5728-20-1

Basic information

• Product Name: 3,4-Dichloro-1,2,5-thiadiazole
• Synonyms: DCTD;3,4-DICHLORO-1,2,5-THIADIAZOLE;3,4-Dichloro-1,2,5-Triadiazole;4ETHYL4AMINOBIPHENYL;3,4-Dichlor-1,2,5-thiadiazol;3,4-DICHLORO-1,2,5-THIADIAZOLE 99+%;4,5-Dichloro-2,1,3-thiadiazole;,4-Dichloro-1,2,5-thiadiazole
• CAS NO: 5728-20-1
• Molecular Formula: C₂Cl₂N₂S
• Molecular Weight: 155.01
• EINECS: 227-232-7
• Product Categories: Xanthones;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Thiadiazoles;ThiadiazolesHeterocyclic Building Blocks;Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 5728-20-1.mol
• Article Data: 3

Chemical Properties

• Melting Point: 82-83 °C
• Boiling Point: 158°C
• Flash Point: >100°C
• Appearance: liquid
• Density: 1.648
• Vapor Pressure: 3.47mmHg at 25°C
• Refractive Index: 1.561
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Soluble in chloroform and methanol.
• PKA: -3.82±0.10(Predicted)
• Sensitive: Hygroscopic
• BRN: 606585
• CAS DataBase Reference: 3,4-Dichloro-1,2,5-thiadiazole(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-Dichloro-1,2,5-thiadiazole(5728-20-1)
• EPA Substance Registry System: 3,4-Dichloro-1,2,5-thiadiazole(5728-20-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• RIDADR: UN2810
• WGK Germany: 2
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 5728-20-1(Hazardous Substances Data)

Usage

Description

3,4-Dichloro-1,2,5-thiadiazole is a chlorinated thiadiazole compound known for its potent nitrification inhibition properties in soil. It is also recognized as a valuable building block in the synthesis of various pharmaceutical compounds, such as the β-adrenergic blocking agent, Timolol.

Uses

Used in Pharmaceutical Industry:
3,4-Dichloro-1,2,5-thiadiazole is used as a building block for the preparation of the β-adrenergic blocking agent, Timolol (T443700), which is an essential medication for treating conditions like hypertension, angina, and certain heart rhythm disorders.
Used in Chemical Research:
3,4-Dichloro-1,2,5-thiadiazole serves as a guest molecule to investigate solid-state 13C NMR spectra of inclusion compounds of 2,6-dimethyl-bicyclo[3.3.1]nonane-exo-2-exo-6-diol with small organic molecules. This application aids in understanding the structural and chemical properties of these compounds.
Used in Agricultural Industry:
3,4-Dichloro-1,2,5-thiadiazole is used as a potent inhibitor of nitrification in soil, which can help control the conversion of ammonia to nitrate, thereby managing nitrogen levels and potentially reducing environmental pollution from excess nitrogen compounds.
Used in Organic Synthesis:
3,4-Dichloro-1,2,5-thiadiazole is employed in the preparation of [1,2,5]thiadiazol-3-yl-piperazine compounds, which have potential applications in various fields, including pharmaceuticals and materials science.
Chemical Properties:
3,4-Dichloro-1,2,5-thiadiazole is a colorless liquid, which makes it suitable for use in various chemical reactions and processes.

Synthesis Reference(s)

Tetrahedron Letters, 15, p. 1687, 1974 DOI: 10.1016/S0040-4039(01)82554-5

InChI:InChI=1/C2Cl2N2S/c3-1-2(4)6-7-5-1

Synthetic route

dichloroglyoxime (2038-44-0) → 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
With pyridine; disulfur dichloride In acetonitrile at -25℃; for 5h; Inert atmosphere; Reflux;	78%
With sulfur dichloride In N,N-dimethyl-formamide

ethanedinitrile (460-19-5) → 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
With disulfur dichloride In N,N-dimethyl-formamide
With sulfur dichloride

hexa-P-phenyl-P,P'-ethane-1,2-diyldiamino-bis-phosphonium; dichloride (33355-75-8) → 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
With sulfur tetrafluoride; triethylamine In dichloromethane

2-aminoacetonitrile (540-61-4) → 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
With disulfur dichloride; chlorine In N,N-dimethyl-formamide

1,2-diaminoethane dihydrochloride (333-18-6) → 3-Chloro-1,2,5-thiadiazole (5097-45-0) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
With disulfur dichloride; chlorine; iron In N,N-dimethyl-formamide	A 5 g B 115.7 g

piperidine (110-89-4) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-(piperidin-1-yl)-4-chloro-1,2,5-thiadiazole

Conditions	Yield
at 110 - 120℃;	100%
at 90 - 100℃; Inert atmosphere;	94%
In neat (no solvent) at 90℃; for 2h;
In neat (no solvent) at 90℃; for 2h;

4-benzylpyperidine (31252-42-3) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-(4-benzylpiperidin-1-yl)-4-chloro-1,2,5-thiadiazole

Conditions	Yield
at 110 - 120℃;	100%

morpholine (110-91-8) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-Morpholino-4-chloro-1,2,5-thiadiazole (30165-96-9)

