6236-09-5

Basic information

• Product Name: (S)-(+)-CITRAMALIC ACID
• Synonyms: L-(+)-2-METHYLMALIC ACID;L-(+)-CITRAMALIC ACID;2-HYDROXY-2-METHYLBUTANEDIOIC ACID;2-METHYLMALIC ACID;(S)-(+)-2-HYDROXY-2-METHYLBUTANEDIOIC ACID;(S)-(+)-CITRAMALIC ACID;(S)-(+)-CITRAMALIC ACID 98%;(S)-(+)-2-MethylmalicAcid
• CAS NO: 6236-09-5
• Molecular Formula: C₅H₈O₅
• Molecular Weight: 148.11
• EINECS: 228-350-1
• Mol File: 6236-09-5.mol
• Article Data: 11

Chemical Properties

• Melting Point: 109-111 °C(lit.)
• Boiling Point: 188.68°C (rough estimate)
• Flash Point: 146.6 °C
• Appearance: white fine crystalline powder
• Density: 1.2336 (rough estimate)
• Vapor Pressure: 0.000161mmHg at 25°C
• Refractive Index: 1.3920 (estimate)
• PKA: 3.65±0.28(Predicted)
• CAS DataBase Reference: (S)-(+)-CITRAMALIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-CITRAMALIC ACID(6236-09-5)
• EPA Substance Registry System: (S)-(+)-CITRAMALIC ACID(6236-09-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 6236-09-5(Hazardous Substances Data)

Usage

Description

(S)-(+)-CITRAMALIC ACID, an analog of Malic Acid, is a white fine crystalline powder produced from the condensation reaction of pyruvate and acetyl CoA, catalyzed by (R)-citramalate synthase. It possesses unique chemical properties that make it a versatile compound with potential applications in various industries.

Uses

Used in Pharmaceutical Industry:
(S)-(+)-CITRAMALIC ACID is used as an intermediate in the synthesis of various pharmaceutical compounds due to its unique chemical structure and reactivity. Its ability to participate in condensation reactions with other molecules makes it a valuable building block for the development of new drugs.
Used in Chemical Synthesis:
(S)-(+)-CITRAMALIC ACID is used as a key reactant in the chemical synthesis of various organic compounds, including chiral molecules, which are essential in the production of enantiomerically pure pharmaceuticals and agrochemicals.
Used in Research and Development:
(S)-(+)-CITRAMALIC ACID serves as an important research tool in the study of enzyme mechanisms, metabolic pathways, and the development of novel biocatalysts. Its unique properties allow researchers to investigate the role of chirality in biological systems and develop new methods for asymmetric synthesis.
Used in Analytical Chemistry:
(S)-(+)-CITRAMALIC ACID can be employed as a chiral reference standard in analytical chemistry for the determination of enantiomeric purity and the study of stereoselective reactions.
Used in Cosmetics Industry:
(S)-(+)-CITRAMALIC ACID may find applications in the cosmetics industry as an ingredient in the formulation of skincare and hair care products, where its unique properties can contribute to the development of innovative products with enhanced efficacy and safety profiles.

InChI:InChI=1/C5H8O5/c1-5(10,4(8)9)2-3(6)7/h10H,2H2,1H3,(H,6,7)(H,8,9)/t5-/m0/s1

Synthetic route

(R)-4-methyl-4-(trichloromethyl)-2-oxetanone (93239-42-0) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With sodium hydroxide In water 1.) 5 deg C; 2.) room temperature;	96%
With sodium hydroxide at 20℃; Hydrolysis;

(2'R,4'S)-2-<2'-(tert-Butyl)-4'-methyl-1',3'-dioxolan-4'-yl>essigsaeure → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With hydrogenchloride at 80℃; for 19h;	80%

Mesaconic acid (498-24-8) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With formaldehyd; TETRACYCLINE; paraquat dichloride In water at 37℃; for 24h; Clostridium formicoaceticum, phosphate buffer;	69.8%
mit Hilfe eines Mesaconase-Praeparats;

2-hydroxy-2-methylbutane-1,4-dioic acid (597-44-4) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With strychnidin-10-one
With water; brucine

S-(+)-Methyl-γ-iodo-β-carbomethoxy-β-hydroxy-butyrat (32814-40-7) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
(i) NaSH, H2S, EtOH, (ii) Raney-Ni, acetone, (iii) aq. HCl; Multistep reaction;

<(2S,4S)-2-tert-butyl-4-methyl-5-oxo-1,3-dioxolan-4-yl>acetic acid (92572-49-1) → (S)-citramalic acid (6236-09-5)

