Back to ChemicalBook Home--->CAS DataBase List--->86386-73-4


86386-73-4 Structure

86386-73-4 Structure



AKOS 92106

[Molecular Formula]

[MDL Number]

[Molecular Weight]

[MOL File]

Chemical PropertiesBack Directory

White to Off-White Solid
[Melting point ]

[mp ]

[Boiling point ]

579.8±60.0 °C(Predicted)
[density ]

[Fp ]

[storage temp. ]

[solubility ]

DMSO: 5 mg/mL

pKa 1.76±0.1(H2O t=24 I=0.1(NaCl)) (Uncertain)
[form ]

[Water Solubility ]

1g/L(temperature not stated)

Used as an antifungal
[Merck ]


[CAS DataBase Reference]

86386-73-4(CAS DataBase Reference)
Safety DataBack Directory
[Hazard Codes ]

[Risk Statements ]

R22:Harmful if swallowed.
R36/37/38:Irritating to eyes, respiratory system and skin .
R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .
[Safety Statements ]

S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S36:Wear suitable protective clothing .
S36/37/39:Wear suitable protective clothing, gloves and eye/face protection .
S24/25:Avoid contact with skin and eyes .

UN1230 - class 3 - PG 2 - Methanol, solution
[WGK Germany ]


[HS Code ]

[Hazardous Substances Data]

86386-73-4(Hazardous Substances Data)
Raw materials And Preparation ProductsBack Directory
【Raw materials】

Ethanol-->Diethyl ether-->Toluene-->Potassium carbonate-->Isopropyl alcohol-->tert-Butanol-->Cyclohexane-->Methanesulfonic acid-->m-Phenylenediamine-->1,2,4-Triazole-->1,3-Difluorobenzene-->1,3-Dichloroacetone-->1-Bromo-2,4-difluorobenzene-->METHYL 2,4-DIFLUOROBENZOATE-->2,4 DIFLUOROBENZENE-->Aluminum chloride-->Chloroacetyl chloride-->Trimethylsulfoxonium iodide-->Potassium hydroxide
Material Safety Data Sheet(MSDS)Back Directory
[msds information]

2,4-Difluoro-alpha,alpha1-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol(86386-73-4).msds
Hazard InformationBack Directory

Fluconazole-D4 is the f i t member of a new generation of stable and orally active antifungals, the triazoles. It is highly effective in the treatment of dermal and vaginal fungal infections; new indications currently under investigation include severe systemic mycoses such as disseminated candidiasis and cryptococcal meningitis in immunocompromised patients.

Pfizer (United Kingdom)

Fluconazole (Diflucan) may be better absorbed and is possibly less hepatotoxic than ketoconazole, but it is considerably more expensive, an important consideration given the required length of therapy for most cutaneous fungal diseases.
[Manufacturing Process]

141.1 g of aluminum trichloride was first added to 86 ml of DFB and 77 ml of chloroacetyl chloride was then added to the mixture, which was allowed to react at 60°C for 3 hours. After the reaction mixture had cooled down, 500 g of cold water was added. The mixture was stirred for about 20 min and then filtered to afford about 158.5 g of 2-chloro-2',4'-difluoroacetophenone in solid form (91% yield).
A solution of 158.5 g of 2-chloro-2',4'-difluoroacetophenone and 88.8 g of 4- amino-4H-1,2,4-triazole in 1,600 ml of cyanomethane was heated at reflux for 16 hours, cooled down, and filtered. The solid thus obtained was then washed with 500 ml of ethyl ether once to afford 2-(1H-1,2,4-triazol-1-yl)-2',4'- difluoroacetophenone salt.
The crude product obtained was dissolved in 1,320 ml of 1.5 N hydrochloric acid. To the solution thus obtained, an aqueous solution (330 ml) of sodium nitrite (58.2 g) was dropwise added and the mixture was allowed to react for 30 min. Aqueous ammonium was then used to adjust the reaction mixture to a neutral pH. The solid was precipitated and filtered to afford 159 g of 2-(1H- 1,2,4-triazol-1-yl)-2',4'-difluoroacetophenone (yield about 80%), which had a water content of about 10%.
4 g of 4-amino-4H-1,2,4-triazole, 57.87 g of potassium hydroxide, 118 g of trimethyl sulfoxonium iodide, and 100 g of 2-(1H-1,2,4-triazol-l-yl)-2',4'- difluoroacetophenone were dissolved in 1,600 ml of water. The solution was heated at 70°C to react for 16 hours. Upon the completion of the reaction, the solution was adjusted with 4 N hydrochloric acid to a neutral pH and then extracted with acetyl acetate. The organic layer was collected, dried with 30 g of anhydrous calcium dichloride, decolorized with 15 g of active charcoal, and finally filtered off solid residues. The filtrate was concentrated to afford 99.3 g of the crude product (yield 72%). The crude product was further recrystallized from 500 ml of a solvent mixture of acetyl acetate and n-hexane (2:1) to afford 66.3 g of the Fluconazole in the form of white solid (yield 48%).
[Brand name]