Conditions	Yield
	98%
at 110℃; for 2.5h; Inert atmosphere;	95%
at 110 - 120℃;	90%

hexamethylene imine (111-49-9) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-(1-azepanyl)-4-chloro-1,2,5-thiadiazole (1119451-34-1)

Conditions	Yield
at 120℃; for 4h; Inert atmosphere;	98%

(S)-1-tert-butylamino-2,3-dihydroxypropane (30315-46-9) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → (S)-(-)-3-(3-tert-butylamnio-2-hydroxypropoxy)-4-chloro-1,2,5-thiadiazole (26791-15-1)

Conditions	Yield
With potassium tert-butylate In tert-butyl alcohol for 1h; Heating / reflux;	96.6%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 4,5-dimethyl-2-(trimethylsilyl)phenyl triflate → 3-chloro-5,6-dimethyl-1,2-benzoisothiazole (41533-37-3)

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere;	96%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 6-(trimethylsilyl)benzo[d][1,3]dioxol-5-yl triflate (717903-52-1) → 3-chloro-5,6-dioxolo-1,2-benzoisothiazole

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere;	96%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 4,5-dimethoxy-2-(trimethylsilyl)phenyl trifluoromethanesulfonate → 3-chloro-5,6-dimethoxy-1,2-benzoisothiazole

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere;	93%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 2-(Chlorimino)-N-(difluor-λ4-sulfanyliden)-1,1,2-trifluorethanamin (82878-41-9) + 2-Chlor-2-(chlorimino)-N-(difluor-λ4-sulfanyliden)-1,1-difluorethanamin (82878-40-8) + N,N-Dichlor-N'-(difluor-λ4-sulfanyliden)-1,1,2,2-tetrafluor-1,2-ethandiamin (32751-05-6) + Bis<2-<(difluor-λ4-sulfanyliden)amino>-1,1,2,2-tetrafluorethyl>diazen (82878-42-0)

Conditions	Yield
With HgF3 at 140℃; for 1h; further reagent: BrF3;	A n/a B n/a C n/a D 91%
With bromine trifluoride at -15℃; Title compound not separated from byproducts;

1-methyl-piperazine (109-01-3) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-chloro-4-(4-methylpiperazin-1-yl)-1,2,5-thiadiazole (870987-89-6)

Conditions	Yield
In ethanol at 100℃; for 2.5h; Sealed tube; Microwave irradiation;	91%
at 105 - 110℃; for 2.5h;	90.2%
at 105 - 110℃; for 2.5h;	90.2%

4-phenyl-1-piperazine (92-54-6) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-chloro-4-(4-phenylpiperazin-1-yl)-1,2,5-thiadiazole (1048981-72-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃;	91%
at 105 - 110℃; for 2.5h;

4-phenylpiperidine (771-99-3) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1)

Conditions	Yield
at 110 - 120℃;	91%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + lithium hexamethyldisilazane (4039-32-1) → C8H18ClN3SSi2

Conditions	Yield
In n-heptane at -78℃; for 0.5h;	90%

1,3-dimethyl-1,1,3,3-tetraphenyldisilazane (7453-26-1) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → C28H26ClN3SSi2

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -10℃; for 0.5h;	88%

pyrrolidine (123-75-1) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-(pyrrolidin-1-yl)-4-chloro-1,2,5-thiadiazole (173053-55-9)

Conditions	Yield
at 22℃; Inert atmosphere;	87%

titanium tetrachloride (7550-45-0) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → (SN2C2Cl2)2TiCl4 (80044-97-9)

Conditions	Yield
In dichloromethane under N2 and exclusion of air, to a soln. of SN2C2Cl2 in dry CH2Cl2 addn. of TiCl4 in CH2Cl2 under stirring at room temp.; removal of solvent, recrystn. (CH2Cl2), sublimation (vac., room temp.), elem. anal.;	82%

decahydroisoquinoline (2744-08-3, 2744-09-4, 6329-61-9) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-chloro-4-(octahydroisoquinolin-2(1H)-yl)-1,2,5-thiadiazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃;	81%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → C2Cl2N2O3S2

Conditions	Yield
With sulfur trioxide In dichloromethane Ambient temperature;	79%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 4-(4-chloro-[1,2,5]thiadiazol-3-yl)piperazine-1-carboxylic acid tert-butyl ester (291748-19-1)

Conditions	Yield
In N,N-dimethyl-formamide Heating;	77%
With potassium carbonate In acetonitrile	1.54 g (31%)
With diisopropylamine In N,N-dimethyl-formamide at 100℃; for 16h;	2.7 g
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 100℃; for 16h;

2-(trimethylsilyl)phenyl trifluoromethanesulfonate (88284-48-4) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-chloro-1,2-benzisothiazole (7716-66-7)

Conditions	Yield
With cesium fluoride In tetrahydrofuran Reagent/catalyst; Solvent; Inert atmosphere;	76%

1,1,3,3-tetramethyl-1,3-diphenyldisilazane (3449-26-1) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → C18H22ClN3SSi2

