63521-90-4

Basic information

• Product Name: Acetic acid, (methylthio)-, anhydride
• Synonyms: (methylthio)acetic anhydride;2-(methylthio)acetic anhydride;methylsulfanyl-acetic acid-anhydride;Acetic acid,(methylthio)-,anhydride;Methylmercapto-essigsaeure-anhydrid
• CAS NO: 63521-90-4
• Molecular Formula: C6H10O3S2
• Molecular Weight: 194.276
• Mol File: 63521-90-4.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: Acetic acid, (methylthio)-, anhydride(CAS DataBase Reference)
• NIST Chemistry Reference: Acetic acid, (methylthio)-, anhydride(63521-90-4)
• EPA Substance Registry System: Acetic acid, (methylthio)-, anhydride(63521-90-4)

Safety Data

• Hazardous Substances Data: 63521-90-4(Hazardous Substances Data)

Usage

General Description

Acetic acid, (methylthio)-, anhydride is a chemical compound commonly used as a reagent in organic synthesis. It is a colorless to pale yellow liquid with a pungent odor, and is highly reactive and flammable. Acetic acid, (methylthio)-, anhydride is commonly used in the pharmaceutical and agrochemical industries as a building block for the synthesis of various organic compounds. It is also used as a solvent for cellulose acetate and cellulose nitrate, and as an acetylating agent in the production of dyes, perfumes, and flavorings. Additionally, it is used in the preparation of acetic anhydride, which is an important industrial chemical used in the production of cellulose acetate and aspirin. However, it is important to handle this compound with care as it is a corrosive and irritant to the skin, eyes, and respiratory system.

Synthetic route

methylsulfanyl-acetic acid (2444-37-3) → α-(methylthio)acetic acid anhydride (63521-90-4)

Conditions	Yield
With acetic anhydride for 4h; Dehydration; acylation; Heating;	84%
With dicyclohexyl-carbodiimide In diethyl ether for 24h; Inert atmosphere;

α-(methylthio)acetic acid anhydride (63521-90-4) + 11β,21-dihydroxy-6α-methyl-17α-(methylthio)acetoxy-1,4-pregnadiene-3,20-dione (89472-50-4) → 11β-hydroxy-6α-methyl-17α-21-bis<(methylthio)acetoxy>-1,4-pregnadiene-3,20-dione (89472-53-7)

Conditions	Yield
With triethylamine In dichloromethane for 5h; Ambient temperature;	77%

(OC-6-43)-amminedichloro(cyclohexanamine)dihydroxyplatinum(IV) (124721-03-5, 1313200-52-0, 146924-11-0) + α-(methylthio)acetic acid anhydride (63521-90-4) → (OC-6-43)-amminedichloro(cyclohexanamine)bis((methylthio)acetato-O)platinum(IV) (160953-33-3)

Conditions	Yield
In diethyl ether; dichloromethane excess of anhydride, stirring in CH2Cl2/Et2O=4:1 for 24 h; pptn. on Et2O addn. (stirring), collection, drying (vac.); elem. anal.;	73%

α-(methylthio)acetic acid anhydride (63521-90-4) + (1-Phenethyl-piperidin-4-yl)-phenyl-amine (21409-26-7) → N-(1-(2-phenylethyl)-4-piperidinyl)-2-(methylthio)acetanilide (130819-93-1)

Conditions	Yield
In benzene Heating;	70%

α-(methylthio)acetic acid anhydride (63521-90-4) + 3-<2-(3,4-Dimethoxyphenyl)ethylamino>-2-cyclohexen-1-on (27032-09-3) → N-<2-(3,4-dimethoxyphenyl)ethyl>-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide (107199-45-1)

Conditions	Yield
With pyridine at 70 - 80℃; for 1h;	60%

α-(methylthio)acetic acid anhydride (63521-90-4) + 3-<3-(3,4-dimethoxyphenyl)propylamino>-2-cyclohexen-1-one (107199-42-8) → N-<3-(3,4-dimethoxyphenyl)propyl>-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide (107199-46-2)

Conditions	Yield
With pyridine at 70 - 80℃; for 1h;	57%

α-(methylthio)acetic acid anhydride (63521-90-4) + 5,5-dimethyl-3-(phenylamino)cyclohex-2-en-1-one (18940-21-1) → N-(5,5-dimethyl-3-oxo-1-cyclohexen-1-yl)-N-phenyl-α-(methylthio)acetamide (107199-43-9)

Conditions	Yield
With pyridine at 160℃; for 1h;	54%

α-(methylthio)acetic acid anhydride (63521-90-4) + 7-amino-4-chloro-3-propoxyisocoumarin → N-(4-Chloro-1-oxo-3-propoxy-1H-isochromen-7-yl)-2-methylsulfanyl-acetamide

Conditions	Yield
In tetrahydrofuran Ambient temperature;	54%

α-(methylthio)acetic acid anhydride (63521-90-4) + acetic acid 5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester (171292-10-7) → acetic acid 1-(2-(methylsulfanyl)acetyl)-5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester

Conditions	Yield
With pyridine; dmap at 20℃; Acylation;	53%

α-(methylthio)acetic acid anhydride (63521-90-4) + N-cyclohexylidene-2-(3,4-dimethoxyphenyl)ethylamine (82988-55-4) → N-(cyclohex-1-enyl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide (97185-46-1)

Conditions	Yield
In pyridine	46%
In pyridine
With pyridine In benzene 0 deg C to room temp. overnight; Yield given;

α-(methylthio)acetic acid anhydride (63521-90-4) + (Z)-ethyl 2-(pyrrolidin-2-ylidene)acetate (35150-22-2) → ethyl 4-methylthio-3-oxo-2-(pyrrolidinylidene)butanoate + ethyl <1-(methylthio)acetyl-2-pyrrolidinylidene>acetate

Conditions	Yield
In pyridine at 120℃; for 1h; Heating;	A 6% B 43%

α-(methylthio)acetic acid anhydride (63521-90-4) + 11β,21-dihydroxy-17α-methoxyacetoxy-6α-methyl-1,4-pregnadiene-3,20-dione (86282-02-2) → 11β-hydroxy-17α-methoxyacetoxy-6α-methyl-21-(methylthio)acetoxy-1,4-pregnadiene-3,20-dione (89472-48-0)

Conditions	Yield
With triethylamine In dichloromethane for 5h; Ambient temperature;	31%

α-(methylthio)acetic acid anhydride (63521-90-4) + N-benzyl-3-amino-2-cyclohexen-1-one (41609-04-5) → N-benzyl-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide (106344-93-8)

Conditions	Yield
With pyridine at 160℃; for 1h;	23%

α-(methylthio)acetic acid anhydride (63521-90-4) + testosterone (58-22-0) → methylsulfanyl-acetic acid-(3-oxo-androst-4-en-17β-yl ester)

cyclohexanedione monoethylene ketal (4746-97-8) + α-(methylthio)acetic acid anhydride (63521-90-4) + 2-(3,4-dimethoxyphenyl)-ethylamine (120-20-7) → N-(1,4-dioxaspiro<4,5>dec-7-en-8-yl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide (123190-07-8)

Conditions	Yield
With pyridine 1) benzene, reflux, 5 h, 2) benzene, r.t., overnight; Yield given. Multistep reaction;

α-(methylthio)acetic acid anhydride (63521-90-4) + N-cyclohexylidenemethylamine (6407-35-8) → N-Cyclohex-1-enyl-N-methyl-2-methylsulfanyl-acetamide (82988-52-1)

Conditions	Yield
In pyridine

α-(methylthio)acetic acid anhydride (63521-90-4) + (2-Cyclohex-1-enyl-ethyl)-cyclohexylidene-amine (144809-23-4) → N-(cyclohex-1-enyl)-N-<2-(cyclohex-1-enyl)ethyl>-α-(methylthio)acetamide (97185-47-2)

Conditions	Yield
With pyridine In benzene 0 deg C to room temp. overnight; Yield given;

α-(methylthio)acetic acid anhydride (63521-90-4) + (4-Benzyloxy-cyclohexylidene)-[2-(3,4-dimethoxy-phenyl)-ethyl]-amine → N-(4-benzyloxycyclohex-1-enyl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide (97185-49-4)

Conditions	Yield
With pyridine In benzene 0 deg C to room temp. overnight; Yield given;

3-(3,4-dimethoxyphenyl)propylamine (14773-42-3) + α-(methylthio)acetic acid anhydride (63521-90-4) + cyclohexanone (108-94-1) → N-(cyclohex-1-enyl)-N-<3-(3,4-dimethoxyphenyl)propyl>-α-(methylthio)-acetamide (129881-32-9)

Conditions	Yield
With pyridine 1) benzene, reflux, 2) benzene, r.t., overnight; Yield given. Multistep reaction;

α-(methylthio)acetic acid anhydride (63521-90-4) + [2-(3,4-Dimethoxy-phenyl)-ethyl]-(1,4-dioxa-spiro[4.5]dec-8-ylidene)-amine (129881-26-1) → N-(1,4-dioxaspiro<4,5>dec-7-en-8-yl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide (123190-07-8)

Conditions	Yield
In pyridine; benzene Yield given;

α-(methylthio)acetic acid anhydride (63521-90-4) + 5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester of 7-[(6-deoxy-5-C-methyl-4-O-(tetrahydro-2H-pyran-2-yl)-alpha-L-lyxo-hexopyranosyl)oxy]-4-hydroxy-8-methyl-2H-1-benzopyran-2-one (200726-93-8) → 5-methyl-1H-pyrrole-2-carboxylic acid-3'-ester of 7[(6-deoxy-5-C-methyl-4-O-methyl-2-O-(tetrahydro-2H-pyran-2-yl)-alpha-L-lyxo-hexopyranosyl)oxy]-4-hydroxy-8-methyl-3-[(methylthio)acetyl]-2H-1-benzopyran-2-one (200726-94-9)

Conditions	Yield
With dmap In dichloromethane Ambient temperature;

