23593-75-1

Basic information

• Product Name: Clotrimazole
• Synonyms: G imazalil;Tartaric acid Tiamulin;Clotrimazole, >=99%;Levobupivacaine Hydrochloride Injection;Perindopril Tables[ACERTIL(R;chlorophyll、chlorophyl;Clotrimazole impurity;(2-Chlorophenyl)diphenyl-1-imidazolylmethane
• CAS NO: 23593-75-1
• Molecular Formula: C₂₂H₁₇ClN₂
• Molecular Weight: 344.84
• EINECS: 245-764-8
• Product Categories: MYCELEX;API;Broad-spectrum antifungal drugs;Pharmaceutical Intermediates;Active Pharmaceutical Ingredients;API's;Potassium channel;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 23593-75-1.mol

Chemical Properties

• Melting Point: 147-149°C
• Boiling Point: 501.14°C (rough estimate)
• Flash Point: 245.5 °C
• Appearance: Crystalline
• Density: 1.1095 (rough estimate)
• Vapor Pressure: 5.42E-09mmHg at 25°C
• Refractive Index: 1.5940 (estimate)
• Storage Temp.: Store at RT.
• Solubility: Soluble in chloroform, DMSO, DMF and alcohols
• PKA: pKa 4.7(EtOH 50%aq ) (Uncertain)
• Water Solubility: <10mg/L(25 oC)
• Merck: 14,2417
• CAS DataBase Reference: Clotrimazole(CAS DataBase Reference)
• NIST Chemistry Reference: Clotrimazole(23593-75-1)
• EPA Substance Registry System: Clotrimazole(23593-75-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: NI4377000
• Hazardous Substances Data: 23593-75-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Clotrimazole is used as an antifungal agent for treating a broad spectrum of fungal infections, particularly dermatophyte species, yeast, and Malassezia furfur. It is effective against superficial infections and is widely used both externally and vaginally.
Used in Antifungal Compounds:
Clotrimazole is used as a CYP inhibitor, which helps in the treatment of various fungal infections by inhibiting the growth of fungi.
Used in Antimicrobial Applications:
Clotrimazole has antimicrobial effects against streptococci and staphylococci, making it useful in treating bacterial infections as well.
Brand Names:
Some of the brand names for Clotrimazole include Lotrimin (Schering-Plough), Gynix (Teva), Mycelex (Bayer), Canesten, Empecid, and Micosporin.
Chemical Properties:
Clotrimazole is a white powder or colorless crystalline powder with a melting point of 147-149 ℃. It is soluble in ethanol, acetone, and chloroform but almost insoluble in water. It is odorless, tasteless, and subject to rapid decomposition in an acidic solution. Clotrimazole hydrochloride has a melting point of 159 ℃.

Broad-spectrum antifungal drug

Clotrimazole is an artificially synthetic azole antifungal agent with inhibitory effect on a variety of pathogenic fungi. It is also able to directly kill the fungi at high concentration. Clotrimazole, through interfering with cytochrome P450 activity, inhibits the biosynthesis of the fungal ergosterol and other steroids; cause damage of the fungal cell membrane and change its permeability, causing the leakage of many kinds of important material in the cell; it can also inhibit the biosynthesis of the fungal triglyceride and phosphor-lipid; the product can still inhibit the activity of oxidase and peroxidase, causing the over-accumulation of peroxides in the cell, causing the degeneration and necrosis of the fungal subcellular structures. Clotrimazole has broad-spectrum antifungal activity with excellent anti-fungal activity against Epidermophyton, Trichophyton, aspergillosis, coloring fungi, Cryptococcus and Candida species. It also has certain antifungal effect against sporothrix schenckii,blastomycosis dermatitidis, Blastomyces coccidioides as well as Histoplasma. It has good anti-fungal effect against Candida, Cryptococcus, Aspergillus, algae bacteria, dermatophytes, etc in both in vivo and in vitro. It efficacy in treating skin superficial mycoses is similar as griseofulvin while its efficacy in treating deep fungal disease is similar as amphotericin B. It has excellent efficacy in treating visceral pathogenic fungi such as Candida albicans, Cryptococcus neoformans, coccidioidomycosis and histoplasma. Its effect on the Candida albicans is stronger than nystatin. Fungi are not easy to evolve drug resistance to this kind of product. This product is easily absorbed orally and can be used for the treatment of systemic fungal infection such as aspergillosis fumigatus, candidiasis, cryptococcosis, coccidioidomycosis, histoplasmosis (dogs, cats) and fungal septicemia. For severe fungal infection, it is preferably to use it in combination with amphotericin B. Topically it can also be used for the treatment of superficial fungal infections such as ringworm and livestock comb body and hair tinea. However, it is invalid in treating tinea capitis. Clotrimazole also has certain efficacy in treating some kinds of Gram-positive bacteria and Trichomonas vaginalis.

