3119-02-6

Basic information

• Product Name: 4-CYANOBENZENE-1-SULFONAMIDE
• Synonyms: 4-Sulphamoylbenzonitrile;4-Sulphamoylbenzonitrile, 4-(Aminosulphonyl)benzonitrile;p-cyano-benzenesulfonamid;BUTTPARK 48\11-02;4-CYANOBENZENESULFONAMIDE;4-CYANOBENZENE-1-SULFONAMIDE;4-CYANOBENZENE-1-SULPHONAMIDE;p-cyanobenzenesulphonamide
• CAS NO: 3119-02-6
• Molecular Formula: C₇H₆N₂O₂S
• Molecular Weight: 182.2
• EINECS: 221-492-5
• Product Categories: SULFONAMIDE
• Mol File: 3119-02-6.mol

Chemical Properties

• Melting Point: 166 °C
• Boiling Point: 400.7 °C at 760 mmHg
• Flash Point: 196.2 °C
• Appearance: /
• Density: 1.3827 (rough estimate)
• Vapor Pressure: 1.24E-06mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 9.57±0.10(Predicted)
• Water Solubility: 1.111g/L(15 oC)
• CAS DataBase Reference: 4-CYANOBENZENE-1-SULFONAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-CYANOBENZENE-1-SULFONAMIDE(3119-02-6)
• EPA Substance Registry System: 4-CYANOBENZENE-1-SULFONAMIDE(3119-02-6)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36/37/39-36/37
• RIDADR: 3276
• RTECS: DB1582000
• HazardClass: IRRITANT
• Hazardous Substances Data: 3119-02-6(Hazardous Substances Data)

Usage

Uses

4-Cyanobenzene-1-sulfonamide is a carbonic anhydrase inhibitor.

InChI:InChI=1/C7H6N2O2S/c8-5-6-1-3-7(4-2-6)12(9,10)11/h1-4H,(H2,9,10,11)

Synthetic route

p-cyanobenzenesulfonyl chloride (49584-26-1) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
With ammonium hydroxide In tetrahydrofuran at 20℃; for 2h;	94%
With ammonium hydroxide In tetrahydrofuran at 0 - 5℃;	94%
With ammonium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 1h;	88%

4-Chlorobenzenesulfonamide (98-64-6) + potassiumhexacyanoferrate(II) trihydrate → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
With C42H58NO3PPdS(2-); potassium acetate; tert-butyl XPhos In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere; Sealed tube;	91%

zinc(II) cyanide (557-21-1) + 4-Chlorobenzenesulfonamide (98-64-6) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
Stage #1: zinc(II) cyanide With aluminum oxide; Ni(xantphos)(o-tolyl)Cl for 1h; Schlenk technique; Inert atmosphere; Sealed tube; Stage #2: 4-Chlorobenzenesulfonamide In 1-methyl-pyrrolidin-2-one at 20℃; for 24h; Schlenk technique; Inert atmosphere;	91%
With dmap; 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) chloride hexahydrate; zinc In acetonitrile at 80℃; for 7h; Schlenk technique; Inert atmosphere; Sealed tube;	80%
With dmap; 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) chloride hexahydrate; zinc In acetonitrile at 80℃; for 7h; Inert atmosphere; Sealed tube;	80%

4-cyanobenzenethiol (36801-01-1) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
With manganese(IV) oxide; ammonia; oxygen In water; N,N-dimethyl-formamide at 90℃; under 7500.75 Torr; for 20h; Autoclave;	68%

potassium cyanide (151-50-8) + sulfanilamide (63-74-1) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
Stage #1: sulfanilamide With hydrogenchloride; sodium nitrite at 0℃; for 0.166667h; Stage #2: potassium cyanide With copper(II) sulfate In water at 0 - 80℃; for 1h; Further stages.;	66%
Stage #1: sulfanilamide With hydrogenchloride; sodium nitrite Stage #2: potassium cyanide With copper(II) sulfate Sandmayer reaction;	53%

potassium cyanide + sulfanilamide (63-74-1) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
With hydrogenchloride; copper(ll) sulfate pentahydrate; sodium nitrite In water at 0 - 80℃;	60%

