98-30-6

Basic information

• Product Name: 2-Amino-4-(methylsulfonyl)phenol
• Synonyms: 2-amino-4-(methylsulphonyl)phenol;2-Amino-4-Methylsulfonyl Phenol;APMS;2-AMINOPHENOL-4-METHYLSULPHONE;CCRIS 5961;3-Amino-4-hydroxyphenyl Methyl Sulfone;2-amino-4-mesyl-phenol;2-azanyl-4-methylsulfonyl-phenol
• CAS NO: 98-30-6
• Molecular Formula: C₇H₉NO₃S
• Molecular Weight: 187.22
• EINECS: 202-654-4
• Mol File: 98-30-6.mol
• Article Data: 4

Chemical Properties

• Melting Point: 156.0 to 160.0 °C
• Boiling Point: 436.3 °C at 760 mmHg
• Flash Point: 217.6 °C
• Appearance: LIGHT GREAY COLOUR DRY POWDER
• Density: 1.419 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.603
• PKA: 7.36±0.18(Predicted)
• CAS DataBase Reference: 2-Amino-4-(methylsulfonyl)phenol(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Amino-4-(methylsulfonyl)phenol(98-30-6)
• EPA Substance Registry System: 2-Amino-4-(methylsulfonyl)phenol(98-30-6)

Safety Data

• Hazardous Substances Data: 98-30-6(Hazardous Substances Data)

Usage

Chemical Properties

Gray to brown crystalline powder

General Description

Dark brown powder.

Air & Water Reactions

Slightly soluble in water.

Fire Hazard

Flash point data for 2-Amino-4-(methylsulfonyl)phenol are not available; however, 2-Amino-4-(methylsulfonyl)phenol is probably combustible.

InChI:InChI=1/C7H9NO3S/c1-12(10,11)5-2-3-7(9)6(8)4-5/h2-4,9H,8H2,1H3

Synthetic route

2-methoxy-5-(methylsulfonyl)aniline (20945-70-4) → 1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6)

Conditions	Yield
Stage #1: 2-methoxy-5-(methylsulfonyl)aniline With boron tribromide In dichloromethane; chloroform at 0℃; for 0.333333h; Stage #2: With water; sodium hydrogencarbonate pH=7;	15%
With boron tribromide In dichloromethane for 5h; Reflux;
With boron tribromide

2-nitro-4-methanesulfonyl-phenol → 1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6)

Conditions	Yield
With sodium hydroxide; nickel at 130℃; under 36775.4 Torr; Hydrogenation;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + tert-butylisonitrile (119072-55-8, 7188-38-7) → N-(tert-butyl)-2-(tert-butylimino)-6-(methylsulfonyl)-2H-benzo[b][1,4]oxazin-3-amine (1427468-96-9)

Conditions	Yield
With palladium dichloride In 1,4-dioxane at 50℃; for 8h;	89%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + tert-butylisonitrile (119072-55-8, 7188-38-7) → N-(tert-butyl)-5-(methylsulfonyl)benzo[d]oxazol-2-amine (1427468-76-5)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 50℃; for 8h;	88%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + phthalic anhydride (85-44-9) → 2-[2-hydroxy-5-(methylsulfonyl)phenyl]-1H-isoindole-1,3(2H)-dione

Conditions	Yield
With acetic acid at 120℃; for 18h;	80%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + acetophenone (98-86-2) → 2-benzyl-5-(methylsulfonyl)benzoxazole

Conditions	Yield
With N-methylcyclohexylamine; sulfur at 80℃; for 16h; Inert atmosphere; Sealed tube;	80%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + benzaldehyde (100-52-7) → 5-(methylsulfonyl)-2-phenylbenzoxazole

Conditions	Yield
With sulfur; sodium sulfide pentahydrate; dimethyl sulfoxide at 70℃; for 16h; Inert atmosphere;	80%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + dibenzyl disulphide (150-60-7) → 5-(methylsulfonyl)-2-phenylbenzoxazole

Conditions	Yield
With N-methylcyclohexylamine; sulfur; dimethyl sulfoxide at 100℃; for 16h; Inert atmosphere;	74%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + acetophenone (98-86-2) → (5-(methylsulfonyl)benzoxazol-2-yl)(phenyl)methanone