(2R,3S,5S)-5-((R)-1,2-Dihydroxy-ethyl)-3-methyl-tetrahydro-furan-2,3-diol → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With potassium hydroxide; potassium permanganate 1.) water, 4-5 deg C, 1 h; Yield given. Multistep reaction;

(S)-2-Hydroxy-2-methyl-succinic acid 1-((1S,2R)-2-phenyl-cyclohexyl) ester → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With potassium hydroxide In tetrahydrofuran at 60℃; for 24h;

(4S)-(+)-4-methylmuconolactone (32150-78-0) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With nitric acid; ozone 1.) CH2Cl2, -70 deg C; 2.) H2O, 90 deg C; Multistep reaction;

1-benzyl hydrogen 2-hydroxy-2-methylbutanedioate (197069-14-0) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
With potassium hydroxide Hydrolysis;

(2E,4E,7S,8E,10E,12E,14S)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + oxalic acid (144-62-7) + acetic acid (64-19-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

(2E,4E,7S,8E,10E,12E,14S)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + malonic acid (141-82-2) + oxalic acid (144-62-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

14-O-β-D-glucopyranosyl-(2E,4E,7S,8E,10E,12E,14R)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + oxalic acid (144-62-7) + acetic acid (64-19-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

14-O-β-D-glucopyranosyl-(2E,4E,7S,8E,10E,12E,14R)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + malonic acid (141-82-2) + acetic acid (64-19-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

14-O-α-D-glucopyranosyl-(2E,4E,7S,8E,10E,12E,14S)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + oxalic acid (144-62-7) + acetic acid (64-19-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

14-O-α-D-glucopyranosyl-(2E,4E,7S,8E,10E,12E,14S)-7,9,13,17-tetramethyl-7,14-dihydroxy-2,4,8,10,12,16-octadecahexaenoic acid → (S)-citramalic acid (6236-09-5) + malonic acid (141-82-2) + oxalic acid (144-62-7) + 2-oxo-propionic acid (127-17-3)

Conditions	Yield
With ozone In dichloromethane at -78℃; for 0.0833333h; Further byproducts given. Title compound not separated from byproducts;

(2R,5S)-2-(tert-Butyl)-5-methyl-5-(2'-nitroethyl)-1,3-dioxolan-4-on (104194-10-7) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / NaNO2, BuNO2 / dimethylsulfoxide / 16 h / Ambient temperature 2: 80 percent / 2 N HCl / 19 h / 80 °C View Scheme

methyl 5,6-O-cyclohexylidene-3-deoxy-2-C-methyl-β-D-arabino-hexofuranoside (58109-21-0, 58109-22-1, 58109-23-2) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: Dowex 50W-X8 / dioxane; H2O / 1 h / 90 °C 2: 1.) KOH, KMnO4 / 1.) water, 4-5 deg C, 1 h View Scheme

L-2-Hydroxyparaconic acid (32814-34-9) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
Multi-step reaction with 3 steps 2: NaI / acetone 3: (i) NaSH, H2S, EtOH, (ii) Raney-Ni, acetone, (iii) aq. HCl View Scheme

R-(+)-Methyl-γ-(p-toluolsulfonyloxy)-β-carbomethoxy-β-hydroxybutyrat (32814-35-0, 143954-94-3) → (S)-citramalic acid (6236-09-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaI / acetone 2: (i) NaSH, H2S, EtOH, (ii) Raney-Ni, acetone, (iii) aq. HCl View Scheme

diazomethane (186581-53-3, 908094-01-9) + (S)-citramalic acid (6236-09-5) → (R)-2-hydroxy-2-methyl-butan-1,4-dioic acid dimethyl ester (38574-61-7)

Conditions	Yield
In methanol	100%
In methanol; diethyl ether at 0℃;	94%

(S)-citramalic acid (6236-09-5) + Hexafluoroacetone (684-16-2) → [(5S)-2,2-Bis(trifluoromethyl)-5-methyl-4-oxo-1,3-dioxolan-5-yl] acetic acid (184305-30-4)

Conditions	Yield
In dimethyl sulfoxide at 20℃;	89%
In dimethyl sulfoxide	87%
In dimethyl sulfoxide at 20℃;	87%
In dimethyl sulfoxide at 20℃; Cyclization;

bromal (115-17-3) + (S)-citramalic acid (6236-09-5) → [(4S)-4-methyl-5-oxo-2-(tribromomethyl)-1,3-dioxolan-4-yl]acetic acid (1108205-25-9)

