16475-90-4

Basic information

• Product Name: METHYL 5-ACETYLSALICYLATE
• Synonyms: Methyl 5-acetylsalicylate, 98.0%(GC);enzoic acid,5-acetyl-2-hydroxy-, methyl ester;Benzoic acid, 5-acetyl-2-hydroxy-, methyl ester;5-ACETYLSALICYLIC ACID METHYL ESTER;5-ACETYL-2-HYDROXYBENZOIC ACID METHYL ESTER;5-ACETYL 2-METHYLSALICYLATE;METHYL 2-HYDROXY-5-ACETYLBENZOATE;METHYL 5-ACETYLSALICYLATE
• CAS NO: 16475-90-4
• Molecular Formula: C₁₀H₁₀O₄
• Molecular Weight: 194.18
• EINECS: 240-532-2
• Product Categories: Aromatic Esters;Esters;Phenyls & Phenyl-Het;Phenyls & Phenyl-Het;C10 to C11;Carbonyl Compounds;Aromatics;Miscellaneous Reagents
• Mol File: 16475-90-4.mol
• Article Data: 13

Chemical Properties

• Melting Point: 62-64 °C(lit.)
• Boiling Point: 167 °C / 15mmHg
• Flash Point: 138 °C
• Appearance: white to light yellow-orange crystalline powder
• Density: 1.0583 (rough estimate)
• Vapor Pressure: 3.1E-05mmHg at 25°C
• Refractive Index: 1.5168 (estimate)
• Storage Temp.: Refrigerator
• Solubility: Soluble in methanol.
• PKA: 7.96±0.18(Predicted)
• BRN: 2643824
• CAS DataBase Reference: METHYL 5-ACETYLSALICYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: METHYL 5-ACETYLSALICYLATE(16475-90-4)
• EPA Substance Registry System: METHYL 5-ACETYLSALICYLATE(16475-90-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 16475-90-4(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow-orange crystalline powder

Uses

Methyl 5-acetylsalicylate is used in food flavorings and preservatives. It is useful in the relief of headache and muscle and joint aches It is also effective in reducing fever, inflammation, and swelling and thus has been used for treatment of rheumatoid arthritis, rheumatic fever, and mild infection.

Preparation

Obtained by heating a solution of 5-acetyl-2-hydroxybenzoic acid and sulfuric acid in methanol for 24 h (82%).

InChI:InChI=1/C10H10O4/c1-6(11)7-3-4-9(12)8(5-7)10(13)14-2/h3-5,12H,1-2H3

Synthetic route

methanol (67-56-1) + 5-acetylsalicylic acid (13110-96-8) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With sulfuric acid for 24h; Heating;	96%
With thionyl chloride at 65℃; for 24h; Inert atmosphere;

2-acetoxy-5-acetyl-benzoic acid methyl ester → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With ytterbium(III) triflate In isopropyl alcohol for 20h; Deacetylation; Heating;	95%

acetic anhydride (108-24-7) + methyl salicylate (119-36-8) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With aluminium trichloride In dichloromethane for 3h; Friedel-Crafts reaction;	93%
With aluminum (III) chloride In dichloromethane at -5 - 10℃; for 20h; Inert atmosphere;	83.3%
With aluminum (III) chloride In nitrobenzene at 120 - 180℃; for 0.133333h; Temperature; Time; Pressure; Friedel-Crafts Acylation; Microwave irradiation;	100 %Chromat.

5-acetyl-2-(3-methyl-but-2-enyloxy)-benzoic acid methyl ester → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With ytterbium(III) triflate In nitromethane for 1h; Ambient temperature;	74%

3-acetyl-3',3'-dicyano-5-methoxycarbonylxanthyrone (72554-64-4) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + 4-Hydroxyacetophenone (99-93-4)

Conditions	Yield
With water for 3h; Product distribution; Heating; other xanthyrones;	A 41% B 16%

3-acetyl-3'-cyano-3',5-bismethoxycarbonylxanthyrone (72554-63-3) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + 4-Hydroxyacetophenone (99-93-4)

Conditions	Yield
With water for 3h; Product distribution; Heating; other xanthyrones;	A 41% B 16%

acetic acid (64-19-7) + methyl salicylate (119-36-8) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With PPA at 80℃; for 2h;	20%

methyl acetylsalicylate (580-02-9) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With aluminium trichloride; nitrobenzene

