1208-87-3

Basic information

• Product Name: 1-(chloromethyl)-4-(phenylthio)benzene
• Synonyms: 1-(chloromethyl)-4-(phenylthio)benzene;NSC 43056
• CAS NO: 1208-87-3
• Molecular Formula: C₁₃H₁₁ClS
• Molecular Weight: 234.74444
• EINECS: 214-903-4
• Mol File: 1208-87-3.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 372℃
• Flash Point: 167℃
• Appearance: /
• Density: 1.22
• Vapor Pressure: 2.12E-05mmHg at 25°C
• Refractive Index: 1.636
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: 1-(chloromethyl)-4-(phenylthio)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(chloromethyl)-4-(phenylthio)benzene(1208-87-3)
• EPA Substance Registry System: 1-(chloromethyl)-4-(phenylthio)benzene(1208-87-3)

Safety Data

• Hazardous Substances Data: 1208-87-3(Hazardous Substances Data)

Usage

Description

1-(chloromethyl)-4-(phenylthio)benzene, also known as (4-(chloromethyl)phenyl)(phenyl)sulfane, is an organic compound with the molecular formula C13H11ClS. It is a derivative of benzene, featuring a chloromethyl group at the 1st position and a phenylthio group at the 4th position. 1-(chloromethyl)-4-(phenylthio)benzene is characterized by its reactivity and potential use in the synthesis of various pharmaceutical compounds.

Uses

1. Used in Pharmaceutical Industry:
1-(chloromethyl)-4-(phenylthio)benzene is used as a reactant/reagent for the preparation of fenticonazole nitrate. The application reason is its ability to participate in phase transfer-catalyzed benzylation reactions, specifically in the synthesis of fenticonazole nitrate by benzylating (dichlorophenyl)imidazoleethanol with (phenylthio)benzyl chloride.
2. Used in Chemical Synthesis:
1-(chloromethyl)-4-(phenylthio)benzene can be utilized as a building block or intermediate in the synthesis of various organic compounds, particularly those with pharmaceutical or chemical applications. Its unique structure allows for further functionalization and modification to create a wide range of products.
3. Used in Research and Development:
In the field of research and development, 1-(chloromethyl)-4-(phenylthio)benzene can serve as a valuable compound for studying the properties and reactivity of benzene derivatives. It can be used to explore new reaction pathways, develop novel synthetic methods, and investigate the potential applications of its derivatives in various industries.

InChI:InChI=1/C13H11ClS/c14-10-11-6-8-13(9-7-11)15-12-4-2-1-3-5-12/h1-9H,10H2

Synthetic route

4-hydroxymethylphenyl phenyl sulfide (6317-56-2) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
With pyridine; thionyl chloride In dichloromethane at 20 - 25℃; for 2h; Cooling with ice;	97.7%
With pyridine; thionyl chloride In dichloromethane at 20 - 25℃; for 2h;	97.7%
With pyridine; thionyl chloride In dichloromethane at 20 - 24℃; for 2.5h; Temperature;	96.7%

formaldehyd (50-00-0) + diphenyl sulfide (139-66-2) → 4,4'-bis(chloromethyl)diphenyl sulfide (1216-02-0) + 2-(phenylthio)benzyl chloride (1527-15-7) + 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
With hydrogenchloride
With hydrogenchloride Title compound not separated from byproducts;

formaldehyd (50-00-0) + diphenyl sulfide (139-66-2) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
With hydrogenchloride; sulfuric acid; acetic acid

4-(phenylthio)benzoic acid (6310-24-3) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65 percent / NaBH4/AlCl3 / bis-(2-methoxy-ethyl) ether / 2 h / 25 °C 2: 93 percent / aqueous HCl (d 1.18) / petroleum ether / 6 h / 20 - 25 °C View Scheme

4-bromo-benzaldehyde (1122-91-4) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 6 h / 124 - 128 °C 2: sodium tetrahydroborate / methanol / 1 h / 48 °C 3: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1: copper(l) iodide / N,N-dimethyl-formamide / 5.5 h / 125 °C 2: sodium tetrahydroborate / methanol / 55 h / 47 °C 3: pyridine; thionyl chloride / dichloromethane / 2.5 h / 20 - 24 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 6 h / 124 - 128 °C 2: sodium tetrahydroborate / methanol / 1 h / 48 °C 3: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C View Scheme

thiophenol (108-98-5) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 6 h / 124 - 128 °C 2: sodium tetrahydroborate / methanol / 1 h / 48 °C 3: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1: copper(l) iodide / N,N-dimethyl-formamide / 5.5 h / 125 °C 2: sodium tetrahydroborate / methanol / 55 h / 47 °C 3: pyridine; thionyl chloride / dichloromethane / 2.5 h / 20 - 24 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate; copper(l) iodide / N,N-dimethyl-formamide / 6 h / 124 - 128 °C 2: sodium tetrahydroborate / methanol / 1 h / 48 °C 3: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C View Scheme