Pharmacokinetics

This product is rarely absorbed after oral administration. Adult, after oral administration of 3, has the peak of the plasma concentration being only 1.29 mg/L at 2 hour while 0.78 mg/L at 6 hours. Upon continuous administration, because of the induction effect of liver enzymes, the serum concentration can in turn decrease. The elimination half-life is 4.5 to 6 hours. Most of the products is metabolic inactivated in the liver and is further excreted by bile with only a small amount (less than 1% of dose) being subject to urine excretion in its prototype. The urine excrete were mostly inactive metabolites. This product is presented at high concentration in the feces including the non-absorption part of oral administration as well as the fraction via biliary excretion. Clotrimazole is widely distributed in the body with high concentration existing in the liver and adipose tissue. It can’t penetrate normal meninges and get into the cerebrospinal fluid. This product has a serum protein binding rate of 50%.

Clinical application

Clinical topical usage of 1% clotrimazole cream or solution for treating candidiasis ringworm, tinea versicolor, athlete's foot, nail ringworm and other skin infections. Clotrimazole vaginal tablets (100mg) administration can be used for treating candidiasis and trichomoniasis vaginal infections. Side effects include local irritation and burning sensations. Oral administration can be used for the treatment of deep fungal infection but with serious side effects such as gastrointestinal irritation, neutropenia, and liver function abnormalities. 1. Oral administration: (1) can be used for the treatment of oropharyngeal candidiasis. (2) it can also be used for chemotherapy and the prevention of the oropharynegeal candidiasis infection of immunocompromised or defect patients. 2. Topical: (1) skin candidiasis. (2) Tinea, jork itch and ringworm caused by Trichophyton, Epidermophyton and small spores; tinea versicolor caused by Pityrosporum. 3. Vaginal administration: (1) Vaginitis induced by Candida or other fungi. (2) vaginal infection caused by yeast. (3) Vagina super-infection caused by susceptible strains of the drug. The above information is edited by the lookchem of Dai Xiongfeng.

Mechanism

1. Through reducing the activity of cytochrome P450, it inhibit the biosynthesis of ergosterol and other sterols contained in the fungal cell membrane, causing damage of the fungal cell membrane and change its permeability and causing important intracellular material leakage. 2. Clotrimazole can inhibit the biosynthesis of the fungal triglyceride and phospholipid. 3. It can still inhibit the activity of oxidase and peroxidase, leading to the over-accumulation of hydrogen peroxide inside the cell, causing fungal subcellular structures degeneration and necrosis. 4. For Candida albicans, clotrimazole can suppresses the process of its conversion from spores into invasive hyphae.

Drug Interactions

1, the drug can inhibit the metabolism of drugs like sirolimus and dofetilide mediated by cytochrome P450 3A4 so that the plasma concentration of these drugs increases. 2, when being used in combination with tacrolimus and acamprosate, it can slow down the metabolism of these drugs and increasing its toxicity. 3, when clotrimazole is used in combination with betamethasone, it can make the skin be vulnerable to infection and increase the opportunities for microbial growth; the possible mechanism is through inhibiting the local inflammation. 4, when being used in combination with nystatin, amphotericin B and flucytosine, no synergistic antibacterial effect has been observed for inhibiting Candida albicans; moreover, it has antagonism effect in pharmacodynamic when being used in combination with amphotericin B.

