1208-87-3

Usage

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

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

Downstream Products

• 72918-16-2 1,2-Bis<4-(phenylthio)phenyl>ethane 
• 72918-11-7 2-Methoxy-6-<2-(4'-phenylthio)phenethyl>pyridine-3-carboxylic acid 
• 1208-88-4 4-phenylsulfanyl-benzaldehyde 
• 189018-63-1 4-(4-phenylthio)benzyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine 
• 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 
• 72479-26-6 α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether 

Relevant academic research and scientific papers

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.

Synthesis process of fenticonazole nitrate

The invention belongs to the technical field of chemical synthesis, and discloses a synthesis process of fenticonazole nitrate. The synthesis process comprises the following steps: 1) synthesis of intermediate I:4-phenylthio-benzaldehyde; 2) synthesis of intermediate II:4-phenylthio benzyl alcohol; 3) synthesis of intermediate III:4-phenylthio benzyl chloride; 4) synthesis of crude fenticonazole nitrate; 5) refining of the fenticonazole nitrate; 6) preparation of suppository. The synthetic process is simple and feasible and suitable for popularization and use, and has broad market applicationprospects.

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.

Pyrimidine derivatives, method of manufacturing the same, and androgen inhibitor

The invention discloses a pyrimidien derivative expressed in Formula [I]: STR1 where R 1 denotes a hydrogen atom or hydroxyl group, R 2 denotes a hydrogen atom, lower alkoxycarbonyl group, lower alkoxy group, halogen atom, lower alkyl group, cycloalkyl group with 3 to 8 carbon atoms, lower alkoxycarbonyl lower alkyl group, carboxyl group, carboxy lower alkyl group, group: --CONHR 6 (R 6 represents a hydrogen atom, a phenyl group, which may possess halogen atom, or lower alkyl group), cyano group, phenyl group which may possess a group selected from the group consisting of hydroxyl group, halogen atom, lower alkyl group, lower alkoxy group and phenylthio group as a substituent, phenyl lower alkyl group which may possess a group selected from the group consisting of hydroxyl group and lower alkoxy group as a substituent on a phenyl ring, lower alkanoyloxy lower alkyl group, benzoyl group, lower alkanoyl group which may possess a halogen atom, or hydroxy lower alkyl group which may possess a group selected from the group consisting of phenyl group and halogen atom as a substituent, R 3 denotes a hydrogen atom, hydroxyl group, lower alkyl group, cycloalkyl group with 3 to 8 carbon atoms, halogen lower alkyl group, or phenyl group, R 4 denotes a hydrogen atom, lower alkyl group, or lower alkoxy group, and R 5 denotes a hydrogen atom, lower alkyl group, lower alkoxy lower alkyl group, or halogen lower alkyl group; provided that R 2 and R 3 may be bonded to each other to form a lower alkylene group with 3 to 5 carbon atoms, or its pharmaceutically available salt. This derivative is excellent in therapeutic effects of benign prostatic hypertrophy, prostatic carcinoma, female hairiness, male baldness or pimple as an androgen inhibitor.

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.

New α-aryl-β,N-imidazolylethyl benzyl and naphthylmethyl ethers with antimycotic and antibacterial activity

A new series of α-aryl-β,N-imidazolylethyl benzyl and naphthylmethyl ethers was synthesized and tested for antimycotic and antimicrobial activity. All compounds showed antifungal activity; most of them were also active against gram-positive bacteria, whereas no activity was detected against gram-negative bacteria. Structure-activity relationships are discussed. The α-(2,4-dichlorophenyl)-β,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (8), which showed good ski tolerability and in vivo antimycotic activity comparable with or better than 1-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)phenethyl]imidazole (miconazole) and 1-[α-(o-chlorophenyl)benzhydryl]imidazole (clotrimazole), was selected for further researches.

Physico-chemical, structural and analytical studies on fenticonazole, a new drug with antimycotic properties

Physico-chemical properties and methods for the detection and the determination of a new potent antimycotic compound, the α-(2,4-dichlorophenyl)-β-N-imidazolyethyl-4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) and its potential impurities are reported. TLC, GC, and HPLC were the analytical techniques employed.