4-phenylsulfanyl-benzaldehyde (1208-88-4) → 1-phenylthio-4-chloromethyl-benzene (1208-87-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 1 h / 48 °C 2: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 55 h / 47 °C 2: pyridine; thionyl chloride / dichloromethane / 2.5 h / 20 - 24 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol / 1 h / 48 °C 2: pyridine; thionyl chloride / dichloromethane / 2 h / 20 - 25 °C View Scheme

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobezyl ether nitrate

Conditions	Yield
Stage #1: 1-phenylthio-4-chloromethyl-benzene; 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With tetrabutylammomium bromide; sodium hydroxide In water; toluene at 58 - 60℃; for 13.5h; Stage #2: With nitric acid In ethyl acetate; toluene at 25℃; for 3h;	85.1%
Stage #1: 1-phenylthio-4-chloromethyl-benzene; 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With sodium hydroxide In tetrahydrofuran; water for 4.5h; Stage #2: With nitric acid In water	82.1%
Stage #1: 1-phenylthio-4-chloromethyl-benzene; 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With tetrabutylammomium bromide; sodium hydroxide In water; toluene at 58℃; for 13.5h; Stage #2: With nitric acid In ethyl acetate; toluene at 25℃; for 3h;	74.7%
Stage #1: 1-phenylthio-4-chloromethyl-benzene; 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol With tetrabutylammomium bromide; sodium hydroxide In water; toluene at 58 - 60℃; for 13.5h; Stage #2: With nitric acid In ethyl acetate at 25℃; for 3h;	71.4%

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 2-Methoxy-6-methylpyridine-3-carboxylic acid (72918-10-6) → 1,2-Bis<4-(phenylthio)phenyl>ethane (72918-16-2) + 2-Methoxy-6-<2-(4'-phenylthio)phenethyl>pyridine-3-carboxylic acid (72918-11-7)

Conditions	Yield
With lithium diisopropyl amide 1.) THF, hexane, -78 deg C, 30 min, 2.) RT, 5 h; Multistep reaction;	A n/a B 26%
With lithium diisopropyl amide 1.) THF, hexane, -78 deg C, 30 min, 2.) RT, 5 h; Yield given. Multistep reaction;

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride

Conditions	Yield
In N,N-dimethyl-formamide at 100℃; for 15h;

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride + 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride + α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobezyl ether nitrate

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether (72479-26-6)

Conditions	Yield
With sodium hydride 1.) HMPA, 20 degC - 25 degC, 1 h; 50 degC - 60 degC, 2 h; 2.) 50 degC, 20 h; Yield given. Multistep reaction;

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol (24155-42-8) → 1-(β-hydroxyethyl-β,2,4-dichlorophenylethyl)-3-(4-phenylthiobenzyl)imidazolium chloride + 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride + α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether (72479-26-6)

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether (72479-26-6) → 1-<β-(2,4-dichlorophenyl)-β-(4-phenylthiobenzyloxy)-ethyl>-3-(4-phenylthiobenzyl)imidazolium chloride

Conditions	Yield
In N,N-dimethyl-formamide at 100℃; for 15h;

1-phenylthio-4-chloromethyl-benzene (1208-87-3) → 4-phenylsulfanyl-benzaldehyde (1208-88-4)

Conditions	Yield
With hexamethylenetetramine; acetic acid In chloroform Heating;

1-phenylthio-4-chloromethyl-benzene (1208-87-3) → α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-benzenesulfinylbenzyl ether

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) 50percent NaH / 1.) HMPA, 20 degC - 25 degC, 1 h; 50 degC - 60 degC, 2 h; 2.) 50 degC, 20 h 2: 41 percent / 4.6percent H2O2 / acetic acid / 72 h / 20 - 25 °C View Scheme

1-phenylthio-4-chloromethyl-benzene (1208-87-3) → α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-benzenesulfonylbenzyl ether

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) 50percent NaH / 1.) HMPA, 20 degC - 25 degC, 1 h; 50 degC - 60 degC, 2 h; 2.) 50 degC, 20 h 2: 48 percent / 17.4percent H2O2 / acetic acid / 12 h / 70 °C View Scheme

