CN100503558C - Method of synthesizing hexa-2,4-dienedinitrile from 1,4-dihalogen-1,3-butadiene and cuprous cyanide - Google Patents
Method of synthesizing hexa-2,4-dienedinitrile from 1,4-dihalogen-1,3-butadiene and cuprous cyanide Download PDFInfo
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- CN100503558C CN100503558C CNB2006100116982A CN200610011698A CN100503558C CN 100503558 C CN100503558 C CN 100503558C CN B2006100116982 A CNB2006100116982 A CN B2006100116982A CN 200610011698 A CN200610011698 A CN 200610011698A CN 100503558 C CN100503558 C CN 100503558C
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Abstract
The invention discloses a general purpose method to synthesize 2,4-hexadiene dinitrile derivant with multiple substituted radicals, which comprises the following steps: blending 1,4-dihalide-1,3-butadiene derivant and cuprous cyanide; adding N,N-dimethyl formamide solvent to reflow; condensing the product; purifying; obtaining the product. The invention improves the separating rate with wide fitting scale, which is easy to operate.
Description
Technical field
The present invention relates to have multiple substituent 2, the universal synthesis method of 4-hexadiene two carbonitrile derivatives belongs to organic synthesis intermediate and the synthetic field of new functional materials.
Background technology
Have multiple substituent 2,4-hexadiene two carbonitrile derivatives are important organic synthesis intermediates, the nitrile etc. that can be used for making up carbocyclic ring, heterocycle and make up functionalization by conjugate addition reaction, its still precursor compound of very useful nylon monomer simultaneously, present existing document and patent can only be synthesized several hexadiene dintrile products with specified substituent, comprise by phosphoric acid ester and adjacent two reactive ketones and obtain for example hexadiene dintrile (the Tetrahedron Letters of compound (1), 44 (7), 1333-1337; 2003.), obtain compound (2) and compound (3) (Ger.Offen., 19543862,28 May 1997) by the tolylene diamine open loop, obtain compound (4) (PCT Int.Appl., 9701531,16 Jan 1997 by the ethene nitrile; Jpn.KokaiTokkyo Koho, 06279387,04 Oct 1994, Heisei) etc., but these method synthetic types of compounds have very big limitation and reaction preference not high, therefore the generation of other by products is arranged, have multiple substituently 2 at present, 4-hexadiene two carbonitrile derivatives also do not have general synthetic method.
Summary of the invention
The purpose of this invention is to provide a kind of synthetic can have multiple substituent 2, the universal method of 4-hexadiene two carbonitrile derivatives.Technical scheme of the present invention is as follows:
With 1,4-dihalo--1,3-butadiene derivative and cuprous cyanide directly mix earlier, add N, dinethylformamide (DMF) solvent refluxing, and reaction product can obtain 2,4-hexadiene two carbonitrile derivatives through concentrated, purifying.Its primitive reaction formula is as follows:
Wherein:
Described 1, the halogen atom X on 1 and 4 of the 4-dihalo--1,3-butadiene derivative
1And X
2Can be identical or different, preferred bromine, iodine.1, the method that 4-dihalo--1,3-butadiene derivative can provide according to document synthetic (document: C.Xi, S.Huo, T.H.Afifi, R.Hara, T.Takahashi, Tetrahedron Lett.1997,38,4099-4102.).
Synthetic method of the present invention is to raw material 1, and 4-dihalo--1,3-butadiene derivative is not particularly limited, and can have identical or different substituting group on its four C, as following formula 1,2, and 1 shown in 3,4-dihalo--1,3-butadiene derivative, wherein R
1, R
2, R
3, R
4, R can be hydrogen, C1-C10 alkyl and aromatic base or the like.
Formula 1 formula 2 formulas 3
Accordingly, utilize method of the present invention synthetic obtain 2,4-hexadiene two carbonitrile derivatives also can have a plurality of identical or different substituting groups, general formula I for example, II, the compound shown in the III are all within the scope of the present invention.
Described cuprous cyanide useful commercial reagent need not special processing.
Described N, the dinethylformamide solvent also gets final product with commercial reagent, need not special processing.
The mol ratio of described reaction raw materials is preferred:
1,4-dihalo--1,3-butadiene derivative: cuprous cyanide=1.0:2.5
The inventive method is to 1, and the ratio of 4-dihalo--1,3-butadiene derivative and solvent DMF is not particularly limited, as long as reaction solution is evenly stirred, and 1 of preferred 1mmol, 4-dihalo--1,3-butadiene derivative uses the DMF solvent of 2～5mL.
