WO1986002070A1 - Procede de preparation de 4-methyl-4-imidazolin-2-one et de ses derives - Google Patents
Procede de preparation de 4-methyl-4-imidazolin-2-one et de ses derives Download PDFInfo
- Publication number
- WO1986002070A1 WO1986002070A1 PCT/US1984/001562 US8401562W WO8602070A1 WO 1986002070 A1 WO1986002070 A1 WO 1986002070A1 US 8401562 W US8401562 W US 8401562W WO 8602070 A1 WO8602070 A1 WO 8602070A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solvent
- methyl
- imidazolin
- acid
- acetic acid
- 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.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/70—One oxygen atom
Definitions
- the present invention is directed to a process for preparing 4-methyl-4-imidazolin-2-one (l) which comprises reacting acetol and urea in a reaction-inert solvent in the presence of an acid catalyst at 60-140° C.
- the preferred temperature range is 90-130° C.
- the preferred solvent is acetic acid, in which case the solvent itself can serve as catalyst, and the addition of another acid catalyst is optional.
- the preferred acid catalyst is tetrabutylammonium hydrogen sulfate.
- 4-Methyl-4-imidazolin-2-one (I) is useful in the further synthesis of biotin or of biotin precursors (desthiobiotin or so-called des ⁇ arboxybiotin in which the carboxylic acid group of biotin has been replaced by a methyl group).
- biotin or of biotin precursors desthiobiotin or so-called des ⁇ arboxybiotin in which the carboxylic acid group of biotin has been replaced by a methyl group.
- Various chemical transformations of the compound (I) directed to the synthesis of biotin or the above precursors have been long known [see for example Duchinsky et al., J. Am. Chem. Soc. 67, pp. 2079-2084 (1945); Duschinsky et al., J. Am. Chem. Soc, pp. 657-662 (1948); Taguchi et al., Chem. Lett. 1974, pp.
- Microbiological methods for the conversion of desthiobiotin or descarboxybiotin are also known [see for example Izuma et al. in Adv. Applied Microbiology, D. Perlman ed., Vol. 22, pp. 145-176 (1977); Ogino et al., U.S. Patent 3,859,167; Heng-Chun et al., J. Biol. Chem. 243, pp. 6642-6645 (1968)].
- reaction time is likewise not critical, but will generally be sufficient for the reaction to be substantially complete (e.g., in 0.5-24 hours, depending upon temperature).
- reaction-inert solvent refers to a solvent which does not interact with reactants, reagents, intermediates or products in a manner which has a significant adverse effect on the yield of the desired product.
- the 4-methyl-4-imidazolin-2-one is isolated by standard methods. The solvent or a portion thereof is conveniently recovered by distillation under reduced pressure.
- the oil was dissolved in 300 ml of dioxane and reevaporated to azeotropically remove residual acetic acid, then dissolved in 800 ml of water, the pH adjusted to 7.0-8.5 with solid calcium hydroxide, treated with diatomaceous earth and filtered. The filtrate was washed twice with 250 ml of isopropylether, and concentrated in vacuo to a volume of 712 ml.
- the resulting reaction mixture was refluxed for 1.5 hour, then evaporated in vacuo to 94.5 g and the residue taken up in 95 ml of water, the pH adjusted to 7.8 with solid sodium carbonate and the aqueous solution extracted with 3 x 190 ml of n-butanol.
- the combined butanol extracts were washed 1 x 50 ml brine, evaporated to 350 ml, cooled and stored at 0° C. for 16 hours. A white solid separated out and was removed by filtration. The filtrate was evaporated to dryness and the residue taken up in about 10 ml of hot water. On cooling to 0-5° C, title product crystallized and was collected by filtration.
- This salt was dissolved in 25 ml glacial acetic acid, 750 mg (3.95 mmol) p-toluenesulfonic acid monohydrate was added, and the mixture was stirred at room temperature for 2 hours, at which time 25 ml water and 25 ml methylene chloride were added to the mixture and stirring was continued for 10 minutes. The layers were then separated, the aqueous layer was reextracted with 25 ml methylene chloride, and to the combined organic extracts was added 20 ml saturated solution of sodium bicarbonate. Finally, to the mixture was added, dropwise, 40% sodium hydroxide solution to adjust the pH at 9.0.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Le 4-méthyl-4-imidazolin-2-one, utile en tant qu'intermédiaire de la biotine, est préparé en faisant réagir de l'acétol avec de l'urée.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1984/001562 WO1986002070A1 (fr) | 1984-09-26 | 1984-09-26 | Procede de preparation de 4-methyl-4-imidazolin-2-one et de ses derives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1984/001562 WO1986002070A1 (fr) | 1984-09-26 | 1984-09-26 | Procede de preparation de 4-methyl-4-imidazolin-2-one et de ses derives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1986002070A1 true WO1986002070A1 (fr) | 1986-04-10 |
Family
ID=22182276
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1984/001562 Ceased WO1986002070A1 (fr) | 1984-09-26 | 1984-09-26 | Procede de preparation de 4-methyl-4-imidazolin-2-one et de ses derives |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1986002070A1 (fr) |
-
1984
- 1984-09-26 WO PCT/US1984/001562 patent/WO1986002070A1/fr not_active Ceased
Non-Patent Citations (2)
| Title |
|---|
| Berichte, Vol. 40 (1907), page 4801, "Zur Kenntnis Der Glyoxalone", Biltz * |
| Heterocyclic Compounds, Vol. 5, John Wiley and Sons, Inc., New York, 1957, page 247, See Second Reaction, Elderfield (Editor) * |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): FI HU NO RO SU US |
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| WD | Withdrawal of designations after international publication |
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