22551-24-2

Basic information

• Product Name: A-(METHYLTHIO)ACETAMIDE
• Synonyms: A-(METHYLTHIO)ACETAMIDE;2-(Methylthio)acetamide;2-(Methylsulfanyl)acetaMide;Methionyl acetaMide
• CAS NO: 22551-24-2
• Molecular Formula: C₃H₇NOS
• Molecular Weight: 105.16
• Mol File: 22551-24-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 99-102℃
• Boiling Point: 259℃
• Flash Point: 110℃
• Appearance: white solid
• Density: 1.132
• Vapor Pressure: 0.0135mmHg at 25°C
• Refractive Index: 1.504
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: soluble in Methanol
• PKA: 15.65±0.40(Predicted)
• CAS DataBase Reference: A-(METHYLTHIO)ACETAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: A-(METHYLTHIO)ACETAMIDE(22551-24-2)
• EPA Substance Registry System: A-(METHYLTHIO)ACETAMIDE(22551-24-2)

Safety Data

• Hazardous Substances Data: 22551-24-2(Hazardous Substances Data)

Usage

General Description

A-(methylthio)acetamide is a chemical compound that is also known as N-(methylsulfanyl)acetamide. It is a colorless to pale yellow liquid with a strong aromatic odor. A-(METHYLTHIO)ACETAMIDE is commonly used as an intermediate in the synthesis of pharmaceuticals and agrochemicals. It is also utilized in the manufacturing of fragrances and flavors. A-(methylthio)acetamide has potential irritant and sensitizing properties, and should be handled with care and in accordance with proper safety measures.

InChI:InChI=1/C3H7NOS/c1-6-2-3(4)5/h2H2,1H3,(H2,4,5)

Synthetic route

(methylthio)acetyl chloride (35928-65-5) → 2-(methylthio)acetamide (22551-24-2)

Conditions	Yield
With ammonia In diethyl ether at 0℃;	97%
With ammonia In benzene for 0.0833333h;

methyl 2-(methylthio)acetate (16630-66-3) → 2-(methylthio)acetamide (22551-24-2)

Conditions	Yield
With ammonium hydroxide at 20 - 25℃; for 2.25h;	76.2%

methylthioacetic acid ethyl ester (4455-13-4) → 2-(methylthio)acetamide (22551-24-2)

Conditions	Yield
With ammonia

Chloroacetamide (79-07-2) + sodium thiomethoxide (5188-07-8) → 2-(methylthio)acetamide (22551-24-2)

Conditions	Yield
With ethanol

methylthioacetonitrile (35120-10-6) → 2-(methylthio)acetamide (22551-24-2) + methylsulfanyl-acetic acid (2444-37-3)

Conditions	Yield
With potassium phosphate buffer; lyophilized Zea mays nitrilase ZmNIT2 EC 3.5.5.1 In water at 30℃; for 14h; pH=7.15; Title compound not separated from byproducts;

methyl chloroacetate (96-34-4) + sodium thiomethoxide (5188-07-8) → 2-(methylthio)acetamide (22551-24-2)

Conditions	Yield
Stage #1: methyl chloroacetate; sodium thiomethoxide With tetramethylammonium bromide at 20 - 50℃; for 1h; Stage #2: With ammonium hydroxide at 0 - 5℃;	55.85 g

(E)-1-Bromo-2-butene (4784-77-4, 39616-19-8, 29576-14-5) + 2-(methylthio)acetamide (22551-24-2) → 3-Methyl-2-methylsulfanyl-pent-4-enoic acid amide (343269-10-3)

Conditions	Yield
With potassium carbonate for 48h;	95%

2-(methylthio)acetamide (22551-24-2) + 1-bromomethylcyclohexene (37677-17-1) → 2-(2-Methylene-cyclohexyl)-2-methylsulfanyl-acetamide (72730-26-8)