Side effects

1, Oral administration: (1) gastrointestinal reactions: including loss of appetite, nausea, vomiting, abdominal pain and diarrhea. (2) Liver toxicity: Because most of clotrimazole is subjecting to liver metabolism, it can lead to liver damage and causing increased level of serum bilirubin, alkaline phosphatase and aminotransferase. These symptoms can resume after drug withdrawal. (3) There are occasionally transient neuropsychiatric disorders, manifested as depression, hallucinations and disorientation and so on. Once such reactions occur, treatment must be immediately discontinued. (4) There may be occasionally leukopenia. (5) Some patients, after taking the drug, can get a burning sensation in the urethra. At this time, you should drink more water to ensure a high urine output. However, there is no need for stopping the drug. 2, Topical administration may occasionally cause local irritation, itching or burning sensation. Skin can get erythema, papules, vesicles, scaling and so on. There is also report about contact dermatitis. 3, a small amount of vaginal administrators may get vaginal burning sensation, abdominal cramping, and bloating, frequent urination and so on. There may also be varying degrees of allergic reactions such as skin redness and itching, shortness of breath, hypotension or transient feeling, nausea and diarrhea.

Administration instructions

1, the drug can’t be used for systemic fungal infections. Owing to the poor oral absorption of the drug, adverse reactions are common while now we mostly apply topical or vaginal administration. 2, upon using this drug, you should avoid eye contact with the drug. 3, clotrimazole vaginal tablets should be prohibited through oral administration. 4, Administration of the tablets of this product once should overall take 15 to 30 minutes to allow the drug being slowly and completely dissolved. You should avoid chewing or swallowing whole tablet. 5, virginal treatment should be prohibited during menstruation. 6. if there are temporary neuropsychiatric disorder, severe gastrointestinal reactions and local skin allergic reaction happening, you should discontinue the drug immediately.

Production method

It can be obtained from o-benzoic acid via esterification, addition, hydrolysis, chlorination, and condensation. It may also be obtained by chlorination of o-chlorotoluene into o-chloro benzotrichloride, which, in the presence of aluminum chloride, has condensation reaction with benzene to generate diphenyl-(2-chlorophenyl) methyl chloride, which finally has condensation reaction with imidazole to obtain clotrimazole.

Originator

Canesten,Bayer,UK,1973

Indications

Clotrimazole (Lotrimin, Gyne-Lotrimin, Mycelex) is a broad-spectrum fungistatic imidazole drug used in the topical treatment of oral, skin, and vaginal infections with C. albicans. It is also employed in the treatment of infections with cutaneous dermatophytes. Topical use results in therapeutic drug concentrations in the epidermis and mucous membranes; less than 10% of the drug is systemically absorbed. Although clotrimazole is generally well tolerated, local abdominal cramping, increased urination, and transient liver enzyme elevations have been reported.

Manufacturing Process

156.5 g (0.5 mol) o-chlorophenyldiphenylmethyl chloride and 34 g (0.5 mol) imidazole are dissolved in 500 ml acetonitrile, with stirring, and 51 g (0.5 mol) triethylamine are added, whereupon separation of triethylamine hydrochloride occurs even at room temperature. In order to complete the reaction, heating at 50°C is carried out for 3 hours. After cooling, one liter of benzene is added and the reaction mixture is stirred, then washed salt-free with water. The benzene solution is dried over anhydrous sodium sulfate, filtered and concentrated by evaporation; giving 167 g crude 1-(ochlorophenylbisphenylmethyl)-imidazole. By recrystallization from acetone, 115 g (= 71% of the theory) of pure 1-(o-chlorophenylbisphenylmethyl)- imidazole of MP 154° to 156°C are obtained.

Therapeutic Function

Antifungal

Biochem/physiol Actions

Clotrimazole is a specific inhibitor of Ca2+-activated K+ channels. It is an antifungal azole. Clotrimazole is a derivative of imidazole and has similar antimicrobial action and activity to ketoconazole. It inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, altering cell membrane permeability.

Clinical Use

1-(o-Chloro-α,α-diphenylbenzyl)imidazole (Lotrimin, Gyne-Lotrimin, Mycelex) is a broad-spectrum antifungal drug thatis used topically for the treatment of tinea infections and candidiasis.It occurs as a white crystalline solid that is sparinglysoluble in water but soluble in alcohol and most organic solvents.It is a weak base that can be solubilized by dilute mineralacids.Clotrimazole is available as a solution in polyethyleneglycol 400, a lotion, and a cream in a concentration of 1%.These are all indicated for the treatment of tinea pedis, tineacruris, tinea capitis, tinea versicolor, or cutaneous candidiasis.A 1% vaginal cream and tablets of 100 mg and 500 mgare available for vulvovaginal candidiasis. Clotrimazole isextremely stable, with a shelf life of more than 5 years.