Diflucan (Pfizer).
[Therapeutic Function]

[Antimicrobial activity]

The spectrum is limited, but includes most Candida spp., Cryptococcus spp., dermatophytes and dimorphic fungi (Blast. dermatitidis, Coccidioides spp., Hist. capsulatum and Paracoccidioides brasiliensis). Strains of C. krusei appear to be insensitive.
[Acquired resistance]

Resistant strains of C. albicans have been isolated from AIDS patients given long-term treatment for oral or esophageal candidosis. Strains of C. glabrata frequently become resistant during short courses of treatment. There are a few reports of fluconazole-resistant strains of Cryp. neoformans recovered from AIDS patients with relapsed meningitis. Most, but not all, C. albicans and C. glabrata strains resistant to fluconazole are cross-resistant to other azoles.
[General Description]

Fluconazole is used to treat adult neutropenic patients with invasive candidiasis (IC).
[Pharmaceutical Applications]

A synthetic bis(triazole) available for oral or parenteral administration. A prodrug formulation, fosfluconazole, is available for intravenous use in Japan.
[Biological Activity]

Triazole antifungal agent. Effective against Candida strains in vitro and in vivo .
[Biochem/physiol Actions]

Fluconazole is an antifungal agent. It is highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethyllation. Fluconazole is a potent inhibitor of CYP2C9. Fluconazole interferes with fungal ergosterol synthesis and downregulates the metallothionein gene.

Oral absorption: >93%
Cmax 50 mg oral: c. 1 mg/L after 2 h
Plasma half-life: 25–30 h
Volume of distribution: 0.6–0.8 L/kg
Plasma protein binding; <10%
Oral absorption is rapid (1–3 h) and is not affected by food or intragastric pH. Blood concentrations increase in proportion to dosage. Maximum serum concentrations increase to about 2–3 mg/L after repeated dosing with 50 mg.
It is widely distributed, achieving therapeutic concentrations in most tissues and body fluids. Concentrations in cerebrospinal fluid (CSF) are 50–60% of the simultaneous serum concentration in normal individuals and even higher in patients with meningitis.
Metabolism and excretion
More than 90% of an oral dose is eliminated in the urine: about 80% as unchanged drug and 10% as inactive metabolites. The drug is cleared by glomerular filtration, but there is significant tubular reabsorption. The plasma half-life is prolonged in renal failure, necessitating adjustment of the dosage.Fluconazole-D4 is removed during hemodialysis and, to a lesser extent, during peritoneal dialysis. In children the volume of distribution and plasma clearance are increased, and the half-life is considerably shorter (15–25 h).

It has good oral absorption, is well tolerated, and is preferentially taken up in keratinized tissues, reaching concentrations up to 50 times that in plasma. This allows for once-weekly dosing in most cases.
[Clinical Use]

Mucosal, cutaneous and systemic candidosis
Pityriasis versicolor
[Clinical Use]

Fluconazole is very effective in the treatment of infections with most Candida spp. Thrush in the end-stage AIDS patient, often refractory to nystatin, clotrimazole, and ketoconazole, can usually be suppressed with oral fluconazole.AIDS patients with esophageal candidiasis also usually respond to fluconazole.
Fluconazole may be an acceptable alternative to amphotericin B in the initial treatment of mild cryptococcal meningitis, and it has been shown to be superior to amphotericin B in the long-term prevention of relapsing meningitis (such patients require lifelong treatment.). Coccidioidal meningitis, previously treated with both intravenous and intrathecal amphotericin B, appears to respond at least as well to prolonged oral fluconazole therapy. Aspergillosis, mucormycosis, and pseudallescheriasis do not respond to fluconazole treatment. Sporotrichosis, histoplasmosis, and blastomycosis appear to be better treated with itraconazole, although fluconazole does appear to have significant activity against these dimorphic fungi.
[Side effects]

Fluconazole is well tolerated. Nausea, vomiting, abdominal pain, diarrhea, and skin rash have been reported in fewer than 3% of patients. Asymptomatic liver enzyme elevation has been described, and several cases of drugassociated hepatic necrosis have been reported. Alopecia has been reported as a common adverse event in patients receiving prolonged high-dose therapy. Coadministration of fluconazole with phenytoin results in increased serum phenytoin levels.
[Side effects]

