583-91-5

Basic information

• Product Name: 2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID
• Synonyms: DL-2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID;ALPHA-HYDROXY-DL-METHIONINE;2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID;2-hydroxy-4-(methylmercapto)butyricacid;2-hydroxy-4-(methylthio)-butanoicaci;2-hydroxy-4-(methylthio)butanoicacid;2-hydroxy-4-(methylthio)-butyricaci;alimet
• CAS NO: 583-91-5
• Molecular Formula: C₅H₁₀O₃S
• Molecular Weight: 150.2
• EINECS: 209-523-0
• Product Categories: Intermediates & Fine Chemicals;Isotope Labeled Compounds;Pharmaceuticals;Isotope Labelled Compounds
• Mol File: 583-91-5.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 74°C
• Flash Point: 145.2 °C
• Appearance: Light brown liquid
• Density: 1.148 (estimate)
• Vapor Pressure: 3.45E-05mmHg at 25°C
• Refractive Index: 1.5151 (estimate)
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 3.67±0.10(Predicted)
• Merck: 14,5976
• CAS DataBase Reference: 2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID(583-91-5)
• EPA Substance Registry System: 2-HYDROXY-4-(METHYLTHIO)BUTYRIC ACID(583-91-5)

Safety Data

• Statements: 23/24/25
• Safety Statements: 26-36/37/39-45
• RTECS: ET4731500
• Hazardous Substances Data: 583-91-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 583-91-5 differently. You can refer to the following data:
1. Methionine hydroxy analogue
2. 2-Hydroxy-4-(methylthio)butyric Acid is used to improve stem activity to eliminate deoxynivalenol-induced intestinal injury.

General Description

Light brown liquid.

Reactivity Profile

An organosulfide, alcohol, and organic acid. Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid. Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt.

Health Hazard

Corrosive to the eyes and moderately irritating to the skin.

InChI:InChI=1/C5H10O3S/c1-9-3-2-4(6)5(7)8/h4,6H,2-3H2,1H3,(H,7,8)

Synthetic route

3-hydroxyoxolan-2-one (19444-84-9) + sodium thiomethoxide (5188-07-8) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
Stage #1: 3-hydroxyoxolan-2-one; sodium thiomethoxide In N,N-dimethyl-formamide at 153℃; for 3h; Stage #2: With hydrogenchloride; water Product distribution / selectivity;	100%

2-hydroxy-4-(methylthio)butyronitrile (17773-41-0) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With potassium phosphate buffer; nitrilase from Alcaligenes faecalis ATCC8750 at 30℃; for 48h; pH=7.3;	99%
Multi-step reaction with 2 steps 1: 83 percent / borax / KCN / H2O / 1.5 h / 80 °C 2: 90 percent / NaOH / H2O / 3 h / Heating View Scheme
Stage #1: 2-hydroxy-4-(methylthio)butyronitrile With sulfuric acid at 65℃; Stage #2: With water

α-hydroxy-4-methylthiobutyramide (49540-21-8) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With sodium hydroxide In water for 3h; Heating;	90%
With sulfuric acid; water at 110℃; for 250 - 500h; Product distribution / selectivity;
With sulfuric acid; water at 100 - 105℃; Temperature;

phosphoric acid 1,1-dicyano-3-methylsulfanyl-propyl ester diethyl ester → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With hydrogenchloride for 5h; Heating;	85%

methylthiol (74-93-1) + vinyl glycolic acid (600-17-9) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With triethyl borane at 20℃; UV-irradiation;	85%

2-hydroxy-4-(methylthio)butanoic acid calcium salt + sulfuric acid (7664-93-9) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
In water for 1.5h;	85%