Synthesis

Clotrimazole, 1-(o-chloro-α,α-diphenylbenzyl)imidazole (35.2.21), is synthesized by reacting 2-chlorotriphenylmethylchloride (35.2.20) with imidazole in the presence of triethylamine. The starting substance 2-chlorotriphenylmethylchloride is made in various ways. In particular, chlorinating 2-chlorotoluene under light makes 2-chlorotrichloromethylbenzene (35.2.22), which is reacted with benzene in the presence of aluminum chloride to give 2-chlorotriphenylmethylchloride (35.2.20). An alternative way of making 2-chlorotriphenylmethylchloride is a Grignard reaction between 2-chlorobenzolphenone and phenylmagnesium bromide, followed by substitution of the hydroxyl group in the resulting 2-chlorotriphenylmethylcarbinol (35.2.23) with a chlorine using thionyl chloride. And finally, reacting phosphorous pentachloride with 2-chlorobenzophenone gives 2
- chloro-1,1-dichlorodiphenylmethane (35.2.24), which is used for the alkylation of benzene in the presence of aluminum chloride and gives 2-chlorotriphenylmethylchloride (35.2.20).

Veterinary Drugs and Treatments

Topical clotrimazole has activity against dermatophytes and yeasts; it may be useful for localized lesions associated with Malassezia. It is not very effective in treating dermatophytosis in cats. Clotrimazole inhibits the biosynthesis of ergosterol, a component of fungal cell membranes leading to increased membrane permeability and probable disruption of membrane enzyme systems.

InChI:InChI=1/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H

Synthetic route

1H-imidazole (288-32-4) + diphenyl phosphite (102-10-3) + o-chlorotriphenylmethanol (66774-02-5) + 4-methyl-2-pentanone (108-10-1) → clotrimazole (23593-75-1)

Conditions	Yield
With sodium hydroxide	100%
With sodium hydroxide	77%

1H-imidazole (288-32-4) + 2-chlorotrityl chloride (42074-68-0) → clotrimazole (23593-75-1)

Conditions	Yield
With sodium carbonate at 25℃; for 48h; Reagent/catalyst; Solvent; Concentration; Green chemistry;	92%
With sodium carbonate at 20℃; for 48h; Sealed tube;	92%
With triethylamine In acetonitrile Heating;
With triethylamine In toluene at 20 - 50℃; for 3h; Temperature; Solvent; Inert atmosphere;

1H-imidazole (288-32-4) + diphenyl phosphite (102-10-3) + o-chlorotriphenylmethanol (66774-02-5) → clotrimazole (23593-75-1)

Conditions	Yield
In toluene	74.5%
In acetonitrile; benzene	73%

o-chlorotriphenylmethanol (66774-02-5) → clotrimazole (23593-75-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / Heating 2: triethylamine / acetonitrile / Heating View Scheme

clotrimazole (23593-75-1) + 4-((1,3-bis(dodecanoyloxy)propan-2-yl)oxy)-4-oxobutanoic acid (150994-84-6) → 4-((1,3-bis(dodecanoyloxy)propan-2-yl)oxy)-4-oxobutanoate 1-((2-chlorophenyl)diphenylmethyl)-1H-imidazol-3-ium

Conditions	Yield
In acetonitrile at 50℃; for 6h;	100%

clotrimazole (23593-75-1) → o-chlorotriphenylmethanol (66774-02-5)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	93%
With hydrogenchloride; water for 3h; Heating / reflux;	85%
With hydrogenchloride In water; isopropyl alcohol for 17h; Heating;	36%

potassium hexafluorophosphate (17084-13-8) + cis-{Ru(Bipy)(Dppe)Cl2} + clotrimazole (23593-75-1) → [RuCl(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole)(1,2-bis(diphenylphosphino)ethane)(2,2′-bypiridine)]*hexafluorophosphate

Conditions	Yield
Stage #1: potassium hexafluorophosphate; cis-{Ru(Bipy)(Dppe)Cl2} In dichloromethane for 1h; Inert atmosphere; Stage #2: clotrimazole In dichloromethane for 6h; Reflux; Inert atmosphere;	92%

clotrimazole (23593-75-1) → C22H14(2)H3ClN2

Conditions	Yield
With deuteromethanol; di(tertbutyl)phenylphosphine; silver carbonate at 65℃; for 48h; Inert atmosphere;	91%

clotrimazole (23593-75-1) + 1-bromomethyl-3,5-difluoro-benzene (141776-91-2) → 3-[(2-chloro-phenyl)-diphenyl-methyl]-1-(3,5-difluoro-benzyl)-3H-imidazol-1-ium; bromide

