CN102432487A - Catalysis-based amino acetylation method - Google Patents
Catalysis-based amino acetylation method Download PDFInfo
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- CN102432487A CN102432487A CN2011102802499A CN201110280249A CN102432487A CN 102432487 A CN102432487 A CN 102432487A CN 2011102802499 A CN2011102802499 A CN 2011102802499A CN 201110280249 A CN201110280249 A CN 201110280249A CN 102432487 A CN102432487 A CN 102432487A
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Abstract
The invention discloses a catalysis-based amino acetylation method. The catalysis-based amino acetylation method utilizes Lewis alkali ionic liquid [HDBU]OAc as a catalyst, acetic anhydride as an acetylation agent, and an alicyclic amine or an aromatic amine as a substrate. The catalysis-based amino acetylation method comprises the following steps that 1, the substrate undergoes an acetylation reaction in the dis-presence of a solvent at a temperature of 40 to 80 DEG C for 0.3 to 1.5 hours, wherein a mole ratio of acetic anhydride to the substrate is (1.0 to 2.0): 1 and a mole ratio of Lewis alkali ionic liquid [HDBU]OAc to the substrate is in a range of 10 to 30%; 2, after the acetylation reaction, ether is added into the products; 3, the mixture obtained by the step 2 is filtered and separated; 4, the supernatant extract obtained by the step 3 is washed orderly through a saturated NaHCO3 solution and water; 5, the washed supernatant extract is added with waterless Na2SO4 for drying; and 6, the ether is removed by reduced pressure rotary distillation so that a finished product is obtained. The catalysis-based amino acetylation method has the characteristics of wild reaction conditions, high yield, low cost, environmental benefits and high safety.
Description
Technical field
The present invention relates to a kind of methodology of organic synthesis, particularly the catalytic glycyl reaction of Lewis basic ion liquid [HDBU] OAc.
Background technology
Acetylization reaction is one of modal reaction in the organic synthesis, and ethanoyl also is the protection base commonly used in the complicated building-up reactions.According to bibliographical information; The acetylize of hydroxyl protection in alcohols and the phenolic cpd molecule; Normal Acetyl Chloride 98Min. or the diacetyl oxide of adopting carries out under acid or base catalysis, and wherein pyridine, 4-Dimethylamino pyridine (DMAP) and 4-pyrroles's pyridine (PPY) etc. all are the basic catalysts of excellent property.In addition, protonic acid (like tosic acid), Lewis acid (like transition metal halide, fluoroform sulphonate, Yttria-zirconia) and solid acid (if you would take off soil, HBF
4SiO
2, HClO
4SiO
2Deng) etc. an acidic catalyst also can the catalytic amino acetylization reaction.Though above-described catalyzer is applied in laboratory scale even suitability for industrialized production, still exist such as long reaction time, severe reaction conditions, required reagent to cost an arm and a leg and defective such as poisonous and harmful.
1, and 8-diazabicyclo (5.4.0) 11-7-alkene (1,8-diazabicyclo (5.4.0) undec-7-ene; Be called for short DBU) be a kind of organic alkali, structure is shown in S-1, and pure article are colourless or light yellow transparent liquid; Main application is the good organic bases de-acidying agent in synthesizing as medicine; Can replace such as triethylamine, N, N-xylidene(s), pyridine and quinoline etc. are widely used in the organic synthesis.DBU with such as obtaining ionic liquid at room temperature after the common organic acid generation neutralization reactions such as acetate; General structure is shown in S-2; Such ionic liquid can catalysis Michael addition and a series of organic reactions (reference: (a) Tetrahedron Lett.2009 such as Knoevenagel condensation; 50,1653; (b) Arkivoc, 2009, XI, 288; (c) Chem.Res.Chinese Universities, 2009,25,876; (d) J.Chem.Res.2010,30.).
Summary of the invention
The technical problem that the present invention will solve provides a kind of reaction conditions gentleness, yield is high, cost is low, the acetylizad method of the catalytic amino of green safety.
In order to solve the problems of the technologies described above, the present invention provides a kind of catalytic amino acetylizad method, and OAc is a catalyzer with Lewis basic ion liquid [HDBU], and diacetyl oxide is an acetylation reagent, is substrate with aliphatic amide or aromatic amine; Substrate carries out acetylization reaction under condition of no solvent; Temperature of reaction is 40～80 ℃, and the reaction times is 0.3～1.5h;
The mol ratio of diacetyl oxide and substrate is 1.0～2.0: 1, and the mol ratio of Lewis basic ion liquid [HDBU] OAc and substrate is 10%～30%;
After reaction finishes, add ether, filter, separate, upper layer of extraction liquid is used saturated NaHCO successively
3After solution and the water washing, add anhydrous Na
2SO
4Drying, vacuum rotary steam is removed ether, promptly gets product.