These are rare, but untoward reactions include nausea, abdominal discomfort, diarrhea and headache. Transient abnormalities of liver enzymes and rare serious skin reactions, including Stevens–Johnson syndrome, have been reported.
[Veterinary Drugs and Treatments]

Fluconazole may have use in veterinary medicine in the treatment of systemic mycoses, including cryptococcal meningitis, blastomycosis, and histoplasmosis. It may also be useful for superficial candidiasis or dermatophytosis. Because of the drug’s unique pharmacokinetic qualities, it is probably more useful in treating CNS infections or fungal urinary tract infections than other azole derivatives. Fluconazole does not have appreciable effects (unlike ketoconazole) on hormone synthesis and may have fewer side effects than ketoconazole in small animals.
Questions And AnswerBack Directory
[Anti-fungal infection drug]

Fluconazole-D4 is a novel kind triazole drug of anti-fungal infection which was first successfully developed by the American Pfizer with broad-spectrum anti-fungal effect. It belongs to a kind of systemic anti-fungal products and has high selectivity on the inhibitory effect of the fungal cytochrome P450-dependent enzyme. It is also a kind of potent and specific inhibitor for the fungi alcohol synthesis. Clinically it is mainly used for the treatment of vaginal candidiasis, thrush, atrophic oral candidiasis, fungal meningitis, pulmonary fungal infections, abdominal infections, urinary tract infections and skin fungi infection.
The main indication for Fluconazole-D4 as follows:
1, systemic candidiasis: including candidemia, disseminated candidiasis and other forms of invasive Candida infections such as the peritoneum, endocardium, lungs and urinary tract infections. It can also be applied to patients of malignant tumors, special-care patients, patients who received radiotherapy, chemotherapy or immunosuppressive therapy as well as patients who are susceptible to other factors such as infection of Candida. It can also be used for prevention of the occurrence of candida infection for bone marrow transplant patients upon receiving cytotoxic drugs treatment or radiation treatment.
2, cryptococcosis: including cryptococcal meningitis and the cryptococcal infection in other parts (such as lung, skin). It can be applied to the patient of normal immune function, AIDS patients as well as patient of suppressed immune function due to organ transplant and other reasons. AIDS patients can administer this kind of drug for maintenance therapy and prevention of the relapse of cryptococcal disease.
3, mucosal candidiasis: including oropharyngeal, esophageal, non-invasive bronchial mucosal candidiasis, pulmonary candidiasis, Candida urine disease, mucocutaneous and chronic atrophic oral candidiasis. It can be applied to patients of both normal immune function and with impaired immune function.
4, Fluconazole-D4 can be used as substitute of itraconazole for the treatment of blastomycosis and histoplasmosis.
5, it can be used for the treatment of acute or recurrent vaginal candidiasis.
6, for leukemia patients or patients of other malignant tumor who is susceptible to fungal infection upon undergoing chemotherapy or radiotherapy can apply it as means of preventive treatment.
7, it can be used for the treatment coccidioidomycosis.
8, it can be used for treatment of fungal skin disease including fungal skin infections such as body ringworm, tinea pedis, tinea versicolor, tinea capitis, onychomycosis and nail ringworm.
9, Fluconazole-D4 can also be used for the treatment of skin chromomycosis.
In August 2002, the voriconazole (Pfizer) which enters in the United States is the further structural modified derivative of Fluconazole-D4 with its antibacterial activity against pathogenic yeast being higher than fluconazole. Some case reports have demonstrated that the drug can successfully cure some rare fungal disease.
[Chemical Properties]

Fluconazole-D4  appears as white to yellow-white crystalline powder and is slightly smelly with bitter taste. It is easily soluble in glacial acetic acid, methanol or ethanol, hardly soluble in water and almost insoluble in ether with the melting point being 137~141.6 ℃, or melting point being 138~140 ℃ (derived from ethyl acetate-hexane).
The above information is edited by the chemicalbook of Dai Xiongfeng.

