52123-54-3

Basic information

• Product Name: N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE
• Synonyms: N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE;N-Chloromethyl-N-BenzenecarbamoylChloride;(CHLOROMETHYL)PHENYLCARBAMICCHLORIDE;N-chloromethyl-N-benzenecarbamoyl chloride N-chloromethyl-N-benzenecarbamoyl chloride;N-Chlorocarbonyl-N-chloromethylaniline
• CAS NO: 52123-54-3
• Molecular Formula: C₈H₇Cl₂NO
• Molecular Weight: 204.05328
• Mol File: 52123-54-3.mol
• Article Data: 4

Chemical Properties

• Melting Point: 45-46℃
• Boiling Point: 318.8±25.0 °C(Predicted)
• Appearance: /
• Density: 1.385±0.06 g/cm3(Predicted)
• PKA: -0.48±0.50(Predicted)
• CAS DataBase Reference: N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE(52123-54-3)
• EPA Substance Registry System: N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE(52123-54-3)

Safety Data

• Hazardous Substances Data: 52123-54-3(Hazardous Substances Data)

Usage

General Description

N-Chloromethyl-N-phenylcarbamoyl chloride is a chemical compound used in the synthesis of pharmaceuticals and agrochemicals. It is a highly reactive compound that is primarily used as a reagent in organic reactions, particularly in the production of urethanes and carbamates. N-CHLOROMETHYL-N-PHENYLCARBAMOYL CHLORIDE is a powerful chlorinating agent, and is often used in the pharmaceutical industry to introduce the chloromethyl group into various compounds. It is important to handle this compound with care, as it is corrosive and can cause severe irritation to the skin and eyes. Additionally, it should be stored and handled in a well-ventilated area, as it can release toxic gases when exposed to heat or moisture.

Synthetic route

N-methyl-N-phenylformamide (93-61-8) → N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3)

Conditions	Yield
With sulfuryl dichloride; 2,2'-azobis(isobutyronitrile) In tetrachloromethane Substitution; Heating;	64%

N-dichloromethyl-N-phenylcarbamoyl chloride → N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3)

Conditions	Yield
In chlorobenzene Green chemistry;

N-methylaniline (100-61-8) → N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorine / chlorobenzene / 40 °C / Green chemistry 2: chlorobenzene / Green chemistry View Scheme
Multi-step reaction with 2 steps 1: chloroform / 15 - 50 °C 2: 2,2'-azobis(isobutyronitrile); chlorine / 55 °C View Scheme
Multi-step reaction with 2 steps 1: n-butyl formate / 50 - 60 °C / Flow reactor; Large scale 2: hydrogenchloride / 50 - 60 °C / Flow reactor; Large scale View Scheme

N-phenyl-N-methylcarbamoyl chloride (4285-42-1) → N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3)

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); chlorine at 55℃;
With hydrogenchloride at 50 - 60℃; Temperature; Flow reactor; Large scale;

N-tert-butyl-N'-isopropylthiourea (52599-24-3) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → buprofezin (69327-76-0)

Conditions	Yield
Stage #1: N-Chloromethyl-N-phenylcarbamoyl chloride With dipotassium peroxodisulfate; 3,6-dimethyl-3,6-dihydroperoxy-4,5-dioxaoctane at 40 - 45℃; Flow reactor; Large scale; Stage #2: N-tert-butyl-N'-isopropylthiourea With tetradecyltrimethylammonium chloride; calcium hydroxide at 15 - 50℃; Reagent/catalyst; Temperature; Flow reactor; Large scale;	92.3%
With sodium acetate In water; toluene at 30 - 45℃; for 2h; Temperature; Reagent/catalyst;	87%
With sodium hydrogencarbonate In water; chlorobenzene at 0 - 30℃; for 5.5h; Green chemistry;
With ammonia In 1,4-dioxane at 10 - 40℃; for 5h; Reagent/catalyst;

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(2-Fluoro)phenyl-5-mercapto-1,2,4-triazole (261633-13-0) → 2-(2-fluoro-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

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

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3a,4,5,6,7,7a-hexahydro-1H-benzimidazole-2-thiol (30086-64-7) → 3-phenyl-2,3,4b,5,6,7,8,8a-octahydro-1-thia-3,4a,9-triaza-fluoren-4-one

Conditions	Yield
With triethylamine In tetrahydrofuran; benzene Heating;	87%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(4-methoxyphenyl)-1H-1,2,4-triazole-5-thiol (33901-36-9) → 2-(4-methoxy-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	86%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(2,4-dichlorophenyl)-5-mercapto-1,2,4,s-triazole (26028-68-2) → 2-(2,4-dichloro-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	85%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(4-Fluoro)phenyl-5-mercapto-1,2,4-triazole (114058-91-2) → 2-(4-fluoro-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Condensation; Cyclization;	85%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(3-Fluoro)phenyl-5-mercapto-1,2,4-triazole (306298-82-8) → 2-(3-fluoro-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Condensation; Cyclization;	83%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-tert-butyl-5-mercapto-1,2,4-triazole (38449-51-3) → 2-tert-butyl-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	83%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 5-(3,5-dimethyl-phenyl)-2H-[1,2,4]triazole-3-thiol → 2-(3,5-dimethyl-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	82%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-(2,4-Dichloro-5-fluoro)phenyl-5-mercapto-1,2,4-triazole (306298-83-9) → 2-(2,4-dichloro-5-fluoro-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Condensation; Cyclization;	82%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + Benzimidazol-2-thiol (134469-07-1) → 3-phenyl-2,3-dihydro-1-thia-3,4a,9-triaza-fluoren-4-one