2-hydroxy-4-(methylthio)butyronitrile (17773-41-0) → α-hydroxy-4-methylthiobutyramide (49540-21-8) + 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With borax; potassium cyanide In water at 80℃; for 1.5h;	A 83% B 8%
With sulfuric acid; water at 35 - 112℃; for 1.5 - 3.16667h; Product distribution / selectivity;
With sulfuric acid; water at 40 - 125℃; under 1875.19 Torr; for 2.25h; Product distribution / selectivity;
With sulfuric acid; water at 50 - 110℃; under 12 Torr; Product distribution / selectivity; Continuous process;

hydrogen cyanide (74-90-8) + 3-(methylsulfenyl)propanal (3268-49-3) → 2-hydroxy 4-methylthiobutyric acid (583-91-5) + DL-methionine (59-51-8)

Conditions	Yield
With cerium(IV) oxide; ammonia In water at 75℃; for 6h;	A 62.1% B 34.9%
With cerium(IV) oxide; ammonia In water at 75℃; for 6h;	A 44.3% B 52.6%

4-(methylthio)-2-oxo-1-butanol (1003880-00-9) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
Stage #1: 4-(methylthio)-2-oxo-1-butanol With potassium hydroxide; oxygen; copper diacetate In water at 20℃; for 2h; Stage #2: With sulfuric acid; water	46%

DL-methionine (59-51-8) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With silver(I) nitrite; water

L-methionine (63-68-3) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With cis-nitrous acid; sodium bromide In water at 25℃; Rate constant;

2-acetoxy-4-methylthiobutanenitrile → 2-hydroxy 4-methylthiobutyric acid (583-91-5) + 2-acetyloxy-4-(methylthio)butanoic acid (138128-01-5)

Conditions	Yield
With potassium phosphate buffer; nitrilase from Alcaligenes faecalis ATCC8750 at 30℃; for 48h; pH=7.3; Title compound not separated from byproducts;	A 6 % Spectr. B 82 % Spectr.

hydrogen cyanide (74-90-8) + 3-(methylsulfenyl)propanal (3268-49-3) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
In water at 20 - 68℃; for 0.0833333h; pH=4.7 - 5.5;
Stage #1: hydrogen cyanide; 3-(methylsulfenyl)propanal With pyridine; acetic acid at 35 - 45℃; for 1.25h; Stage #2: With sulfuric acid; water at 60 - 90℃; for 2.91667h;

2-acetyloxy-4-(methylthio)butanoic acid (138128-01-5) → brucine salt + 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With brucine In ethanol

1-acetyloxy-3-methylthiopropene + (PPh3)2 PdCl2 + L-menthoxyethyl acetyl-L-2-hydroxy-4-methylthiobutyrate + 2-(2-isopropyl-5-methylcyclohexyloxy)ethanol → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With hydrogenchloride; CO In tetrahydrofuran

1-carboxy-3-methylthiopropyl sulfate → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With water at 80℃; for 24h; Purification / work up;

α-hydroxy-4-methylthiobutyramide (49540-21-8) → 1-carboxy-3-methylthiopropyl sulfate + 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With sulfuric acid; water at 109℃; for 4h; Heating / reflux;

2-hydroxy-4-methylthiobutyric acid ammonium salt (63302-72-7) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
In water; 4-methyl-2-pentanone at 80 - 117℃; Product distribution / selectivity; Inert atmosphere;

sodium α-keto-(γ-methylthio)butyrate (51828-97-8) → 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With hydrogen; rhodium contaminated with carbon In water at 50℃; under 7500.75 Torr; for 6h; Product distribution / selectivity; autoclave;

sodium cyanide (773837-37-9) + 3-(methylsulfenyl)propanal (3268-49-3) + 3-(methylselenyl)-propanal (119353-03-6) → DL-α-hydroxyselenomethionine (873660-49-2) + 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
Stage #1: 3-(methylsulfenyl)propanal; 3-(methylselenyl)-propanal With sodium hydrogensulfite In water at 20℃; for 0.166667h; Stage #2: sodium cyanide In water at 20℃; for 2h; Reflux; Stage #3: With hydrogenchloride; water for 5h; Reflux;

methyl 2-hydroxy-4-(methylthio)butanoate (52703-96-5) → methylthiol (74-93-1) + 2-hydroxy 4-methylthiobutyric acid (583-91-5)

Conditions	Yield
With sodium hydrosulfide monohydrate In dimethyl sulfoxide at 50℃; for 24h; Temperature; Inert atmosphere; Schlenk technique;	A n/a B 93 %Spectr.