Conditions	Yield
With potassium carbonate for 48h;	92%

2-(methylthio)acetamide (22551-24-2) → α-(Methylsulfinyl)-acetamide (81442-38-8)

Conditions	Yield
With NaJO4 In methanol; water Ambient temperature; overnight;	90%
With dihydrogen peroxide; acetone

2-(methylthio)acetamide (22551-24-2) + (2-aminophenyl)(phenyl)methanone (2835-77-0) → 2-amino-3-benzoyl-α-(methylthio)benzeneacetamide (78281-61-5)

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; (2-aminophenyl)(phenyl)methanone With N-chloro-succinimide In dichloromethane at -45 - 8℃; Stage #2: With triethylamine In dichloromethane Product distribution / selectivity;	86.4%
Stage #1: (2-aminophenyl)(phenyl)methanone With N-chloro-succinimide In dichloromethane at -35 - -25℃; for 0.5h; Stage #2: 2-(methylthio)acetamide In dichloromethane at 0 - 10℃; for 2h; Solvent;	80.27%
Stage #1: 2-(methylthio)acetamide; (2-aminophenyl)(phenyl)methanone With N-chlorophthalimide In dichloromethane at -20 - -5℃; for 3.5h; Stage #2: With triethylamine In dichloromethane Stage #3: With potassium hydroxide In dichloromethane; water Temperature; Concentration;	63.1%

2-(methylthio)acetamide (22551-24-2) + prenyl bromide (870-63-3) → 3,3-Dimethyl-2-methylsulfanyl-pent-4-enoic acid amide (73876-77-4)

Conditions	Yield
With potassium carbonate for 48h;	67%

(E)-1-bromo-2-heptene (35349-80-5) + 2-(methylthio)acetamide (22551-24-2) → 2-Methylsulfanyl-3-vinyl-heptanoic acid amide (75414-63-0) + 2-Methylsulfanyl-3-vinyl-2-(1-vinyl-pentyl)-heptanoic acid amide

Conditions	Yield
With potassium carbonate for 144h;	A 64% B n/a

2-(methylthio)acetamide (22551-24-2) + aniline (62-53-3) → 2-(2-aminophenyl)-2-(methylthio)acetamide (53512-44-0)

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; aniline With N-chlorophthalimide In dichloromethane at -20 - -15℃; for 2h; Stage #2: With triethylamine; potassium hydroxide In dichloromethane; water at -8℃;	59%

2-(methylthio)acetamide (22551-24-2) + 4-chloro-aniline (106-47-8) → 2-(2-amino-5-chlorophenyl)-2-(methylthio)acetamide

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; 4-chloro-aniline With N-chlorophthalimide In dichloromethane at -20 - -15℃; for 2h; Stage #2: With triethylamine; potassium hydroxide In dichloromethane; water at -8℃;	55%

2-methyl-3-bromo-1-propene (1458-98-6) + 2-(methylthio)acetamide (22551-24-2) → 4-Methyl-2-methylsulfanyl-pent-4-enoic acid amide (73892-17-8) + 4-Methyl-2-(2-methyl-allyl)-2-methylsulfanyl-pent-4-enoic acid amide

Conditions	Yield
With potassium carbonate for 120h;	A 45% B n/a

2-(methylthio)acetamide (22551-24-2) + p-toluidine (106-49-0) → 2-(2-amino-5-methylphenyl)-2-(methylthio)acetamide

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; p-toluidine With N-chlorophthalimide In dichloromethane at -20 - -15℃; for 2h; Stage #2: With triethylamine; potassium hydroxide In dichloromethane; water at -8℃;	41%

2-(methylthio)acetamide (22551-24-2) + 2-Amino-5-chlorobenzophenone (719-59-5) → 2-amino-3-benzoyl-5-chloro-α-(methylthio)phenylacetamide (78281-60-4)

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; 5-chloro-2-aminobenzophenone With N-chlorophthalimide In dichloromethane at -20 - -5℃; for 3.5h; Stage #2: With triethylamine In dichloromethane Stage #3: With potassium hydroxide In dichloromethane; water	36.5%

