55912-20-4|(4-Chloro-3-nitrophenyl)methanol| Ambeed

CAS No. :	55912-20-4
Formula :	C₇H₆ClNO₃
M.W :	187.58
SMILES Code :	OCC1=CC(=C(Cl)C=C1)[N+]([O-])=O
MDL No. :	MFCD00007086
InChI Key :	QLLRQJDSYJIXTN-UHFFFAOYSA-N
Pubchem ID :	91933

Safety of [ 55912-20-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 55912-20-4 ]

* 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.

Downstream synthetic route of [ 55912-20-4 ]

[ 55912-20-4 ] Synthesis Path-Downstream 1~54

1
[ 16588-16-2 ]
[ 55912-20-4 ]

References: [1]Journal of the American Chemical Society,1959,vol. 81,p. 4328,4330,4333.

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[ 55912-20-4 ]
[ 57403-35-7 ]

References: [1]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 3434 - 3436.
[2]Journal of the American Chemical Society,1959,vol. 81,p. 4328,4330,4333.
[3]Journal of Organic Chemistry,1962,vol. 27,p. 1520 - 1523.
[4]Chinese Journal of Chemistry,2011,vol. 29,p. 2205 - 2208.

3
[ 79-01-6 ]
[ 55912-20-4 ]
[ 20797-44-8 ]

References: [1]Tetrahedron Letters,1968,p. 4979 - 4982.

4
[ 55912-20-4 ]
[ 3360-45-0 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphorus tribromide; In toluene;	4-(bromomethyl)-1-chloro-2-nitrobenzene To a solution of <strong>[55912-20-4](4-chloro-3-nitrophenyl)methanol</strong> (5.0 g, 26.6 mmol) in toluene (100 mL) was added phosphorus tribromide (0.879 mL, 9.32 mmol) at 40 C. The reaction mixture was stirred at 100 C. for 15 mins and partitioned between water and ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound.
	With phosphorus tribromide; In dichloromethane; at 0℃; for 1h;	Step 1: To a 0C solution of compound 30-1 (0.5 g, 2.67 mmol) in DCM (30 mL) was added PBr3 (0.87 g, 3.20 mmol) drop wise. The reaction was stirred at 0C for 1 nr. then quenched with water (10 m L) and extracted with DCM (30 mL x 3). The combined organic layer was washed with water and brine, dried over Na2S04 and evaporated. The residue was purified by column chromatography (eluent: PE/EA = 10/1) to give 30-2 as a colorless oil. NMR (300 MHz, CDC13) δ 7.90 (s, 1H), 7.60 - 7.51 (m, 2H), 4.47 (s, 2H).
	With phosphorus tribromide; In toluene; at 40 - 100℃; for 0.25h;	To a solution of <strong>[55912-20-4](4-chloro-3-nitrophenyl)methanol</strong> (5.0 g, 26.6 mmol) in toluene (100 mL) was added phosphorustribromide (0.879 mL, 9.32 mmol) at 40 C. The reaction mixture was stirred at 100 C for 15 mins and partitionedbetween water and ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to givethe title compound.

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6254 - 6276.
[2]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6715 - 6727.
[3]Journal of Medicinal Chemistry,1989,vol. 32,p. 1757 - 1763.
[4]Patent: US2010/267634,2010,A1 .
[5]Chinese Journal of Chemistry,2011,vol. 29,p. 2205 - 2208.
[6]Patent: WO2014/28669,2014,A1 .Location in patent: Paragraph 00562.
[7]Patent: EP2419404,2015,B1 .Location in patent: Paragraph 0536.

5
[ 55912-20-4 ]
[ 16588-34-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With oxygen; sodium carbonate; In water; for 1.5h;Reflux;	General procedure: A mixture of alcohol (1 mmol), Na2CO3(2 mmol), and Fe3O4SiO2/CuO nanocatalyst (0.04 g) in water was stirred under oxygen at reflux condition. After reaction completion, the catalyst was separated from the reaction mixture by external magnetic field, washed with hot EtOAc (2 × 5 mL), and dried for consecutive reaction runs. Then, the filtrate was cooled to room temperature, quenched with 2 MHCl aqueous solution, filtered, and extracted with dichloromethane. The solvent was evaporated and the organic layer dried over anhydrous Na2SO4. Evaporation of the solvent followed by column chromatography on silica gel (n-hexane/ethyl acetate 9:1 as v/v%) afforded the pure products.

References: [1]Synthetic Communications,2008,vol. 38,p. 2638 - 2645.
[2]Research on Chemical Intermediates,2021,vol. 47,p. 2527 - 2538.
[3]Tetrahedron Letters,2006,vol. 47,p. 13 - 17.
[4]Angewandte Chemie - International Edition,2018,vol. 57,p. 10535 - 10539.
Angew. Chem.,2018,vol. 130,p. 10695 - 10699,5.