α-(methylthio)acetic acid anhydride (63521-90-4) + acetic acid 5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester (171292-10-7) → 5-Hydroxy-1-(2-methylsulfanyl-acetyl)-1,5-dihydro-pyrrol-2-one + acetic acid 1-(2-(methylsulfanyl)acetyl)-5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester

Conditions	Yield
Stage #1: α-(methylthio)acetic acid anhydride; acetic acid 5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester With pyridine; dmap at 20℃; Acylation; Stage #2: With lipase B of Candida antarctica In hexane; tert-butyl alcohol at 20℃; for 23h; Hydrolysis; transesterification;

propan-1-ol (71-23-8) + α-(methylthio)acetic acid anhydride (63521-90-4) → propyl 2-(methylsulfanyl)acetate (103222-13-5)

Conditions	Yield
With toluene-4-sulfonic acid In diethyl ether for 120h;

ethanol-d6 (1516-08-1) + α-(methylthio)acetic acid anhydride (63521-90-4) → [D5]ethyl 2-(methylsulfanyl)acetate (1351524-26-9)

Conditions	Yield
With toluene-4-sulfonic acid In diethyl ether for 3h; Inert atmosphere;

α-(methylthio)acetic acid anhydride (63521-90-4) + butan-1-ol (71-36-3) → butyl 2-(methylsulfanyl)acetate (67746-25-2)

Conditions	Yield
With toluene-4-sulfonic acid In diethyl ether for 120h;

Upstream product

• 2444-37-3 methylsulfanyl-acetic acid 

Downstream Products

• 130819-93-1 N-(1-(2-phenylethyl)-4-piperidinyl)-2-(methylthio)acetanilide 
• 129881-32-9 N-(cyclohex-1-enyl)-N-<3-(3,4-dimethoxyphenyl)propyl>-α-(methylthio)-acetamide 
• 107199-46-2 N-<3-(3,4-dimethoxyphenyl)propyl>-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide 
• 97185-49-4 N-(4-benzyloxycyclohex-1-enyl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide 
• 97185-47-2 N-(cyclohex-1-enyl)-N-<2-(cyclohex-1-enyl)ethyl>-α-(methylthio)acetamide 
• 97185-46-1 N-(cyclohex-1-enyl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide 
• 106344-93-8 N-benzyl-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide 
• 107199-45-1 N-<2-(3,4-dimethoxyphenyl)ethyl>-N-(3-oxo-1-cyclohexen-1-yl)-α-(methylthio)acetamide 
• 107199-43-9 N-(5,5-dimethyl-3-oxo-1-cyclohexen-1-yl)-N-phenyl-α-(methylthio)acetamide 
• 82988-52-1 N-Cyclohex-1-enyl-N-methyl-2-methylsulfanyl-acetamide 
• 123190-07-8 N-(1,4-dioxaspiro<4,5>dec-7-en-8-yl)-N-<2-(3,4-dimethoxyphenyl)ethyl>-α-(methylthio)acetamide 
• 67746-25-2 butyl 2-(methylsulfanyl)acetate 
• 103222-13-5 propyl 2-(methylthio)-acetate 
• 160953-33-3 (OC-6-43)-amminedichloro(cyclohexanamine)bis((methylthio)acetato-O)platinum(IV) 

Relevant articles and documents

(Methylsulfanyl)alkanoate ester biosynthesis in Actinidia chinensis kiwifruit and changes during cold storage

Four 3-(methylsulfanyl)propionate esters, ethyl 3-(methylsulfanyl)prop-2-enoate, two 2-(methylsulfanyl)acetate esters and their possible precursors 2-(methylsulfanyl)ethanol, 3-(methylsulfanyl)propanol and 3-(methylsulfanyl)propanal were quantified from the headspace of Actinidia chinensis 'Hort 16A' kiwifruit pulp by GC-MS-TOF analysis. The majority of these compounds were specific for eating-ripe fruit and their levels increased in parallel with the climacteric rise in ethylene, accumulating towards the very soft end of the eating firmness. No ethylene production could be observed after long-term storage (4-6 months) at 1.5 °C and the levels of all methylsulfanyl-volatiles, except methional, declined by 98-100% during that period. This depletion of (methylsulfanyl)alkanoate-esters after prolonged cold storage points towards little flavour impact of these compounds on commercial 'Hort 16A' kiwifruits. However, ethyl 3-(methylsulfanyl)propionate is suggested to be odour active in ripe 'Hort 16A' fruit that has not been stored. Gene expression measured by q-RT PCR of six ripening-specific alcohol acyltransferase (AAT) expressed sequence tags and (methylsulfanyl)alkanoate-ester production of cell-free extracts were also significantly decreased after prolonged cold storage. However, (methylsulfanyl)alkanoate-ester synthesis of cell-free extracts and AAT gene transcript levels could be recovered by ethylene treatment after five months at 1.5 °C indicating that the biosynthesis of (methylsulfanyl)alkanoate-esters in 'Hort 16A' kiwifruit is likely to depend on ethylene-regulated AAT-gene expression. That the composition but not the concentration of (methylsulfanyl)alkanoate-esters in fresh fruit could be restored after ethylene treatment suggests that substrate availability might also have an impact on the final levels of these volatiles.