Conditions	Yield
With triethylamine In tetrahydrofuran; benzene Heating;	82%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 5-(4-ethyl-phenyl)-2H-[1,2,4]triazole-3-thiol → 2-(4-ethyl-phenyl)-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	81%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 3-methyl-5-mercapto-1,2,4-triazole (7271-44-5) → 2-methyl-5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	81%

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 1H-1,2,4-triazole-5-thiol (3179-31-5) → 5-phenyl-5,6-dihydro-7-thia-1,3,3a,5-tetraaza-inden-4-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	78%

1-(3,4-dichlorobenzyl)-3-(2,2,2-trifluoroethyl)thiourea + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-(2,2,2-trifluoroethylimino)-3-(3,4-dichlorobenzyl)-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In benzene

1-(4-phenoxybenzyl)-3-(2,2,2-trifluoroethyl)thiourea + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-(2,2,2-trifluoroethylimino)-3-(4-phenoxybenzyl)-5-phenyl-tetrahydro-1,3,5-thiadiazin-one (123108-34-9)

Conditions	Yield
In benzene

1-(4-trifluoromethoxybenzyl)-(2,2,2-trifluoroethyl)thiourea + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-(2,2,2-trifluoroethylimino)-3-(4-trifluoromethoxybenzyl)-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In ethyl acetate; benzene

aqueous potassium hydroxide + N-tert-butyl-N'-isopropylthiourea (52599-24-3) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-tert-butylimino-3-isopropyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazin-4-one

Conditions	Yield
In N-methyl-acetamide; acetone

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + N,N-dimethylthiourea (534-13-4) → 2-Methylimino-3-methyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In water; benzene

1-methyl-3-benzyl thiourea (2740-94-5) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-Benzylimino-3-methyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In aqueous potassium hydroxide

1-isopropyl-3-methylthiourea (4041-94-5) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-Isopropylimino-3-methyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In toluene

1-isopropyl-3-isobutylthiourea (25343-73-1) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-Isopropylimino-3-isobutyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
With dimethyl sulfoxide; triethylamine In tetrahydrofuran

1-cyclohexyl-3-(tert-butyl)thiourea (34780-32-0) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-t-Butylimino-3-cyclohexyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
With pyridine

N-methyl-N'-octylthiourea (51793-62-5) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-n-Octylimino-3-methyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
With sodium hydroxide In hydrogenchloride; ethanol

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + N-(2-butyl)-N'-phenylthiourea (15093-37-5) → 2-s-Butylimino-3,5-diphenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
With sodium carbonate; dimethyl sulfoxide In ethyl acetate

1-methyl-3-o-tolyl-thiourea (2827-17-0) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 1,8-diazabicyclo[5.4.0]undec-7-ene (6674-22-2) → 3-methyl-5-phenyl-2-o-tolylimino-[1,3,5]thiadiazinan-4-one (69327-55-5)

Conditions	Yield
In benzene

N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) + 1,3-diisopropylthiourea (2986-17-6) → buprofezin

Conditions	Yield
With sodium carbonate In water; acetone; benzene

1-(4-trifluoromethoxybenzyl)-3-(2,2,2-trifluoroethyl)thiourea (128273-53-0) + N-Chloromethyl-N-phenylcarbamoyl chloride (52123-54-3) → 2-(2,2,2-trifluoroethylimino)-3-(4-trifluoromethoxybenzyl)-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

Conditions	Yield
In ethyl acetate; benzene

Upstream product

• 4285-42-1 N-phenyl-N-methylcarbamoyl chloride 
• 100-61-8 N-methylaniline 
• 93-61-8 N-methyl-N-phenylformamide 

Downstream Products

• 69327-76-0 buprofezin 
• 953030-84-7 2-tert-butylimino-3-isopropyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazin-4-one 

Relevant articles and documents

Method for continuously synthesizing buprofezin

The invention discloses a method for continuously synthesizing buprofezin, and belongs to the technical field of chemical synthesis. The method for continuously synthesizing buprofezin comprises the following steps: S1, continuously acylating N-methylaniline and phosgene in a solvent, and continuously deacidifying to obtain an acyl chloride solution; S2, carrying out continuous chlorination and continuous deacidification on the acyl chloride solution and chlorine under the action of an initiator to obtain a chloride solution; S3, adding buprothiourea, a catalyst and an acid-binding agent intothe chloride solution, carrying out continuous mixing reaction, crystallizing and drying a reaction product to obtain buprofezin of which the content is greater than or equal to 99.0% and the total yield is greater than or equal to 88% based on N-methylaniline. The method for continuously synthesizing buprofezin solves the defects caused by batch production in China, has the advantages of continuous reaction, high automation degree, small equipment size, high operation safety, few side reaction products, high conversion rate and good product quality, can effectively improve the production efficiency and reduce the production cost, and has very good popularization and application values.

Buprofenzin process for the preparation of

The invention relates to a preparation method of buprofezin, which comprises the following steps of actinism, chlorination, synthesis and distillation crystallization. The actinism step employs dioxane or chloroform, the chlorination step employs dioxane or N-chloromethyl-N-phenyl carbamyl chloride as a solvent; and the synthesis step employs organic amine to participate in condensation. According to the invention, dioxane, chloroform or N-chloromethyl-N-phenyl carbamyl chloride are employed as the solvents, so that good dissolving performance is provided to the raw material, and the dioxane, chloroform or N-chloromethyl-N-phenyl carbamyl chloride has little solubility to HCL and is in favor of reaction, the production yield can reach as high as more than 82%; organic amine is employed for replacing ammonium bicarbonate as alkali for synthesis reaction, and can be recovered so that the discharge of ammonia nitrogen in waste water is reduced.