2-(methylthio)acetamide (22551-24-2) + allyl bromide (106-95-6) → 2-Methylsulfanyl-pent-4-enoic acid amide (73876-71-8) + 2-Allyl-2-methylsulfanyl-pent-4-enoic acid amide

Conditions	Yield
With potassium carbonate for 72h;	A 36% B n/a

2-(methylthio)acetamide (22551-24-2) + 4-nitro-aniline (100-01-6) → 2-(2-amino-5-nitrophenyl)-2-(methylthio)acetamide

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; 4-nitro-aniline With N-chlorophthalimide In dichloromethane at -20 - -15℃; for 2h; Stage #2: With triethylamine; potassium hydroxide In dichloromethane; water at -8℃;	22%

2-(methylthio)acetamide (22551-24-2) + 3-nitro-aniline (99-09-2) → 2-(2-amino-4-nitrophenyl)-2-(methylthio)acetamide

Conditions	Yield
Stage #1: 2-(methylthio)acetamide; 3-nitro-aniline With N-chlorophthalimide In dichloromethane at -20 - -15℃; for 2h; Stage #2: With triethylamine; potassium hydroxide In dichloromethane; water at -8℃;	13%

2-(methylthio)acetamide (22551-24-2) → methylthioacetonitrile (35120-10-6)

Conditions	Yield
With phosphorus pentoxide under 20 Torr;

2-(methylthio)acetamide (22551-24-2) + methyl iodide (74-88-4) → carbamoylmethyl-dimethyl sulfonium ; iodide (114253-36-0)

Conditions	Yield
With ethanol

2-(methylthio)acetamide (22551-24-2) → acetamide radical (2597-34-4)

Conditions	Yield
With perchloric acid; dinitrogen monoxide at 15℃; pH=1.2; G-values; Further Variations:; pH-values; pulse radiolysis;

tert-butylhypochlorite (507-40-4) + 2-(methylthio)acetamide (22551-24-2) + 2-Amino-5-chlorobenzophenone (719-59-5) → 2-amino-3-benzoyl-5-chloro-α-(methylthio)phenylacetamide (78281-60-4)

Conditions	Yield
With triethylamine In dichloromethane

tert-butylhypochlorite (507-40-4) + 2-(methylthio)acetamide (22551-24-2) + 2-Amino-5-chlorobenzophenone (719-59-5) → 2-Amino-3-benzoyl-5-chloro-α-(methylthio)pentylacetamide

Conditions	Yield
With triethylamine In dichloromethane

2-(methylthio)acetamide (22551-24-2) + (2-aminophenyl)(phenyl)methanone (2835-77-0) → 2-amino-3-benzoyl-5-chloro-α-(methylthio)phenylacetamide (78281-60-4) + 2-Amino-5-chlorobenzophenone (719-59-5)

Conditions	Yield
Stage #1: (2-aminophenyl)(phenyl)methanone With tert-butylhypochlorite In dichloromethane at -70℃; for 0.166667h; Stage #2: 2-(methylthio)acetamide In tetrahydrofuran; dichloromethane at -70 - 0℃; Stage #3: With triethylamine In tetrahydrofuran; dichloromethane at 0 - 20℃;

2-(methylthio)acetamide (22551-24-2) + (2-aminophenyl)(phenyl)methanone (2835-77-0) → 2-amino-3-benzoyl-5-chloro-α-(methylthio)phenylacetamide (78281-60-4) + 2-amino-3-benzoyl-α-(methylthio)benzeneacetamide (78281-61-5)

Conditions	Yield
Stage #1: (2-aminophenyl)(phenyl)methanone With tert-butylhypochlorite In dichloromethane at -70℃; for 0.75h; Inert atmosphere; Stage #2: 2-(methylthio)acetamide In tetrahydrofuran; dichloromethane at -70 - 15℃; for 1.33333h; Stage #3: With triethylamine In tetrahydrofuran; dichloromethane at -70 - 20℃;

