16188-55-9

Basic information

• Product Name: 4-Methylthiophenylacetic acid
• Synonyms: 4-(METHYLTHIO)PHENYLACETIC ACID;RARECHEM AL BO 0923;(4-METHYLSULFANYL-PHENYL)-ACETIC ACID;2-(4-(methylthio)phenyl)acetic acid;4-(Methylthio)benzeneacetic acid;4-(Methylthio)phenylacetic acid,98%;4-Methylthiophenylac;2-[4-(Methylsulfanyl)phenyl]acetic acid
• CAS NO: 16188-55-9
• Molecular Formula: C₉H₁₀O₂S
• Molecular Weight: 182.24
• Product Categories: C9;Carbonyl Compounds;Carboxylic Acids;Building Blocks;Carbonyl Compounds;Carboxylic Acids;Chemical Synthesis;Organic Building Blocks
• Mol File: 16188-55-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 97-98 °C(lit.)
• Boiling Point: 274.2°Cat760mmHg
• Flash Point: 125.4°C
• Appearance: /
• Density: 1.16g/cm³
• Vapor Pressure: 0.00475mmHg at 25°C
• Refractive Index: 1.562
• Storage Temp.: 2-8°C
• PKA: 4.34±0.10(Predicted)
• CAS DataBase Reference: 4-Methylthiophenylacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methylthiophenylacetic acid(16188-55-9)
• EPA Substance Registry System: 4-Methylthiophenylacetic acid(16188-55-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 16188-55-9(Hazardous Substances Data)

Usage

Chemical Properties

Cream crystalline powder

General Description

TiO2 photocatalytic one-electron oxidation of 4-(methylthio)phenylacetic acid has been reported by time-resolved diffuse reflectance spectroscopy.

InChI:InChI=1/C9H10OS/c1-7-2-4-8(5-3-7)6-9(10)11/h2-5H,6H2,1H3,(H,10,11)

Synthetic route

2-(4-(methylthio)phenyl)-2-oxoacetic acid (53066-99-2) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)-2-oxoacetic acid With sodium iodide In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With chloro-trimethyl-silane In dichloromethane at 20℃; for 2h; Inert atmosphere; regioselective reaction;	91%
Stage #1: 2-(4-(methylthio)phenyl)-2-oxoacetic acid With sodium hydroxide; hydrazine In water at 75℃; for 120h; Wolff-Kishner Reduction; Heating / reflux; Stage #2: With hydrogenchloride In water pH=1.5;

2-[4-(methylsulfanyl)phenyl]acetonitrile (38746-92-8) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
Stage #1: 2-[4-(methylsulfanyl)phenyl]acetonitrile With potassium hydroxide; water for 8h; Reflux; Stage #2: With hydrogenchloride; water at 20℃;	82%
With sodium hydroxide In ethylene glycol; ethyl acetate
With sulfuric acid; water for 1h; Reflux;

4-chlorophenylacetic Acid (1878-66-6) + sodium thiomethoxide (5188-07-8) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
With copper(I) bromide In N,N-dimethyl-formamide at 130℃; for 24h; Inert atmosphere;	79.3%

sodium thiomethoxide (5188-07-8) + 2-(4-bromophenyl)-acetic acid (1878-68-8) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
With copper(I) bromide In N,N-dimethyl-formamide at 130℃; Inert atmosphere;	76.1%

4-(Methylthio)acetophenone (1778-09-2) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
With morpholine; sulfur for 20h; Heating;	53%
Stage #1: 4-(Methylthio)acetophenone With morpholine; sulfur at 130℃; for 48h; Willgerodt reaction; Stage #2: With sodium hydroxide; water at 130℃; for 24h; Stage #3: With hydrogenchloride In water

(4-iodophenyl)acetic acid (1798-06-7) + cuprous methylmercaptide (4856-13-7) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
With quinoline at 200℃;

morpholine (110-91-8) + 4-(Methylthio)acetophenone (1778-09-2) + sulfur → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
Erhitzen des Reaktionsgemisches mit wss. HCl;

1-<4-methylsulfanyl-phenyl>-ethanone-(1) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
With morpholine; sulfur Erhitzen des Reaktionsgemisches mit wss. Salzsaeure;

methyl-phenyl-thioether (100-68-5) → 2-(4-(methylthio)phenyl)acetic acid (16188-55-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / AlCl3 / CHCl3 / 0 - 5 °C 2: 53 percent / S8, Morpholin / 20 h / Heating View Scheme

methanol (67-56-1) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → (4-methylsulfanyl-phenyl)-acetic acid methyl ester (70290-37-8)

