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
• Article Data: 10

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

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

Downstream Products

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

Relevant articles and documents

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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.

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

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