Reflux time is slightly different according to different raw materials, detects to disappear with raw material to be as the criterion general 2-6 hours.Reflux course can adopt oil bath (for example silicone oil, paraffin wet goods) or other modes to heat, as long as can make the boiling of DMF solvent.
Described concentration process can adopt methods such as air distillation, underpressure distillation, for example uses the Rotary Evaporators vacuum concentration.
Described purge process can be made eluent with certain polar solvent, and chromatographic separation gets final product.Solvent or its mixture of the preferred polarity of described eluent between sherwood oil and ether, the mixed solvent of volume ratio sherwood oil: ether=10:1 for example, employed chromatogram is laboratory silica gel column chromatography commonly used or high performance liquid chromatography etc. for example.
The present invention has adopted the organic halogen reagent of successive that reaction is eliminated in the oxidation addition of cuprous cyanide/reduction, utilize be easy to get 1,4-dihalo--1,3-butadiene derivatives and cuprous cyanide reaction, very the high productivity preparation 2,4-hexadiene two carbonitrile derivatives, synthetic method is scientific and reasonable, thereby provide one synthetic have multiple substituent 2, the universal method of 4-hexadiene two carbonitrile derivatives, raw material is easy to get, applied widely, high isolated yield, experimental installation and operation is simple is convenient to industrialization.
Embodiment
Further describe the present invention below in conjunction with embodiment:
Embodiment 1
One of I compounds (R in the structural formula
1=R
2=R
3=R
4=n-Pr): 2,3,4,5-tetrapropyl-2,4-hexadiene dintrile synthetic:
In the round-bottomed flask of 20mL, add 1mmol 5,6-dipropyl-4,7-two iodo-4,6-decadiene and 2.5mmol cuprous cyanide add 5mL DMF solvent, reflux, magnetic agitation reaction six hours.The reaction back concentrates, and the silicagel column decolouring separates, and use sherwood oil: the mixed solvent of ether=10:1 is made eluent, obtains straight product 2,3,4,5-tetrapropyl-2,4-hexadiene dintrile 0.248g (purity〉98%, colourless liquid), isolated yield 91%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows:
1H NMR (300MHz, CDCl
3): δ 0.96-1.03 (m, 12H), 1.42-1.49 (m, 4H), 1.61-1.73 (m, 4H), 2.28-2.33 (m, 8H).
13C NMR (75MHz, CDCl
3): δ 13.02,13.85,20.59,20.9231.47,32.51,114.27,118.09,155.70.HRMS:calcd for C
18H
28N
2272.2253, found 272.2255.
Embodiment 2
Two (R of I compounds in the structural formula
1=R
2=n-Et, R
3=R
4=Ph): 2,3-diethyl-4,5-phenylbenzene-2,4-hexadiene dintrile synthetic
Synthetic route is the same substantially.This synthetic raw material dihalide compound that sets out is a 3-ethyl-1,2-phenylbenzene-1,4-two iodo-1,3-hexadiene.Obtain straight product 0.300g (purity〉98%, colorless solid, fusing point: 105-106 ℃), isolated yield 96%.The nuclear-magnetism of this compound, high resolution mass spectrum and ultimate analysis data are as follows:
1H NMR (300MHz, CDCl
3): δ 1.09 (t, J=7.5Hz, 3H), 1.34 (t, J=7.5Hz, 3H), 2.26 (br, 2H), 2.50 (q, J=7.5Hz, 2H), 7.06-7.31 (m, 10H).
13C NMR (75MHz, CDCl
3): δ 12.06,12.52,23.65,24.28,115.88,117.28,118.38,118.53,128.64,128.78,129.03,129.38,129.65,129.80,133.15,134.42,154.83,156.72.HRMS:calcdfor C
22H
20N
2312.1627, found 312.1617.Anal.Calcd for C
22H
20N
2: C, 84.64; H, 6.54, N, 8.97.Found:C, 84.58; H, 6.45, N, 8.97.
Embodiment 3
Three (R of I compounds in the structural formula
1=R
4=n-Bu, R
2=R
3=H): 2,5-dibutyl-2,4-hexadiene dintrile synthetic
Synthetic route is the same substantially.This synthetic raw material dihalide compound that sets out is 5,8-two bromo-5,7-12 diene.Obtain straight product 0.182g (purity〉98%, colourless liquid), isolated yield 84%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows:
1HNMR (300MHz, CDCl
3): δ 0.95 (t, J=7.5Hz, 6H), 1.31-1.44 (m, 4H), 1.54-1.64 (m, 4H), 2.36 (t, J=7.5Hz, 4H), 6.97 (s, 2H).