Conditions	Yield
In ethyl acetate for 48h; Heating;	90%

potassium hexafluorophosphate (17084-13-8) + dichloro[1,4-bis(diphenylphosphino)butane](2,2'-bipyridine)ruthenium(II) (200358-34-5, 200259-33-2) + clotrimazole (23593-75-1) → [RuCl(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole)(1,4-bis(diphenylphosphino)butane)(2,2′-bypiridine)]*hexafluorophosphate

Conditions	Yield
Stage #1: potassium hexafluorophosphate; dichloro[1,4-bis(diphenylphosphino)butane](2,2'-bipyridine)ruthenium(II) In dichloromethane for 1h; Inert atmosphere; Stage #2: clotrimazole In dichloromethane for 6h; Reflux; Inert atmosphere;	90%

[dichloro(p-cymene)(triphenylphosphane)ruthenium(II)] (52490-94-5) + clotrimazole (23593-75-1) + hexafluorophosphate salt → [RuCl(clotrimazole)(η6-p-cymene)(PPh3)]PF6

Conditions	Yield
In methanol for 8h; Reflux; Inert atmosphere;	90%

copper(II) acetate monohydrate (6046-93-1) + clotrimazole (23593-75-1) → [Cu(clotrimazole)2(Ac)2]*H2O

Conditions	Yield
In methanol at 25℃; for 24h;	90%

[RhCl2(p-cymene)]2 + clotrimazole (23593-75-1) → [(η6-p-cymene)RuCl(clotrimazole)2]Cl (1581279-26-6)

Conditions	Yield
In methanol; chloroform for 5h; Reflux;	89%

silver(I) hexafluorophosphate (26042-63-7) + [RhCl2(p-cymene)]2 + clotrimazole (23593-75-1) → [(η6-p-cymene)Ru(clotrimazole)3](PF6)2

Conditions	Yield
In methanol; chloroform for 3h; Reflux;	86%

potassium hexafluorophosphate (17084-13-8) + cis-[RuCl2(1,1′-bis(diphenylphosphino)ferrocene)(2,2′-bipyridine)] + clotrimazole (23593-75-1) → [RuCl(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole)(1,1′-bis(diphenylphosphino)ferrocene)(2,2′-bypiridine)]*hexafluorophosphate

Conditions	Yield
Stage #1: potassium hexafluorophosphate; cis-[RuCl2(1,1′-bis(diphenylphosphino)ferrocene)(2,2′-bipyridine)] In dichloromethane for 1h; Inert atmosphere; Stage #2: clotrimazole In dichloromethane for 6h; Reflux; Inert atmosphere;	86%

copper(II) nitrate trihydrate + clotrimazole (23593-75-1) → [Cu(clotrimazole)2(H2O)(NO3)](NO3)*2H2O

Conditions	Yield
In methanol at 25℃; for 24h;	84%

clotrimazole (23593-75-1) → triphenylmethane (519-73-3)

Conditions	Yield
With tetraethylammonium perchlorate; triethylamine In dimethyl sulfoxide at 20℃; for 24h; Electrolysis; Green chemistry;	81%

di-μ-chloro-bis(1,5-cyclooctadiene)dirhodium (12092-47-6) + clotrimazole (23593-75-1) → RhCl(1,5-cyclooctadiene)(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole) (209979-92-0)

Conditions	Yield
In ethanol N2-atmosphere; stoich. amts., stirring at room temp. for 1 h; collection (filtration), washing (MeOH), drying (vac.); elem. anal.;	80%

clotrimazole (23593-75-1) → 4-chloro-1-((2-chlorophenyl)diphenylmethyl)-1H-imidazole (1605347-53-2)

Conditions	Yield
With N-chloro-N-fluoro-benzenesulfonamide In acetonitrile at 20℃; Reagent/catalyst;	80%
With N-chloro-N-fluoro-benzenesulfonamide In acetonitrile at 20℃; regioselective reaction;	77%
With 2-chloro-1,3-bis(methoxycarbonyl)guanidine In chloroform at 20℃; for 12h; Solvent; regioselective reaction;	72%

clotrimazole (23593-75-1) + (bromomethylcyclohexane) (2550-36-9) → 3-[(2-chloro-phenyl)-diphenyl-methyl]-1-cyclohexylmethyl-3H-imidazol-1-ium; bromide