1-phenylthio-4-chloromethyl-benzene (1208-87-3) → 1-cyanomethyl-4-phenylthiobenzene (6317-59-5)

Conditions	Yield
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide

1-phenylthio-4-chloromethyl-benzene (1208-87-3) + 4H-pyrazolo[1,5-a]pyrimidin-7-one (57489-79-9) → 4-(4-phenylthio)benzyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine (189018-63-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide

aqueous sodium chloride + 1-phenylthio-4-chloromethyl-benzene (1208-87-3) → 1-cyanomethyl-4-phenylthiobenzene (6317-59-5)

Conditions	Yield
In (2S)-N-methyl-1-phenylpropan-2-amine hydrate

Upstream product

• 6317-56-2 4-hydroxymethylphenyl phenyl sulfide 
• 1208-88-4 4-phenylsulfanyl-benzaldehyde 
• 108-98-5 thiophenol 
• 1122-91-4 4-bromo-benzaldehyde 
• 6310-24-3 4-(phenylthio)benzoic acid 
• 50-00-0 formaldehyd 
• 139-66-2 diphenyl sulfide 

Downstream Products

• 6317-59-5 1-cyanomethyl-4-phenylthiobenzene 
• 655243-98-4 3-chloro-5,6-bis-(4-phenylsulfanyl-benzyloxy)-benzo[b]thiophene-2-carboxylic acid methyl ester 
• 1208-88-4 4-phenylsulfanyl-benzaldehyde 
• 72479-26-6 α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether 
• 72918-16-2 1,2-Bis<4-(phenylthio)phenyl>ethane 
• 72918-11-7 2-Methoxy-6-<2-(4'-phenylthio)phenethyl>pyridine-3-carboxylic acid 
• 189018-63-1 4-(4-phenylthio)benzyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine 

Relevant articles and documents

Refining process, detection standard and application of fenticonazole nitrate

The invention belongs to the technical field of chemical synthesis and discloses a refining process of fenticonazole nitrate. The refining process comprises the following steps: 1) synthesizing an intermediate I, namely 4-benzene sulfydryl benzaldehyde; 2) synthesizing an intermediate II, namely 4-benzene sulfydryl phenylcarbinol; 3) synthesizing an intermediate III, namely 4-benzene sulfydryl benzyl chloride; 4) synthesizing a crude product of fenticonazole nitrate; and 5) refining fenticonazole nitrate. The invention further discloses a detection method of an intermediate of the fenticonazole nitrate and an application of the fenticonazole nitrate in medicines.

Method for synthesizing fenticonazole nitrate

The invention belongs to the technical field of chemical synthesis, and discloses a method for synthesizing fenticonazole nitrate. By the aid of a phase transfer catalytic method, condensation reaction is performed at the presence of sodium hydroxide. The method particularly includes the steps: 1) synthesizing 4-mercaptophenyl-benzaldehyde; 2) synthesizing 4-mercaptophenyl benzyl alcohol; 3) synthesizing 4-mercaptophenyl-benzyl chloride; 4) synthesizing fenticonazole nitrate crude products. Used reagents are low in cost and easy to obtain, synthesis cost is greatly reduced, operation is simpleand convenient, special requirements on equipment are omitted, and the method is more suitable for scale production.

Pyrazolotriazine compounds

Pyrazolotriazine compounds of the formula: STR1 wherein R1 is OH or alkanoyloxy; R2 is H, OH, or SH; R3 is (1) unsaturated N- or S-containing heterocyclic group optionally having 1-2 substituents of halogen, nitro or phenylthio, (2) naphthyl, (3) phenyl optionally having 1-3 substituents of (i) alkyl, (ii) phenyl, (iii) alkoxycarbonyl, (iv) cyano, (v) nitro, (vi) alkoxy, (vii) phenylalkoxy (viii) phenylthio-alkyl, (ix) phenoxy, (x) STR2 R is alkyl, halo-substituted alkyl, phenyl optionally having 1-3 substituents, or pyridyl, and l is 0, 1 or 2, (xi) halogen, (xii) phenylalkyl, (xiii) carboxy, (xiv) alkanoyl, (xv) benzoyl optionally having 1-3 substituents, (xvi) amino, (xvii) OH, (xviii) alkanoyloxy, (xix) STR3 or (xx) STR4 (A is alkylene), said compounds having a xanthine oxidase inhibitory activity and are useful for the prophylaxis and treatment of gout.