US3723477A - 4-fluoro-3-methylphenyl 5-nitro-2-furyl ketone - Google Patents
4-fluoro-3-methylphenyl 5-nitro-2-furyl ketone Download PDFInfo
- Publication number
- US3723477A US3723477A US00037923A US3723477DA US3723477A US 3723477 A US3723477 A US 3723477A US 00037923 A US00037923 A US 00037923A US 3723477D A US3723477D A US 3723477DA US 3723477 A US3723477 A US 3723477A
- Authority
- US
- United States
- Prior art keywords
- fluoro
- methylphenyl
- nitro
- furyl ketone
- ketone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- RXYYRHXSZORLFG-UHFFFAOYSA-N (4-fluoro-3-methylphenyl)-(5-nitrofuran-2-yl)methanone Chemical compound C1=C(F)C(C)=CC(C(=O)C=2OC(=CC=2)[N+]([O-])=O)=C1 RXYYRHXSZORLFG-UHFFFAOYSA-N 0.000 title abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 229940121375 antifungal agent Drugs 0.000 abstract 1
- 239000003429 antifungal agent Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 5
- -1 4-FLUORO-3-METHYLPHENYL Chemical class 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DQJAAEADFORVGZ-UHFFFAOYSA-N 2-chloro-1-(5-nitrofuran-2-yl)ethanone Chemical compound [O-][N+](=O)C1=CC=C(C(=O)CCl)O1 DQJAAEADFORVGZ-UHFFFAOYSA-N 0.000 description 1
- QUAFTMJUVQDZHE-UHFFFAOYSA-N 3-(4-chloroanilino)-6-hydroxy-9-methylcarbazole-1,4-dione Chemical compound ClC1=CC=C(C=C1)NC1=CC(C=2N(C3=CC=C(C=C3C=2C1=O)O)C)=O QUAFTMJUVQDZHE-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/70—Nitro radicals
- C07D307/71—Nitro radicals attached in position 5
Definitions
- a noteworthy characteristic of the compounii of this invention is its low order of irritation to the skin.
- the compound of this invention can be compounded in various forms such as unguents, solutions, suspensions, powders, sprays and the like using readily available and commonly used excipients and carriers known to the compounding art and with which there is compatibility.
- the compound of this invention is readily prepared by nitration of 4-fluoro-3-methylphenyl 2-furyl ketone. The method now preferred is briefly described:
- Nitric acid 9.5 ml, 0.15 mole) containing 0.2 ml of concentrated sulfuric acid was added dropwise to 33 ml (0.35 mole) of acetic anhydride with stirring and cooling to maintain the temperature at 2530.
- 4- Fluoro-3-methylphenyl-2-furyl ketone (10.2 g, 0.05 mole) was added in portions over a period of 20 minutes at 4 to l. After the mixture was stirred for 5 minutes, 50 ml of water and 55 g of trisodium phosphate (Na,PO -l2l-l,O) were added. The mixture was heated, with stirring, at 50-55 for 1 hour and cooled in an ice water bath. The solid was collected by filtration, washed with water, and recrystallized twice from methanol to give 1.3 g (10%) of 4-fluoro-3- methylphenyl 5-nitro-2-furyl ketone.
Abstract
4-Fluoro-3-methylphenyl 5-nitro-2-furyl ketone is a potent antifungal agent.
Description
fie 11% Pelmsii, H112.
[ 1 Mar. 27, 11973 1541 -FLUQQ-METHYLPHENI/L 5= NITRO-Z-F URYIL KE'IFUNIE [75] Inventor Stanfurd 0. Pehnsi, Jun, Norwich,
[52] ILLS. CI .260/3417Z0, 424/285 [51] Km. E1. A ..C07I 5/30 [58] Field of 260/3473 [56] Reierences Cited UNITED STATES PATENTS 3.349.095 10/1967 Haber et al... 260/3473 2,319,481 5/1943 Stillman et al... v ..260/347.8 2,976,300 3/1961 Hayes et a1. .....260/347.8 3,164,521 1/1965 Gray et a1 ..260/347.8
OTHER PUBLICATIONS Tamura et a1. Chem. Abstracts (1967) vol. 67 734584 Primary Examiner-A1ex Maze] Assistant Examiner-Bemard Dentz Attorney-Bradford S. Allen [57] ABSTRAQT 4-Fluoro-3-methy1phenyl 5-nitro-2-fury1 ketone is a potent anti-fungal agent 1 Claim, No Drawings 4-FLUORO-3-METHYLPHENYL S-NITRO-Z- FURYL KETONE This invention relates to the compound 4-fluoro-3- methylphenyl 5nitro-2-furyl ketone of the formula:
Cone. in Diameter of zone of inhibition Compound mcgJml. in mm. at days C. albicans M. cam: 2 4 6 8 4 6 8 4-Fluoro-3- methylphen l-5- nitro-Z-fury ketone 545 1616 l3 12 32 23 2! The diluent carrier for the compound in this test is 50% ethanol which exhibits no antifungal activity.