Conditions	Yield
With 4-methyl-morpholine; sulfur; dimethyl sulfoxide at 110℃; for 16h; Inert atmosphere;	74%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 3-tert-butylcyclohexanone (936-99-2) → (5aS*,11aS*,15S*)-15-(tert-butyl)-2,8-bis(methylsulfonyl)-6,12-dihydro-5a,11a-butanobenzo[b]benzo[5,6][1,4]oxazino[2,3-e][1,4]oxazine

Conditions	Yield
With sulfur; acetic acid; dimethyl sulfoxide at 80℃; for 16h; Inert atmosphere; stereoselective reaction;	72%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 1-[trans-4-(ethyloxy)-1-methylcyclohexyl]-4-piperidinone (950772-15-3) → 2-({1-[trans-4-(ethyloxy)-1-methylcyclohexyl]-4-piperidinyl}amino)-4-(methylsulfonyl)phenol (1134197-45-7)

Conditions	Yield
Stage #1: 1-hydroxy-2-amino-4-methylsulphonyl-benzene; 1-[trans-4-(ethyloxy)-1-methylcyclohexyl]-4-piperidinone With polymer supported cyanoborohydride; acetic acid In tetrahydrofuran at 100℃; for 0.5h; Microwave; Stage #2: With ammonia In methanol; dichloromethane	67%
With acetic acid In dichloromethane at 100℃; Microwave irradiation;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + potassium ethyl xanthogenate (140-89-6) → 5-(methylsulfonyl)benzoxazole-2-thione (93614-45-0)

Conditions	Yield
With pyridine for 3h; Heating;	57%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + acrolein (107-02-8) → 5-(methylsulfonyl)quinolin-8-ol (1417737-57-5)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In water for 2h; Skraup, Doebner-Miller Synthesis; Reflux;	57%
With hydrogenchloride In water at 100℃; for 1h; Skraup Quinoline Synthesis; Inert atmosphere;	52%

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 1-[trans-1-methyl-4-(propyloxy)cyclohexyl]-4-piperidinone (950772-26-6) → 2-({1-[trans-1-methyl-4-(propyloxy)cyclohexyl]-4-piperidinyl}amino)-4-(methylsulfonyl)phenol (1134197-77-5)

Conditions	Yield
Stage #1: 1-hydroxy-2-amino-4-methylsulphonyl-benzene; 1-[trans-1-methyl-4-(propyloxy)cyclohexyl]-4-piperidinone With polymer supported cyanoborohydride; acetic acid In tetrahydrofuran at 100℃; for 1.5h; Microwave; Stage #2: With ammonia In methanol; dichloromethane	35%
With acetic acid In dichloromethane at 100℃; Microwave irradiation;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 2-Bromoacetyl bromide (598-21-0) → 6-(methylsulfonyl)-2H-1,4-benzoxazin-3(4H)-one (459190-08-0)

Conditions	Yield
With sodium hydrogencarbonate In chloroform; water at 0 - 20℃;	33%
With caesium carbonate In N,N-dimethyl-formamide

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + para-chlorobenzoic acid (74-11-3) → 2-(4-chlorophenyl)-5-(methylsulfonyl)benzo[d]oxazole

Conditions	Yield
With polyphosphoric acid Heating;	21%

phosgene (75-44-5) + 1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 5-methanesulfonyl-3H-benzooxazol-2-one (13920-98-4)

Conditions	Yield
With alkaline solution

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 2-amino-4-methanesulfonyl-6-nitrophenol (101861-04-5)

Conditions	Yield
With sulfuric acid; water; nitric acid

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 2-hydroxy-5-methanesulfonyl-benzenediazonium-betaine (854450-37-6)

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 4,4'-stilbenedicarbonyl dichloride (52238-17-2) → C30H26N2O8S2

Conditions	Yield
Heating;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 1,4-naphthalenedicarboxylic acid dichloride (13234-52-1) → Naphthalene-1,4-dicarboxylic acid bis-[(2-hydroxy-5-methanesulfonyl-phenyl)-amide] (40349-94-8)

Conditions	Yield
Heating;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 2-Chloro-5-methanesulfonyl-benzooxazole (177268-37-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 57 percent / pyridine / 3 h / Heating 2: 100 percent / thionyl chloride, DMF / 0.5 h / 65 - 70 °C View Scheme