4-Sulfamoyl-benzenediazonium (14289-29-3) + sodium cyanide (143-33-9) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
With water; copper(II) sulfate
With water; nickel dichloride

4-(hydroxyimino-methyl)-benzenesulfonic acid amide (98276-92-7) + formamide (77287-34-4, 77287-35-5, 60100-09-6) → 4-cyanobenzenesulfonamide (3119-02-6)

4-(aminosulfonyl)-benzoic acid (138-41-0) → 4-cyanobenzenesulfonamide (3119-02-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: PCl5 / 60 °C / Erhitzen dann auf 110grad, 150grad und zuletzt auf 200grad 2: water; ammonia View Scheme

4-cyanobenzenesulfonamide (3119-02-6) → 4-homosulfanilamide (138-39-6)

Conditions	Yield
With hydrogenchloride; palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 4h;	95%
With sodium methylate; nickel In methanol at 45℃; Product distribution; Further Variations:; Temperatures; current density; Electrochemical reaction;	85%
With ammonium hydroxide; hydrogen In tetrahydrofuran; methanol at 20℃; for 0.5h; Inert atmosphere;	82.2%

4-cyanobenzenesulfonamide (3119-02-6) → N'-hydroxy-4-sulfamoylbenzimidamide (4476-10-2)

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol for 6h; Reflux;	93%
With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol for 6h; Reflux;	93%
With hydroxylamine In tetrahydrofuran; water at -25 - 20℃; for 16h;

4-cyanobenzenesulfonamide (3119-02-6) + tert-butyl 2-(acetoxymethyl)hepta-2,3-dienoate → tert-butyl (S)-1-((4-cyanophenyl)sulfonyl)-5-propyl-2,5-dihydro-1H-pyrrole-3-carboxylate

Conditions

Yield

Stage #1: 4-cyanobenzenesulfonamide With cyclopentyl methyl ether; (11R,13R)-11,13-dimethyl-12-phenyl-4,5,6,7,12,13-hexahydro-11H-diindeno[7,1-cd:1',7'-ef]phosphocine; sodium phenoxide In toluene at 20℃; for 0.0833333h; Inert atmosphere; Sealed tube; Stage #2: tert-butyl 2-(acetoxymethyl)hepta-2,3-dienoate In toluene at 40℃; for 24h; Reagent/catalyst; Inert atmosphere; Sealed tube; enantioselective reaction;

91%

methyl 2-octynoate (111-12-6) + 4-cyanobenzenesulfonamide (3119-02-6) → methyl (Z)-3-amino-2-(4-cyanophenyl)oct-2-enoate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16h; Sealed tube;	91%

4-cyanobenzenesulfonamide (3119-02-6) + 2-chloro-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid → 2-chloro-N-(4-cyanophenyl)sulfonyl-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxamide

Conditions	Yield
Stage #1: 2-chloro-6-[3-[[1-(trifluoromethyl)cyclopropyl]methoxy]pyrazol-1-yl]pyridine-3-carboxylic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 2h; Stage #2: 4-cyanobenzenesulfonamide With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 3h;	88%

4-cyanobenzenesulfonamide (3119-02-6) + 2-(1-phenylvinyl)-N-(pyridin-2-yl)benzamide → 4-cyano-N-((3-oxo-1-phenyl-2-(pyridin-2-yl)isoindolin-1-yl)methyl)benzenesulfonamide

Conditions	Yield
With [bis(acetoxy)iodo]benzene; sodium acetate; [Cp*Rh(MeCN)3][SbF6]2 In dichloromethane at 20℃; for 16h; Schlenk technique;	88%

4-cyanobenzenesulfonamide (3119-02-6) → 4-formyl-benzenesulfonamide (3240-35-5)

