-5 ]
Reference: [1] Journal of Organic Chemistry, 2015, vol. 80, # 17, p. 8657 - 8667
  • 10
  • [ 4107-65-7 ]
  • [ 39835-11-5 ]
  • [ 84224-29-3 ]
Reference: [1] Journal of Organic Chemistry, 2006, vol. 71, # 18, p. 7103 - 7105
  • 11
  • [ 82380-18-5 ]
  • [ 39835-11-5 ]
Reference: [1] Patent: WO2005/111044, 2005, A1
  • 12
  • [ 556-64-9 ]
  • [ 150-19-6 ]
  • [ 39835-11-5 ]
Reference: [1] Synthetic Communications, 1990, vol. 20, # 1, p. 71 - 84
  • 13
  • [ 39835-05-7 ]
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Reference: [1] Journal of Organic Chemistry, 2001, vol. 66, # 17, p. 5866 - 5874
  • 14
  • [ 17861-16-4 ]
  • [ 108-24-7 ]
  • [ 39835-11-5 ]
Reference: [1] Chemische Berichte, 1934, vol. 67, p. 859,864
[2] Biochemical Journal, 1936, vol. 30, p. 1303,1313
[3] Chemische Berichte, 1934, vol. 67, p. 859,864
[4] Biochemical Journal, 1936, vol. 30, p. 1303,1313
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