2224-02-4

Basic information

• Product Name: 1,2-Dithiolane-4-carboxylicacid(6CI,7CI,8CI,9CI)
• Synonyms: 1,2-Dithiolane-4-carboxylicacid(6CI,7CI,8CI,9CI);ASPARAGUSICACID;1,2-Dithiolane-4-carboxylic acid
• CAS NO: 2224-02-4
• Molecular Formula: C₄H₆O₂S₂
• Molecular Weight: 150.22
• Product Categories: CARBOXYLICACID
• Mol File: 2224-02-4.mol

Chemical Properties

• Melting Point: 76.5-77.5 °C
• Boiling Point: 323.9°Cat760mmHg
• Flash Point: 149.7°C
• Appearance: /
• Density: 1.503g/cm³
• Vapor Pressure: 5.19E-05mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: 2-8°C
• PKA: 3.88±0.20(Predicted)
• CAS DataBase Reference: 1,2-Dithiolane-4-carboxylicacid(6CI,7CI,8CI,9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2-Dithiolane-4-carboxylicacid(6CI,7CI,8CI,9CI)(2224-02-4)
• EPA Substance Registry System: 1,2-Dithiolane-4-carboxylicacid(6CI,7CI,8CI,9CI)(2224-02-4)

Safety Data

• Hazardous Substances Data: 2224-02-4(Hazardous Substances Data)

Usage

Synthesis Reference(s)

Synthesis, p. 607, 1973 DOI: 10.1055/s-1973-22265

InChI:InChI=1/C4H6O2S2/c5-4(6)3-1-7-8-2-3/h3H,1-2H2,(H,5,6)

Synthetic route

3-benzylthio-2-((benzylthio)methyl)propanoic acid (81079-79-0) → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
Stage #1: 3-benzylthio-2-((benzylthio)methyl)propanoic acid With ammonia; sodium In toluene at -78℃; for 0.583333h; Stage #2: With iron(III) chloride; oxygen In water; toluene for 2h;	89%
Stage #1: 3-benzylthio-2-((benzylthio)methyl)propanoic acid With ammonia; sodium at -78℃; for 0.583333h; Stage #2: With iron(III) chloride; oxygen In water for 2h;	89%

3-bromo-2-(bromomethyl)propionic acid (41459-42-1) → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
With piperidinium thiotungstate at 25℃; for 4h;	77%
With piperidinium thiotungstate In N,N-dimethyl-formamide at 28℃; for 5h;	77%

dihydroasparagusic acid (7634-96-0) → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
With dimethyl sulfoxide	60%

diethyl 1,2-dithiolane-4,4-dicarboxylate (120987-04-4) → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
With hydrogenchloride for 3h; Heating;	33%

3-mercapto-2-(mercaptomethyl)propanoic acid (7634-96-0) → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
With sodium hydrogencarbonate Behandeln der mit Eisen(III)-chlorid versetzten Reaktionsloesung mit Sauerstoff;
In dimethyl sulfoxide at 75℃; for 15h; Inert atmosphere; Schlenk technique;	1.21 g
With air In acetonitrile at 20℃; for 30h; pH=8;

3-mercapto-2-(mercaptomethyl)propanoic acid (7634-96-0) + iron(III) chloride (7705-08-0) + aqueous sodium hydrogencarbonate + oxygen → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

1,2-dithiolan-4-carboxylic acid 6-D-glucopyranose ester → 1,2-dithiolane-4-carboxylic acid (2224-02-4)

Conditions	Yield
Stage #1: 1,2-dithiolan-4-carboxylic acid 6-D-glucopyranose ester With sodium hydroxide In water at 110℃; for 2h; Stage #2: With hydrogenchloride In water pH=5;

1,2-dithiolane-4-carboxylic acid (2224-02-4) + tetrakis(triphenylphosphine)platinum (14221-02-4) → [Pt(PPh3)2(S2(CH2)2CH(C(O)OH))]

Conditions	Yield
In benzene-d6 N2; 1:1 mixt., pptd.; filtered off, dried (vac.), elem. anal.;	61%

1,2-dithiolane-4-carboxylic acid (2224-02-4) + 6-amino-4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinoline-3-carbonitrile → N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyanoquinolin-6-yl)-1,2-dithiolane-4-carboxamide

Conditions	Yield
With N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride In 1-methyl-pyrrolidin-2-one at 90℃; for 12h;	37%
With 1-methyl-pyrrolidin-2-one; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 90℃; for 12h; Inert atmosphere;	37%

1,2-dithiolane-4-carboxylic acid (2224-02-4) + 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-ethoxy-quinoline-3-carbonitrile (361162-95-0) → N-(4-((3-chloro-4-fluorophenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-1,2-dithiolane-4-carboxamide

Conditions	Yield
With N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride In 1-methyl-pyrrolidin-2-one at 20℃; for 2h; Darkness;	30%

1,2-dithiolane-4-carboxylic acid (2224-02-4) + 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-amino-7-ethoxyquinoline-3-carbonitrile (848133-14-2) → N-(4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-1,2-dithiolane-4-carboxamide

Conditions	Yield
With N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride In 1-methyl-pyrrolidin-2-one at 20℃; for 2h; Darkness;	30%

1,2-dithiolane-4-carboxylic acid (2224-02-4) + biphenyl-4-methylchloride (1667-11-4) → S,S'-bis(p-phenylbenzyl)dihydroasparagusate (94751-35-6)

Conditions	Yield
With ammonia; sodium In tetrahydrofuran at -33℃; for 1h;	15%

1,2-dithiolane-4-carboxylic acid (2224-02-4) + ethyl iodide (75-03-6) → 2-Ethylsulfanylmethyl-acrylic acid (32687-42-6)

Conditions	Yield
(i) aq. NaOH, (ii) /BRN= 505934/, EtOH; Multistep reaction;

1,2-dithiolane-4-carboxylic acid (2224-02-4) → 2-(2-Carboxy-allyldisulfanylmethyl)-acrylic acid

Conditions	Yield
With sodium hydroxide

1,2-dithiolane-4-carboxylic acid (2224-02-4) + diethyl cyanophosphonate (2942-58-7) + methyl 3-aminopropanoate hydrochloride (3196-73-4) → methyl 3-(1,2-dithiolan-4-ylcarbonyl)aminopropionate

Conditions	Yield
With sodium chloride; triethylamine In tetrahydrofuran; N-methyl-acetamide; hexane; water; ethyl acetate

1,2-dithiolane-4-carboxylic acid (2224-02-4) + diethyl cyanophosphonate (2942-58-7) + glycine ethyl ester hydrochloride (5680-79-5) → methyl 1,2-dithiolan-4-ylcarbonylaminoacetate

Conditions	Yield
With sodium chloride; triethylamine In tetrahydrofuran; N-methyl-acetamide; hexane; water; ethyl acetate

1,2-dithiolane-4-carboxylic acid (2224-02-4) → 2,5-dioxopyrrolidin-1-yl 1,2-dithiolane-4-carboxylate (98661-66-6)

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; Fmoc-Lys-OH; dicyclohexyl-carbodiimide In acetonitrile at 25℃; for 1.5h;

Upstream product

• 7634-96-0 3-mercapto-2-(mercaptomethyl)propanoic acid 
• 41459-42-1 3-bromo-2-(bromomethyl)propionic acid 
• 120987-04-4 diethyl 1,2-dithiolane-4,4-dicarboxylate 
• 7634-96-0 dihydroasparagusic acid 
• 7705-08-0 iron(III) chloride 
• 81079-79-0 3-benzylthio-2-((benzylthio)methyl)propanoic acid 

Downstream Products

• 94751-35-6 S,S'-bis(p-phenylbenzyl)dihydroasparagusate 

Relevant articles and documents

Identification of sensory-active phytochemicals in asparagus (Asparagus officinalis L.)

Sensory-directed fractionation of extracts prepared from raw and cooked asparagus (Asparagus officinalis L.), respectively, followed by LC-TOF-MS, LC-MS/MS, and 1D/2D-NMR experiments revealed the chemical structures of nine bitter tasting mono- and bidesm

Activation of disulfide bond cleavage triggered by hydrophobization and lipophilization of functionalized dihydroasparagusic acid

Concisely synthesized and functionalized dihydroasparagusic acid (DHAA) derivatives were used to show that the introduction of a hydrophobic functional group dramatically reduced air oxidation activity at the dithiol moieties and dominantly activated the cleavage of S-S bonds in proteins, presumably due to the hydrophobization and lipophilization. Notably, the reaction sites of water-reactive dithiol moieties behaved similarly to hydrophobic and lipophilic functional groups, which suggests impersonation of the reaction site.

Synthesis of Asparagusic Acid Modified Lysine and its Application in Solid-Phase Synthesis of Peptides with Enhanced Cellular Uptake

Cyclic disulfides, such as asparagusic acid, enhance the uptake of a variety of cargoes into live cells. Here, we report a robust and scalable synthesis of an asparagusic acid modified lysine. This amino acid can be used in solid-phase peptide synthesis. We confirmed that incorporation of this building block into the sequence of a peptide increases its cellular uptake substantially.

1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS

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1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS

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Dithiolan derivatives, their preparation and their therapeutic effect

A compound of formula (I): wherein one of m and n represents 0, and the other represents 0, 1 or 2; k represents 0 or 1 to 12; R1 is hydrogen, an aryl, a heterocyclic, an alkyl, a hydroxy or -OR7, wherein R7 is an alkyl, an alkenyl or an aralkyl; A is -CON(R2)SO2-, wherein R2 is hydrogen, an alkyl or an aralkyl; B is a single bond; and pharmaceutically acceptable salts thereof. The compounds have the ability to enhance the activity of glutathione reductase and can therefore be used for the treatment and prevention of a variety of diseases including cataracts.

Novel Alkylation with Tetrathiotungstates and Tetrathiomolybdates: Facile Synthesis of Disulfides from Alkyl Halides

A novel reaction of alkyl halides with piperidinium tetrathiotungstate or piperidinium tetrathiomolybdate (MS42-) has been found to afford disulfides in good to excellent isolated yields under very mild reaction conditions.

Synthesis and Thermal Stability of 4-Substituted 1,2-Dithiolanes

Disodium 2-cyano-3,3-bis(sulfido)propenamide (6) has been used as a double synthon for SH- in the preparation of 1,3-dithiols.Oxidation of the dithiols gives 4-substituted 1,2-dithiolanes, e.g. asparagusic acid (3).The energy splits between the first and second ionization potantials in 3 and the other 1,2-dithiolanes (8-11) have been determined by ultraviolet photoelectron spectroscopy.The relative stability of these compounds do not correlate with the measured ΔE values.Hence, factors besides the S-S torsional angle must influence these stabilities.

Biosynthesis of Sulfur Compounds. Investigations of the Biosinthesis of Asparagusic Acid.

Investigations of the biosynthesis of the naturally occuring 1,2-dithiolane asparagusic acid (1) in Asparagus officinalis have shovn that the substance is derived from inobutyric acid via the intermediacy of methacrylic acid, 2-methyl-3-mercaptopropionic acid, and S-(2-carboxy-n-propyl) cysteine.The conversion of isobutyric acid to methacrylic acid in Asparagus has also been shown to proceed by oxidation of the 2-pro-S methyl group of isobutyrate.Finally, the absolute configuration of naturally occuring S-(2-carboxy-n-propyl)cysteine has been determined.