CS245189B1 - Method of 1-(2,6-dimethylphenoxy)-2-propanone preparation - Google Patents
Method of 1-(2,6-dimethylphenoxy)-2-propanone preparation Download PDFInfo
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- CS245189B1 CS245189B1 CS848176A CS817684A CS245189B1 CS 245189 B1 CS245189 B1 CS 245189B1 CS 848176 A CS848176 A CS 848176A CS 817684 A CS817684 A CS 817684A CS 245189 B1 CS245189 B1 CS 245189B1
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- CS
- Czechoslovakia
- Prior art keywords
- dimethylphenoxy
- mol
- organic solvent
- organic acid
- aliphatic
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 10
- XDJULAUHYAJQBU-UHFFFAOYSA-N 1-(2,6-dimethylphenoxy)propan-2-one Chemical compound CC(=O)COC1=C(C)C=CC=C1C XDJULAUHYAJQBU-UHFFFAOYSA-N 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title abstract description 5
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 claims abstract description 12
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- -1 2,6-dimethylphenoxy Chemical group 0.000 claims abstract description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 5
- 239000011630 iodine Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- 238000009835 boiling Methods 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 159000000011 group IA salts Chemical class 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical group C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- 150000001447 alkali salts Chemical class 0.000 claims 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- VQFAIAKCILWQPZ-UHFFFAOYSA-N bromoacetone Chemical compound CC(=O)CBr VQFAIAKCILWQPZ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Spósob přípravy l-/2,6-dimetylfenoxy/- -2-propanónu z 2,6-dimetylfenolu, chlóracetonu a jódu za přítomnosti slabej anorganickéj alebo organickéj kyseliny, ktorý sa používá ako medziprodukt pri výrobě liečiv vo farmaceutickom priemyslePreparation method 1- (2,6-dimethylphenoxy) - Of 2-propanone from 2,6-dimethylphenol, chloroacetone and iodine in the presence of a weak inorganic or an organic acid which is used as an intermediate in the manufacture of medicaments in the pharmaceutical industry
Description
ktorý sa používá ako medziprodukt pri výrobě liečiv.which is used as an intermediate in the manufacture of pharmaceuticals.
Doposial sa táto zlúčenina vyrábala z 2,6-dimetylfenolu a brómacetónu za přítomnosti uhličitanu draselného v prostředí acetonu s výtažkom 27 až 37 * /D. S. Tarbell: J. Org.To date, this compound has been produced from 2,6-dimethylphenol and bromoacetone in the presence of potassium carbonate in an acetone medium of 27-37% yield. S. Tarbell, J. Org.
Chem. 7. 251 /1942//. Druhou popísanou metodou přípravy zlúčeniny I je oxidácia L-/2,6-dimetylfenoxy/-2-propanolu róznymi oxidačnými činidlami /D. Hesek a spol.: Csl. AO 223436 /1983//.Chem. 7, 251 (1942). The second method described for the preparation of compound I is the oxidation of L- (2,6-dimethylphenoxy) -2-propanol with various oxidizing agents (D). Hesek et al., Csl. AO 223436 (1983).
Spósob přípravy zlúčeniny I je založený na reakcii 1 mol. dielu 2,6-dimetylfenolu s 1,0 až 1,5 mol. dielom chloracetonu a 0,005 až 0,1 mol. dielom jódu za přítomnosti 0,5 až 1,5 mol. dielu alkalickej soli slabej anorganickej alebo organickej kyseliny v prostředí organického rozpúšťadla pri teplote 40 °C až teplote varu použitého rozpúšťadla.The process for preparing Compound I is based on a 1 mol reaction. % of 2,6-dimethylphenol with 1.0 to 1.5 mol. % of chloroacetone and 0.005 to 0.1 mol. % iodine in the presence of 0.5 to 1.5 mol. % of an alkaline salt of a weak inorganic or organic acid in an organic solvent medium at a temperature of 40 ° C to the boiling point of the solvent used.
Ako alkalickú sol slabej anorganickej alebo organickej kyseliny možno použit uhličitany /hydrogénuhličitan sodný, uhličitan sodný alebo draselný/, připadne octany /octan sodný alebo draselný/.As the alkaline salt of a weak inorganic or organic acid, carbonates (sodium bicarbonate, sodium or potassium carbonate) or acetates (sodium or potassium acetate) may be used.
Ako organické rozpúšťadlo možno použit alifatické alkoholy s počtom uhlíkov 1 až 4, napr. metanol, etanol, 2-propanol, n.butanol, 2-metylpropanol, alebo alifatické ketony s počtom uhlíkov 3 až 6, napr. aceton, metyl-etyl-ketan, metyl-terc. butylketon. Je výhodné použiť bezvodé rozpúšťadlá s maxímálnym obsahom 0,1 % vody.As organic solvent, aliphatic alcohols having a carbon number of 1 to 4, e.g. methanol, ethanol, 2-propanol, n-butanol, 2-methylpropanol, or aliphatic ketones having a carbon number of 3 to 6, e.g. acetone, methyl ethyl ketane, methyl tert. ketone. It is preferred to use anhydrous solvents with a maximum water content of 0.1%.
