US3661977A - Novel dioximes and processes for preparing the same - Google Patents
Novel dioximes and processes for preparing the same Download PDFInfo
- Publication number
- US3661977A US3661977A US813293A US3661977DA US3661977A US 3661977 A US3661977 A US 3661977A US 813293 A US813293 A US 813293A US 3661977D A US3661977D A US 3661977DA US 3661977 A US3661977 A US 3661977A
- Authority
- US
- United States
- Prior art keywords
- alkyl
- hydroxylamine
- dioximes
- novel
- preparing
- 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
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract description 11
- 102000004190 Enzymes Human genes 0.000 abstract description 3
- 108090000790 Enzymes Proteins 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical class C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 150000002923 oximes Chemical class 0.000 description 5
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011369 resultant mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- OYQVQWIASIXXRT-UHFFFAOYSA-N ethyl 2,4-dioxopentanoate Chemical compound CCOC(=O)C(=O)CC(C)=O OYQVQWIASIXXRT-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
Definitions
- Exemplary of such compounds is ethyl 2,4-dihydroxyliminoacetylpyruvate and is useful as an intermediate for sulfa drugs or inhibitors for monoamine oxidation enzyme.
- Alkyl 2,4-dihydroxyliminoacylpyruvates are prepared by treating alkyl acylpyruvates with hydroxylamine.
- the products are also prepared by treating one of alkyl 4- hydroxyliminoacylpyruvates obtainable by the previous treatment of the alkylacylpyruvates with hydroxylamine, with hydroxylamine.
- the reaction inevitably yields two kinds of isomers, namely 3-alkyl-5- alkoxy-carbonylisooxazol [III] and 3-alkoxycarbonyl-5- alkylisooxazol [V] as end products, due to the fact that the alkyl acylpyruvates [I] are having two keto groups in one molecule and therefore two kinds [II], [IV] of monooximes are resulted therefrom.
- RCOCH COCOOR' wherein R and R have the same meanings as above, or alkyl 4-hydroxyliminoacylpyruvates of the formula:
- the alkyl 4-hydroxyliminoacylpyruvates the precursors of the 3-alkyl- -alkoxycarbonylisooxazols which have been of poor utility, can be converted into 3-alkoxycarbonyl-5-alkylisooxazols [V] which are useful as raw materials for sulfa drugs or inhibitors for monoamine oxidation enzyme, or into the alkyl 2-hydroxyliminoacylpyruvates [IV], the precursor of the isooxazol [V], and a great commercial significance can be derived therefrom.
- dioximes of the present invention are also useful as an intermediate for preparing 3-alkyl-5-alkoxycarbonylpyrazol having a hypoglycemic activity or antidiabetic activity.
- Example 1 To a mixture of hydroxylamine hydrochloride (139 g., 2 mol) and 80% aqueous ethanol (500 ml.), added 158 g. (1 mol) of ethyl acetopyruvate under cooling and the combined mixture was stirred at -30 C. for 10 min.
- the resultant mixture was then distilled under reduced pressure at a temperature below 80 C. to remove water and alcohol up to nearly dried state, and thereafter extracted with ethyl acetate.
- the extract was further distilled to remove the ethyl acetate and was washed with benzene to obtain the crude dioxime.
- Example 2 To a solution of hydroxylamine hydrochloride (76.4 g., 1.1 mol) in 160 ml. of water, added solution of sodium hydroxide to neutralize and to adjust the pH value of the solution to 6 while being cooled below 10 C.
- reaction mixture After being combined with 600 ml. of an alcohol solution including 173 g. (1 mol) of ethyl 4-hydroxyliminoacetylpyruvate, the reaction mixture was kept under stirring at about 60 C. for 7 hours while being subjected to the occasional addition of a solution of sodium hydroxide to maintain the pH value Within the range from 6 to 7.
- the resultant mixture was filtered to remove the precipitated sodium chloride and distilled the alcohol off, and thereafter the mixture was poured into 1200 ml. of ethyl acetate and washed thrice with each 40 ml. of water.
- RO-GHzC-OOOR' wherein R and R each represents an alkyl group of 1 to 3 carbons.
- RCOCH COCOOR wherein R and R have the same meaning as above, with hydroxylamine under substantially neutral conditions at a temperature at or below C. and for a time period of up to 7 hours.
- R and R each represents an alkyl group, with hydroxylamine.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2791868 | 1968-04-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3661977A true US3661977A (en) | 1972-05-09 |
Family
ID=12234248
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US813293A Expired - Lifetime US3661977A (en) | 1968-04-25 | 1969-04-03 | Novel dioximes and processes for preparing the same |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US3661977A (enrdf_load_stackoverflow) |
| CH (1) | CH525868A (enrdf_load_stackoverflow) |
| DE (1) | DE1921212A1 (enrdf_load_stackoverflow) |
| GB (1) | GB1230349A (enrdf_load_stackoverflow) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4205180A (en) * | 1974-12-19 | 1980-05-27 | Takeda Chemical Industries, Ltd. | α-Alkoxyimino-β-oxo-γ-Bromobutyric acid |
-
1969
- 1969-04-03 US US813293A patent/US3661977A/en not_active Expired - Lifetime
- 1969-04-24 CH CH628369A patent/CH525868A/de not_active IP Right Cessation
- 1969-04-25 DE DE19691921212 patent/DE1921212A1/de active Pending
- 1969-04-25 GB GB1230349D patent/GB1230349A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4205180A (en) * | 1974-12-19 | 1980-05-27 | Takeda Chemical Industries, Ltd. | α-Alkoxyimino-β-oxo-γ-Bromobutyric acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CH525868A (de) | 1972-07-31 |
| GB1230349A (enrdf_load_stackoverflow) | 1971-04-28 |
| DE1921212A1 (de) | 1969-11-13 |
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