65685-01-0

Basic information

• Product Name: 3-PHENYLBENZENESULFONYL CHLORIDE
• Synonyms: Biphenyl-3-sulphonyl chloride;1,1'-biphenyl-3-sulfonyl chloride;3-Phenylbenzenesulphonyl chloride, 3-(Chlorosulphonyl)biphenyl;3-PHENYLBENZENESULFONYL CHLORIDE;3-PHENYLBENZENESULPHONYL CHLORIDE;BIPHENYL-3-SULFONYL CHLORIDE
• CAS NO: 65685-01-0
• Molecular Formula: C₁₂H₉ClO₂S
• Molecular Weight: 252.72
• Mol File: 65685-01-0.mol
• Article Data: 8

Chemical Properties

• Melting Point: 38-40 °C
• Boiling Point: 397.824 °C at 760 mmHg
• Flash Point: 194.397 °C
• Appearance: /
• Density: 1.321 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.596
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• CAS DataBase Reference: 3-PHENYLBENZENESULFONYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-PHENYLBENZENESULFONYL CHLORIDE(65685-01-0)
• EPA Substance Registry System: 3-PHENYLBENZENESULFONYL CHLORIDE(65685-01-0)

Safety Data

• Hazard Codes: C,Xi
• Statements: 36
• Safety Statements: 26
• Hazardous Substances Data: 65685-01-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C12H9ClO2S/c13-16(14,15)12-8-4-7-11(9-12)10-5-2-1-3-6-10/h1-9H

Synthetic route

[1,1'-biphenyl]-3-yl(benzyl)sulfane (94306-39-5) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
With N-chloro-succinimide; acetic acid In water at 20℃;	59%
With N-chloro-succinimide; acetic acid In water at 20℃;	59%

3-bromobiphenyl (2113-57-7) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
With sulfuryl dichloride; tert.-butyl lithium In diethyl ether at -78 - 20℃; for 7h;	49%
In tetrahydrofuran
Multi-step reaction with 2 steps 1: 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere; Sealed tube 2: N-chloro-succinimide; acetic acid / water / 20 °C View Scheme

3-bromobiphenyl (2113-57-7) + tert.-butyl lithium (594-19-4) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
With sulfuryl dichloride In hexane; ethyl acetate	49%

3-bromobiphenyl (2113-57-7) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
With sulfuryl dichloride; tert.-butyl lithium In hexane; ethyl acetate	49%

1-Bromo-3-iodobenzene (591-18-4) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; ethanol; toluene / 2 h / 90 °C / Inert atmosphere; Sealed tube 2: 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere; Sealed tube 3: N-chloro-succinimide; acetic acid / water / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; ethanol; toluene / 2 h / 90 °C / Inert atmosphere; Sealed tube 2: N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene / 1,4-dioxane / 100 °C / Inert atmosphere; Sealed tube 3: N-chloro-succinimide; acetic acid / water / 20 °C View Scheme

phenylboronic acid (98-80-6) → biphenyl-3-sulfonyl chloride (65685-01-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; ethanol; toluene / 2 h / 90 °C / Inert atmosphere; Sealed tube 2: 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere; Sealed tube 3: N-chloro-succinimide; acetic acid / water / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate; tetrakis(triphenylphosphine) palladium(0) / water; ethanol; toluene / 2 h / 90 °C / Inert atmosphere; Sealed tube 2: N-ethyl-N,N-diisopropylamine; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene / 1,4-dioxane / 100 °C / Inert atmosphere; Sealed tube 3: N-chloro-succinimide; acetic acid / water / 20 °C View Scheme

4-(N-cyclohexylcarbonyl-N-(2-methyl-3-phenyl-2-(E)-propenyl)aminomethyl)piperidine trifluoroacetic acid salt + biphenyl-3-sulfonyl chloride (65685-01-0) → C35H44N2O3S

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 16h;	98%

biphenyl-3-sulfonyl chloride (65685-01-0) + 3-(4-(aminomethyl)benzyl)-7-ethyl-1H-purine-2,6(3H,7H)-dione trifluoroacetic acid salt → N-(4-((7-ethyl-2,6-dioxo-1H-purin-3(2H,6H,7H)-yl)methyl)benzyl)-[1,1′-biphenyl]-3-sulfonamide

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 12h;	96%

biphenyl-3-sulfonyl chloride (65685-01-0) → (1,1′-biphenyl)-3-sulfonamide (91569-33-4)

Conditions	Yield
With ammonium hydroxide In dichloromethane; water at 20℃; for 6.5h; Cooling with ice;	93%

biphenyl-3-sulfonyl chloride (65685-01-0) + 3,4,5-Trimethoxyaniline (24313-88-0) → N-(3,4,5-trimethoxyphenyl)biphenyl-3-sulfonamide (1311195-74-0)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide	91.7%
With triethylamine In N,N-dimethyl-formamide	91.7%

biphenyl-3-sulfonyl chloride (65685-01-0) + N-methyl-4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]aniline (1481-11-4) → biphenyl-3-sulfonic acid methyl-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-amide

