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

Chemical Properties

Colorless liquid

Uses

Different sources of media describe the Uses of 5728-20-1 differently. You can refer to the following data:
1. 3,4-Dichloro-1,2,5-thiadiazole is a chlorinated thiadiazole that is a potent inhibitors of nitrification in soil. 3,4-Dichloro-1,2,5-thiadiazole is used as a building block in the preparaton of the β-adrenergic blocking agent, Timolol.
2. 3,4-Dichloro-1,2,5-thiadiazole has been employed:as 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 moleculesin preparation of [1,2,5]thiadiazol-3-yl-piperazine compounds
3. 3,4-Dichloro-1,2,5-thiadiazole is a chlorinated thiadiazole that is a potent inhibitors of nitrification in soil. 3,4-Dichloro-1,2,5-thiadiazole is used as a building block in the preparaton of the β-adrenergic blocking agent, Timolol (T443700).

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

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

Downstream Products

• 676609-18-0 C₁₇H₂₃ClN₆OS 
• 7716-66-7 3-chloro-1,2-benzisothiazole 
• 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 
• 870987-89-6 3-chloro-4-(4-methylpiperazin-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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