Conditions	Yield
With sulfuric acid; acetic acid at 0℃; for 2h;	87%

bromal (115-17-3) + (S)-citramalic acid (6236-09-5) → [(4S)-4-methyl-5-oxo-2-(tribromomethyl)-1,3-dioxolan-4-yl]acetic acid

Conditions	Yield
With sulfuric acid; acetic acid at 0℃; for 2h;	77%

(S)-citramalic acid (6236-09-5) → (S)-(-)-2-Methylbutane-1,2,4-triol (60299-29-8)

Conditions	Yield
Stage #1: (S)-citramalic acid With methanol; sulfuric acid Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran Further stages.;	72%
With dimethylsulfide borane complex In tetrahydrofuran; methanol at 0 - 60℃; for 1.5h;
Multi-step reaction with 2 steps 1: CH2Cl2; ethanol 2: LiAlH4 / tetrahydrofuran / Heating View Scheme
Multi-step reaction with 2 steps 2: 93 percent / lithium aluminium hydride / tetrahydrofuran / 18 h / Heating View Scheme

nickel(II) chloride hexahydrate + (S)-citramalic acid (6236-09-5) + water (7732-18-5) → diaqua((S)-2-hydroxy-2-methyl-butanedioate)nickel(II)

Conditions	Yield
With KOH In ethanol; water High Pressure; heated at 180°C for 2 d; cooled, ppt. washed and rinsed (water, ethanol); elem. anal., TGA;	71%

cobalt(II) chloride hexahydrate + (S)-citramalic acid (6236-09-5) + water (7732-18-5) → diaqua((S)-2-hydroxy-2-methyl-butanedioate)cobalt(II)

Conditions	Yield
With KOH In ethanol; water High Pressure; heated at 180°C for 2 d; cooled, ppt. washed and rinsed (water, ethanol); elem. anal., TGA;	67%

manganese(II) chloride tetrahydrate + (S)-citramalic acid (6236-09-5) + water (7732-18-5) → diaqua((S)-2-hydroxy-2-methyl-butanedioate)manganese(II)

Conditions	Yield
With KOH In ethanol; water High Pressure; heated at 180°C for 2 d; cooled, ppt. washed and rinsed (water, ethanol); elem. anal., TGA;	59%

(S)-citramalic acid (6236-09-5) → 3-Hydroxybutyric acid (300-85-6, 625-71-8)

Conditions	Yield
With 2,6-dimethylpyridine; 4,4'-dichlorodiphenyl disulfide; 10-methyl-9-(2,4,6-trimethylphenyl) acridinium tetrafluoroborate In 1,2-dichloro-ethane at 20℃; for 14h; Irradiation; Inert atmosphere; regioselective reaction;	52%

[2,2]bipyridinyl (366-18-7) + vanadium(IV) oxide sulfate hydrate (12440-03-8, 772292-34-9, 121437-28-3, 22534-68-5) + (S)-citramalic acid (6236-09-5) → [ΔVO(S-Hcitmal)(2,2′-bipyridine)]*2H2O

Conditions	Yield
With potassium hydroxide In ethanol; water	39%

(S)-citramalic acid (6236-09-5) + C20H23F2N3O2*(x)ClH → (S)-4-(3-((2-(difluoromethoxy)-6-methylpyridin-3-yl)carbamoyl)-3-(2-isopropylphenyl)azetidin-1-yl)-2-hydroxy-2-methyl-4-oxobutanoic acid

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere;	29%

ethanol (64-17-5) + (S)-citramalic acid (6236-09-5) → (S)-(+)-Citramalsaeure-diethylester (42108-93-0)

Conditions	Yield
With sulfuric acid

methanol (67-56-1) + (S)-citramalic acid (6236-09-5) → (R)-2-hydroxy-2-methyl-butan-1,4-dioic acid dimethyl ester (38574-61-7)

Conditions	Yield
With hydrogenchloride at 55℃; for 48h;
With hydrogenchloride Esterification;	58.7 mg
With thionyl chloride
With thionyl chloride at 20℃;
With thionyl chloride at 20℃; for 3h; Cooling;

(S)-citramalic acid (6236-09-5) → (+/-)-2-methylbutane-1,2,4-triol (62875-07-4)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating;

