CN1995006A - (2-alkoxy-4-oxo)-penta-2-enoate compound preparation method - Google Patents
(2-alkoxy-4-oxo)-penta-2-enoate compound preparation method Download PDFInfo
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- CN1995006A CN1995006A CN 200610148161 CN200610148161A CN1995006A CN 1995006 A CN1995006 A CN 1995006A CN 200610148161 CN200610148161 CN 200610148161 CN 200610148161 A CN200610148161 A CN 200610148161A CN 1995006 A CN1995006 A CN 1995006A
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Abstract
The invention discloses a making method of 2-alkoxy-4-oxo-peta-2-alkylene acid ester compound in the organic chemical technical domain, which is characterized by the following: shortening reacting time; improving receiving rate; avoiding three-slag pollution; condensing acetylacetonate and orthoformate in the aliphatic alcohol catalyzed by acid to obtain the product.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to a kind of preparation method of (2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester compound (I).
R in the formula
1=R
2=C
1-C
4Alkyl.
Background technology
(2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester compound (I) is Synthetic 20 (S)-camptothecin [20 (S)-Camptothecins] antitumor drug such as camptothecine compounds (Camptothecin), the hydroxycamptothecine (important intermediate of 20 (S)-10-Hydroxycamptothecin), topotecan (Topotecan) irinotecan (Irinotecan) etc. and biologically active natural drug.
Claiser etc. once reported (Chem Ber, 1907,40,3903) in the presence of ammonium chloride with methyl ethyl diketone acid esters ethyl ester and triethyl orthoformate the method for condensation prepared (2-oxyethyl group-4-oxo)-penta-2-olefin(e) acid ethyl ester (I) in dehydrated alcohol, but this method reaction times reaches 7 days can finish and aftertreatment loaded down with trivial details.The Chinese patent notification number is that 1216992 Chinese patent described with methylsulfonic acid or the vitriol oil etc. is that catalyzer makes methyl ethyl diketone acid esters and ortho-formiate condensation reaction prepare the method for I compounds, though this method reaction times shortens significantly, but have a large amount of waste acid waters to produce, environmental pollution is serious or equipment corrosion is strong.
Summary of the invention
The object of the invention is to provide the preparation method of (2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester compound (I) of short and non-environmental-pollution of a kind of reaction times.
The preparation method of the described compound (I) that the present invention proposes, be in the presence of acid catalyst, methyl ethyl diketone acid esters and ortho-formiate are carried out condensation reaction make accordingly (2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester compound (I) in alkyl alcohol, yield is 85-95%, content 〉=98.5%.This method has easy and simple to handle, the reaction conditions gentleness, and product purity height, acid catalyst recovery set repeatedly such as use at characteristics.
Synthetic route of the present invention is as follows:
In the present invention, used acid catalyst be the loaded by polystyrene Lewis acid (as loaded by polystyrene aluminum chloride, loaded by polystyrene boron trifluoride, loaded by polystyrene iron trichloride, loaded by polystyrene Zinc Chloride Anhydrous and loaded by polystyrene titanium tetrachloride etc. any) and perfluor replace resin sulfonic acid (as the Nafion-H resin) etc. very high catalytic effect all arranged, the reaction conditions gentleness, easy and simple to handle and these catalyzer are all recyclable to be applied mechanically.The mol ratio of methyl ethyl diketone acid esters, ortho-formiate and acid catalyst is 1: 1.1-10: 0.05-0.1, reaction can be finished smoothly.C such as Fatty Alcohol(C12-C14 and C12-C18) that condensation reaction is used such as anhydrous methanol, dehydrated alcohol, anhydrous n-propyl alcohol, anhydrous normal butyl alcohol, anhydrous isopropyl alcohol
1-C
4Fatty Alcohol(C12-C14 and C12-C18) all can be used as reaction solvent.These solvent wide material sources, cheap and easy to get, it is convenient to reclaim.The weightmeasurement ratio of methyl ethyl diketone acid esters and Fatty Alcohol(C12-C14 and C12-C18) is 1: 1.3-40 (g/ml) can make reaction finish smoothly.Temperature of reaction is controlled at 25-80 ℃, and the reaction times is controlled at and is 2-50h, and reaction can be finished.
Preferable reaction conditions of the present invention is:
The mol ratio of methyl ethyl diketone acid esters, ortho-formiate and acid catalyst is 1: 1.2-2: 0.05-0.1.
Methyl ethyl diketone acid esters and C
1-C
4The weightmeasurement ratio of Fatty Alcohol(C12-C14 and C12-C18) is 1: 1.3-5.5 (g/ml).
Acid catalyst is loaded by polystyrene iron trichloride or loaded by polystyrene aluminum chloride or Nafion-H resin, and these three kinds of catalyst effects are best and easy to prepare, cheap and easy to get, recyclable applying mechanically.
Fatty Alcohol(C12-C14 and C12-C18) is anhydrous methanol or dehydrated alcohol, and is cheap and easy to get, wide material sources, and it is convenient to reclaim.
Temperature of reaction is 45-50 ℃.
Reaction times is 5-10h.
Reaction conditions gentleness of the present invention, easy and simple to handle, catalyzer is recyclable to be applied mechanically, and environmental pollution is little, is suitable for suitability for industrialized production
Embodiment
Further specifically describe the present invention below by embodiment, but be not limited to these embodiment.
Embodiment 1:(2-methoxyl group-4-oxo)-preparation of penta-2-olefin(e) acid methyl esters (I)
With the acetopyruvic acid methyl esters (14.4g, 0.1mol), trimethyl orthoformate (11.7g, 0.11mol), the loaded by polystyrene iron trichloride (6.8g, 0.01mol) and anhydrous methanol (25mL) put in the dry reaction bottle, fully stir 5h in 45 ℃.Reaction is finished, and is cooled to room temperature, filters, and reclaims catalyzer, and filtrate decompression reclaims methyl alcohol.In residuum, add ethyl acetate (150mL), continue to stir 5min, leave standstill, tell organic layer, use 10% sodium carbonate solution (20mL * 5) successively, water (20mL * 3), saturated aqueous common salt (20mL * 2) washing, anhydrous magnesium sulfate drying.After reclaiming solvent, 107-109 ℃/13mmHg cut is collected in underpressure distillation, gets faint yellow oily thing I (R
1=R
2=CH
3, 13.4g, 85%).Purity is 98.2% (GC-MS).
1H?NMR(CDCl
3)：δ＝6.36(s，1H，CH)，3.58(s，3H，OCH
3)，3.86(s，3H，CO
2CH
3)，2.25(s，3H，CH
3)ppm.
EI-MS：(m/z)＝158(M
+)，143(M
+-CH
3).
Embodiment 2:(2-methoxyl group-4-oxo)-preparation of penta-2-olefin(e) acid methyl esters (I)
With the acetopyruvic acid methyl esters (14.4g, 0.1mol), trimethyl orthoformate (31.9g, 0.3mol), the loaded by polystyrene titanium tetrachloride (139.8g, 0.2mol) and anhydrous methanol (50mL) put in the dry reaction bottle, fully stir 2h in 60 ℃.Reaction is finished, and is cooled to room temperature, filters, and reclaims catalyzer, and filtrate decompression reclaims methyl alcohol.In residuum, add ethyl acetate (200mL), continue to stir 5min, leave standstill, tell organic layer, use 10% sodium carbonate solution (30mL * 5) successively, water (30mL * 3), saturated aqueous common salt (30mL * 2) washing, anhydrous magnesium sulfate drying.After reclaiming solvent, 107-109 ℃/13mmHg cut is collected in underpressure distillation, gets faint yellow oily product I (R
1=R
2=CH
3, 14.2g, 90%).Purity is 98% (GC-MS).
1HNMR is all consistent with embodiment 1 with MS.
Embodiment 3:(2-oxyethyl group-4-oxo)-preparation of penta-2-olefin(e) acid ethyl ester (I)
With ethyl acetopyruvate (15.8g, 0.1mol), triethyl orthoformate (16.3g, 0.11mol), the loaded by polystyrene iron trichloride (6.8g, 0.01mol) and dehydrated alcohol (25mL) put in the dry reaction bottle, fully stir 5h in 45 ℃.Reaction is finished, and is cooled to room temperature, filters, and reclaims catalyzer, and filtrate decompression reclaims methyl alcohol.In residuum, add ethyl acetate (150mL), continue to stir 5min, leave standstill, tell organic layer, use 10% sodium carbonate solution (20mL * 5) successively, water (20mL * 3), saturated aqueous common salt (20mL * 2) washing, anhydrous magnesium sulfate drying.After reclaiming solvent, 127-129 ℃/11mmHg cut is collected in underpressure distillation, gets faint yellow oily thing I (R
1=R
2=C
2H
5, 16.7g, 90%).Purity is 98.2%.(GC-MS)。
1H?NMR(CDCl
3)：δ＝6.36(s，1H，CH)，4.15(q，2H，OCH
2)，4.29(q，2H，CO
2CH
2)，2.25(t，3H，CH
3)，1.31(q，3H，CH
3)，1.26(q，3H，CH
3)ppm.