Improvement as the acetylizad method of catalytic amino of the present invention: the preparation method of Lewis basic ion liquid [HDBU] OAc is following:
In reactor drum, add 1,8-diazabicyclo (5.4.0) 11-7-alkene (DBU) is under the ice-water bath condition; Drip the Glacial acetic acid min. 99.5 of (slowly dripping) equimolar amount, during to keep temperature be 0～5 ℃, after dropwising; Remove ice-water bath, at room temperature react 22～26h, gains are dry 22～26h (drying temperature is 50～70 ℃) under vacuum condition; Obtain faint yellow full-bodied Lewis basic ion liquid [HDBU] OAc, its structural formula is following:
As the acetylizad further improvements in methods of catalytic amino of the present invention: adopt TLC and GC monitoring reaction process.
As the acetylizad further improvements in methods of catalytic amino of the present invention: aliphatic amide can be selected benzylamine, n-Butyl Amine 99, hexahydroaniline, quadrol etc. for use; Aromatic amine can be selected aniline, para-totuidine, Ortho Toluidine, p-Nitroaniline, o-Nitraniline, m-anisidine, o-trifluoromethyl aniline, Ortho-Chloro aniline, p-Chlorobenzoic acid amide, para-fluoroaniline etc. for use.
Its English name of Lewis basic ion liquid of the present invention is Lewis basic ionic liquid.Room temperature refers generally to 10～30 ℃.In the present invention, the substrate of every 10mmol is used the ether of 10～30ml.
The reaction formula of Lewis basic ion liquid [HDBU] OAc is following:
The reaction formula of acetylization reaction of the present invention is following:
R＝aryl，alkyl。
Adopt method of the present invention, the purity of products therefrom is generally 96%～99%.If needed, can separate purification with column chromatography according to routine techniques.
The catalytic glycyl reaction of Lewis basic ion liquid of the present invention [HDBU] OAc has following advantage:
1, catalyzer raw material DBU price is relatively cheap, processes to have solved it behind the ionic liquid at room temperature and have the problem of unhappy smell, and is convenient to preserve;
2, in contrast to pyridine, DMAP, 4-pyrroles's pyridine acetylation catalysts such as (PPY), significantly reduced catalyst levels, reaction conditions is gentle more, and the reaction times is short, and yield is high, has simplified post-reaction treatment, and reaction is green more friendly;
3, in contrast to transition metal salt catalyzer, [HDBU] OAc is all insensitive to water and air, and does not have the residual problem of heavy metal ion, and is little to equipment corrosion;
4, catalyst preparation process is simple, is convenient to operation.
Embodiment
Ionic liquid described in following examples [HDBU] OAc is Lewis basic ion liquid [HDBU] OAc that informs in the preceding text.
Embodiment 1, ionic liquid [HDBU] OAc preparation, carry out following steps successively:
In the 50mL there-necked flask, add 7.6g (50mmol) DBU, add ice-water bath, open magnetic agitation.Measure Glacial acetic acid min. 99.5 3.0g (50mmol), change constant pressure funnel over to, slowly splash in the flask, during keep temperature of reaction to be lower than 5 ℃.Treat that Glacial acetic acid min. 99.5 dropwises, remove ice-water bath, stirring reaction 24h under the room temperature.Gained oily reactant obtains light yellow viscous liquid behind 60 ℃ of following vacuum-drying 24h, be ionic liquid [HDBU] OAc, places in the moisture eliminator to preserve.Its structural formula is following:
The glycyl method of embodiment 2, a kind of Lewis basic ion liquid catalyst, OAc is a catalyzer with ionic liquid [HDBU], carries out following steps successively:
(1.07g, 10mmol) (1.03g 10.1mmol), adds catalyzer [HDBU] OAc (0.42g, that is, 20% mol ratio) again, opens magnetic agitation, slowly is warming up to 50 ℃ with the new diacetyl oxide that steams in being furnished with the 25mL flask of spherical condensation tube, to add benzylamine.TLC (developping agent: EtOAc/hexanes=1: 4, V/V) with GC monitoring reaction process.Benzylamine transforms and finishes behind the 30min, adds 20mL ether dilute reaction solution, filters, and can isolate the upper strata product, and the organic phase of gained (upper layer of extraction liquid that promptly contains product) is used the saturated NaHCO of 10mL successively
3After solution and the 10mL water washing, add the 0.5g anhydrous Na
2SO
4Drying, decompression (O.02MPa) are revolved to steam and are removed ether, promptly get white solid 1.37g (yield 92%,, purity is 97.3%), melting range 60.3-62.2 ℃.