2-methoxybenzoic acid methyl ester (606-45-1) + acetyl chloride (75-36-5) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With carbon disulfide; aluminium trichloride

3'-acetyl-3,5,5'-trismethoxycarbonylglaucyrone (74823-33-9, 78075-03-3) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With water for 3h; Product distribution; Heating; other glaucyrones;

acetyl chloride (75-36-5) + methyl salicylate (119-36-8) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With aluminium trichloride In 1,1,2,2-tetrachloroethylene
In 1,1,2,2-tetrachloroethylene

3-carbomethoxy-4-hydroxy-α-bromoacetophenone (36256-45-8) → 2-Hydroxy-5-((R)-1-hydroxy-ethyl)-benzoic acid methyl ester + methyl 5-(2-bromo-1-hydroxyethyl)-2-hydroxybenzoate + (R)-methyl 5-(2-bromo-1-hydroxyethyl)-2-hydroxybenzoate + estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
With sodium formate; cetyltrimethylammonim bromide; sodium dodecyl-sulfate; (R,R)-TsDPEN; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer In water at 28℃; for 5h; Title compound not separated from byproducts;

aspirin (50-78-2) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / AlCl3 / nitrobenzene / 1 h 2: 96 percent / H2SO4 / 24 h / Heating View Scheme

1,1,2,2-tetrachloroethylene (127-18-4) + acetyl chloride (75-36-5) + methyl salicylate (119-36-8) → estere metilico dell'acido 5-acetilsalicilico (16475-90-4)

Conditions	Yield
aluminium chloride	40 g (43%)

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + benzyl bromide (100-39-0) → 5-acetyl-2-benzyloxybenzoic acid methyl ester (27475-09-8)

Conditions	Yield
With potassium carbonate In acetonitrile at 85℃; for 9h;	100%
With potassium carbonate In acetonitrile at 75℃; for 16h;	100%
With potassium carbonate In acetonitrile for 24h;	96.6%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + ethylene glycol (107-21-1) → 2-[4-hydroxy-3-(methoxycarbonyl)phenyl]-2-methyl-1,3-dioxolane (467429-12-5)

Conditions	Yield
With Triisopropoxymethan; cerium triflate In hexane at 25℃; for 2h;	99%
With toluene-4-sulfonic acid In toluene for 16h; Heating;	91%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) → 1-(4'-hydroxy-3'-methoxycarbonylphenyl)ethanol (66654-06-6)

Conditions	Yield
With CdS(x)Se(1-x) x:0-1;; cesium acetate; para-thiocresol In toluene for 10h; Sealed tube; Inert atmosphere; Irradiation;	99%
With sodium tetrahydroborate; boric acid for 1.5h;	60 % Chromat.

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + benzyl chloride (100-44-7) → 5-acetyl-2-benzyloxybenzoic acid methyl ester (27475-09-8)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 50 - 65℃; for 2h;	98.5%
With sodium carbonate In N,N-dimethyl-formamide at 110 - 115℃; for 2h;	84.7%
With sodium In ethanol for 30h; Heating;	55%
With sodium carbonate; sodium iodide In acetonitrile for 16h; Heating / reflux;	55%
With potassium carbonate

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + trimethyleneglycol (504-63-2) → 2-[4-hydroxy-3-(methoxycarbonyl)phenyl]-2-methyl-1,3-dioxane (1171247-80-5)

Conditions	Yield
With Triisopropoxymethan; cerium triflate In hexane at 25℃; for 2h;	98%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + heptyl halide → methyl 5-acetyl-2-heptyloxybenzoate (1373427-92-9)

Conditions	Yield
Stage #1: estere metilico dell'acido 5-acetilsalicilico With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: heptyl halide In N,N-dimethyl-formamide at 50℃; for 5h;	97.6%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + methyl halide → 5-acetyl-2-methoxybenzoic acid methyl ester (39971-36-3)

Conditions	Yield
Stage #1: estere metilico dell'acido 5-acetilsalicilico With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: methyl halide In N,N-dimethyl-formamide at 50℃; for 5h;	97%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + methyl iodide (74-88-4) → 5-acetyl-2-methoxybenzoic acid methyl ester (39971-36-3)