6
[ 4858-85-9 ]
[ 55912-20-4 ]
[ 203661-08-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium sulfide; sodium chloride; In dimethyl sulfoxide;	Production Example 98 4-[(3-Chloropyrazin-2-yl)thio]-3-nitrobenzyl alcohol 1.876 g of <strong>[55912-20-4]4-chloro-3-nitrobenzyl alcohol</strong> was dissolved in 20 ml of dimethyl sulfoxide. After adding 820 mg of anhydrous sodium sulfide, the resulting mixture was stirred at room temperature for 15 hours. After adding 1.19 g of 2,3-dichloropyrazine thereto, the reaction mixture was stirred at 100 C. for 1 hour. After adding ice/water, the reaction mixture was extracted with ethyl acetate, washed successively with water, 1 N hydrochloric acid, water, 1 N sodium hydroxide, and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluted with ethyl acetate/n-hexane) to thereby give 1.60 g of the title compound as yellow crystals. 1H-NMR(DMSO-d6) δ ppm: 4.46(d, J=5.9 Hz, 2H), 5.61(t, J=5.9 Hz, 1H), 7.70(dd, J=1.8, 8.1 Hz, 1H), 7.76(d, J=8.1 Hz, 1H), 8.09(d, J=1.8 Hz, 1H), 8.33(d, J=2.6 Hz, 1H), 8.41(d, J=2.6 Hz, 1H)

References: [1]Heterocycles,2005,vol. 65,p. 403 - 410.
[2]Patent: US6518423,2003,B1 .

7
[ 4858-85-9 ]
[ 55912-20-4 ]
[ 203661-08-9 ]
[ 35350-36-8 ]

References: [1]Heterocycles,2005,vol. 65,p. 403 - 410.

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[ 55912-20-4 ]
[ 237769-24-3 ]
2-benzyl-3-(4-chloro-3-nitrobenzyloxy)-3-phenyl-2,3-dihydroisoindol-1-one [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6209 - 6221.

9
[ 55912-20-4 ]
(3-amino-4-chlorophenyl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%		To a solution of (4-chloro-3-nitro-phenyl)-methanol (4.96 g, 26.4 mmol) in MeOH (60 mL) and conc HCl (22 ml) was added iron powder (4.43 g, 3 eq) in portions. The mixture was then heated at reflux (65 C.) for 6 h, cooled and poured on ice water. The solution was neutralised with dilute NaOH and filtered. The filtrate was extracted with EA several times. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The product was recovered as a greyish solid (3.8 g, 92%).
92%		To a solution of (4-chloro-3-nitro-phenyl)-methanol (4.96 g, 26.4 mmol) in MeOH (60 mL) and cone HCl (22 ml) was added iron powder (4.43 g, 3 eq) in portions. The mixture was then heated at reflux (65C) for 6h, cooled and poured on ice water. The solution was neutralised with dilute NaOH and filtered. The filtrate was extracted with EA several times. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The product was recovered as a greyish solid (3.8 g, 92%).
85%	With ammonium formate; iron; In water; toluene; for 4h;Heating / reflux;	EXAMPLE 23; Synthesis of N4-lH-benzimidazol-2-yl-N5-[2-chloro-5-(hydroxymethyl)phenyl]- lH-imidazole-4,5-dicarboxamide; Synthesis of 3-Amino-4-chlorophenyl)methanol; [00200] A 100 mL flask was charged with <strong>[55912-20-4](4-chloro-3-nitrophenyl)methanol</strong> (commercially available from Acros; 1.0 g, 5.5 mmol), ammonium formate (1.4 g, 22 <n="116"/>mmol), and iron powder (1.2 g, 22 mmol). Toluene (15 mL) and water (15 mL) were added to the flask and the mixture was heated to reflux for 4 hours, after which time, the mixture was filtered through a plug of Celite. The supernatant was washed with ethyl acetate (3 x 50 ml). The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate and filtered. The organic solvent was removed on a rotary evaporator under reduced pressure to yield (3-amino-4-chlorophenyl)methanol (0.74 g, 85 % yield). The material was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, IH), 6.56 (d, IH), 6.40 (s, IH), 5.85 (bs, 2H), 5.39 (bs, IH), 5.85 (bs, IH), 4.79 (s, 2H): MS (EI): 158 (MH+).

61%

With iron; acetic acid; In ethanol; at 95℃; for 2h;Inert atmosphere;

In a 500 mL round-bottomed flask was <strong>[55912-20-4]4-chloro-3-nitrobenzyl alcohol</strong> (12 g, 64.0 mmol) and iron (17.86 g, 320 mmol) in AcOH (160 ml) and EtOH (80 ml) to give a light black suspension. The mixture was heated at 95 C for 2 h. After cooling down to room temperature, most AcOH and EtOH were stripped off and the remaining residue was shaken with EtOAc/MeOH/CH2Cl2 and filtered. The solids were washed with these solvents. The combined organic solution was further partitioned between EtOAc and saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried with Na2SO4, and concentrated to a tan oil, which solidified upon adding a little hexane. The solid was recrystallized from CH2Cl2/hexane. Tan crystals were collected and washed with hexanes to afford 4.43 g of the titled product. The mother liquid was concentrated and purified by flash column chromatograph (FCC) up to 80% EtOAc/hexane from 0 to 80% to provided an off-white solid (1.72 g). Combined product (6.15 g, 61%) was used without further characterizations. MS (ESI) [M + H]+ = 158.

References: [1]Patent: US2009/275588,2009,A1 .Location in patent: Page/Page column 10.
[2]Patent: WO2007/116374,2007,A1 .Location in patent: Page/Page column 24.
[3]Patent: WO2008/42282,2008,A2 .Location in patent: Page/Page column 114-115.
[4]Bioorganic and Medicinal Chemistry Letters,2021,vol. 43.

10
[ 55912-20-4 ]
[ 203661-09-0 ]

References: [1]Heterocycles,2005,vol. 65,p. 403 - 410.
[2]Heterocycles,2005,vol. 65,p. 403 - 410.

11
[ 55912-20-4 ]
[ 203660-01-9 ]

References: [1]Heterocycles,2005,vol. 65,p. 403 - 410.
[2]Heterocycles,2005,vol. 65,p. 403 - 410.

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[ 55912-20-4 ]
[ 269734-49-8 ]