EI-MS：(m/z)＝187(M
+1)，186(M
+)，157(M
+-C
2H
5).
Embodiment 4:(2-oxyethyl group-4-oxo)-preparation of penta-2-olefin(e) acid ethyl ester (I)
With ethyl acetopyruvate (15.8g, 0.1mol), triethyl orthoformate (16.3g, 0.11mol), the loaded by polystyrene titanium tetrachloride (139.8g, 0.2mol) and dehydrated alcohol (50mL) put in the dry reaction bottle, fully stir 2h in 60 ℃.Reaction is finished, and is cooled to room temperature, filters, and reclaims catalyzer, and filtrate decompression reclaims methyl alcohol.In residuum, add ethyl acetate (200mL), continue to stir 5min, leave standstill, tell organic layer, use 10% sodium carbonate solution (30mL * 5) successively, water (30mL * 3), saturated aqueous common salt (30mL * 2) washing, anhydrous magnesium sulfate drying.After reclaiming solvent, 127-129 ℃/11mmHg cut is collected in underpressure distillation, gets faint yellow oily thing I (R
1=R
2=C
2H
5, 16.1g, 87%).Purity is 98% (GC-MS).
1H NMR is all consistent with embodiment 3 with MS.
Claims (7)
- The method of 1, a kind of preparation (2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester (I),
R in the formula 1=R 2=C 1-C 4Alkyl,It is characterized in that in the presence of acid catalyst methyl ethyl diketone acid esters and ortho-formiate carry out condensation reaction and obtain (2-alkoxyl group-4-oxo)-penta-2-olefin(e) acid ester compound (I) in Fatty Alcohol(C12-C14 and C12-C18), concrete preparation condition is:(1) acid catalyst of condensation reaction is that loaded by polystyrene Lewis acid or perfluor replace resin sulfonic acid; With Fatty Alcohol(C12-C14 and C12-C18) be C 1-C 4Fatty Alcohol(C12-C14 and C12-C18);(2) mol ratio of methyl ethyl diketone acid esters, ortho-formiate and acid catalyst is 1: 1.1-10: 0.05-0.5;(3) weightmeasurement ratio of methyl ethyl diketone acid esters and Fatty Alcohol(C12-C14 and C12-C18) is 1: 1.3-40;(4) temperature of reaction is 25-80 ℃;(5) reaction times is 2-50h. - 2, method according to claim 1, the mol ratio that it is characterized in that methyl ethyl diketone acid esters, ortho-formiate and acid catalyst is 1: 1.2-2: 0.05-0.1.
- 3, method according to claim 1, the weightmeasurement ratio that it is characterized in that methyl ethyl diketone acid esters and Fatty Alcohol(C12-C14 and C12-C18) is 1: 1.3-5.5.
- 4, method according to claim 1 is characterized in that used acid catalyst is loaded by polystyrene iron trichloride or loaded by polystyrene aluminum chloride or Nafion-H resin.
- 5, method according to claim 1 is characterized in that used Fatty Alcohol(C12-C14 and C12-C18) is anhydrous methanol or dehydrated alcohol.
- 6, the method for claim 1 is characterized in that temperature of reaction is 45-50 ℃.
- 7, the method for claim 1 is characterized in that the reaction times is 5-10h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100424878C (en) * | 2006-11-21 | 2008-10-08 | 华中科技大学 | Ferroelectric film capacity used for ferroelectric memorizer and its manufacturing method |
-
2006
- 2006-12-28 CN CN 200610148161 patent/CN1995006A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100424878C (en) * | 2006-11-21 | 2008-10-08 | 华中科技大学 | Ferroelectric film capacity used for ferroelectric memorizer and its manufacturing method |
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