Conditions	Yield
In ethyl acetate for 48h; Heating;	79%

bis(triphenylphosphino)copper(I) nitrate (14494-93-0, 23751-62-4, 106678-35-7) + clotrimazole (23593-75-1) → [Cu(PPh3)2(1-[(2-chlorophenyl)-diphenylmethyl]-1H-imidazole)2]NO3

Conditions	Yield
In acetonitrile for 24h;	79%

C14H20B9(1-)*C4H12N(1+) + clotrimazole (23593-75-1) → C36H36B9ClN2

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dimethoxyethane at 20℃; for 5h; Inert atmosphere; Schlenk technique;	78%

water (7732-18-5) + clotrimazole (23593-75-1) + zinc(II) chloride (7646-85-7) → [ZnCl2(N2C3H3C(C6H5)2C6H4Cl)2(H2O)2]*3H2O

Conditions	Yield
In ethanol; water hot soln. (60 °C) of metal chloride added to hot soln. (60 °C) of CLMZ, mixt. stirred under reflux for 1 h; pptn., filtration, washing (ethanol/water, petroleum ether), elem. anal.;	77%

clotrimazole (23593-75-1) → C22H16BrClN2

Conditions	Yield
With N-chloro-N-fluoro-benzenesulfonamide; potassium bromide In acetonitrile at 20℃; for 0.25h;	77%

clotrimazole (23593-75-1) + methyl iodide (74-88-4) → 3-[(2-chloro-phenyl)-diphenyl-methyl]-1-methyl-3H-imidazol-1-ium; iodide

Conditions	Yield
In dichloromethane at 45℃; for 0.25h; Microwave irradiation;	75%
In ethyl acetate at 20℃; for 48h;	49%

tetrakis(actonitrile)copper(I) hexafluorophosphate (64443-05-6) + clotrimazole (23593-75-1) → [Cu(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole)2]PF6

Conditions	Yield
In dichloromethane stoich. amts., room temp., 24 h; vol. reduction (N2-stream), Et2O addn., cooling to -5°C (pptn.), collection (filtration), washing (Et2O), drying (vac.); elem. anal.;	75%

manganese(II) chloride dihydrate + water (7732-18-5) + clotrimazole (23593-75-1) → [MnCl2(N2C3H3C(C6H5)2C6H4Cl)2(H2O)2] (1311268-76-4)

Conditions	Yield
In ethanol; water hot soln. (60 °C) of metal chloride added to hot soln. (60 °C) of CLMZ, mixt. stirred under reflux for 1 h; pptn., filtration, washing (ethanol/water, petroleum ether), elem. anal.;	75%

[RhCl2(p-cymene)]2 + clotrimazole (23593-75-1) → [(η6-p-cymene)RuCl2(clotrimazole)]

Conditions	Yield
In methanol; chloroform at 20℃; for 0.075h; Reflux;	75%

zinc(II) nitrate hexahydrate + clotrimazole (23593-75-1) → [Zn(clotrimazole)2(H2O)(NO3)](NO3)*4H2O

Conditions	Yield
In methanol at 25℃; for 0.5h;	74%

clotrimazole (23593-75-1) → C22H13(2)H4ClN2

Conditions	Yield
With water-d2; potassium carbonate; silver carbonate; cyclohexyldiphenylphosphine In toluene at 120℃; for 12h;	73%

Upstream product

• 288-32-4 1H-imidazole 
• 42074-68-0 2-chlorotrityl chloride 
• 66774-02-5 o-chlorotriphenylmethanol 
• 102-10-3 diphenyl phosphite 
• 108-10-1 4-methyl-2-pentanone 

