CN106748949B - A kind of method of synthesis α, β unsaturated acyl amine compounds - Google Patents
A kind of method of synthesis α, β unsaturated acyl amine compounds Download PDFInfo
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- CN106748949B CN106748949B CN201710025520.1A CN201710025520A CN106748949B CN 106748949 B CN106748949 B CN 106748949B CN 201710025520 A CN201710025520 A CN 201710025520A CN 106748949 B CN106748949 B CN 106748949B
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
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Abstract
A kind of method of synthesis α, β unsaturated acyl amine compounds, is related to α, β unsaturated amides.A kind of a kind of using the stable cyclic tertiary amide being easy to get as raw material, the higher synthesis α of efficiency, the method for β unsaturated acyl amine compounds are provided.By teritary amide be added halogenated hydrocarbon solvent in, with Trifluoromethanesulfonic anhydride, organic base, aromatic aldehyde carry out condensation reaction after, through extraction, drying, concentration, after purification to get α, β unsaturated acyl amine compounds.To stablize the cyclic tertiary amide being easy to get as raw material, one kind α, β unsaturated acyl amine compounds are expeditiously synthesized；Operation, separation are simple, and reagent used is common agents, cheap and easy to get.
Description
Technical field
The present invention relates to α, β unsaturated amides, more particularly, to a kind of synthesis α, the method for β unsaturated acyl amine compounds.
Background technique
Currently, the synthesis of α, β unsaturated amides is compared to α, the synthesis of β unsaturated aldehyde, ketone and ester, related document is less,
And lack very effective one-step method for synthesizing.It before, the use of more method is by Huo Naer-Wordsworth-Ai Mengsi
Reaction and the gloomy reaction of Peter, but these methods still remain some insurmountable problems.For example these methods are from one
The amide that α-phosphorus replaces and α-silicon substrate replaces sets out to synthesize α, and β unsaturated amides can not be free of these functional groups from one
General amide set out and synthesize this compound；In addition, some methods are because low yield is restricted its application.This and α, β
The importance of unsaturated amides is compared and forms very big contrast.α, β unsaturated amides unsaturated amides are prevalent in naturally
In product structure, these natural products have compared with Johnson & Johnson's object and insecticidal activity, such as (±)-Isoanantine and (±)-
anantine.Meanwhile α, β unsaturated amides are also useful organic synthesis stripping and slicing.
1989, M.K.Tay group reports reacted building chain by phosphate with isocyanates or carbonic acid esteramides
Synthesize α, β unsaturated amides after alpha-phosphate esteramides with aldehyde reaction again.This method has good substrate applicability, but can only use
In building chain α, β unsaturated amides.Compound is write a Chinese character in simplified form: LDA is lithium diisopropylamine.
2000, Satoshi Kojima group reported α-silicon substrate amide and aldehyde reaction obtains α, β unsaturated amides
Method, this method for aldehyde substrate have stronger substrate applicability, but for amide substrate substrate applicability compared with
It is low, it only reported the amide and aldehyde reaction for only having silicon substrate to replace on α carbon of amide in text, thus this method can only construct in double bond
Disubstituted α, β unsaturated amides.The above both methods and carried out in strong basicity system, for having in substrate
The substrate for the functional group that strong basicity system does not tolerate is also not suitable for.Compound is write a Chinese character in simplified form: LDA is lithium diisopropylamine, and base is
Organic base, Ar are aryl, and Alkyl is alkyl, and Alkenyl is alkenyl.
Chinese patent CN1561326A1 discloses a kind of method for preparing alpha-haloenamine, and this method includes by teritary amide and five
Valence phosphorus halide is mixed to form α-halogen inferior amine salt in a solvent, and the α-halogen inferior amine salt is then converted to α-halogen alkene with alkali
Amine, the pentavalent phosphorus halide have at least two halogen atoms being keyed on pentavalent phosphorous atom.
Summary of the invention
The purpose of the present invention is to provide a kind of using the stable cyclic tertiary amide being easy to get as raw material, a kind of higher conjunction of efficiency
At α, the method for β unsaturated acyl amine compounds.
Synthetic route of the invention are as follows:
Wherein, R1=C3~C8 alkyl；R2,R3=H, C1~C5 alkyl or C6~C10 aromatic radical；Compound 1 is tertiary acyl
Amine, compound 2 are α, β unsaturated acyl amine compounds.
Specific step is as follows for synthetic method of the invention:
Teritary amide is added in halogenated hydrocarbon solvent, after carrying out condensation reaction with Trifluoromethanesulfonic anhydride, organic base, aromatic aldehyde,
Through extraction, drying, concentration, after purification to get α, β unsaturated acyl amine compounds.