Conditions	Yield
With sulfuric acid at 50℃; for 16h;	100%
With thionyl chloride at 0 - 20℃; for 48h;	100%
With sulfuric acid for 19h; Heating / reflux;	98%
With sulfuric acid In benzene at 0 - 80℃; for 16h; Inert atmosphere;	83.1%
With hydrogenchloride

2-(phenyl)pyrrolidine (1006-64-0) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → 2-(4-(methylthio)phenyl)-1-(2-phenylpyrrolidin-1-yl)ethan-1-one

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 14h; Inert atmosphere;	100%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → (4-methylsulfanyl-phenyl)-acetic acid methyl ester (70290-37-8)

Conditions	Yield
With sulfuric acid In methanol	98%
With sulfuric acid In methanol	98%
With sulfuric acid In methanol	92%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + methyl iodide (74-88-4) → (4-methylsulfanyl-phenyl)-acetic acid methyl ester (70290-37-8)

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With sodium hydrogencarbonate In N,N-dimethyl-formamide for 0.25h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 24h;	97%
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With sodium hydrogencarbonate In N,N-dimethyl-formamide for 0.25h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 24h;	97%

ethanol (64-17-5) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → ethyl 4-methylthiophenylacetate (14062-27-2)

Conditions	Yield
With sulfuric acid for 8h; Heating;	96%
With sulfuric acid for 8h; Heating / reflux;	96%
With sulfuric acid	79%

N-hydroxyphthalimide (524-38-9) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → 1,3-dioxoisoindolin-2-yl 2-(4-(methylthio)phenyl)acetate

Conditions	Yield
With dmap; diisopropyl-carbodiimide In tetrahydrofuran at 20℃; Inert atmosphere;	96%
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 0.5h;	72%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → 2-[4-(methylmercapto)phenyl]-1-ethanol (81227-89-6)

Conditions	Yield
With borane In tetrahydrofuran at 0℃; for 5h;	94%
With sodium hydroxide In tetrahydrofuran; methanol; diethyl ether	84.4%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) + 1,1'-carbonyldiimidazole (530-62-1) → N-methoxy-N-methyl-4-(methylthio)benzeneacetamide

Conditions	Yield
In dichloromethane	93%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → N-methoxy-N-methyl-4-(methylthio)benzeneacetamide

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With 1,1'-Carbonyl-di-(1,2,4-triazole) In dichloromethane at 20℃; for 0.333333h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane at 20℃;	93%

aqueous sodium chloride + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + (1R,2R)-pseudoephedrine (321-97-1) + pivaloyl chloride (3282-30-2) → N-[2(R)-hydroxy-1(R)-methyl-2(R)-phenyl-ethyl]-N-methyl-2-(4-methylsulfanyl-phenyl)-acetamide (436141-37-6)

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water; toluene	92.6%

4-amino-3-(4-methylthiobenzyl)-5-mercapto-1,2,4-triazole + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → C19H18N4S3 (1144110-74-6)

Conditions	Yield
With trichlorophosphate for 8h; Heating;	91%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + monomethyl auristatin E → C48H75N5O8S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dimethyl sulfoxide for 1h;	90%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → (4-methylthiophenyl)acetic acid hydrazide (1257393-74-0)

Conditions	Yield
With hydrazine hydrate In ethanol for 8h; Reflux;	86%
Multi-step reaction with 2 steps 1: Acidic conditions 2: hydrazine hydrate / ethanol / 8 h / Reflux View Scheme

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + dibenzylamine (103-49-1) → N,N-dibenzyl-2-(4-(methylthio)phenyl)acetamide

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 14h; Inert atmosphere;	86%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 2-(pyrimidin-5-yl)phenol → 2-(pyrimidin-5-yl)phenyl 2-(4-(methylthio)phenyl)acetate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 12h; Sealed tube;	86%

di-tert-butyl-diazodicarboxylate (870-50-8) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → di-tert-butyl 1-(4-(methylthio)benzyl)hydrazine-1,2-dicarboxylate

Conditions	Yield
With iron(III) sulfate; bis[(2-pyridyl)methyl]amine In 1,2-dichloro-ethane at 20℃; for 24h; Inert atmosphere; Sealed tube; Irradiation;	86%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 2-bromo-1-(4-fluorophenyl)-1-butanone → 5-ethyl-4-(4-fluoro-phenyl)-5-hydroxy-3-(4-methylsulfanyl-phenyl)-5H-furan-2-one

