CN107082771B - Double alpha-cyano imines substituted isochroman class compounds and its synthetic method - Google Patents
Double alpha-cyano imines substituted isochroman class compounds and its synthetic method Download PDFInfo
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Abstract
The present invention relates to a kind of double alpha-cyano imines substituted isochroman class compounds, the structural formulas of the compound are as follows:
Description
Technical field
The present invention relates to a kind of double alpha-cyano imines substituted isochroman class compounds and its synthetic methods.
Background technique
Heterochromatic to be full of one kind quite by heterocyclic compound concerned by people, the basic ring system composition as some antibiotic is extensive
It is present in nature.Wherein, in aromatic ring and dihydropyran ring simultaneously substituted heterochromatic compound its be widely used, this
Class compound has the function of anti-inflammatory, analgesia, blood pressure lowering and antitumor pharmacological property, and causing the great interest of people, (see reference text
It offers: Andrieux, J.et al Bull.Soc.chim.Fr.1973,3421).Many is with heterochromatic full ring structure in fragrance
Referred to as heterochromatic full fragrance, most outstanding representative is exactly Jiale muskiness；The cannabinol for being used clinically for relieving pain also has heterochromatic
Man Huan, it is to extract to obtain from the strain of hemp female flower and flower spike.In recent years, the heterochromatic with various pharmacological activity is derivative
The synthesis of object causes the great interest of people, has been synthesized in succession with the heterochromatic of anticoagulation, blood pressure lowering and antitumor isoreactivity
Full class compound (see reference document: Croston, G.E.et al R.J.Med.Chem.2002,45,4950).Therefore, efficiently
There are various substituted heterochromatic derivatives to be of great significance for building.
Alpha-cyano imine compound is a kind of highly useful organic synthesis intermediate, can be used for rapid build structure
Other organic compounds more complicated and changeable.For example, Jursic seminar realizes α-in certain density hydrochloric acid solution
The hydrolysis of cyano imines skeleton, obtaining alpha-carbonyl carboxylic acid compound, (see reference document: Jursic, B.S.et
al.Tetrahedron Lett.,2002,43,5361).Levov group is real in the DMF solution of ammonium chloride using sodium azide
The cyclization for having showed alpha-cyano imines skeleton, obtaining substituted trinitrogen azole compound, (see reference document: Levov, A.N.et
al.Chem.Heterocycl.Compd.,2005,41,7).In addition, alpha-cyano imine compound is also used as synthesis acyl
Amine, amidine, amino-pyrazol, N- alkyl ketene amine etc. precursor (see reference document: Zhu, J.P.et al.Chem.Eur.J.,
2012,18,14812；Bhaduri,A.P.et al.,Synth.Commun.,2006,36,715；Liu,Y.H.et al.,
Org.Chem.Front.,2014,1,940).Other than the application in terms of organic transformation, the alpha-cyano imines under metal catalytic
Class skeleton can be used as cyano sources, realize the direct cyanalation reaction of c h bond.For example, Shen seminar in palladium-copper system with
2- phenylpyridine class be substrate synthesized replace benzonitrile compound (see reference document: Shen, J.K.et al., RSC
Adv.,2016,6,64234).In addition to this, alpha-cyano imine compound also exhibits the bioactivity of multiplicity, by people
Extensive concern.For example, the inhibition function of showing to be caused to shrink by histamine or acetylcholine-induced in rat ileum is (see ginseng
Examine document: Fichtner, K.et.al, Pharmazie, 1983,38,449).
Reported in document synthesis alpha-cyano imine compound method mainly include the following types:
(1) Yoshihiko et al. is substrate in 0 DEG C, the boron trifluoride ether solution of 15mol% using tert-butyl isonitrile
Cationic reaction occurs, obtains N- tert-butyl-α-tertiarybutylimido nitrile.But the condition of this method is harsh, by-product is more
Complicated (see reference document: Ito, Y.etal.J.Org.Chem., 1969,34,4040).
(2) Yamamoto et al. is translated into methanesulfonates, then in front three using oxime compound as substrate first
With the help of base cyanogen silane and diethyl aluminum chloride, the migration and intramolecular nucleophilic reaction of intramolecular are completed, N- penta has been synthesized
Base-α-hexyl imines nitrile, but this method it is cumbersome (see reference document: Yamamoto, H.et.al,
J.Am.Chem.Soc.,1983,105,2831)。
(3) Toshihiko et al. then realizes the fracture of C-X key under Pd catalysis using benzene as solvent, while carrying out different
Nitrile intercalation reaction and tri-tert cyanogen stannane provide cyano sources and complete nucleophilic displacement of fluorine, have synthesized N- tert-butyl-α-phenyl imine
Nitrile.But this method Atom economy is poor, and there are problem of environmental pollution (see reference document: Migita, T.et al.,
Chem.Lett., 1986,15,1197-1200).