Conditions	Yield
With formic acid; aluminum nickel Stephen reduction;	86%
With hydrogenchloride; diethyl ether und anschliessenden Behandeln mit einer Loesung von Zinn(II)-chlorid und Chlorwasserstoff in Aether;
With formic acid; nickel for 1h; Heating;
With formic acid

4-cyanobenzenesulfonamide (3119-02-6) + ammonia (7664-41-7) + copper dichloride → C14H16CuN6O4S2 (1398545-79-3)

Conditions	Yield
In ethanol at 20℃;	80%

4-cyanobenzenesulfonamide (3119-02-6) + tert-butyl 2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]-thiophene-3-carboxylate (207743-78-0) → tert-butyl 2-(3-(4-cyanobenzenesulfonyl)thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1452776-83-8)

Conditions	Yield
With potassium carbonate In acetone for 20h; Reflux;	76%

4-cyanobenzenesulfonamide (3119-02-6) → 4-sulfamoylbenzoselenoamide

Conditions	Yield
With selenium; sodium tetrahydroborate In ethanol for 6h; Inert atmosphere; Reflux;	76%

succinic acid anhydride (108-30-5) + 4-cyanobenzenesulfonamide (3119-02-6) + methyl iodide (74-88-4) + ArgoGel-Rink-NH-Fmoc resin → 4-cyano-N-methylbenzenesulfonamide (56236-82-9)

Conditions	Yield
Multistep reaction.;	75%

2,3-dichloroquinoxaline (2213-63-0) + 4-cyanobenzenesulfonamide (3119-02-6) → N-(3-chloroquinoxalin-2-yl)-4-cyanobenzenesulfonamide

Conditions	Yield
With lithium hydroxide In N,N-dimethyl acetamide at 50℃; for 18h; Product distribution / selectivity;	73%

morpholine (110-91-8) + 4-cyanobenzenesulfonamide (3119-02-6) → (E)-4-cyano-N-(morpholinomethylene)benzenesulfonamide

Conditions	Yield
With copper(I) bromide In dimethyl sulfoxide at 100℃; for 24h; Schlenk technique; stereoselective reaction;	72%

4-cyanobenzenesulfonamide (3119-02-6) + 1-methyl-4-((3-methoxyphenyl)amino)-7-chloro-1H-indole-2-carboxylic acid → 1-methyl-4-((3-methoxyphenyl)amino)-7-chloro-N-(4-cyanophenylsulfonyl)-1H-indole-2-carboxamide

Conditions	Yield
With dmap; triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; Inert atmosphere;	71.4%

4-cyanobenzenesulfonamide (3119-02-6) + 2-(prop-1-en-2-yl)-N-(pyridin-2-yl)benzamide → 4-cyano-N-((1-methyl-3-oxo-2-(pyridin-2-yl)isoindolin-1-yl)methyl)benzenesulfonamide

Conditions	Yield
With [bis(acetoxy)iodo]benzene; sodium acetate; [Cp*Rh(MeCN)3][SbF6]2 In dichloromethane at 20℃; for 16h; Schlenk technique;	71%

4-cyanobenzenesulfonamide (3119-02-6) → (E)-N'-hydroxy-4-sulfamoylbenzimidamide (1233243-50-9, 4476-10-2)

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydrogencarbonate In methanol at 75℃; for 6h;	70%
With hydroxylamine hydrochloride; sodium hydrogencarbonate In methanol at 75℃; for 6h;	70%

bis(1-methyl-1-phenylethyl)peroxide (80-43-3) + 4-cyanobenzenesulfonamide (3119-02-6) → 4-cyano-N-methylbenzenesulfonamide (56236-82-9)

Conditions	Yield
With copper acetylacetonate In acetone at 120℃; for 8h; Sealed tube;	70%

4-cyanobenzenesulfonamide (3119-02-6) → 4-cyanobenzenesulfonyl azide (1026020-39-2)