2-hydroxy 4-methylthiobutyric acid (583-91-5) → 2-hydroxy-4-(methylthio)butanoic acid calcium salt

Conditions	Yield
With calcium oxide In ethanol at 100℃; for 24h; Reagent/catalyst;	98.09%
Stage #1: 2-hydroxy 4-methylthiobutyric acid With sodium hydroxide In water at 20℃; pH=~ 9.0; Stage #2: With calcium chloride In water at 20℃; for 5.5h;	84%
With calcium oxide In water at 120℃; Reagent/catalyst; Temperature;
Multi-step reaction with 2 steps 1.1: sodium hydroxide / 0.5 h / 20 °C 2.1: sodium hydroxide; water / 45 - 50 °C 2.2: 0.5 h View Scheme
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol / 1 h / 0 °C 1.2: 0 °C 2.1: sodium hydroxide; water / 45 - 50 °C 2.2: 0.5 h View Scheme

2-hydroxy 4-methylthiobutyric acid (583-91-5) + trichloromethyl chloroformate (503-38-8) → 5-(2-(methylthio)ethyl)-1,3-dioxolan-2,4-dione (1161721-72-7)

Conditions	Yield
In tetrahydrofuran	97%

methanol (67-56-1) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → methyl 2-hydroxy-4-(methylthio)butanoate (52703-96-5)

Conditions	Yield
With sodium hydroxide at 20℃; for 0.5h;	91.7%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + methyl p-toluene sulfonate (80-48-8) → methyl 2-hydroxy-4-(methylthio)butanoate (52703-96-5)

Conditions	Yield
Stage #1: 2-hydroxy 4-methylthiobutyric acid With potassium hydroxide In ethanol at 20℃; for 0.5h; Stage #2: methyl p-toluene sulfonate In ethanol at 20℃;	90.3%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + carbonic acid dimethyl ester (616-38-6) → methyl 2-hydroxy-4-(methylthio)butanoate (52703-96-5)

Conditions	Yield
Stage #1: 2-hydroxy 4-methylthiobutyric acid With potassium hydroxide In methanol at 0℃; for 1h; Stage #2: carbonic acid dimethyl ester In methanol at 0℃;	90.1%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + 2,2-dimethoxy-propane (77-76-9) → 2,2-dimethyl-5-(2-(methylthio)ethyl)-1,3-dioxolan-4-one (1161721-65-8)

Conditions	Yield
In tetrahydrofuran	89%

BF3.2H2O + 2-hydroxy 4-methylthiobutyric acid (583-91-5) + MgBr2.2Et2O → 2,2-dimethyl-5-(2-(methylthio)ethyl)-1,3-dioxolan-4-one (1161721-65-8)

Conditions	Yield
zinc(II) chloride In diethyl ether; water; acetone	87%

dichlorotricarbonylruthenium(II) dimer + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → Ru(CO)3Cl2(H3CS(CH2)2CH(OH)CO2H)

Conditions	Yield
In acetone at 20℃; for 24h; Inert atmosphere; Schlenk technique;	83%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + tetradecanoyl chloride (112-64-1) → C14-HE + C14-HE

Conditions	Yield
at 65℃; Overall yield = 2.6 g;	A 80.5% B 19.5%

Triisopropyl borate (5419-55-6) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → D,L-2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (57296-04-5)

Conditions	Yield
at 95℃; for 10h;	72%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + n-octanoic acid chloride (111-64-8) → C8-HE + C8-HE + C8-HE

Conditions	Yield
at 65℃;	A 25.6% B 5.3% C 68.4%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + hexan-1-ol (111-27-3) → 2-hydroxy-4-(methylthio)butanoic acid hexyl ester (161193-00-6)