Downstream Products

• 66774-02-5 o-chlorotriphenylmethanol 
• 56153-60-7 1-(2-chlorophenyl)-1,1-diphenyl methane 
• 209979-94-2 AuCl₃(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole) 
• 209979-92-0 RhCl(1,5-cyclooctadiene)(1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole) 
• 150151-92-1 [(1-[(2-chlorophenyl)diphenyl]methyl-1H-imidazole)2Ru(II)Cl₂] 
• 393828-29-0 [Au(1-[[(2-chlorophenyl)diphenyl]methyl]-1H-imidazole)(PPh₃)]PF₆ 
• 393828-25-6 [Cu(1-[[(2-chlorophenyl)diphenyl]methyl]-1H-imidazole)Cl₂]2 
• 1311268-74-2 CrCl₂((C₆H₅)2C(C₆H₄Cl)N₂C₃H₃)2(H₂O)2⁽¹⁺⁾*Cl^(1-)=[CrCl₂(N₂C₃H₃C(C₆H₅)2C₆H₄Cl)2(H₂O)2]Cl 
• 1311268-76-4 [MnCl₂(N₂C₃H₃C(C₆H₅)2C₆H₄Cl)2(H₂O)2] 

Relevant articles and documents

Preparation method of clotrimazole

The invention provides a preparation method of clotrimazole. The preparation method comprises the following steps: step 1, chlorinating (2-chlorphenyl) diphenyl methanol into (2-chlorphenyl) diphenylchloromethane; 2, subjecting (2-chlorphenyl) diphenyl chloromethane and imidazole to condensation to form clotrimazole; the total reaction flow formula is shown in the specification. The invention provides a preparation method of clotrimazole. The initial raw materials (2-chlorphenyl) diphenyl methanol and imidazole are easy to obtain and stable in performance; reaction condition mildness, a product which is unstable when meeting water and synthesized in step 1 does not need to be separated and purified, and can be applied directly in step 2, not only are the requirements on equipment and operation reduced, but also the risk of influencing the quality of the raw material medicine is reduced; the preparation method is simple in operation, short in process period, high in product purity andsuitable for industrial production, , in addition, the reaction solvent in the step 1 is also the reaction solvent in the step 2, emission of three wastes is reduced, and environmental protection is better facilitated.

Synthesis method of clotrimazole

The invention discloses a synthesis method of clotrimazole, and belongs to the technical field of chemical synthesis. According to the method, 2-chlorotrityl chloride and imidazole are taken as raw materials, hexafluoroisopropanol is taken as a solvent, and reaction is performed in an alkali environment. The method has the advantages that the raw materials 2-chlorotrityl chloride and imidazole areeasy to get; the reaction can be performed at room temperature, and the reaction condition is mild; other than previous multistep reaction, the method adopts one-step synthesis and is simple to operate; the method is high in reaction activity, the yield reaches 92 percent, and the raw materials are completely converted; products are convenient to separate, and the reaction has green economical efficiency, and is environmentally friendly.

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This article reports an efficient synthesis of triarylmethanes and tetraarylmethanes from chlorohydrocarbons with miscellaneous nucleophiles in fluorinated alcohols, featuring metal-free, wide substrate scope, excellent functional group tolerance, and mild reaction conditions.

Solid Pharmaceutical Preparations Containing Copolymers Based On Polyethers Combined With Poorly Water-Soluble Polymers

The invention relates to dosage forms which contain preparations of poorly water-soluble substances in a polymer matrix of polyether copolymers, said polyether copolymers being obtained by the radically initiated polymerization of a mixture from 30 to 80% by weight of N-vinyl lactam, 10 to 50% by weight of vinyl acetate and 10 to 50% by weight of a polyether, and at least one poorly water-soluble polymer, the poorly water-soluble substance being present in the polymer matrix as an amorphous substance.

Chemical compounds having ion channel blocking activity for the treatment of immune dysfunction

The present invention relates to chemical compounds having inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca), and the use of such compounds for the treatment or alleviation of diseases or conditions relating to immune dysfunction. Moreover, the invention relates to a method of screening a chemical compound for inhibitory activity on an intermediate conductance Ca 2+ activated potassium channel (IK Ca).

Synthesis and antifungal activity of a series of difluorotritylimidazoles

1-[(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) (15) was selected among a series of mono-, di- and trifluorotrityl-imidazole antifungal agents as the most potent fluorine containing analogue of clotrimazole.

Process for preparing N-tritylimidazole compounds

A process for preparing N-tritylimidazole compounds of the formula: STR1 by the reaction between a tritylcarbinol derivative of the formula: STR2 and an imidazole derivative of the formula: STR3 , characterized in that the reaction is effected in the presence of a phosphorus compound of the formula: STR4