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide	96.5%
With sodium carbonate In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 3h;	96.5%
With sodium carbonate In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 3h;	96.5%

trifluoromethylsulfonic anhydride (358-23-6) + estere metilico dell'acido 5-acetilsalicilico (16475-90-4) → 5-acetyl-2-(trifluoro-methyl-sulfonyloxy)-benzoic acid,methyl ester (343338-97-6)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h;	96%
With pyridine In dichloromethane at 0℃; for 0.833333h;	96%
With triethylamine at -40℃;
With 2,6-dimethylpyridine; dmap In dichloromethane at -30 - 20℃; for 3h;

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + hexyl halide → methyl 5-acetyl-2-hexyloxybenzoate (1373427-91-8)

Conditions	Yield
Stage #1: estere metilico dell'acido 5-acetilsalicilico With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: hexyl halide In N,N-dimethyl-formamide at 50℃; for 5h;	95.9%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + octyl halide → methyl 5-acetyl-2-octyloxybenzoate (1373427-93-0)

Conditions	Yield
Stage #1: estere metilico dell'acido 5-acetilsalicilico With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: octyl halide In N,N-dimethyl-formamide at 50℃; for 5h;	93.5%

estere metilico dell'acido 5-acetilsalicilico (16475-90-4) + butyl halide → methyl 5-acetyl-2-butoxybenzoate

Conditions	Yield
Stage #1: estere metilico dell'acido 5-acetilsalicilico With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: butyl halide In N,N-dimethyl-formamide at 50℃; for 5h;	92%

Upstream product

• 580-02-9 methyl acetylsalicylate 
• 72554-64-4 3-acetyl-3',3'-dicyano-5-methoxycarbonylxanthyrone 
• 108-24-7 acetic anhydride 
• 119-36-8 methyl salicylate 
• 127-18-4 1,1,2,2-tetrachloroethylene 
• 75-36-5 acetyl chloride 
• 50-78-2 aspirin 
• 36256-45-8 3-carbomethoxy-4-hydroxy-α-bromoacetophenone 
• 64-19-7 acetic acid 
• 67-56-1 methanol 
• 13110-96-8 5-acetylsalicylic acid 
• 74823-33-9 3'-acetyl-3,5,5'-trismethoxycarbonylglaucyrone 
• 72554-63-3 3-acetyl-3'-cyano-3',5-bismethoxycarbonylxanthyrone 
• 606-45-1 2-methoxybenzoic acid methyl ester 

Downstream Products

• 16475-91-5 5-[1-(2,4-dinitro-phenylhydrazono)-ethyl]-2-hydroxy-benzoic acid methyl ester 
• 72492-12-7 5-acetylspiro[benzo[b]furan-2(3H),1'-cyclopropane]-3-one 
• 94243-46-6 1H,3H-8-acetyl-4,5-dihydronaphto<1,2-c:4,3-b'>difuran-1-one 
• 72492-92-3 5-Acetyl-2-(2-oxo-tetrahydro-furan-3-yloxy)-benzoic acid 
• 80901-29-7 methyl 5-acetyl-2-<(tetrahydro-2-oxo-3-furanyl)oxyl>benzoate 
• 27475-09-8 5-acetyl-2-benzyloxybenzoic acid methyl ester 
• 76310-74-2 5-acetyl-2-ethoxybenzoic acid methyl ester 
• 260371-57-1 methyl 5-acetyl-2-(cyclohexylmethoxy)benzoate 
• 343338-97-6 5-acetyl-2-(trifluoro-methyl-sulfonyloxy)-benzoic acid,methyl ester 
• 36039-22-2 2-acetyl-9H-xanthen-9-one 
• 946570-23-6 5-acetyl-2-(3-bromo-propoxy)-benzoic acid methyl ester 
• 260371-61-7 (R)-methyl 2-(cyclohexylmethoxy)-5-(1-hydroxyethyl)benzoate 
• 260371-51-5 (R)-2-(cyclohexylmethoxy)-5-(1-hydroxyethyl)benzamide 
• 475200-38-5 (S)-methyl 2-(cyclohexylmethoxy)-5-(1-hydroxyethyl)benzoate 

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