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → (5-Methanesulfonyl-benzooxazol-2-yl)-prop-2-ynyl-amine (1027247-39-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 57 percent / pyridine / 3 h / Heating 2: 100 percent / thionyl chloride, DMF / 0.5 h / 65 - 70 °C 3: 21 percent / triethylamine / acetonitrile / 0.5 h / 65 - 70 °C View Scheme

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 6-Methanesulfonyl-2H-9-oxa-1,4a-diaza-fluorene

Conditions	Yield
Multi-step reaction with 4 steps 1: 57 percent / pyridine / 3 h / Heating 2: 100 percent / thionyl chloride, DMF / 0.5 h / 65 - 70 °C 3: 21 percent / triethylamine / acetonitrile / 0.5 h / 65 - 70 °C 4: silver tetrafluoroborate / CD3CN / 40 °C View Scheme

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 1-(2-hydroxy-5-methanesulfonyl-phenylazo)-3-methanesulfonyl-cyclopenta-2,4-dienecarboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 2: water / bei der Einwirkung von Sonnenlicht View Scheme

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) → 3-methanesulfonyl-1-(5-methanesulfonyl-2-methoxy-phenylazo)-cyclopenta-2,4-dienecarboxylic acid

Conditions	Yield
Multi-step reaction with 3 steps 2: water / bei der Einwirkung von Sonnenlicht 3: aq. NaOH solution View Scheme

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 1-{trans-4-[(cyclopropylmethyl)oxy]-1-methylcyclohexyl}-4-piperidinone (1134198-09-6) → 2-[(1-{trans-1-methyl-4-[(cyclopropylmethyl)oxy]cyclohexyl}-4-piperidinyl)amino]-4-(methylsulfonyl)phenol (1134198-10-9)

Conditions	Yield
With acetic acid In tetrahydrofuran at 100℃; for 1.5h; Microwave;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + 1-{trans-1-methyl-4-[(1-methylethyl)oxy]cyclohexyl}-4-piperidinone (1134198-16-5) → 2-[(1-{trans-1-methyl-4-[(1-methylethyl)oxy]cyclohexyl}-4-piperidinyl)amino]-4-(methylsulfonyl)phenol (1134198-17-6)

Conditions	Yield
With acetic acid In tetrahydrofuran at 100℃; for 1h; Microwave;

1-hydroxy-2-amino-4-methylsulphonyl-benzene (98-30-6) + naphthalene-2-carboxylate (93-09-4) → 5-(methylsulfonyl)-2-(naphthalen-2'-yl)benzo[d]oxazole (1118624-27-3)

Conditions	Yield
With polyphosphoric acid at 110 - 120℃; for 16h;	1.157 g

Upstream product

• 20945-70-4 2-methoxy-5-(methylsulfonyl)aniline 

Downstream Products

• 13920-98-4 5-methanesulfonyl-3H-benzooxazol-2-one 
• 101861-04-5 2-amino-4-methanesulfonyl-6-nitrophenol 
• 854450-37-6 2-hydroxy-5-methanesulfonyl-benzenediazonium-betaine 
• 459190-08-0 6-(methylsulfonyl)-2H-1,4-benzoxazin-3(4H)-one 
• 1134198-17-6 2-[(1-{trans-1-methyl-4-[(1-methylethyl)oxy]cyclohexyl}-4-piperidinyl)amino]-4-(methylsulfonyl)phenol 
• 1134198-10-9 2-[(1-{trans-1-methyl-4-[(cyclopropylmethyl)oxy]cyclohexyl}-4-piperidinyl)amino]-4-(methylsulfonyl)phenol 
• 1134197-77-5 2-({1-[trans-1-methyl-4-(propyloxy)cyclohexyl]-4-piperidinyl}amino)-4-(methylsulfonyl)phenol 

Relevant articles and documents

Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of duchenne muscular dystrophy

Figure Presented. A series of novel 2-arylbenzoxazoles that upregulate the production of utrophin in murine H2K cells, as assessed using a luciferase reporter linked assay, have been identified. This compound class appears to hold considerable promise as a potential treatment for Duchenne muscular dystrophy. Following the delineation of structure-activity relationships in the series, a number of potent upregulators were identified, and preliminary ADME evaluation is described. These studies have resulted in the identification of 1, a compound that has been progressed to clinical trials.

COMPOUNDS FOR THE TREATMENT OF MULTI-DRUG RESISTANT BACTERIAL INFECTIONS

The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans.