105827-91-6

Basic information

• Product Name: 2-Chloro-5-chloromethylthiazole
• Synonyms: 2-CHLORO-5-CHLOROMETHYLTHIAZOLE;2-CHLORO-5-CHLOROMETHYL-1,3-THIAZOLE;2-chloro-5-(chloromethyl)thiozole;Thiazole, 2-chloro-5-(chloromethyl)- (9CI);2-Chloro-5-(chlormethyl)thiazole;2-Chloro-5-chloromehtylthiazole;2-Chloro-5-Chloromethyl;ccmt
• CAS NO: 105827-91-6
• Molecular Formula: C₄H₃Cl₂NS
• Molecular Weight: 168.04
• EINECS: 429-830-5
• Product Categories: HALOMETYL;Miscellaneous;API;Thiazoles;Pesticide intermediate
• Mol File: 105827-91-6.mol
• Article Data: 43

Chemical Properties

• Melting Point: 31
• Boiling Point: 268.6 °C at 760 mmHg
• Flash Point: 116.3 °C
• Appearance: white to pale yellow crystal or colorless liquid
• Density: 1.503 g/cm³
• Vapor Pressure: 0.0126mmHg at 25°C
• Refractive Index: n20/D1.571
• Storage Temp.: 2-8°C
• Solubility: soluble in Methanol
• PKA: 0.19±0.10(Predicted)
• BRN: 5861439
• CAS DataBase Reference: 2-Chloro-5-chloromethylthiazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-5-chloromethylthiazole(105827-91-6)
• EPA Substance Registry System: 2-Chloro-5-chloromethylthiazole(105827-91-6)

Safety Data

• Hazard Codes: Xi,N,T
• Statements: 36/37/38-51/53-43-34-24-22
• Safety Statements: 26-37-61-45-36/37/39
• RIDADR: 2922
• WGK Germany: 3
• HazardClass: 8
• PackingGroup: Ⅱ
• Hazardous Substances Data: 105827-91-6(Hazardous Substances Data)

Usage

Description

2-Chloro-5-chloromethylthiazole is used as pharmaceutical and agrochemical intermediate. It is also used as intermediate of insecticides Thiamethoxam and Clothianidin. It is also useful in in the synthesis of Ritonavir (R535000); a second-generation anti-AIDS drug and a selective HIV protease inhibitor.

Chemical Properties

White crystal or powder

InChI:InChI=1/C4H3Cl2NS/c5-1-3-2-7-4(6)8-3/h2H,1H2

Synthetic route

2-chloro-3-isothiocyanato-1-propene (14214-31-4) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With hydrogenchloride; chlorine In 1,2-dichloro-ethane at 0 - 60℃; for 1h; Temperature;	98%
With chlorine In dichloromethane at 20 - 30℃;	96%
With sulfuryl dichloride In chloroform at 36℃; for 3h;	94.6%

3-chloro-1-isothiocyanato-1-propene (196406-44-7) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With sulfuryl dichloride; sodium hydrogencarbonate	91.2%
With sulfuryl dichloride; sodium carbonate In chloroform	69.2%
With sulfuryl dichloride; sodium carbonate	68.3%
With sodium carbonate In chloroform	62.4%
With sulfuryl dichloride; sodium carbonate	45.3%

5-(chloromethyl)-2-(phenylthio)thiazole → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With hydrogenchloride; chlorine In water; chlorobenzene at 20 - 25℃; for 6h;	90%

5-methylene-1,3-thiazolidine-2-thione (52829-72-8) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With sulfuryl dichloride In dichloromethane; water for 1h; Chlorination;	80%
With sulfuryl dichloride In dichloromethane; water at 0 - 20℃; for 1h;	70%
With sodium hydroxide; chlorine In water; acetic acid at 10 - 15℃; for 2 - 3h;	56%
With sodium hydroxide; sulfuryl dichloride In dichloromethane; water at -5℃; for 0.0833333h;	31%
In chloroform; ethyl acetate

2-chloro-5-methyl-thiazole (33342-65-3) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With N-chloro-succinimide In chloroform at 50℃; for 5h;	65%
With N-chloro-succinimide In chloroform at 50℃; for 5h; Time;	65%
With N-chloro-succinimide; dibenzoyl peroxide In tetrachloromethane Chlorination; Heating;	50%
With N-chloro-succinimide; dibenzoyl peroxide In tetrachloromethane at 20℃; for 72h; Heating / reflux;

(E)-3,3'-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (764-28-3) + N-allyl isothiocyanate (57-06-7) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With N-chloro-succinimide; sulfuryl dichloride In dichloromethane	64.5%
With N-chloro-succinimide; chlorine In dichloromethane	57%
With N-chloro-succinimide; sulfuryl dichloride In 1,1-dichloroethane	56.3%

2-benzylsulfanyl-5-chloromethyl-thiazole (192439-48-8) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
In dichloromethane for 2h; Chlorination;	60%

2-chloroallylisonitrile → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With sulfur dichloride In tetrachloromethane at 40℃; for 4h; Cyclization;	50%
With thionyl chloride; sulphur dichloride In tetrachloromethane

N-allyl isothiocyanate (57-06-7) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With N-chloro-succinimide; sulfuryl dichloride In dichloromethane	48%
With sulfuryl dichloride

N-(2-chloroallyl)formamide (188988-52-5) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
With thionyl chloride; sulfur dichloride for 24h; Cyclization; chlorination; Heating;	42%
With thionyl chloride; sulphur dichloride	42%

2,3-Dichloroprop-1-ene (78-88-6) + sodium thiocyanide (540-72-7) → α-Cl-β-thiazolyl chloride (105827-91-6)

Conditions	Yield
Stage #1: 2,3-Dichloroprop-1-ene; sodium thiocyanide In acetonitrile at 85℃; for 6h; Stage #2: With hydrogenchloride In dichloromethane; water for 6h; Solvent; Temperature; Electrochemical reaction;

ethylamine (75-04-7) + α-Cl-β-thiazolyl chloride (105827-91-6) → N-((2-chlorothiazol-5-yl)methyl)ethylamine

Conditions	Yield
In water; 1,2-dichloro-ethane at 20 - 50℃;	98.5%
In ethanol; water at 0 - 20℃; for 7h;	85%
With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In chloroform; water at 20℃;	3.37 g

α-Cl-β-thiazolyl chloride (105827-91-6) + 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5-oxadiazin-4-amine (153719-38-1) → thiamethoxam (153719-23-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 16h;	98%
Stage #1: 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5-oxadiazin-4-amine With potassium carbonate In ethanol for 0.5h; Autoclave; Stage #2: α-Cl-β-thiazolyl chloride In ethanol at 120℃; for 4h; Temperature; Autoclave;	95.2%
With N-ethyl-N,N-diisopropylamine; carbonic acid dimethyl ester at 20 - 40℃; for 1h; Temperature; Reagent/catalyst;	94.3%

α-Cl-β-thiazolyl chloride (105827-91-6) + tert-butyl methyl(piperidin-4-yl)carbamate (108612-54-0) → tert-butyl N-methyl-N-{1-[(2-chlorothiazol-5-yl)methyl]piperidin-4-yl}carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h;	98%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h;	92.7 g

α-Cl-β-thiazolyl chloride (105827-91-6) + (piperidin-4-yl)carbamic acid tert-butyl ester (73874-95-0) → tert-butyl N-{1-[(2-chlorothiazol-5-yl)methyl]piperidin-4-yl}carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h;	98%

α-Cl-β-thiazolyl chloride (105827-91-6) → 5-(azidomethyl)-2-chlorothiazole (1088445-95-7)

Conditions	Yield
With sodium azide In ethanol for 4h; Inert atmosphere; Reflux;	97%
With sodium azide In ethanol Reflux;
With sodium azide In dimethyl sulfoxide at 25 - 40℃; for 18h;
With sodium azide In ethanol Reflux;

4-hydroxy-benzaldehyde (123-08-0) + α-Cl-β-thiazolyl chloride (105827-91-6) → 4-((2-chlorothiazol-5-yl)methoxy)benzaldehyde (338393-48-9)

Conditions	Yield
With potassium carbonate In ethanol for 6h; Reflux;	95.7%
With potassium carbonate In ethanol for 8h; Reflux;

tricaprylylmethyl ammoniumchloride + tert-butyl methyl ether (1634-04-4) + pyrographite (7440-44-0) + α-Cl-β-thiazolyl chloride (105827-91-6) → 2-chloro-5-(hydroxymethyl)thiazole (145015-15-2)

Conditions	Yield
With sodium hydroxide; aq. NaOH; sodium formate In n-heptane	94.4%

α-Cl-β-thiazolyl chloride (105827-91-6) → [(2-chloro-5-thiazolyl)methyl]amine (120740-08-1)

Conditions	Yield
With hexamethylenetetramine In chloroform for 3h; Heating;	94.3%
With ammonium hydroxide In ethanol at 20℃;	32.4%
With ammonium hydroxide; sodium hydroxide In ethanol; dichloromethane; acetonitrile

vanillin (121-33-5) + α-Cl-β-thiazolyl chloride (105827-91-6) → 3-methoxy-4-((2-chlorothiazol-5-yl)methoxy)benzaldehyde (339018-41-6)

Conditions	Yield
With potassium carbonate In ethanol for 6h; Reflux;	93.6%

3-methyl-4-nitroimino-1,3,5-oxadiazine + α-Cl-β-thiazolyl chloride (105827-91-6) → thiamethoxam (153719-23-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 30 - 70℃;	92.88%
Stage #1: 3-methyl-4-nitroimino-1,3,5-oxadiazine With tetrabutylammomium bromide; potassium carbonate In water; acetonitrile at 70℃; for 1h; Stage #2: α-Cl-β-thiazolyl chloride In water; acetonitrile at 70℃; for 5h;

α-Cl-β-thiazolyl chloride (105827-91-6) + methylamine (74-89-5) → N-(2-chloro-5-thiazolylmethyl)-N-methylamine (120740-06-9)

Conditions	Yield
In ethanol; water at 0 - 20℃; for 5h;	92%

2-(nitroimino)imidazolidine (5465-96-3) + α-Cl-β-thiazolyl chloride (105827-91-6) → (EZ)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-N-nitroimidazolidin-2-ylideneamine

Conditions	Yield
With potassium carbonate In acetonitrile Reflux;	91.5%
With tetrabutylammomium bromide; potassium carbonate In toluene at 47℃; for 7h; Temperature;	91.4%
With potassium carbonate In acetonitrile for 4h; Heating;	66%

α-Cl-β-thiazolyl chloride (105827-91-6) + 1-[6-methyl-4-(4-methylphenyl)-2-thioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-1-ethanone → 1-[1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-methylsulfanyl)-4-methyl-6-(4-tolyl)-1,6-dihydropyrimidin-5-yl]ethanone (1133378-44-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	91%

α-Cl-β-thiazolyl chloride (105827-91-6) + 1-methyl-2-nitroimino-5-n-propyl-1,3,5-triazacyclohexane (141856-46-4) → C11H17ClN6O2S

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; Condensation;	90%

α-Cl-β-thiazolyl chloride (105827-91-6) + 5-acetyl-4-(4-methoxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine (219806-93-6) → 1-[1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-methylsulfanyl)-6-(4-methoxyphenyl)-4-methyl-1,6-dihydropyrimidin-5-yl]ethanone (1133378-45-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	90%

α-Cl-β-thiazolyl chloride (105827-91-6) + triphenylphosphine (603-35-0) → ((2-chlorothiazol-5-yl)methyl)triphenylphosphonium chloride (1168140-08-6)

Conditions	Yield
In chloroform for 48h; Reflux;	90%

α-Cl-β-thiazolyl chloride (105827-91-6) + tralopyril (122454-29-9) → 4-bromo-2-(4-chlorophenyl)-1-(2-chloro-5-thiazolylmethyl)-5-trifluoromethylpyrrole-3-carbonitrile

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 2h; Temperature;	90%

5-(4-methyl-1,2,3-thiadiazol-5-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (1260230-40-7) + α-Cl-β-thiazolyl chloride (105827-91-6) → 5-(5-(((2-chlorothiazol-5-yl)methyl)thio)-4-phenyl-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole (1569752-99-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; under 10343.2 Torr; for 0.25h; Microwave irradiation;	89%

6-chloroquinazolin-4-one (16064-14-5) + α-Cl-β-thiazolyl chloride (105827-91-6) → 6-chloro-3-((2-chlorothiazol-5-yl)methyl)quinazolin-4(3H)-one

Conditions	Yield
Stage #1: 6-chloroquinazolin-4-one With tetra-(n-butyl)ammonium iodide; potassium hydroxide In toluene at 70℃; for 0.166667h; Stage #2: α-Cl-β-thiazolyl chloride In toluene at 70℃; for 1h;	89%

α-Cl-β-thiazolyl chloride (105827-91-6) + 5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol (15264-63-8) → 2-(((2-chlorothiazol-5-yl)methyl)thio)-5-(pyridin-4-yl)-1,3,4-oxadiazole

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide under 10343.2 Torr; for 0.25h; Microwave irradiation; Heating;	88%

α-Cl-β-thiazolyl chloride (105827-91-6) + 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5-oxadiazin-4-amine (153719-38-1) → thiamethoxam

Conditions	Yield
With potassium carbonate; cesium iodide In butanone at 60℃; for 10h;	88%

5-methylcarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (144459-98-3, 31864-21-8) + α-Cl-β-thiazolyl chloride (105827-91-6) → 1-[1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-methylsulfanyl)-4-methyl-6-phenyl-1,6-dihydropyrimidin-5-yl]ethanone (1029433-40-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	87%

α-Cl-β-thiazolyl chloride (105827-91-6) + 1-[4-(4-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-1-ethanone → 1-[6-(4-chlorophenyl)-1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-methylsulfanyl)-4-methyl-1,6-dihydropyrimidin-5-yl]ethanone (1133378-43-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	87%

methyl 2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetate (19414-86-9) + α-Cl-β-thiazolyl chloride (105827-91-6) → methyl 2-(1-((2-chlorothiazol-5-yl)methyl)-5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetate (1383843-32-0)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 65℃; for 2h;	87%

5-(4-chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (1245623-49-7) + α-Cl-β-thiazolyl chloride (105827-91-6) → 5-(4-chlorophenyl)-2-[(2-chloro-1,3-thiazol-5-yl)methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (1332502-88-1)

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 1.5h;	87%

tert-butyl (1-methyl-1H-pyrazol-3-yl)carbamate (128883-86-3) + α-Cl-β-thiazolyl chloride (105827-91-6) → tert-butyl N-[(2-chlorothiazol-5-yl)methyl]-N-(1-methylpyrazol-3-yl)carbamate

Conditions	Yield
Stage #1: tert-butyl (1-methyl-1H-pyrazol-3-yl)carbamate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: α-Cl-β-thiazolyl chloride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h;	87%

Upstream product

• 52829-72-8 5-methylene-1,3-thiazolidine-2-thione 
• 33342-65-3 2-chloro-5-methyl-thiazole 
• 188988-52-5 N-(2-chloroallyl)formamide 
• 192439-48-8 2-benzylsulfanyl-5-chloromethyl-thiazole 
• 14214-31-4 2-chloro-3-isothiocyanato-1-propene 
• 1074-82-4 potassium phtalimide 
• 145015-15-2 2-chloro-5-(hydroxymethyl)thiazole 
• 78-88-6 2,3-Dichloroprop-1-ene 
• 540-72-7 sodium thiocyanide 
• 196406-44-7 3-chloro-1-isothiocyanato-1-propene 
• 764-28-3 (E)-3,3'-(diazene-1,2-diyl)bis(2-methylpropanenitrile) 
• 57-06-7 N-allyl isothiocyanate 

