74431-50-8

Basic information

• Product Name: 3-(Benzoylthio)-2-methylpropionic acid
• Synonyms: (±)-3-(benzoylthio)-2-methylpropionic acid;3-(BENZOYLTHIO)-α-METHYLPROPIONIC ACID;2-Methyl-3-[(phenylcarbonyl)sulphanyl]propanoic acid;Propanoic acid,3-(benzoylthio)-2-Methyl
• CAS NO: 74431-50-8
• Molecular Formula: C₁₁H₁₂O₃S
• Molecular Weight: 224.28
• EINECS: 277-867-9
• Product Categories: API intermediates
• Mol File: 74431-50-8.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 367.5 °C at 760 mmHg
• Flash Point: 176 °C
• Appearance: /
• Density: 1.249 g/cm³
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.20±0.10(Predicted)
• CAS DataBase Reference: 3-(Benzoylthio)-2-methylpropionic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(Benzoylthio)-2-methylpropionic acid(74431-50-8)
• EPA Substance Registry System: 3-(Benzoylthio)-2-methylpropionic acid(74431-50-8)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 74431-50-8(Hazardous Substances Data)

Usage

General Description

3-(Benzoylthio)-2-methylpropionic acid is a chemical compound with the molecular formula C12H14O3S. It is a derivative of 2-methylpropionic acid (also known as isobutyric acid) that has a benzoylthio group attached to the carbon 3 position. 3-(Benzoylthio)-2-methylpropionic acid is often used in organic synthesis and pharmaceutical research as a building block for creating more complex molecules. Its unique structure and reactivity make it a valuable tool for creating novel pharmaceutical compounds and other chemical products.

InChI:InChI=1/C11H12O3S/c1-8(10(12)13)7-15-11(14)9-5-3-2-4-6-9/h2-6,8H,7H2,1H3,(H,12,13)

Synthetic route

thiobenzoic acid (98-91-9) + poly(methacrylic acid) (79-41-4) → (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8)

toluene-ethyl acetate + (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) + (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, methyl ester, hydrochloride (78183-55-8) → methyl (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

Conditions	Yield
With thionyl chloride; triethylamine In tetrahydrofuran; chloroform	80.5%

methyldopa (555-30-6) + (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → N-(S-benzoyl-3-mercapto-2-methylpropanoyl)-L-α-methyldopa (79559-48-1, 79559-49-2)

Conditions	Yield
With sodium borate; triethylamine; isobutyl chloroformate 1.) THF, -10 deg C, 10 min, 2.) THF, water, room temperature, 1h; Yield given. Multistep reaction;

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (D)-3-(benzoylthio)-2-methylpropanoic acid chloride (76740-20-0)

Conditions	Yield
With thionyl chloride at 30 - 40℃; for 2h;
With thionyl chloride at 50℃; for 3h; Heating;
With thionyl chloride In toluene

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-3-Benzoylsulfanyl-2-methyl-propionic acid (74407-70-8)

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (2S)-3-(benzoylthio)-2-methylpropionic acid (72679-02-8)

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) + L-thioproline (34592-47-7) → (4R)-3-<(2S)-S-benzoyl-3-mercapto-2-methylpropanoyl>-4-thiazolidinecarboxylic acid (67714-38-9)

Conditions	Yield
With triethylamine; isobutyl chloroformate 1) tetrahydrofuran, RT, 10 min, 2) water, RT, 30 min; Yield given. Multistep reaction;

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) + L-Tryptophan (73-22-3) → (S)-2-(3-Benzoylsulfanyl-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid (78818-51-6, 78818-53-8)

Conditions	Yield
With 2.) aq. alkali Yield given. Multistep reaction;

methanol (67-56-1) + (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-(+)-3-benzoylthio-2-methylpropanoic acid methyl ester

Conditions	Yield
In toluene at 40℃; lipase PS-30;

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → tert-butyl (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (77832-24-7, 77832-28-1, 84641-55-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / 3 h / 50 °C / Heating 2: 81.6 percent / triethyl amine / tetrahydrofuran / 4 h / Ambient temperature View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (2S)-3-benzoylthio-2-methylpropionyl chloride (72679-01-7)

Conditions	Yield
Multi-step reaction with 2 steps 2: thionyl chloride View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (S)-3-(benzoylthio)-2-methylpropanoylchloride (74654-91-4)

Conditions	Yield
Multi-step reaction with 2 steps 2: thionyl chloride View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (77832-25-8, 77832-29-2, 77972-27-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 3 h / 50 °C / Heating 2: 81.6 percent / triethyl amine / tetrahydrofuran / 4 h / Ambient temperature 3: trifluoroacetic acid / 1 h / Ambient temperature View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → benzyl (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (87022-29-5, 87022-30-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / 3 h / 50 °C / Heating 2: 96.2 percent / triethyl amine / tetrahydrofuran / 4 h / 5 - 10 °C View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-2-((S)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester (87022-29-5, 87022-30-8)