(4) Erick et al. is using substituted imine compound as raw material, by gradually with bromine simple substance, potassium cyanide and hydrogen
Change sodium reaction, one kettle way obtain target product (see reference document: Alonso, E.R.et.al, Tetrahedron Lett.,
2001,42,3921–3923).The potassium cyanide of severe toxicity has been used in reaction.
(5) Zhu et al., by three component reactions, is obtained at room temperature using aldehyde, amine and trimethylsilyl cyanide as substrate
Alpha-cyano imines skeleton.IBX/TBAB is added into unsegregated system, alpha-cyano imines can be obtained through peroxidization
Class compound.This method is easy to operate, mild condition, and until outstanding in yield, but the adaptability of substrate is poor that (see reference text
It offers: Zhu, J.P.et.al, Org.Lett., 2008,10,1509).
(6) Shen et al. is reacted by the insert continually twice of isonitrile under palladium chtalyst, is obtained using halogenated hydrocarbons as substrate
Alpha-cyano imine compound.But this method need to use aryl halide costly and palladium catalyst and phosphorus-containing ligand (see
Bibliography: Shen, J.K.et.al, J.Org.Chem., 2016,81,1610).
In conclusion the synthetic method of alpha-cyano imine compound mainly has above several, it but is that multistep is anti-mostly
Answer, substrate is complicated and is related to toxic cyanide, or with than relatively severe condition.And it is sub- for double alpha-cyanos in document
Amine substituted compound and synthetic method have not been reported, and lack efficient synthetic method.
Summary of the invention
One of the objects of the present invention is to provide a kind of double alpha-cyano imines substituted isochroman class compounds.
The second object of the present invention is to provide the synthetic method of the compound.
In order to achieve the above objectives, the reaction mechanism that the method for the present invention uses are as follows:
Wherein: R1For phenyl, methyl, bromine, furyl；
R2For phenyl, methyl, cyclohexyl.
According to above-mentioned reaction mechanism, present invention employs the following technical solutions:
A kind of double alpha-cyano imines substituted isochroman class compounds, it is characterised in that the structural formula of the compound are as follows:
Wherein: R1For phenyl, methyl, bromine or furyl；
R2For phenyl, methyl or cyclohexyl.
It is a kind of to prepare above-mentioned double alpha-cyano imines substituted isochroman class compounds, it is characterised in that this method has as follows
Step: under an inert atmosphere, heterochromatic full, tert-butyl isonitrile, trifluoro-methane sulfonic acid silver, dichlorocyanobenzoquinone (DDQ) are pressed
1.0:(3.0~5.0): (0.1~0.2): the molar ratio of (1.0~3.0) is added in chloro benzene solvent, is stirred at 80~90 DEG C
Reaction to reaction raw materials are mixed to disappear；After reaction, ethyl acetate extracts product, and water and saturated salt solution wash respectively, organic
Crude product is obtained after mutually removing solvent after drying；The crude product arrives double alpha-cyano imines substituted isochromans through separating-purifying
Class compound；The heterochromatic full structural formula are as follows:
The method of the present invention raw material is simple and easy to get, under the action of dichlorocyanobenzoquinone, using tert-butyl isonitrile as anti-
The cyano sources answered show higher reactivity under the catalysis of trifluoro-methane sulfonic acid silver；It is easy to operate in reaction process, item
Part is mild, environmental-friendly, and yield generally arrives medium.
The product of generation has more special double alpha-cyano imines substituent group skeletons, and a series of chemical conversions can occur,
Generate various substituted heterochromatic derivatives, for example, double alpha-cyano imines substituted isochroman products can under palladium chtalyst with benzene
Yl pyrimidines reaction, high productivity generate important bisamide substituted isochroman and cyano-aryl pyrimidine simultaneously.And this kind of double acyl
Amine replaces heterochromatic full, there is no effective synthetic method in document at present, there is good development prospect in the industrial production.