A noteworthy characteristic of the compounii of this invention is its low order of irritation to the skin. When applied daily in the form of a suspension at concentrations of up to 4 percent in 2 percent aqueous solutions of methyl cellulose (Methocel (R) l500-DOW) to the shaved back of rabbits, no skin irritation is elicited over a period of 3 days.
The compound of this invention can be compounded in various forms such as unguents, solutions, suspensions, powders, sprays and the like using readily available and commonly used excipients and carriers known to the compounding art and with which there is compatibility.
The compound of this invention is readily prepared by nitration of 4-fluoro-3-methylphenyl 2-furyl ketone. The method now preferred is briefly described:
Nitric acid 9.5 ml, 0.15 mole) containing 0.2 ml of concentrated sulfuric acid was added dropwise to 33 ml (0.35 mole) of acetic anhydride with stirring and cooling to maintain the temperature at 2530. 4- Fluoro-3-methylphenyl-2-furyl ketone (10.2 g, 0.05 mole) was added in portions over a period of 20 minutes at 4 to l. After the mixture was stirred for 5 minutes, 50 ml of water and 55 g of trisodium phosphate (Na,PO -l2l-l,O) were added. The mixture was heated, with stirring, at 50-55 for 1 hour and cooled in an ice water bath. The solid was collected by filtration, washed with water, and recrystallized twice from methanol to give 1.3 g (10%) of 4-fluoro-3- methylphenyl 5-nitro-2-furyl ketone.
Anal. Calcd. for C ,H,FNO C, 57.84; H, 3.23; N,
Found: C, 57.89; H, 3.19; N, 5.55.
What is claimed is:
l. The compound 4-fluoro-3-methylphenyl S-nitro- 2-furyl ketone of the formula:
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3792370A | 1970-05-15 | 1970-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3723477A true US3723477A (en) | 1973-03-27 |
Family
ID=21897083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00037923A Expired - Lifetime US3723477A (en) | 1970-05-15 | 1970-05-15 | 4-fluoro-3-methylphenyl 5-nitro-2-furyl ketone |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3723477A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3983244A (en) * | 1972-11-13 | 1976-09-28 | Uniroyal Inc. | Method of controlling pests using certain ketones of furan |
| EP1498109A1 (en) * | 2003-07-15 | 2005-01-19 | L'oreal | Furan derivatives and dyeing composition comprising a furan derivative as coupler |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2319481A (en) * | 1941-05-31 | 1943-05-18 | Norwich Pharma Co | Antiseptic |
| US2976300A (en) * | 1959-02-20 | 1961-03-21 | Norwich Pharma Co | Method of preparing methyl 5-nitro-2-furyl ketone |
| US3164521A (en) * | 1962-08-22 | 1965-01-05 | Norwich Pharma Co | Antimycotic compositions comprising chloromethyl 5-nitro-2-furyl ketone |
| US3349095A (en) * | 1964-04-05 | 1967-10-24 | Abic Ltd | 1-(5'-nitrofuryl)-1, 3-diketopropane derivatives and their preparation |
-
1970
- 1970-05-15 US US00037923A patent/US3723477A/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2319481A (en) * | 1941-05-31 | 1943-05-18 | Norwich Pharma Co | Antiseptic |
| US2976300A (en) * | 1959-02-20 | 1961-03-21 | Norwich Pharma Co | Method of preparing methyl 5-nitro-2-furyl ketone |
| US3164521A (en) * | 1962-08-22 | 1965-01-05 | Norwich Pharma Co | Antimycotic compositions comprising chloromethyl 5-nitro-2-furyl ketone |
| US3349095A (en) * | 1964-04-05 | 1967-10-24 | Abic Ltd | 1-(5'-nitrofuryl)-1, 3-diketopropane derivatives and their preparation |
Non-Patent Citations (1)
| Title |
|---|
| Tamura et al. Chem. Abstracts (1967) vol. 67 734584 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3983244A (en) * | 1972-11-13 | 1976-09-28 | Uniroyal Inc. | Method of controlling pests using certain ketones of furan |
| EP1498109A1 (en) * | 2003-07-15 | 2005-01-19 | L'oreal | Furan derivatives and dyeing composition comprising a furan derivative as coupler |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: NORWICH EATON PHARMACEUTICALS, INC., 17 EATON AVE. Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:MORTON-NORWICH PRODUCTS, INC., A CORP. OF DE;REEL/FRAME:004085/0126 Effective date: 19820609 |