Conditions	Yield
With 3-azidosulfonyl-3H-imidazole-1-ium hydrogen sulfate; potassium carbonate In water; isopropyl alcohol at 20℃; for 18h;	68%

4-cyanobenzenesulfonamide (3119-02-6) + Benzoylformic acid (611-73-4) → N-((4-cyanophenyl)sulfonyl)-2-oxo-2-phenylacetamide

Conditions	Yield
Stage #1: Benzoylformic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; Inert atmosphere; Stage #2: 4-cyanobenzenesulfonamide With dmap; triethylamine In ethyl acetate; toluene at 0 - 20℃; for 18h; Inert atmosphere;	66%

N-[(E)-4-bromo-2-butenyl]-N-(tert-butyloxycarbonyl)-[3,4-bis(dodecyloxy)]benzenesulfonamide (861397-78-6) + 4-cyanobenzenesulfonamide (3119-02-6) → (E,E)-1,11-bis(tert-butyloxycarbonyl)-6-[(4-cyanophenyl)sulfonyl]-1,11-bis{[(3,4-didodecyloxy)phenyl]sulfonyl}-1,6,11-triazaundeca-3,8-diene (1453119-71-5)

Conditions	Yield
With potassium carbonate In acetonitrile for 24h; Reflux;	65%

Upstream product

• 14289-29-3 4-Sulfamoyl-benzenediazonium 
• 143-33-9 sodium cyanide 
• 98276-92-7 4-(hydroxyimino-methyl)-benzenesulfonic acid amide 
• 77287-34-4 formamide 
• 49584-26-1 p-cyanobenzenesulfonyl chloride 
• 151-50-8 potassium cyanide 
• 63-74-1 sulfanilamide 
• 138-41-0 4-(aminosulfonyl)-benzoic acid 
• 98-64-6 4-Chlorobenzenesulfonamide 
• 557-21-1 zinc(II) cyanide 
• 36801-01-1 4-cyanobenzenethiol 
• 10252-84-3 p-(tert.-Butylsulfamoyl)-benzonitril 

Downstream Products

• 91091-24-6 acetoacetyl-(4-cyano-benzenesulfonyl)-amine 
• 54951-45-0 4-carbamimidoyl-benzenesulfonic acid amide 
• 3240-35-5 4-formyl-benzenesulfonamide 
• 138-39-6 4-homosulfanilamide 
• 6306-24-7 4-amidobenzylsulfonamide 
• 57870-15-2 4-sulfamoyl-benzimidic acid ethyl ester 
• 56236-74-9 p-Sulfamoyl-thiobenzamid 
• 4476-10-2 N′-hydroxy-4-sulfamoylbenzene-1-carboximidamide 
• 98594-82-2 4-(ureidomethyl)benzenesulfonamide 
• 90417-63-3 acetyl-(4-cyano-benzenesulfonyl)-amine 
• 4370-20-1 4-(formylamino-methyl)-benzenesulfonic acid amide 
• 105899-95-4 N-<(p-cyanophenyl)sulfonyl>-P,P,P-yriphenylphospha-λ⁵-azene 
• 5887-58-1 2-<(4-Aminosulfonyl)phenyl>-1,3-benzimidazol 
• 138-41-0 4-(aminosulfonyl)-benzoic acid 

Relevant articles and documents

Chemoselective Cleavage of Acylsulfonamides and Sulfonamides by Aluminum Halides

The chemoselective cleavage of C-N bonds of amides, sulfonamides, and acylsulfonamides by aluminum halides is described. AlCl3and AlI3display complementary reactivities toward N-alkyl and N-acyl moieties. N-Alkylacylsulfonamides, sec

METHOD FOR PRODUCING OXIDE USING BETA-MANGANESE DIOXIDE

With the object of efficiently producing an oxidation product, the present invention provides a method for producing an oxidation product by oxidizing a raw material compound in the presence of oxygen, wherein the raw material compound is oxidized in the presence of manganese dioxide having a crystal structure of β-type.

Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76percent inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.

Alkene Syn- And Anti-Oxyamination with Malonoyl Peroxides

Malonoyl peroxide 6 is an effective reagent for the syn- or anti-oxyamination of alkenes. Reaction of 6 and an alkene in the presence of O-tert-butyl-N-tosylcarbamate (R3 = CO2 tBu) leads to the anti-oxyaminated product in up to 99% yield. Use of O-methyl-N-tosyl carbamate (R3 = CO2Me) as the nitrogen nucleophile followed by treatment of the product with trifluoroacetic acid leads to the syn-oxyaminated product in up to 77% yield. Mechanisms consistent with the observed selectivities are proposed.

One-pot aerobic oxidative sulfonamidation of aromatic thiols with ammonia by a dual-functional β-MnO2 nanocatalyst

High-surface-area β-MnO2 (β-MnO2-HS) nanoparticles could act as effective heterogeneous catalysts for the one-pot oxidative sulfonamidation of various aromatic and heteroaromatic thiols to the corresponding sulfonamides using molecular oxygen (O2) and ammonia (NH3) as respective oxygen and nitrogen sources, without the need for any additives.

BIARYL UREA DERIVATIVE OR SALT THEREOF, AND MANUFACTURING AND APPLICATION OF SAME

The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.

NOVEL TETRAZOLE COMPOUNDS AND THEIR USE IN THE TREATMENT OF TUBERCULOSIS

The invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis.

Preparation method of aromatic nitrile compound or heteroaromatic nitrile compound

The invention discloses a preparation method of an aromatic nitrile compound or a heteroaromatic nitrile compound. The preparation method comprises: under the protection of an inert gas, in a solvent,under the actions of a nickel catalyst, a ligand, metal zinc and an additive, carrying out a reaction on a cyanation reagent and halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon. According to the present invention, by using the inexpensive and easily-available nickel catalyst and the ligand, the halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon,especially the chlorinated aromatic hydrocarbon or chlorinated heteroaromatic hydrocarbon with characteristics of low price, easy obtaining and low reaction activity can mildly and efficiently react with the cyanation reagent with low toxicity to prepare the aromatic nitrile compound or heteroaromatic nitrile compound; and the preparation method has advantages of simple operation, mildness, high efficiency and the like, and further has characteristics of good functional group compatibility, good universality of substrate and the like.

Method for catalytic synthesis of N-benzyl benzene sulfonamide compounds by boric acid/oxalic acid catalytic system under microwave radiation

The invention discloses a method for catalytic synthesis of N-benzyl benzene sulfonamide compounds by a boric acid/oxalic acid catalytic system under microwave radiation. The method includes: adoptingbenzyl alcohol and derivatives thereof and benzene sulfonamide derivatives as raw materials, adopting the boric acid/oxalic acid system as a catalyst, and adopting fluorobenzene as a solvent; performing reaction in a microwave reactor under certain temperature and power conditions, performing vacuum concentration after reaction for a period of time, and subjecting a product to column chromatographic purification to realize efficient catalytic preparation of the N-benzyl benzene sulfonamide compounds. Compared with the prior art, the method has advantages of evidently higher reaction speed than that of conventional heating, mild reaction conditions, simplicity in operation, high yield, safety, low cost and environmental friendliness.

Discovery of new 2, 5-disubstituted 1,3-selenazoles as selective human carbonic anhydrase IX inhibitors with potent anti-tumor activity

A series of disubstituted selenazole derivatives was synthetized and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV, VA, VB and IX, involved in a variety of diseases including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. The investigated compounds showed potent inhibition against the tumor-associated transmembrane hCA IX, with KIs in the subnanomolar – low nanomolar range, and were evaluated for their effects on cell viability against the human prostate (PC3) and breast (MDA-MB-231) cancer cell lines, showing effective anti-tumor activity. These selenazoles are interesting leads for the development of new, isoform-selective CA IX inhibitors.