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With potassium hydroxide In water; N,N-dimethyl-formamide at 25 - 30℃; Stage #2: 2-bromo-1-(4-fluorophenyl)-1-butanone In water; N,N-dimethyl-formamide at 25 - 30℃;	83%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → 2-(4-(methylsulfinyl)phenyl)acetic acid (118362-28-0)

Conditions	Yield
With sodium periodate In methanol; water at 0 - 20℃; for 2h;	82%
With perchloric acid; dihydrogen peroxide In ethanol; water at 25℃; Rate constant;
With sodium periodate In ethanol at 25℃; Rate constant;
With 3-chloro-benzenecarboperoxoic acid at 25℃; Rate constant; also in the presence α-cyclodextrin; pH 1.6;

Benzylidenemalononitrile (2700-22-3) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → 2-(2-(4-(methylthio)phenyl)-1-phenylethyl)malononitrile

Conditions	Yield
With iron(III) sulfate; bis[(2-pyridyl)methyl]amine In 1,2-dichloro-ethane at 20℃; for 12h; Inert atmosphere; Sealed tube; Irradiation;	81%

2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (2564-83-2, 45842-10-2) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + diazomethyl-trimethyl-silane (18107-18-1) → methyl 2-(4-(methylthio)phenyl)-2-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)acetate

Conditions

Yield

Stage #1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 2-(4-(methylthio)phenyl)acetic acid With N4,N4,N7,N7-tetramethyl-1,10-phenanthroline-4,7-diamine; iron(II) acetate In tetrahydrofuran at 60℃; for 24h; Molecular sieve; Inert atmosphere; Schlenk technique; Stage #2: diazomethyl-trimethyl-silane With methanol In tetrahydrofuran; hexane for 1h; Inert atmosphere; Stage #3: With acetic acid In tetrahydrofuran; hexane; ethyl acetate chemoselective reaction;

81%

phthalic anhydride (85-44-9) + 2-(4-(methylthio)phenyl)acetic acid (16188-55-9) → (Z)-3-(4-methylsulfanylbenzylidene)isobenzofuran-1-one

Conditions	Yield
With sodium acetate In benzene at 230 - 240℃;	80%
With sodium acetate Heating;	65%
With sodium acetate Heating;
With sodium acetate In toluene at 210 - 245℃; Inert atmosphere;
With sodium acetate In toluene at 210 - 245℃; Dean-Stark; Inert atmosphere;

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 2-bromo-1-(4-methoxyphenyl)butan-1-one (881-43-6) → 5-ethyl-4-hydroxy-4-(4-methoxy-phenyl)-3-(4-methylsulfanyl-phenyl)-dihydro-furan-2-one + 5-ethyl-5-hydroxy-4-(4-methoxy-phenyl)-3-(4-methylsulfanyl-phenyl)-5H-furan-2-one

Conditions	Yield
With potassium hydroxide In water; N,N-dimethyl-formamide at 25℃; for 6h; Product distribution; Further Variations:; Temperatures; Reagents; substrate/reagent ratios, inert/O2 atmosphere;	A 16% B 79%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 2-bromo-1-phenylbutan-1-one (877-35-0) → 5-ethyl-5-hydroxy-3-(4-methylsulfanylphenyl)-4-phenyl-2,5-dihydro-2-furanone (503174-32-1)

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With potassium hydroxide In water; N,N-dimethyl-formamide at 25 - 30℃; Stage #2: 2-bromo-1-phenylbutan-1-one In water; N,N-dimethyl-formamide at 25 - 30℃;	77%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 5-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-5-amino-2,2-dimethyl-1,3-dioxane (1400872-56-1) → 5-[O-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)oxymethyl]-5-{N-[(4-methylthiobenzyl)carboximido]}-2,2-dimethyl-1,3-dioxane (1400872-58-3)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 24h; Inert atmosphere;	76%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + 2,4-Dihydroxybenzaldehyde (95-01-2) → 3-(4-methylthiophenyl)-7-hydroxycoumarin

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid; 2,4-Dihydroxybenzaldehyde With sodium acetate; acetic anhydride at 160℃; for 10h; Inert atmosphere; Stage #2: With lithium hydroxide In tetrahydrofuran; methanol; water for 3h;	74.2%