Specific embodiment
Embodiment one: N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-t-butyl
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N, N'- di-t-butyl use following step: 1. anti-at 1000 milliliters
Answer 9.4 grams of heterochromatic full, 17.4 grams of tert-butyl isonitriles of addition, 1.8 grams of silver trifluoromethanesulfonates, 15.9 grams of 2,3- bis- chloro- 5,6- in kettle
Dicyano-Isosorbide-5-Nitrae-benzoquinones, 700 milliliters of chlorobenzenes, is heated to 80 DEG C.It is tracked and is reacted with thin-layer chromatography method, until reaction raw materials disappear
It loses；2. after reaction, ethyl acetate extracts product, saturated salt solution washs respectively, is removed after dry with Rotary Evaporators molten
Agent obtains crude product；3. crude product column chromatographs (petroleum ether: ethyl acetate=100:1) and purifies, 14.71 grams of N, bis- uncle of N'- are obtained
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of butyl, structural formula are as follows:Yield is 60%.Fusing point: 114 DEG C.
IR(KBr,cm-1):2979,2216,1643,1476,1464,1208,914,754；
1H NMR(CDCl3, 500MHz): δ 7.28 (dd, J=7.3Hz, 1.2,1H), 7.19-7.15 (m, 2H), 6.90 (d,
J=7.9Hz, 1H), 4.05 (t, J=5.6Hz, 2H), 2.97 (t, J=5.6Hz, 2H), 1.39 (s, 18H)；
13C NMR(CDCl3,125MHz):139.7,134.8,130.0,129.2,128.4,127.8,125.5,111.2,
85.0,62.0,59.1,29.1,28.1；
LC-MS(ESI)m/z:351[M+H]；
HRMS(ESI)m/z:calcd for C21H26N4O[M+H]351.2185,found 351.2186。
Embodiment two: N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-t-butyl -5- methyl
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N, N'- di-t-butyl -5- methyl use following step: 1. existing
It is heterochromatic full that 10.4 grams of 5- methyl are added in 1000 milliliters of reaction kettles, 17.4 grams of tert-butyl isonitriles, 3.6 grams of silver trifluoromethanesulfonates,
15.9 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 700 milliliters of chlorobenzenes, are heated to 80 DEG C.With thin-layer chromatography method with
Track reaction, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturated salt solution washs respectively, after dry
Remove solvent with Rotary Evaporators, obtains crude product；3. crude product column chromatographs (petroleum ether: ethyl acetate=100:1) and purifies, obtain
To 19.12 grams of N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-t-butyl -5- methyl, structural formula are as follows:Yield is 75%.Fusing point: 104 DEG C.
IR(KBr,cm-1):2976,2220,1643,1467,1367,1211,1096,1028,782；
1H NMR(CDCl3, 500MHz): δ 7.14 (d, J=7.3Hz, 1H), 7.08 (t, J=7.6Hz, 1H), 6.75 (d, J
=7.8Hz, 1H), 4.06 (t, J=5.6Hz, 2H), 2.82 (t, J=5.6Hz, 2H), 2.27 (s, 3H), 1.39 (s, 18H)；
13C NMR(CDCl3,125MHz):139.8,136.4,133.3,129.7,127.7,127.4,124.8,111.1,
85.1,61.6,58.9,28.9,25.6,19.1；
LC-MS(ESI)m/z:365[M+H]；
HRMS(ESI)m/z:calcd for C22H28N4O 365.2341[M+H],found 365.2332.
Embodiment three: N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-t-butyl -7- phenyl
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N, N'- di-tert-butyl -7- phenyl use following step: 1. existing
It is heterochromatic full that 14.7 grams of 7- phenyl are added in 1000 milliliters of reaction kettles, 17.4 grams of tert-butyl isonitriles, 2.7 grams of silver trifluoromethanesulfonates,
15.9 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 700 milliliters of chlorobenzenes, are heated to 80 DEG C.With thin-layer chromatography method with
Track reaction, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturated salt solution washs respectively, after dry
Remove solvent with Rotary Evaporators, obtains crude product；3. crude product column chromatographs (petroleum ether: ethyl acetate=100:1) and purifies, obtain
To 23.87 grams of N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-tert-butyl -7- phenyl, structural formula are as follows:Yield is 80%.Fusing point: 125 DEG C.