1H NMR (400MHz, CDCl
3, TMS): 7.33-7.24 (m, 5H), 6.15 (br s, 1H), 4.38 (d, J=5.70Hz, 2H), 1.99 (s, 3H).
13C NMR (100MHz, CDCl
3): 169.95,138.16,128.57,127.46,127.28,43.50, the 23.19. product is confirmed as N-acetyl benzylamine.
The glycyl method of embodiment 3, a kind of Lewis basic ion liquid catalyst, OAc is a catalyzer with ionic liquid [HDBU], carries out following steps successively:
(0.93g, 10mmol) (1.03g 10.1mmol), adds catalyzer [HDBU] OAc (0.42g, that is, 20% mol ratio) again, opens magnetic agitation, slowly is warming up to 50 ℃ with the new diacetyl oxide that steams in being furnished with the 25mL flask of spherical condensation tube, to add aniline.TLC (developping agent: EtOAc/hexanes=1: 4, V/V) with GC monitoring reaction process.Aniline transforms and finishes behind the 45min, adds 20mL ether dilute reaction solution, filters, and can isolate the upper strata product, and gained organic phase (upper layer of extraction liquid that promptly contains product) is used the saturated NaHCO of 10mL successively
3After solution and the 10mL water washing, add the 0.5g anhydrous Na
2SO
4Drying, vacuum rotary steam is removed ether, promptly gets white solid 1.28g (yield 95%, purity are 96.8%), melting range 113.4-114.9 ℃.
1H NMR (400MHz, CDCl
3, TMS): 7.88 (br s, 1H), 7.50 (d, J=7.6Hz, 2H), 7.29 (t, J=7.5Hz, 2H), 7.09 (t, J=7.4Hz, 1H), 2.14 (s, 3H).
13C NMR (100MHz, CDCl
3): 168.93,138.01,128.87,124.26,120.13, the 24.39. product is confirmed as monoacetylaniline.
The glycyl method of embodiment 4, a kind of Lewis basic ion liquid catalyst, OAc is a catalyzer with ionic liquid [HDBU], carries out following steps successively:
(1.07g, 10mmol) (1.03g 10.1mmol), adds catalyzer [HDBU] OAc (0.42g, that is, 20% mol ratio) again, opens magnetic agitation, slowly is warming up to 50 ℃ with the new diacetyl oxide that steams in being furnished with the 25mL flask of spherical condensation tube, to add para-totuidine.TLC (developping agent: EtOAc/hexanes=1: 4, V/V) with GC monitoring reaction process.Para-totuidine transforms and finishes behind the 45min, adds 20mL ether dilute reaction solution, filters, and isolates the upper strata product, and gained organic phase (upper layer of extraction liquid that promptly contains product) is used the saturated NaHCO of 10mL successively
3After solution and the 10mL water washing, add the 0.5g anhydrous Na
2SO
4Drying, vacuum rotary steam is removed ether, promptly gets white solid 1.40g (yield 94%, purity are 97.5%), melting range 144.3-145.5 ℃.
1H NMR (400MHz, CDCl
3, TMS): 7.36 (d, J=8.4Hz, 2H), 7.28 (br s, 1H), 7.11 (d, J=8.2Hz, 2H), 2.31 (s, 3H), 2.15 (s, 3H).
13C NMR (100MHz, CDCl
3): 169.04,135.60,133.53,129.40,120.36,24.38, the 20.95. product is confirmed as the N-acetyl-p-toluidine.
The glycyl method of embodiment 5, a kind of Lewis basic ion liquid catalyst, OAc is a catalyzer with ionic liquid [HDBU], carries out following steps successively:
(1.07g, 10mmol) (1.03g 10.1mmol), adds catalyzer [HDBU] OAc (0.42g, that is, 20% mol ratio) again, opens magnetic agitation, slowly is warming up to 50 ℃ with the new diacetyl oxide that steams in being furnished with the 25mL flask of spherical condensation tube, to add Ortho Toluidine.TLC (developping agent: EtOAc/hexanes=1: 4, V/V) with GC monitoring reaction process.Para-totuidine transforms and finishes behind the 45min, adds 20mL ether dilute reaction solution, filters, and isolates the upper strata product, and gained organic phase (upper layer of extraction liquid that promptly contains product) is used the saturated NaHCO of 10mL successively
3After solution and the 10mL water washing, add the 0.5g anhydrous Na
2SO
4Drying, vacuum rotary steam is removed ether, promptly gets white solid 1.39g (yield 93%, purity are 97.2%), melting range 102.1-103.8 ℃.