Conditions	Yield
Multi-step reaction with 3 steps 2: thionyl chloride 3: triethyl amine / tetrahydrofuran / 4 h / 5 - 10 °C View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester (87022-29-5, 87022-30-8)

Conditions	Yield
Multi-step reaction with 3 steps 2: thionyl chloride 3: triethyl amine / tetrahydrofuran / 4 h / 5 - 10 °C View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (S)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester (87022-29-5)

Conditions	Yield
Multi-step reaction with 3 steps 2: thionyl chloride 3: 90 percent / triethyl amine / tetrahydrofuran / 4 h / 5 - 10 °C View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (S)-2-(3-Benzoylsulfanyl-2-methyl-propionylamino)-4-methylsulfanyl-butyric acid (110949-46-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: SOCl2 / 2 h / 30 - 40 °C 2: 1N NaOH / acetone / Ambient temperature View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-2-[(3-Benzoylsulfanyl-2-methyl-propionyl)-methyl-amino]-3-benzylsulfanyl-propionic acid (110949-48-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: SOCl2 / 2 h / 30 - 40 °C 2: 1N NaOH / acetone / Ambient temperature View Scheme

(D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (R)-2-(3-Benzoylsulfanyl-2-methyl-propionylamino)-3-benzylsulfanyl-propionic acid (110949-47-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: SOCl2 / 2 h / 30 - 40 °C 2: 1N NaOH / acetone / Ambient temperature View Scheme

(trans)-4-methoxy-L-proline (910878-12-5) + 3-benzoylthio-2-methylpropionyl acid chloride + (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (cis)-4-methoxy-1-[3-(benzoylthio)-2-methyl-1-oxopropyl]-L-proline

Conditions	Yield
With thionyl chloride

4-hydroxyproline (51-35-4, 913000-57-4) + (D)-3-(benzoylthio)-2-methylpropanoic acid chloride (76740-20-0) + (D)-3-(Benzoylthio)-2-methylpropanoic acid (74431-50-8) → (trans)-1-[D-3-(benzoylthio)-2-methyl-1-oxopropyl]-4-hydroxy-L-proline

Conditions	Yield
With thionyl chloride; sodium carbonate In N-methyl-acetamide; water; toluene

Upstream product

• 98-91-9 thiobenzoic acid 
• 79-41-4 poly(methacrylic acid) 

Downstream Products

• 87022-29-5 (S)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester 
• 87022-29-5 (R)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester 
• 87022-29-5 (R)-2-((S)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester 
• 87022-29-5 benzyl (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 
• 77832-25-8 (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 
• 74654-91-4 3-(benzoylthio)-2(S)-methylpropionyl chloride 
• 72679-01-7 (2S)-3-benzoylthio-2-methylpropionyl chloride 
• 77832-24-7 tert-butyl (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 
• 67714-38-9 (4R)-3-<(2S)-S-benzoyl-3-mercapto-2-methylpropanoyl>-4-thiazolidinecarboxylic acid 
• 72679-02-8 (2S)-3-(benzoylthio)-2-methylpropionic acid 
• 74407-70-8 (R)-3-Benzoylsulfanyl-2-methyl-propionic acid 
• 76740-20-0 (D)-3-(benzoylthio)-2-methylpropanoic acid chloride 
• 79559-48-1 N-(S-benzoyl-3-mercapto-2-methylpropanoyl)-L-α-methyldopa 

Relevant articles and documents

Optical resolution of DL-3-acylthio-2-methylpropanoic acid

An optically active amine compound and a method for preparing same are provided which compound has the structure STR1 in the form of its R-(+) enantiomer or S-(-) enantiomer, wherein R and R1 are independently H, lower alkyl or halogen, R2 is H or lower alkyl and R3 is lower alkyl, the optically active amine is useful in the optical resolution of DL-3-acylthio-2-methylpropanoic acid wherein acyl is acetyl or benzoyl. The optically active D-(+)-3-acylthio-2-methylpropanoic acids are used as intermediated for preparing antihypertensive agents, such as captopril.

1,1'-[DITHIOBIS(2-ALKYL-1-OXO-3,1-PROPANEDIYL)]-BIS[2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC ACIDS AND DERIVATIVES

Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: STR1 wherein: n is 1 or 0; R 1 is hydrogen, lower alkyl, aryl or aralkyl;R 2 is hydrogen or lower alkyl; R 3 is hydrogen, lower alkyl or aroyl; R. sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;R 4 is-SH, STR2 wherein L is O, NR 7 or S (where R 7 is hydrogen or lower alkyl); M is R 8, OR 8, SR 8, or NR 9 R 10 (where R 8 is hydrogen, lower alkyl, aryl, or aralkyl; and R 9 and R 10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR 13 or S;R 11 and R 12 are, independently, hydrogen, alkyl, aralkyl or aryl; R. sub. 13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3; R 20 is hydrogen or aryl; andR. sub. 21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.