IR(KBr,cm-1):2977,2216,1638,1475,1364,1202,1108,762,693；
1H NMR(CDCl3, 500MHz): δ 7.53-7.51 (m, 3H), 7.45 (t, J=7.6Hz, 2H), 7.36 (d, J=
7.9Hz, 1H), 7.28 (d, J=7.9Hz, 1H), 7.18 (s, 1H), 4.11 (t, J=5.3Hz, 2H), 3.03 (t, J=5.3Hz,
2H),1.43(s,18H)；
13C NMR(CDCl3,125MHz):140.7,139.6,138.4,133.8,129.5,128.8,128.5,128.1,
127.3,126.8,111.1,85.1,62.0,59.1,29.0,27.8；
LC-MS(ESI)m/z:427[M+H]；
HRMS(ESI)m/z:calcd for C27H30N4O 427.2498[M+H],found 427.2489.
Example IV: heterochromatic full -4, the 4- of N, N'- di-t-butyl -1,2- dihydro -4H- benzo [f] bis- (carbonamidine bases) two cyanidings
Object
Under bis- (carbonamidine base) dicyanide of heterochromatic full -4, the 4- of N, N'- di-t-butyl -1,2- dihydro -4H- benzo [f] use
State step: 1. addition 12.9 grams of Isosorbide-5-Nitraes-dihydro -2H- benzo [f] is heterochromatic full in 1000 milliliters of reaction kettles, and 17.4 grams of tert-butyls are different
Nitrile, 1.8 grams of silver trifluoromethanesulfonates, 15.9 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 700 milliliters of chlorobenzenes are heated to
90℃.It is tracked and is reacted with thin-layer chromatography method, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturation
Brine It removes solvent with Rotary Evaporators after drying, obtains crude product；3. crude product chromatographs (petroleum ether: acetic acid second with column
Ester=80:1) purifying, obtain 19.61 grams of N, the heterochromatic bis- (carbonamidines of full -4,4- of N'- di-t-butyl -1,2- dihydro -4H- benzo [f]
Base) dicyanide, structural formula are as follows:Yield is 70%.Fusing point: 140 DEG C
IR(KBr,cm-1):2978,2220,1643,1464,1367,1209,1099,1062,810；
1H NMR(CDCl3, 500MHz): δ 7.99 (d, J=7.8Hz, 1H), 7.84 (d, J=8.6Hz, 1H), 7.64 (d, J
=8.7Hz, 1H), 7.59-7.53 (m, 2H), 7.00 (d, J=8.7Hz, 1H), 4.20 (t, J=5.6Hz, 2H), 3.33 (t, J
=5.6Hz, 2H), 1.40 (s, 18H)；
13C NMR(CDCl3,125MHz):139.7,132.8,131.6,128.5,126.6,126.4,126.3,125.3,
123.1,111.0,85.3,61.4,59.1,29.0,24.7；
LC-MS(ESI)m/z:401[M+H]；
HRMS(ESI)m/z:calcd for C25H28N4O 401.2342[M+H],found 401.2335.
Embodiment five: N, bis- (carbonamidine base) dicyanide of N'- di-t-butyl-(5- furans -3- base) heterochromatic full -1,1-
Heterochromatic bis- (carbonamidine base) dicyanide of full -1,1- of N, N'- di-t-butyl-(5- furans -3- base) use following steps
Rapid: 1. 14.0 grams of 5- (furans -3- base) of addition are heterochromatic full in 1000 milliliters of reaction kettles, 17.4 grams of tert-butyl isonitriles, and 1.8 gram three
Fluorine methanesulfonic acid silver, 15.9 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 700 milliliters of chlorobenzenes are heated to 80 DEG C.Use thin layer
Chromatography method tracking reaction, until reaction raw materials disappear；2. after reaction, ethyl acetate extraction product, saturated common salt water washing,
Remove solvent with Rotary Evaporators after drying, obtains crude product；3. crude product chromatographs (petroleum ether: ethyl acetate=100:1) with column
Purifying, obtains 23.89 grams of N, N'- di-t-butyl -5- furans -3- base) heterochromatic bis- (carbonamidine base) dicyanide of full -1,1-, it ties
Structure formula are as follows:Yield is 82%.Fusing point: 114 DEG C.