Upstream product

• 32814-35-0 R-(+)-Methyl-γ-(p-toluolsulfonyloxy)-β-carbomethoxy-β-hydroxybutyrat 
• 32814-34-9 L-2-Hydroxyparaconic acid 
• 58109-21-0 methyl 5,6-O-cyclohexylidene-3-deoxy-2-C-methyl-β-D-arabino-hexofuranoside 
• 104194-10-7 (2R,5S)-2-(tert-Butyl)-5-methyl-5-(2'-nitroethyl)-1,3-dioxolan-4-on 
• 197069-14-0 1-benzyl hydrogen 2-hydroxy-2-methylbutanedioate 
• 32150-78-0 (4S)-(+)-4-methylmuconolactone 
• 93239-42-0 (R)-4-methyl-4-(trichloromethyl)-2-oxetanone 
• 92572-49-1 <(2S,4S)-2-tert-butyl-4-methyl-5-oxo-1,3-dioxolan-4-yl>acetic acid 
• 32814-40-7 S-(+)-Methyl-γ-iodo-β-carbomethoxy-β-hydroxy-butyrat 
• 597-44-4 2-hydroxy-2-methylbutane-1,4-dioic acid 
• 498-24-8 Mesaconic acid 

Downstream Products

• 62875-07-4 (+/-)-2-methylbutane-1,2,4-triol 
• 511309-78-7 N-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-[(5S)-5-methyl-4-oxo-2,2-bis(trifluoromethyl)-1,3-dioxolan-5-yl]acetamide 
• 76794-58-6 (+)-(S)-2-(2,2,4-trimethyl-1,3-dioxolan-4-ethyl) tosylate 
• 327620-53-1 3-phenylpropionic acid (2S)-2-(methyloxiranyl)ethyl ester 
• 327620-54-2 (1S,5R)-5-methyl-1-phenethyl-2,7,8-trioxabicyclo[3.2.1]octane 
• 327620-58-6 (2S,4R)-(2,4-dimethyl-2-phenethyl[1,3]dioxan-4-yl)methanol 
• 327620-52-0 3-phenylpropionic acid (3S)-3,4-dihydroxy-3-methylbutyl ester 
• 327620-60-0 4-(1-ethyl-1-methyl-3-phenylpropoxy)-2-methylbutane-1,2-diol 
• 327620-51-9 3-phenylpropionic acid (4S)-2-(2,2-diethyl-4-methyl-[1,3]dioxolan-4-yl)ethyl ester 
• 107127-75-3 (S)-2-methyl-2-<2-(phenylmethoxy)ethyl>oxirane 
• 131700-29-3 (S)-2-methyl-4-(2-phenylmethoxy)butane-1,2-diol 
• 131700-28-2 (S)-2,2,4-trimethyl-4-<2-(phenylmethoxy)ethyl>-1,3-dioxolane 
• 131700-30-6 (S)-2-hydroxy-2-methyl-4-(2-phenylmethoxy)butyl methanesulphonate 

Relevant articles and documents

Glycosides of polyenoic branched fatty acids from myxomycetes

The determination of chemical structures of five novel compounds, i.e. one multibranched polyunsaturated fatty acid ((2E,4E,7S,8E,10E,12E,14S)-7,9,13,17-tetramethyl-7,14-dihydroxy-2, 4,8,10,12,16-octadecahexaenoic acid) and its four glycosides from seven different myxomycetes is described. The absolute configuration of both hydroxyl groups was determined. The glycosides containing glucose, mannose and rhamnose. These compounds were identified by means of 1H and 13C NMR, MS, UV and IR spectra. Three of them were identified in Arcyria cinerea (Bull.) Pers., two in A. denudata (L.) Wetts., and A. nutans (Bull.) Grev., Fuligo septica (L.) Wigg., Lycogala epidendrum (L.) Fries, Physarum polycephalum Schwein., and Trichia varia Pers. contained one of the identified glycosides each.

Asymmetric Allylation of Carbonyl Compounds with Tartrate-Modified Chiral Allylic Tin Reagents

Chiral allylating reagents, readily generated in situ from tin(II) catecholate [SnII(O2C6H4)], allyl halides, chiral dialkyl tartrates, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), reacted smoothly with aldehydes or reactive ketones at - 78 °C in the presence of a catalytic amount of copper salts to afford the corresponding optically active homoallyl alcohols. Allylation of aromatic aldehydes and pyruvates by the present chiral tin reagents proceeded in high yields (81-99%) with high enantioselectivities (89-94%ee). In addition, both enantiomers of dimethyl citramalate were prepared from the allylation products of benzyl pyruvate.

Stereochemistry of Enzymic Cyclisation of 3-Methyl-cis,cis-muconic Acid to form 3- and 4-Methylmuconolactone

Enzyme-catalysed cyclisation of 3-methyl-cis,cis-muconic acids proceeds by syn addition of carboxyl groups to double bonds to form (4S)-3-methylmuconolactone in Aspergillus niger and (4S)-4-methylmuconolactone in Pseudomonas putida.