1H NMR (400MHz, CDCl
3, TMS): 7.62 (d, J=8.0Hz, 1H), 7.30 (br s, 1H), 7.14 (d, J=7.1Hz, 1H), 7.06 (d, J=7.3Hz, 1H), 2.20 (s, 3H), 2.13 (s, 3H).
13C NMR (100MHz, CDCl
3): 168.72,135.60,130.44,130.09,126.54,125.46,123.96,24.00, the 17.76. product is confirmed as N-acetyl Ortho Toluidine.
Embodiment 6～11 is basic identical with the operation steps of embodiment 2～5, adopts different substrates, and the difference of reaction times according to substrate changes to some extent, and therefore the result with embodiment 6～11 classifies table 1 as, so that contrast.
Table 1
At last, it is also to be noted that what more than enumerate only is several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.All distortion that those of ordinary skill in the art can directly derive or associate from content disclosed by the invention all should be thought protection scope of the present invention.
Claims (4)
1. the acetylizad method of catalytic amino, it is characterized in that: OAc is a catalyzer with Lewis basic ion liquid [HDBU], diacetyl oxide is an acetylation reagent, is substrate with aliphatic amide or aromatic amine; Substrate carries out acetylization reaction under condition of no solvent; Temperature of reaction is 40～80 ℃, and the reaction times is 0.3～1.5h;
The mol ratio of said diacetyl oxide and substrate is 1.0～2.0: 1, and the mol ratio of Lewis basic ion liquid [HDBU] OAc and substrate is 10%～30%;
After reaction finishes, add ether, filter, separate, upper layer of extraction liquid is used saturated NaHCO successively
3After solution and the water washing, add anhydrous Na
2SO
4Drying, vacuum rotary steam is removed ether, promptly gets product.
2. the acetylizad method of catalytic amino according to claim 1 is characterized in that: the preparation method of said Lewis basic ion liquid [HDBU] OAc is following:
In reactor drum, add 1,8-diazabicyclo (5.4.0) 11-7-alkene is under the ice-water bath condition; Drip the Glacial acetic acid min. 99.5 of equimolar amount, during to keep temperature be 0～5 ℃, after dropwising; Remove ice-water bath, at room temperature react 22～26h, gains are dry 22～26h under vacuum condition; Obtain Lewis basic ion liquid [HDBU] OAc, its structural formula is following:
3. the acetylizad method of catalytic amino according to claim 2 is characterized in that: adopt TLC and GC monitoring reaction process.
4. according to claim 1, the acetylizad method of 2 or 3 described catalytic aminos, it is characterized in that:
Said aliphatic amide is benzylamine, n-Butyl Amine 99, hexahydroaniline or quadrol;
Said aromatic amine is aniline, para-totuidine, Ortho Toluidine, p-Nitroaniline, o-Nitraniline, m-anisidine, o-trifluoromethyl aniline, Ortho-Chloro aniline, p-Chlorobenzoic acid amide or para-fluoroaniline.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114920648A (en) * | 2022-05-11 | 2022-08-19 | 浙江新化化工股份有限公司 | Synthesis method and catalyst of 3- (3-oxo-2-pentyl) cyclopentyl malonic acid dimethyl ester |
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2011
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Non-Patent Citations (4)
| Title |
|---|
| JAFAR AKBARI等: "Protic ionic liquid [TMG][Ac] as an efficient, homogeneous and recyclable catalyst for Boc protection of amines", 《C. R. CHIMIE》 * |
| KRISTIN E. PRICE等: "Mild and Efficient DBU-Catalyzed Amidation of Cyanoacetates", 《ORGANIC LETTERS》 * |
| M. BAIDYA等: "Nucleophilicities and carbon basicities of DBU and DBN", 《CHEM. COMMUN.》 * |
| 应安国: "离子液体在有机合成中的应用研究进展", 《有机化学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114920648A (en) * | 2022-05-11 | 2022-08-19 | 浙江新化化工股份有限公司 | Synthesis method and catalyst of 3- (3-oxo-2-pentyl) cyclopentyl malonic acid dimethyl ester |
| CN114920648B (en) * | 2022-05-11 | 2023-09-01 | 浙江新化化工股份有限公司 | Synthesis method and catalyst of 3- (3-oxo-2-amyl) cyclopentyl dimethyl malonate |
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