Downstream Products

• 145015-15-2 2-chloro-5-(hydroxymethyl)thiazole 
• 1033619-94-1 (2-chloro-thiazol-5-ylmethyl)-(4-fluorophenyl)-carbamic acid tert-butyl ester 
• 1033833-07-6 1-benzyl-N-((2-chlorothiazol-4-yl)methyl)-N-p-tolyl-1H-imidazole-4-carboxamide 
• 1107009-17-5 (2-chlorothiazol-5-yl)methyl 3,3-bis(4-fluorophenylthio)-N-(phenyl)thiopropionimidate 
• 440109-54-6 N,N'-bis[(2-chloro-1,3-thiazol-5-yl)methyl]cyclohexane-1,2-diamine 
• 1269145-75-6 2-(((2-chlorothiazol-5-yl)methyl)amino)ethanol 
• 1168140-08-6 ((2-chlorothiazol-5-yl)methyl)triphenylphosphonium chloride 
• 1266222-04-1 (S)-1-((2-chlorothiazol-5-yl)methyl)-5-(2-phenyl-1-ethyloxycarbonylethyl)-1,3,5-hexahydrotriazine-2-N-nitroimine 
• 120740-07-0 N-((2-chlorothiazol-5-yl)methyl)ethylamine 
• 1261235-53-3 tert-butyl N-methyl-N-{1-[(2-chlorothiazol-5-yl)methyl]piperidin-4-yl}carbamate 
• 939986-54-6 tert-butyl N-{1-[(2-chlorothiazol-5-yl)methyl]piperidin-4-yl}carbamate 
• 153719-23-4 thiamethoxam 
• 101012-12-8 2-chloro-1,3-thiazole-5-carboxylic acid 
• 45438-77-5 5-thiazolylmethyl chloride 

Relevant articles and documents

Synthesis, characterization and crystal structure of n-(3-((2-chlorothiazol-5-yl)methyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene)nitramide

N-(3-[(2-chlorothiazol-5-yl)methyl]-5-methyl-1,3,5-oxadiazinan-4-ylidene)nitramide (I), i.e., thiamethoxam, it is a broad-spectrum insecticide that effectively controls insects, being a second generation neonicotinoid compound belonging to the chemical subclass the thianicotinyls. It was prepared from 5-(chloromethyl)-2-(phenylthio)thiazole (1) via chlorination by Cl2/HCl system and then condensation by K2CO3/CsI. The product was characterized by NMR and LC-MS. The crystal structure of compound I was investigated using X-ray diffraction and SHELXTL-97 software. The result indicated that compound I crystallized in the monoclinic system, space group P 21/n with a = 6.488(13), b = 28.786 (6), c = 6.804(14) ?, V=1225.1 (5) ?3; Z4.

Synthesis method of 2-chloro-5-chloromethylthiazole by photocatalytic chlorination

The invention relates to the technical field of synthesis of 2-chloro-5-chloromethylthiazole, and provides a synthesis method of 2-chloro-5-chloromethylthiazole by photocatalytic chlorination, which comprises the following steps: S1. adding 2-chloropropenyl thioisocyanate, sulfonyl chloride and acetonitrile into a tower reactor, and stirring to dissolve; S2, adding a catalyst, irradiating with ultraviolet light, and starting chlorination reaction; S3, carrying out reduced pressure distillation to remove the solvent acetonitrile; S4, dissolving distilled residues in dichloromethane, respectively washing with a NaHCO3 solution and water to be neutral, and carrying out reduced pressure distillation to obtain a 2-chloro-5-chloro methylthiazole product. Through the technical scheme, the problems of poor product quality and low yield in the prior art are solved.

Tower reactor preparation 2 chloro -5 chloro - methylthiazole

The invention relates to the technical field 2 chlorine -5 chlorine - methylthiazole preparation, in particular to a tower reactor for preparing 2 chloro -5 chloro - methylthiazole, which comprises the following steps: S1. The sodium thiocyanate and the catalyst tetrabutylammonium bromide are added into the tower reactor, and then are metered into 2, 3 - dichloropropene and toluene respectively, stirred and heated to reflux. S2, followed by addition of tetrabutylammonium bromide, and isomerization reaction was performed after the temperature increase, and after completion of the reaction, negative pressure distillation was performed to obtain 2 - chloroallyl isothiocyanate. To the method, pollution to the environment can be reduced, hydrogen chloride gas generated in the reaction process can be reused, and the problem that the color of the product 2 chlorine -5 chlorine - methyl thiazole is too deep can be solved.