2-(4-(methylthio)phenyl)acetic acid (16188-55-9) + (1R,2R)-pseudoephedrine (321-97-1) + pivaloyl chloride (3282-30-2) → N-[2(R)-hydroxy-1(R)-methyl-2(R)-phenyl-ethyl]-N-methyl-2-(4-methylsulfanyl-phenyl)-acetamide (436141-37-6)

Conditions	Yield
Stage #1: 2-(4-(methylthio)phenyl)acetic acid With potassium carbonate In tetrahydrofuran at 25 - 26℃; for 0.5h; Stage #2: pivaloyl chloride In tetrahydrofuran at -10 - -5℃; for 1h; Stage #3: (1R,2R)-pseudoephedrine at -10 - 0℃; for 3.25h;	73.1%

Upstream product

• 1778-09-2 4-(Methylthio)acetophenone 
• 512-56-1 trimethyl phosphite 
• 39161-84-7 4-mercaptophenylacetic acid 
• 5188-07-8 sodium thiomethoxide 
• 1878-68-8 2-(4-bromophenyl)-acetic acid 
• 1878-66-6 4-chlorophenylacetic Acid 
• 38746-92-8 2-[4-(methylsulfanyl)phenyl]acetonitrile 
• 53066-99-2 2-(4-(methylthio)phenyl)-2-oxoacetic acid 
• 100-68-5 methyl-phenyl-thioether 
• 110-91-8 morpholine 
• 1798-06-7 (4-iodophenyl)acetic acid 
• 4856-13-7 cuprous methylmercaptide 

Downstream Products

• 70290-37-8 (4-methylsulfanyl-phenyl)-acetic acid methyl ester 
• 14062-27-2 ethyl 4-methylthiophenylacetate 
• 20101-45-5 α--p-nitro-trans-zimtsaeure 
• 562069-24-3 1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl-2-(4-methylsulfanylphenyl)acetate 

Relevant articles and documents

Crystal structure of [4-(methylsulfanyl)phenyl]acetic acid

The title compound, C9H10O2S, (I), crystallizes in the triclinic space group, P - 1, with unit cell parameters a = 6.2249(3), b = 7.3733(5), c = 19.5708(12), A, α = 86.746(5)°, β = 88.682(5)°, γ = 86.988(5)°, Z = 4. The molecule consists of a methyl sulfanyl group bonded to benzyl acetic acid at the 4 position crystallizing with two molecules in the asymmetric unit. The carboxylic acid group from the acetic acid moiety in these two molecules forms a classic O-H???O hydrogen bonded dimer with O???O distances of 2.673(2) and 2.646(2) A, in a R22 (8) graph-set motif which link the molecules into pairs around inversion centers in the unit cell. The dihedral angles between the mean planes of the R2 2 (8) graph-set motif with the mean planes of the two nearby benzyl groups within the same dimer in the unit cell are 64.1(6)° and 71.3(4)°, respectively. Within the same dimer the dihedral angle between the two benzyl groups is 45.2(1)°. The structure is supported by a weak intermolecular C-H???Cg π-ring interaction and gives support to molecular packing stability in the unit cell. Comparison to a MOPAC AM1 computational calculation provides support to these observations.

Chlorotrimethylsilane and Sodium Iodide: A Useful Combination for the Regioselective Deoxygenation of Arylalkyl-α-Diketones

An efficient regioselective deoxygenation of arylalkyl-1,2-diketones by the couple trimethylsilylchloride/sodium iodide has been reported. In all cases, the deoxygenation takes place on the carbonyl group (Cα=O) proximal to the aromatic ring in methylene chloride at room temperature in good yields, furnishing a series of variously functionalized alkylbenzylketones. A large range of functional groups were well tolerated on the ortho-, meta- and para-positions by this mild process regardless of their electronic effects, demonstrating the general character of the present methodology. The trimethylsilylchloride/sodium iodide reducing process was also successfully applied to reduce α-ketoacid and α-ketoester substrates. (Figure presented.).

Exalted resonance demands in the substituent effects on the acetolyses of 2-arylethyl trifluoromethanesulfonates destabilized by cn and cf3 groups

Substituent effects on the acetolysis rates of 2-aryl-l-cyano-l- (trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (ss-OTf) were investigated by using LArSR equation. The obtained p and r+ values were p = -3.28, r+ = 0.98 and p = -3.48,r+ = 0.93 for the acetolysis of α-OTf and ss-OΥi, respectively. The obtained p values are comparable to those for typical aryl-assisted solvolyses, but the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the ss-aryl group.