Conditions	Yield
With sodium hydrogen sulfate In toluene for 5.5h; Dean-Stark; Reflux;	64.1%
With sodium hydrogen sulfate In toluene Dean-Stark; Reflux;	61.1%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + acetyl chloride (75-36-5) → 2-acetyloxy-4-(methylthio)butanoic acid (138128-01-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	63.1%
Stage #1: 2-hydroxy 4-methylthiobutyric acid With triethylamine In dichloromethane at 0℃; Stage #2: acetyl chloride In dichloromethane at 0 - 20℃;	63.1%
With triethylamine In dichloromethane at 0 - 20℃;
at 20℃; for 3h; Temperature; Large scale;

2-hydroxy 4-methylthiobutyric acid (583-91-5) + butan-1-ol (71-36-3) → 2-hydroxy-4-(methylthio)butanoic acid butyl ester

Conditions	Yield
With sodium hydrogen sulfate In toluene for 5h; Dean-Stark; Reflux;	62.3%

1-octadecanol (112-92-5) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → octadecyl 2-hydroxy-4-(methylthio)butanoate (1446404-60-9)

Conditions	Yield
With sodium hydrogen sulfate In toluene Dean-Stark; Reflux;	61%

Isopropyl acetate (108-21-4) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → D,L-2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (57296-04-5)

Conditions	Yield
With sulfuric acid at 80 - 90℃; for 6h; Temperature; Reagent/catalyst; Large scale;	57.5%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + butanone (78-93-3) → 2-ethyl-2-methyl-5-(2-(methylthio)ethyl)-1,3-dioxolan-4-one (1161721-66-9)

Conditions	Yield
	56%

octanol (111-87-5) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → 2-hydroxy-4-(methylthio)butanoic acid octyl ester (1446404-55-2)

Conditions	Yield
With sodium hydrogen sulfate In toluene Dean-Stark; Reflux;	45%
With sodium hydrogen sulfate In toluene for 5.5h; Dean-Stark; Reflux;	45%

2-hydroxy 4-methylthiobutyric acid (583-91-5) + n-hexadecanoyl chloride (112-67-4) → 4-(methylthio)-2-(palmitoyloxy)butanoic acid

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃;	45%

1-Decanol (112-30-1) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → 2-hydroxy-4-(methylthio)butyric acid decyl ester (161193-01-7)

Conditions	Yield
With sodium hydrogen sulfate In toluene for 6h; Reflux;	44%
With sodium hydrogen sulfate In toluene Dean-Stark; Reflux;	43.5%
With sodium hydrogen sulfate In toluene for 6h; Dean-Stark;	43.5%

1-dodecyl alcohol (112-53-8) + 2-hydroxy 4-methylthiobutyric acid (583-91-5) → dodecyl 2-hydroxy-4-(methylthio)butanoate (1446404-58-5)

Conditions	Yield
With sodium hydrogen sulfate In toluene Dean-Stark; Reflux;	42%

Upstream product

• 63-68-3 L-methionine 
• 17773-41-0 2-hydroxy-4-(methylthio)butyronitrile 
• 74-90-8 hydrogen cyanide 
• 3268-49-3 3-(methylsulfenyl)propanal 
• 59-51-8 DL-methionine 
• 52703-96-5 methyl 2-hydroxy-4-(methylthio)butanoate 
• 7664-93-9 sulfuric acid 
• 773837-37-9 sodium cyanide 
• 119353-03-6 3-(methylselenyl)-propanal 
• 51828-97-8 sodium α-keto-(γ-methylthio)butyrate 
• 63302-72-7 2-hydroxy-4-methylthiobutyric acid ammonium salt 
• 19444-84-9 3-hydroxyoxolan-2-one 
• 5188-07-8 sodium thiomethoxide 
• 49540-21-8 α-hydroxy-4-methylthiobutyramide 

Downstream Products

• 75-52-5 Nitromethane 
• 25731-06-0 Nitro-methanol 
• 557-41-5 zinc(II) formate 
• 57296-04-5 D,L-2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester 
• 39638-34-1 (R)-2-hydroxy-4-(methylthio)butanoic acid 
• 38565-99-0 C₆H₁₃O₃S⁽¹⁺⁾*I^(1-) 
• 1374125-32-2 C₁₂H₁₇O₃S⁽¹⁺⁾*Br^(1-) 
• 19444-84-9 3-hydroxyoxolan-2-one 
• 138128-01-5 2-acetyloxy-4-(methylthio)butanoic acid 