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -10℃; for 0.5h;	75%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + C19H26F3IO5SSi3 → 3-chloro-5,6-oxadisilole-1,2-benzoisothiazole

Conditions	Yield
Stage #1: C19H26F3IO5SSi3 With cesium fluoride Stage #2: 3,4-dichloro-1,2,5-thiadiazole In tetrahydrofuran at 60℃; for 3h;	75%

2,2,6,6-tetramethyl-piperidine (768-66-1) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 2-chloro-2-(2,2,6,6-tetramethyl-1-piperidinylthio)iminoacetonitrile (895167-58-5)

Conditions	Yield
Stage #1: 2,2,6,6-tetramethyl-piperidine With n-butyllithium In tert-butyl methyl ether at -20℃; Stage #2: 3,4-dichloro-1,2,5-thiadiazole In tert-butyl methyl ether at -50℃;	74%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + KF → 3,4-Difluoro-1,2,5-thiadiazole (82878-37-3) + 3-chloro-4-fluoro-1,2,5-thiadiazole (82878-38-4)

Conditions	Yield
In sulfolane at 180℃; for 10h;	A 73% B 24%
In sulfolane at 180℃; for 10h; further reagent: 18-Crown<6>, XeF2;	A 48% B 24%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + lithium hexamethyldisilazane (4039-32-1) → 2-chloro-2-(N,N-bis(trimethylsilyl)aminothio)iminoacetonitrile (895167-57-4)

Conditions	Yield
In tetrahydrofuran; diethyl ether; cyclohexane at -78℃; for 1h;	73%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 2-methoxy-6-(trimethylsilyl)phenyltrifluoromethanesulfonate (881009-83-2) → 3-chloro-4-methoxy-1,2-benzoisothiazole (103486-06-2)

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere; regioselective reaction;	70%

4-bromo-2-methoxy-6-(trimethylsilyl)phenyl trifluoromethanesulfonate + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) → 3-chloro-4-methoxy-6-bromo-1,2-benzoisothiazole + 3-chloro-5-bromo-7-methoxy-1,2-benzoisothiazole

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere; regioselective reaction;	A 69% B 9%

2-(trimethylsilyl)phenyl trifluoromethanesulfonate (88284-48-4) + 3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + malonic acid dimethyl ester (108-59-8) → 3-Amino-benzo[b]thiophene-2-carboxylic acid methyl ester (35212-85-2) + dimethyl 2,1-benzoisothiazole-3-malonate

Conditions	Yield
Stage #1: 2-(trimethylsilyl)phenyl trifluoromethanesulfonate; 3,4-dichloro-1,2,5-thiadiazole With cesium fluoride In tetrahydrofuran at 20 - 65℃; Inert atmosphere; Stage #2: malonic acid dimethyl ester With sodium methylate In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;	A 11% B 68%

3,4-dichloro-1,2,5-thiadiazole (5728-20-1) + 3,6-dimethyl-2-(trimethylsilyl)phenyl triflate (780820-44-2) → 3-chloro-4,7-dimethyl-1,2-benzoisothiazole

Conditions	Yield
With cesium fluoride In tetrahydrofuran Inert atmosphere;	67%

Upstream product

• 460-19-5 ethanedinitrile 
• 33355-75-8 hexa-P-phenyl-P,P'-ethane-1,2-diyldiamino-bis-phosphonium; dichloride 
• 540-61-4 2-aminoacetonitrile 
• 2038-44-0 dichloroglyoxime 
• 333-18-6 1,2-diaminoethane dihydrochloride 

Downstream Products

• 7716-66-7 3-chloro-1,2-benzisothiazole 
• 506-77-4 cyanogen chloride 
• 870987-89-6 3-chloro-4-(4-methylpiperazin-1-yl)-1,2,5-thiadiazole 
• 35212-85-2 3-Amino-benzo[b]thiophene-2-carboxylic acid methyl ester 
• 1154574-50-1 3-(4-benzylpiperidin-1-yl)-4-chloro-1,2,5-thiadiazole 
• 460-19-5 ethanedinitrile 
• 16681-13-3 chlorine isothiocyanate 
• 160039-33-8 cyanogen N-sulfide 
• 1119451-34-1 3-(1-azepanyl)-4-chloro-1,2,5-thiadiazole 
• 173053-54-8 3-(piperidin-1-yl)-4-chloro-1,2,5-thiadiazole 
• 173053-55-9 3-(pyrrolidin-1-yl)-4-chloro-1,2,5-thiadiazole 
• 1048981-72-1 3-chloro-4-(4-phenylpiperazin-1-yl)-1,2,5-thiadiazole 
• 183803-84-1 chloronitrile sulfide 
• 7704-34-9 sulfur 

Relevant articles and documents

Synthesis of aryloxy-substituted 1,2,5-thiadiazoles by the Ullmann reaction

3-Aryloxy-1,2,5-thiadiazoles were synthesized by the Ullmann reaction either from 3-chloro-1,2,5-thiadiazoles and phenols having donor substituents or from 3-hydroxy-1,2,5-thiadiazoles and chlorobenzenes containing acceptor substituents.

A general synthetic system for 1,2,5-thiadiazoles

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