The temperature that teritary amide is added in halogenated hydrocarbon solvent can be -78~0 DEG C；The structural formula of the teritary amide are as follows:
Wherein, R1It can be C3~C8 alkyl；R2,R3It can be H, C1~C5 alkyl or C6~C10 aromatic radical；The halogenated hydrocarbons
Solvent can be selected from one of halogenated hydrocarbons of C1~C4 etc., preferably methylene chloride or 1,2- dichloroethanes etc.；The organic base can
Select organic amine etc., preferably one of diisopropyl ethyl amine, triethylamine etc.；Heteroaromatic aldehyde or benzene can be selected in the aromatic aldehyde
Benzaldehyde compound；The molar ratio that the tertiary acyl amine ︰ trifluoro Loprazolam acid anhydride ︰ has machine alkali ︰ aromatic aldehyde can be 1 ︰, 2 ︰, 2 ︰ 3.
The present invention expeditiously synthesizes one kind α, β unsaturated acyl amine compounds to stablize the cyclic tertiary amide being easy to get as raw material
Object.Operation of the invention, separation are simple, and reagent used is common agents, cheap and easy to get.
Specific embodiment
Below by embodiment, the present invention is further illustrated.
Embodiment 1
1- cyclohexyl pyrrolidone (being denoted as compound 1a) (115mg, 0.69mmol) is dissolved in methylene chloride (6mL) solvent
In, trifluoromethanesulfanhydride anhydride (0.23mL, 1.4mmol) is added under -78 DEG C and argon atmospher, benzene first is added dropwise in -78 DEG C of stirring 45min
Aldehyde (0.20mL, 2.0mmol) rises to 0 DEG C after -78 DEG C of stirring 5min, is added dropwise triethylamine (0.20mL, 1.4mmol), room temperature reaction
1h.After (1N) the hydrochloric acid reaction of 10mL is added, liquid separation is stood, water phase is extracted with methylene chloride (3 × 20mL).Merge organic
Phase is washed with saturated sodium bicarbonate solution (30mL) and saturated salt solution (20mL), is dried over anhydrous sodium sulfate, and is filtered, decompression
Concentration, obtains 1- cyclohexyl -3- benzyl vinyl pyrrolidone (being denoted as compound 2a) after purification, and gained compound 2a is colourless liquid
(74mg, 42%).IR(film)3051,2936,2855,1672,1643,1492,1448,1423,1296,1280,952,
764,694；1H NMR(400MHz,CDCl3)δ1.05-1.20(m,1H),1.35-1.52(m,4H),1.65-1.90(m,5H),
2.98-3.09 (m, 2H), 3.47 (t, J=6.5Hz, 2H), 4.05-4.21 (m, 1H), 7.24-7.43 (m, 4H), 7.43-7.51
(m,2H)；13C NMR(100MHz,CDCl3)δ24.5,25.4(2C),25.5,29.6,30.2(2C),40.4,51.2,128.1,
128.6(2C),129.4(2C),131.9,136.1,168.4；MS(ESI,m/z):256(M+H+, 100%).
Embodiment 2
1- benzyl-pyrrole alkanone (1b) 121mg, 0.69mmol) is dissolved in methylene chloride (6mL) solvent, in -78 DEG C and
Trifluoromethanesulfanhydride anhydride (0.23mL, 1.4mmol) is added under argon atmospher, -78 DEG C of stirring 45min, dropwise addition benzaldehyde (0.20mL,
2.0mmol), 0 DEG C is risen to after -78 DEG C of stirring 5min, is added dropwise triethylamine (0.20mL, 1.4mmol), and 1h is reacted at room temperature.It is added
After (1N) the hydrochloric acid reaction of 10mL, liquid separation is stood, water phase is extracted with methylene chloride (3 × 20mL).Merge organic phase, with full
It washs, is dried over anhydrous sodium sulfate with sodium bicarbonate solution (30mL) and saturated salt solution (20mL), filter, be concentrated under reduced pressure, it is pure
After change 1- benzyl -3- benzyl vinyl pyrrolidone (being denoted as compound 2b), gained compound 2b be colourless liquid (109mg,
60%).IR (film) 3082,3028,2923,2850,1674,1645,1495,1448,1434,1422,1295,1282,
1255,1120,1076,763,696；1H NMR(400MHz,CDCl3) δ 2.99-3.08 (m, 2H), 3.38 (t, J=6.4Hz,
2H),4.62(s,2H),7.22-7.45(m,9H),7.45-7.52(m,2H)；13C NMR(100MHz,CDCl3)δ24.3,
44.0,47.3,127.6,128.3(2C),128.4,128.6(2C),128.7(2C),129.5(2C),130.4,130.8,
135.8,136.4,169.1；MS(ESI,m/z):264(M+H+, 100%).