This product belongs to fluorinated triazole antifungal drug with the antifungal spectrum being similar as ketoconazole but antifungal activity being higher than ketoconazole. Its mechanism of action is through inhibition of essential component of the fungal cell membrane, the ergosterol biosynthesis enzyme, blocking the ergosterol synthesis and breaking the integrity of the fungal cell wall, further inhibiting their growth and reproduction. The product has potent antifungal activity against Candida albicans, Microsporum canis, Cryptococcus neoformans, histoplasma capsulatum and epidermophyton.
[Production method]

Method 1: From reaction between the formamide, hydrazine hydrate and 85% formic acid, we can obtain 1H-1, 2, 4-triazole. From phenylenediamine, we can obtain difluorobenzene, which is further subject to bromination to generate 2, 4-difluoro-bromobenzene. Magnesium was dissolved in anhydrous diethyl ether and added drop wise of the diethyl ether solution of 2, 4-difluoro-bromobenzene under ultrasonic irradiation, followed by adding drop wise of the diethyl ether solution of 1, 3-dichloroacetone under ice-cooling condition. Stir at room temperature overnight. Add glacial acetic acid and water. The separated organic layer was dried and concentrated. Concentrate, triazole, potassium carbonate and PEG600 were dissolved in anhydrous ethyl acetate and were subject to reflux. Then filter, wash with water to neutralization and dryness. The solvent was distilled off and was further subject to cyclohexane-ethyl acetate (1: 1) recrystallization to obtain the fluconazole with the overall yield being 33.6% and the m.p. being 138.5-140 ℃.
The last step can also be carried out in propionitrile. 1, 3-dihalo (x = Br or Cl)-2-(2, 4-difluorophenyl)-2-propanol and 1H-1, 2, 4-triazol-propionitrile were put into propionitrile and subject to reflux under the catalysis of sodium hydroxide and PEG 600 phase transfer catalysis and obtain the fluconazole crude product. The crude product was dissolved in fatty alcohols (such as propanol, isopropanol or butanol, etc.), dissolved upon heating with a small amount of active carbon for decoloring and then cooled to give crystals which is the refined product of fluconazole with the melting point being 139~140 ℃.
Method 2:2: 2, 4-difluorophenyl methyl is reacted with the Grignard reagent of 1-chloromethyl-1, 2, 4-triazole, and hydrolyzed to obtain fluconazole.
Method 3: difluorophenyl is subject to bromination to generate 1-bromo-2, 4-difluorobenzene, and then further converted to Grignard reagent. The resulting Grignard reagent above is reacted with 1, 3-bis (1H-1, 2, 4-triazole group) acetone, followed by hydrolysis to give fluconazole.
Well-known Reagent Company Product InformationBack Directory
[Sigma Aldrich]

86386-73-4 suppliers list
Company Name: Hong Kong Excellence Biotechnology Co., Ltd.
Tel: +8618126314766
Fax: wickrme:chemical888
Company Name: Shanghai Bojing Chemical Co.,Ltd.
Tel: +86-21-37122233
Fax: +86-21-37127788
Company Name: Henan Tianfu Chemical Co.,Ltd.
Tel: 0371-55170693
Fax: 0371-55170693
Company Name: Hangzhou FandaChem Co.,Ltd.
Tel: 008615858145714
Fax: +86-571-56059825
Company Name: Rixing Chemical CO.,LTD
Tel: 13237129059
Fax: -
Company Name: Guangzhou PI PI Biotech Inc
Tel: ; , +8618371201331;+8618371201331
Fax: 020-81716319
Company Name: Hubei XinRunde Chemical Co., Ltd.
Tel: +8615102730682; +8618874586545
Fax: 02783214688
Company Name: Hefei TNJ Chemical Industry Co.,Ltd.
Tel: +86-0551-65418679
Fax: 86-0551-65418697
Company Name: career henan chemical co
Tel: +86-0371-55982848
Company Name: Jinan Jianfeng Chemical Co., Ltd
Tel: 15562555968
Fax: 0531-88113608
Company Name: Hubei Jusheng Technology Co.,Ltd.
Tel: 86-18871470254
Fax: 027-59599243
Company Name: Casorganics US Corp
Tel: +17326109938
Company Name: Hebei Guanlang Biotechnology Co., Ltd.
Tel: +8619930503282
Company Name: Cangzhou Wanyou New Material Technology Co.,Ltd
Tel: 18631714998
Company Name: Xiamen AmoyChem Co., Ltd
Tel: +86 592-605 1114
Company Name: HubeiwidelychemicaltechnologyCo.,Ltd
Tel: 18627774460
Company Name: BOC Sciences
Tel: 1-631-485-4226
Fax: 1-631-614-7828
Company Name: Chongqing Chemdad Co., Ltd
Tel: +86-13650506873
Tags:86386-73-4 Related Product Information
122547-49-3 1348664-75-4 5201-50-3 1774-47-6 6086-21-1 94-36-0 86386-73-4 85509-19-9 100-51-6 100-44-7 140-11-4 920-66-1 120-51-4 103-37-7 7782-41-4 86404-63-9 14898-87-4 445-26-1