2-(methylthio)acetamide (22551-24-2) + aniline (62-53-3) → 3-methylsulfanyl-1,3-dihydroindol-2-one (40800-64-4)

Conditions	Yield
Gassman Oxindole Synthesis;

2-(methylthio)acetamide (22551-24-2) + p-toluidine (106-49-0) → 5-methyl-3-(methylthio)indolin-2-one (40800-66-6)

Conditions	Yield
Gassman Oxindole Synthesis;

2-(methylthio)acetamide (22551-24-2) + 4-chloro-aniline (106-47-8) → 5-chloro-3-(methylthio)indolin-2-one (61394-53-4)

Conditions	Yield
Gassman Oxindole Synthesis;

Upstream product

• 79-07-2 Chloroacetamide 
• 5188-07-8 sodium thiomethoxide 
• 35928-65-5 (methylthio)acetyl chloride 
• 96-34-4 methyl chloroacetate 
• 4455-13-4 methylthioacetic acid ethyl ester 
• 16630-66-3 methyl 2-(methylthio)acetate 
• 35120-10-6 methylthioacetonitrile 

Downstream Products

• 72730-26-8 2-(2-Methylene-cyclohexyl)-2-methylsulfanyl-acetamide 
• 78281-61-5 2-amino-3-benzoyl-α-(methylthio)benzeneacetamide 
• 40800-70-2 3-(methylthio)-4-nitroindolin-2-one 
• 40800-69-9 3-Methylthio-5-nitro-2-oxindol 
• 61394-53-4 5-Chlor-3-methylthiooxindol 
• 40800-64-4 3-methylsulfanyl-1,3-dihydroindol-2-one 
• 53512-44-0 2-(2-aminophenyl)-2-(methylthio)acetamide 
• 78281-60-4 2-amino-3-benzoyl-5-chloro-α-(methylthio)phenylacetamide 
• 719-59-5 5-chloro-2-aminobenzophenone 
• 35120-10-6 methylthioacetonitrile 

Relevant articles and documents

Preparation method of nepafenac

The invention discloses a preparation method of nepafenac. The method comprises the following steps: 1, synthesizing 2-(methylthio) acetamide; 2, synthesizing alpha-methylthio (2-amino-3-benzoyl) phenylacetamide; 3, synthesizing the nepafenac. Compared with the prior art, the preparation method of the nepafenac has the advantages that raw materials are easy to buy, excessive chlorinated impurities of a side reaction are easily purified, the less energy is consumed by increasing reaction temperature, and the final product does not need to be subjected to octadecyl silane (ODS) reverse phase rapid chromatography.

Enzymatic nitrile hydrolysis catalyzed by nitrilase ZmNIT2 from maize. An unprecedented β-hydroxy functionality enhanced amide formation

To explore the synthetic potential of nitrilase ZmNIT2 from maize, the substrate specificity of this nitrilase was studied with a diverse collection of nitriles. The nitrilase ZmNIT2 showed high activity for all the tested nitriles except benzonitrile, producing both acids and amides. For the hydrolysis of aliphatic, aromatic nitriles, phenylacetonitrile derivatives and dinitriles, carboxylic acids were the major products. Unexpectedly, amides were found to be the major products in nitrilase ZmNIT2-catalyzed hydrolysis of β-hydroxy nitriles. The hydrogen bonding between the hydroxyl group and nitrogen in the enzyme-substrate complex intermediates that disfavors the loss of ammonia and formation of acyl-enzyme intermediate, which was further hydrolyzed to acid, was proposed to be responsible for the unprecedented β-hydroxy functionality assisted high yield of amide formation.

Ene reaction with pummerer reaction intermediates of a-(methylsulfinyl)-acetamides: A novel synthesis of pellitorine

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