13C NMR (75MHz, CDCl
3): δ 13.68,21.92,30.06,34.37,116.74,120.60,138.42.HRMS:calcd for C
14H
20N
2216.1627, found 216.1625.
Embodiment 4
One of II compounds (R=n-Pr) in the structural formula: 2,5-dipropyl-3,4-(tetramethylene)-2,4-hexadiene dintrile synthetic:
Synthetic route is the same substantially.This synthetic raw material dihalide compound that sets out is 1,2-is two-and (1-iodo-butylidene)-hexanaphthene.Obtain straight product 0.226g (purity〉98%, colourless liquid), isolated yield 93%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows:
1H NMR (300MHz, CDCl
3): δ 0.97-1.02 (m, 6H), 1.50-1.75 (m, 6H), 1.93-2.11 (m, 4H), 2.23-2.39 (m, 4H), 2.83-2.88 (m, 2H).
13C NMR (75MHz, CDCl
3): δ 13.39,21.51,27.41,31.91,32.01,111.07,118.38,155.48.HRMS:calcd for C
16H
22N
2242.1783, found 242.1778.
Embodiment 5
One of III compounds (R=n-Et): 2-[3-in the structural formula (4-cyano group-3-hexene)-yl]-benzene nitrile synthetic:
Synthetic route is the same substantially.This synthetic raw material dihalide compound that sets out is 2-[3-(4-iodo-3-hexene)-yl]-the 1-iodobenzene.Obtain straight product 0.197g (purity〉98%, colourless liquid), isolated yield 94%.The nuclear-magnetism of this compound and high resolution mass spectrum data are as follows:
1H NMR (300MHz, CDCl
3): δ 0.98 (t, J=7.5Hz, 3H), 1.27 (t, J=7.5Hz, 3H), 2.46 (q, J=7.5Hz, 2H), 2.61 (q, J=7.5Hz, 2H), 7.30-7.33 (m, 1H), 7.44-7.49 (m, 1H), 7.61-7.66 (m, 1H), 7.70-7.73 (m, 1H).
13C NMR (75MHz, CDCl
3): δ 11.93,12.90,23.53,26.91,111.73,116.82,117.34,117.94,128.86,129.04,132.96,133.14,143.87,155.73.HRMS:calcdfor C
14H
14N
2210.1157, found 210.1157.
Claims (8)
1. Synthetic 2, the method of 4-hexadiene two carbonitrile derivatives, earlier with 1,4-dihalo--1,3-butadiene derivatives and cuprous cyanide directly mix, add N, the dinethylformamide solvent refluxing, reaction product can obtain 2 through concentrated, purifying, 4-hexadiene two carbonitrile derivatives, wherein said 1,4-dihalo--1,3-butadiene derivative is the compound shown in formula 1, formula 2 or the formula 3:
Formula 1 formula 2 formulas 3
Described 2,4-hexadiene two carbonitrile derivatives are general formula I, the compound shown in II or the III:
X wherein
1, X
2Identical or different, be bromine or iodine; R
1, R
2, R
3, R
4, R is identical or different, is hydrogen or C1-C10 alkyl.
2. the method for claim 1 is characterized in that, and is described 1, and 4-dihalo--1,3-butadiene derivative: the mol ratio of cuprous cyanide is 1.0:2.5.
3. the method for claim 1 is characterized in that, described N, and the usage quantity of dinethylformamide solvent is 1 of 1mmol, 4-dihalo--1,3-butadiene derivative uses the N of 2～5mL, dinethylformamide solvent.
4. the method for claim 1 is characterized in that, described return time is 2～6 hours.
5. the method for claim 1 is characterized in that, described concentration method is air distillation or underpressure distillation.
6. the method for claim 1 is characterized in that, described purge process adopts solvent or its mixture of polarity between sherwood oil and ether to make eluent, chromatographic separation.
7. the method for claim 1 is characterized in that, described purge process adopts the volume ratio sherwood oil: the mixed solvent of ether=10:1 is as eluent, chromatographic separation.
8. as claim 6 or 7 described methods, it is characterized in that described chromatogram is silica gel column chromatography or high performance liquid chromatography.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3709921A (en) * | 1969-09-03 | 1973-01-09 | Exxon Research Engineering Co | Method of forming dicyano compounds |
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