Embodiment 3
1- (1- phenylethyl) pyrrolidones (1c) (131mg, 0.69mmol) is dissolved in methylene chloride (6mL) solvent,
Trifluoromethanesulfanhydride anhydride (0.23mL, 1.4mmol) is added under -78 DEG C and argon atmospher, benzaldehyde is added dropwise in -78 DEG C of stirring 45min
(0.20mL, 2.0mmol) rises to 0 DEG C after -78 DEG C of stirring 5min, is added dropwise triethylamine (0.20mL, 1.4mmol), room temperature reaction
1h.After (1N) the hydrochloric acid reaction of 10mL is added, liquid separation is stood, water phase is extracted with methylene chloride (3 × 20mL).Merge organic
Phase is washed with saturated sodium bicarbonate solution (30mL) and saturated salt solution (20mL), is dried over anhydrous sodium sulfate, and is filtered, decompression
Concentration, obtains 1- (1- phenylethyl) -3- benzyl vinyl pyrrolidone (being denoted as compound 2c) after purification, and gained compound 2c is colourless
Liquid (88mg, 46%).IR(film)3084,3023,2978,2919,1670,1645,1491,1437,1418,1281,
1212,1182,1069,1028,926,784,763,688；1H NMR(400MHz,CDCl3) δ 1.60 (d, J=7.1Hz, 3H),
2.86-3.15 (m, 3H), 3.38-3.50 (m, 1H), 5.70 (q, J=7.1Hz, 1H), 7.22-7.43 (m, 9H), 7.43-7.51
(m,2H)；13C NMR(100MHz,CDCl3)δ16.1,24.2,29.6,39.7,49.7,127.2(2C),127.5,128.3,
128.5(2C),128.6(2C),129.4(2C),130.2,131.4,135.9,140.0,168.6；MS(ESI,m/z):278(M
+H+, 100%).
Claims (8)
1. a kind of method of synthesis α, β unsaturated acyl amine compounds, it is characterised in that its synthetic route are as follows:
Wherein, R1=C3~C8 alkyl；R2,R3=H, C1~C5 alkyl or C6~C10 aromatic radical；Compound 1 is teritary amide, is changed
Conjunction object 2 is α, β unsaturated acyl amine compounds.
2. a kind of synthesis α as described in claim 1, the method for β unsaturated acyl amine compounds, it is characterised in that its synthetic method
Specific step is as follows:
Teritary amide is added in halogenated hydrocarbon solvent, after carrying out condensation reaction with Trifluoromethanesulfonic anhydride, organic base, benzaldehyde, warp
Extraction, is concentrated, after purification to get α, β unsaturated acyl amine compounds drying.
3. a kind of synthesis α as claimed in claim 2, the method for β unsaturated acyl amine compounds, it is characterised in that described by teritary amide
The temperature being added in halogenated hydrocarbon solvent is -78~0 DEG C.
4. a kind of synthesis α as claimed in claim 2, the method for β unsaturated acyl amine compounds, it is characterised in that the halogenated hydrocarbons is molten
Agent is selected from one of the halogenated hydrocarbons of C1~C4.
5. a kind of synthesis α as claimed in claim 4, the method for β unsaturated acyl amine compounds, it is characterised in that the halogenated hydrocarbons is molten
Agent is selected from methylene chloride or 1,2- dichloroethanes.
6. a kind of synthesis α as claimed in claim 2, the method for β unsaturated acyl amine compounds, it is characterised in that the organic base choosing
Use organic amine.
7. a kind of synthesis α as claimed in claim 6, the method for β unsaturated acyl amine compounds, it is characterised in that the organic amine choosing
With diisopropyl ethyl amine or triethylamine.
8. a kind of synthesis α as claimed in claim 2, the method for β unsaturated acyl amine compounds, it is characterised in that the teritary amide:
The molar ratio that trifluoro Loprazolam acid anhydride ︰ has machine alkali ︰ benzaldehyde is 1 ︰, 2 ︰, 2 ︰ 3.
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| CN104262255A (en) * | 2014-09-22 | 2015-01-07 | 四川大学 | Method for asymmetric catalytic synthesis of gamma-nitropyrazole amide compound |
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| CN104262255A (en) * | 2014-09-22 | 2015-01-07 | 四川大学 | Method for asymmetric catalytic synthesis of gamma-nitropyrazole amide compound |
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