Relevant articles and documents

A contribution to the rational design of Ru(CO)3Cl2L complexes for in vivo delivery of CO

A few ruthenium based metal carbonyl complexes, e.g. CORM-2 and CORM-3, have therapeutic activity attributed to their ability to deliver CO to biological targets. In this work, a series of related complexes with the formula [Ru(CO)3Cl2L] (L = DMSO (3), l-H3CSO(CH2)2CH(NH2)CO2H) (6a); d,l-H3CSO(CH2)2CH(NH2)CO2H (6b); 3-NC5H4(CH2)2SO3Na (7); 4-NC5H4(CH2)2SO3Na (8); PTA (9); DAPTA (10); H3CS(CH2)2CH(OH)CO2H (11); CNCMe2CO2Me (12); CNCMeEtCO2Me (13); CN(c-C3H4)CO2Et) (14)) were designed, synthesized and studied. The effects of L on their stability, CO release profile, cytotoxicity and anti-inflammatory properties are described. The stability in aqueous solution depends on the nature of L as shown using HPLC and LC-MS studies. The isocyanide derivatives are the least stable complexes, and the S-bound methionine oxide derivative is the more stable one. The complexes do not release CO gas to the headspace, but release CO2 instead. X-ray diffraction of crystals of the model protein Hen Egg White Lysozyme soaked with 6b (4UWN) and 8 (4UWV) shows the addition of RuII(CO)(H2O)4 at the His15 binding site. Soakings with 7 (4UWU) produced the metallacarboxylate [Ru(COOH)(CO)(H2O)3]+ bound to the His15 site. The aqueous chemistry of these complexes is governed by the water-gas shift reaction initiated with the nucleophilic attack of HO- on coordinated CO. DFT calculations show this addition to be essentially barrierless. The complexes have low cytotoxicity and low hemolytic indices. Following i.v. administration of CORM-3, the in vivo bio-distribution of CO differs from that obtained with CO inhalation or with heme oxygenase stimulation. A mechanism for CO transport and delivery from these complexes is proposed. This journal is

Clean preparation method of high-purity methionine hydroxyl analogue calcium salt

The invention discloses a clean preparation method of high-purity methionine hydroxyl analogue calcium salt. The clean preparation method comprises the following specific steps: adding water into 2-hydroxy-4-methylthiobutyronitrile serving as a raw material, carrying out a hydration reaction under the catalytic action of solid acid/solid alkali, adding strong acid or strong alkali for hydrolysis to obtain 2-hydroxy-4-methylthiobutyric acid, then adding CaO or Ca(OH)2, carrying out a salt forming reaction to obtain an aqueous solution of a mixture, carrying out chromatographic desalination treatment on the aqueous solution of the mixture to obtain an aqueous solution of a methionine hydroxyl analogue, and finally carrying out spray drying on the aqueous solution of the methionine hydroxyl analogue to obtain a target product. Compared with a traditional method, the method disclosed by the invention has the advantages that the step of neutralizing and alkali washing after the reaction is finished is avoided, the generation of a byproduct, namely inorganic ammonium salt is avoided, reaction is simple, conditions are mild, and the method is safe and environment-friendly; and in addition, a catalyst, namely the solid acid or solid alkali adopted in the method can be recycled, so production cost is reduced.

DEMETHYLATION OF METHYL ESTER OF METHIONINE AND ITS HYDROXY ANALOG

The following invention regards a process of demethylating a methyl ester of methionine or its hydroxy analog and producing methane thiol as a side-product. The methionine and its hydroxy analog are suitable as an animal feed additive and as a food additive. The methane thiol may be consumed in a hydrothiolation step such as in a step of preparing the methyl ester of methio- nine or its hydroxy analog from from methyl vinyl glycolate.