Postup podlá vynálezu sa uskutočňuje tak, že k zmesi 2,6-dimetylfenolu, jódu a alkalickej soli slabej anorganickej alebo organickej kyseliny v organickom rozpúšťadle vyhriatej minimálně na teplotu 40 °C až teplotu varu organického rozpúšťadla sa za miešania přidává po častiach chloraceton a na doreagovanie sa ohrieva na teplotu spíitného varu po dobu 5 až 20 hod. Pri víičších návažkach je vhodné.přidávat chloraceton zriedený použitým organickým rozpúšťadlom.The process according to the invention is carried out by adding chloroacetone in portions with stirring to a mixture of 2,6-dimethylphenol, iodine and an alkaline salt of a weak inorganic or organic acid in an organic solvent heated to a temperature of at least 40 ° C to boiling point of the organic solvent. is heated to reflux temperature for 5 to 20 hours. For larger samples it is advisable to add chloroacetone diluted with the organic solvent used.
Izolácia zlúčeniny I sa uskutočňuje tak, že sa k reakčnej zmesi najprv odseparujú anorganické soli odsátím alebo odfiltrováním na tlakovom filtri a získaný filtrát sa vákuovo destiluje.The isolation of compound I is effected by first separating inorganic salts into the reaction mixture by suction or filtering on a pressure filter and the filtrate obtained is distilled under vacuum.
Hlavnou. výhodou postupu podlá vynálezu oproti prvej z popísaných metod přípravy zlúčeniny I je dosiahnutie podstatné vyšších výlažkov. Oproti druhej z popísaných metod přípravy zlúčeniny I má postup podlá vynálezu výhodu v 1-stupňovej, oproti doteraz 2-stupňovej syntéze.A major. The advantage of the process according to the invention over the first of the described methods for the preparation of the compound I is to achieve substantially higher yields. Compared to the second method described for the preparation of compound I, the process according to the invention has the advantage of a 1-step synthesis over the hitherto 2-stage synthesis.
V ďalšom je predmet vynálezu popísaný v příklade prevedenia bez toho, že by sa na tento obmedzoval.Hereinafter, the invention is described in an exemplary embodiment without being limited thereto.
Příklad 1Example 1
K zmesi 50 g 2,6-dimetylfenolu, 57 g bezvodého uhličitanu draselného a 3 g jódu v 200 ml acetonu, vyhriatej k varu sa za miešania v priebehu 5 min. přidá po malých dávkách 50 g chloracetonu v 50 ml acetonu. Zmes sa zahrieva k varu za neustálého miešania počas 12 hod. Potom sa reakčná zmes ochladí na cca 25 °c, anorganické soli odfiltrujú a premyjú acetonom. Filtrát sa zahustí na rotačnej vákuovej odparke a získaný surový produkt sa vákuovo predestiluje /88 až 82 °C pri 93 až 135 Pa/. Získá sa cca 69 g 1-/2,6-dimetylfenoxy/-2-propanonu o obsahu cca 94 i, čo představuje výťažok cca 88 %, vTo a mixture of 50 g of 2,6-dimethylphenol, 57 g of anhydrous potassium carbonate and 3 g of iodine in 200 ml of acetone heated to boiling is stirred for 5 min. add in small portions 50 g of chloroacetone in 50 ml of acetone. Heat the mixture to boiling with stirring for 12 hours. Then, the reaction mixture is cooled to about 25 ° C, the inorganic salts are filtered off and washed with acetone. The filtrate is concentrated on a rotary evaporator and the crude product obtained is distilled under vacuum (88-82 ° C at 93-135 Pa). 69 g of 1- (2,6-dimethylphenoxy) -2-propanone are obtained with a content of about 94%, which represents a yield of about 88%,
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS848176A CS245189B1 (en) | 1984-10-29 | 1984-10-29 | Method of 1-(2,6-dimethylphenoxy)-2-propanone preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS848176A CS245189B1 (en) | 1984-10-29 | 1984-10-29 | Method of 1-(2,6-dimethylphenoxy)-2-propanone preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS817684A1 CS817684A1 (en) | 1985-12-16 |
| CS245189B1 true CS245189B1 (en) | 1986-08-14 |
Family
ID=5431976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS848176A CS245189B1 (en) | 1984-10-29 | 1984-10-29 | Method of 1-(2,6-dimethylphenoxy)-2-propanone preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS245189B1 (en) |
-
1984
- 1984-10-29 CS CS848176A patent/CS245189B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS817684A1 (en) | 1985-12-16 |
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