Conditions	Yield
With 2,6-dimethylpyridine In acetone at 60℃; for 24h;	90%

biphenyl-3-sulfonyl chloride (65685-01-0) + C13H15N3O → (biphenyl-3-yl)sulfonyl-(R)-phenylalanylaminocyclopropane nitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;	89%

biphenyl-3-sulfonyl chloride (65685-01-0) + C10H17N3O → (biphenyl-3-yl)sulfonyl-(R)-leucylaminocyclopropane nitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;	78%

biphenyl-3-sulfonyl chloride (65685-01-0) + (-)-alpha-Methyltryptamine (7795-52-0) → (R)-N-(1-(1H-indol-3-yl)propan-2-yl)-[1,1'-biphenyl]-3-sulfonamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h;	77%

biphenyl-3-sulfonyl chloride (65685-01-0) + 4-Aminosalicylic acid (65-49-6) → 4-[(biphenyl-3-ylsulfonyl)amino]-2-hydroxybenzoic acid (1353433-22-3)

Conditions	Yield
With pyridine In dichloromethane at 60℃; for 4h;	74%

biphenyl-3-sulfonyl chloride (65685-01-0) + (S)-2-amino-N-(1-cyanocyclopropyl)-3-phenylpropanamide → (biphenyl-3-yl)sulfonyl-(S)-phenylalanylaminocyclopropane nitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;	71%

methyl 4-{3-[2-(2-aminoethyl)-5-chloro-1-(diphenylmethyl)-1H-indol-3-yl]propyl}benzoate (540522-70-1) + biphenyl-3-sulfonyl chloride (65685-01-0) → methyl 4-[3-(1-benzhydryl-2-{2-[(1,1'-biphenyl-3-ylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)propyl]benzoate (1019217-38-9)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane; water Schotten-Baumann reaction;	65%

biphenyl-3-sulfonyl chloride (65685-01-0) + 4-chloro-3-methyl-5-amino isoxazole (166964-09-6) → N-(4-chloro-3-methyl-5-isoxazolyl)-3-biphenylsulfonamide

Conditions	Yield
	63%

biphenyl-3-sulfonyl chloride (65685-01-0) + 6-((2-chloro-6-fluorobenzyl)oxy)indoline → 1-([1,1’-biphenyl]-3-ylsulfonyl)-6-((2-chloro-6-fluorobenzyl)oxy)indoline

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	63%

methyl 4-{2-[2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoate amine (540522-69-8) + biphenyl-3-sulfonyl chloride (65685-01-0) → methyl 4-[2-(1-benzhydryl-2-{2-[(1,1'-biphenyl-3-ylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoate (1019216-96-6)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane; water Schotten-Baumann reaction;	61%

biphenyl-3-sulfonyl chloride (65685-01-0) + C15H21N3O → (biphenyl-3-yl)sulfonyl-(S)-leucylphenylalanine nitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;	58%

biphenyl-3-sulfonyl chloride (65685-01-0) + N-(1-cyanocyclopropyl)-L-leucinamide → (biphenyl-3-yl)sulfonyl-(S)-leucylaminocyclopropane nitrile

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 20h; Inert atmosphere;	51%

4-(4-chlorophenyl)-2-thiazolamine (2103-99-3) + biphenyl-3-sulfonyl chloride (65685-01-0) → N-[4-(4-chlorophenyl)thiazol-2-yl]-3-phenylbenzenesulfonamide

Conditions	Yield
With pyridine at 80℃; for 8h;	47%

N-Boc-trans-1,4-bis(aminomethyl)cyclohexane + biphenyl-3-sulfonyl chloride (65685-01-0) → tert-butyl [(trans-4-{[(biphenyl-3-ylsulfonyl)amino]methyl}cyclohexyl)methyl]carbamate

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	42%

biphenyl-3-sulfonyl chloride (65685-01-0) + 5'-amino-6'-chloro-N-methyl-[3,3'-bipyridine]-5-carboxamide → 5’-([1,1'-biphenyl]-3-sulfonamido)-6'-chloro-N-methyl-[3,3'-bipyridine]-5-carboxamide

Conditions	Yield
With pyridine at 20℃; for 6h; Inert atmosphere;	38%

hexan-1-amine (111-26-2) + biphenyl-3-sulfonyl chloride (65685-01-0) + methyl 1-(3-(chloromethyl)phenyl)-5-((trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylate → 1-(3-((N-hexyl-[1,1'-biphenyl]-3-ylsulfonamido)methyl)phenyl)-5-((trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid

Conditions

Yield

Stage #1: hexan-1-amine; biphenyl-3-sulfonyl chloride With N-ethyl-N,N-diisopropylamine In acetonitrile for 0.0166667h; Stage #2: methyl 1-(3-(chloromethyl)phenyl)-5-((trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylate With sodium hydride In acetonitrile; mineral oil at 140℃; for 0.0166667h; Microwave irradiation; Stage #3: With potassium hydroxide In water; acetonitrile; mineral oil Microwave irradiation;

32%

biphenyl-3-sulfonyl chloride (65685-01-0) + novenamine hydrochloride → C31H32N2O11S

Conditions	Yield
With pyridine at -40 - 23℃; for 12h; Inert atmosphere; Sealed tube;	32%

biphenyl-3-sulfonyl chloride (65685-01-0) + 4-bromo-3-methyl-5-aminoisoxazole (33084-49-0) → N-(4-bromo-3-methyl-5-isoxazolyl)-3-biphenylsulfonamide

Conditions	Yield
	22%

biphenyl-3-sulfonyl chloride (65685-01-0) + sodium methylate (124-41-4) → biphenyl-3-sulfonic acid methyl ester

Conditions	Yield
With methanol

5-ethoxy-pyrrolidin-2-one (39662-63-0) + biphenyl-3-sulfonyl chloride (65685-01-0) → 1-(Biphenyl-3-sulfonyl)-5-ethoxy-pyrrolidin-2-one (111711-71-8)

Conditions	Yield
With n-butyllithium 1.) THF, hexane, -70 deg C, 45 min, 2.) THF, hexane, -70 deg C, 2 h; Yield given. Multistep reaction;

5-amino-3,4-dimethylisoxazol (19947-75-2) + biphenyl-3-sulfonyl chloride (65685-01-0) → N-(3,4-dimethyl-5-isoxazolyl)-3-biphenylsulfonamide

biphenyl-3-sulfonyl chloride (65685-01-0) + 3-(3-(S)-amino-2-oxopyrrolidin-1-ylmethyl)benzonitrile hydrochloride → Biphenyl-3-sulfonic acid [(S)-1-(3-cyano-benzyl)-2-oxo-pyrrolidin-3-yl]-amide (1027145-58-9)

Conditions	Yield
With triethylamine In dichloromethane for 2h; Condensation; amidation;

Upstream product

• 2113-57-7 3-bromobiphenyl 
• 41949-30-8 3-biphenylmonosulfonic acid 
• 2905-24-0 3-Bromobenzenesulfonyl chloride 
• 98-80-6 phenylboronic acid 
• 94306-39-5 [1,1'-biphenyl]-3-yl(benzyl)sulfane 
• 591-18-4 1-Bromo-3-iodobenzene 
• 594-19-4 tert.-butyl lithium 

Downstream Products

• 1161342-60-4 N-(3-(benzo[d]thiazol-2-yl)thiophen-2-yl)biphenyl-3-sulfonamide 
• 1161341-91-8 N-(3-(benzo[d]thiazol-2-yl)-4-methylthiophen-2-yl)biphenyl-3-sulfonamide 
• 1554494-13-1 N-[(4-cyanophenyl)methyl]-3-phenylbenzene-1-sulfonamide 
• 1416048-52-6 C₉₁H₁₄₄N₁₆O₂₄S 
• 1353433-22-3 4-[(biphenyl-3-ylsulfonyl)amino]-2-hydroxybenzoic acid 
• 583813-98-3 C₂₈H₃₁N₃O₃S 
• 1019217-38-9 methyl 4-[3-(1-benzhydryl-2-{2-[(1,1'-biphenyl-3-ylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)propyl]benzoate 
• 1027145-58-9 Biphenyl-3-sulfonic acid [(S)-1-(3-cyano-benzyl)-2-oxo-pyrrolidin-3-yl]-amide 
• 111711-71-8 1-(Biphenyl-3-sulfonyl)-5-ethoxy-pyrrolidin-2-one 

Relevant articles and documents

Synthesis method of biphenyl-3-sulfonyl chloride derivative

The invention discloses a synthesis method of a biphenyl-3-sulfonyl chloride derivative. According to the method, 3-bromobenzene sulfonyl chloride and a phenylboronic acid derivative which are cheap and easy to obtain are used as raw materials, and a target compound is obtained through two steps of Suzuki coupling reaction and chlorination reaction. The method not only avoids the problem that biphenyl 3-position is difficult to sulfonate, but also has the advantages of high reaction activity, simplicity and convenience in operation, lower danger coefficient of the used reagent and lower environmental pollution, and can be used as a potential route for industrial large-scale production of biphenyl sulfonic acid derivatives.

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Biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin

Biphenylsulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, bicyclic or tricyclic carbon or heterocyclic ring biphenylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.