IR(KBr,cm-1):3130,2977,2216,1641,1506,1466,1364,1234,1210,1108,1055,
951,791,749；
1H NMR(CDCl3, 500MHz): δ 7.51 (d, J=17.7Hz, 2H), 7.31 (d, J=7.4Hz, 1H), 7.20 (t,
J=7.7Hz, 1H), 6.88 (d, J=7.8Hz, 1H), 6.57 (s, 1H), 4.00 (t, J=5.4Hz, 2H), 2.96 (t, J=
5.4Hz,2H),1.40(s,18H)；
13C NMR(CDCl3,125MHz):142.8,140.2,139.7,132.9,132.5,129.3,129.2,127.9,
125.1,124.2,111.4,111.1,85.2,61.8,59.0,28.9,27.3；
LC-MS(ESI)m/z:417[M+H]；
HRMS(ESI)m/z:calcd for C25H28N4O2 417.2290[M+H],found 417.2298。
Embodiment six: N, bis- (carbonamidine base) dicyanide of N'- di-t-butyl -6H- benzo [c] chromene -6,6-
Bis- (carbonamidine base) dicyanide of N, N'- di-t-butyl 6H benzo [c] chromene -6,6- uses following step: 1. existing
It is heterochromatic full that 12.7 grams of 6H- benzos [c] are added in 1000 milliliters of reaction kettles, 23.2 grams of tert-butyl isonitriles, 1.8 grams of trifluoromethanesulfonic acids
Silver, 31.8 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 600 milliliters of chlorobenzenes are heated to 85 DEG C.Use thin-layer chromatography method
Tracking reaction, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturated common salt water washing is used after dry
Rotary Evaporators remove solvent, obtain crude product；3. crude product column chromatographs (petroleum ether: ethyl acetate=50:1) and purifies, obtain
25.09 grams of N, N'- di-t-butyl -6H- benzo [c] chromene -6,6-, bis- (carbonamidine base) dicyanide, structural formula are as follows:Yield is 90%.Fusing point: 158 DEG C.
IR(KBr,cm-1):2978,2216,1645,1471,1446,1364,1236,1204,1059,1035,752；
1H NMR(CDCl3, 500MHz): δ 7.81 (d, J=7.8Hz, 1H), 7.70 (d, J=7.8Hz, 1H), 7.50 (t, J
=7.6Hz, 1H), 7.36 (t, J=7.6Hz, 1H), 7.29 (t, J=7.5Hz, 1H), 7.21 (d, J=8.0Hz, 1H), 7.10
(t, J=7.5Hz, 1H), 7.02 (d, J=7.6Hz, 1H), 1.33 (s, 18H)；
13C NMR(CDCl3,125MHz):150.3,137.2,130.0,129.9,129.8,127.7,127.2,126.8,
123.3,122.9,122.7,121.8,118.7,110.7,86.6,59.3,28.9；
LC-MS(ESI)m/z:399[M+H]；
HRMS(ESI)m/z:calcd for C25H26N4O 399.2185[M+H],found 399.2170。
Embodiment seven: N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-t-butyl -3,3- dimethyl
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N, N'- di-t-butyl -3,3- dimethyl use following step: 1.
It is heterochromatic full that 11.3 grams of 3,3- dimethyl are added in 1000 milliliters of reaction kettles, 23.2 grams of tert-butyl isonitriles, 1.8 grams of trifluoromethanesulfonic acids
Silver, 31.8 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 600 milliliters of chlorobenzenes are heated to 90 DEG C.Use thin-layer chromatography method
Tracking reaction, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturated common salt water washing is used after dry
Rotary Evaporators remove solvent, obtain crude product；3. crude product column chromatographs (petroleum ether: ethyl acetate=50:1) and purifies, obtain
15.09 grams of N, N'- di-t-butyl -3, bis- (methyl amidine) dicyanide of heterochromatic full -1, the 1- of 3- dimethyl, structural formula areYield is 57%.Fusing point: 102 DEG C.
IR(KBr,cm-1):2979,2212,1646,1465,1371,1208,1076,921,758；
1H NMR(CDCl3, 500MHz): δ 7.26 (t, J=7.5Hz, 1H), 7.16 (t, J=7.5Hz, 1H), 7.12 (d, J
=7.4Hz, 1H), 6.97 (d, J=7.7Hz, 1H), 2.86 (s, 2H), 1.34 (s, 18H), 1.31 (s, 6H)；
13C NMR(CDCl3,125MHz):140.6,134.2,130.3,129.1,128.5,126.8,125.2,111.4,
83.8,74.3,58.5,40.1,28.8,28.3；
LC-MS(ESI)m/z:379[M+H]；
HRMS(ESI)m/z:calcd for C23H30N4O 379.2498[M+H],found 379.2491。
Embodiment eight: N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-tert-butyl -3- phenyl
Bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N, N'- di-tert-butyl -3- phenyl use following step: 1. existing
It is heterochromatic full that 14.7 grams of 3- phenyl are added in 1000 milliliters of reaction kettles, 44.4 grams of n-butyl acrylates, 23.2 grams of tert-butyl isonitriles,
1.8 grams of silver trifluoromethanesulfonates, 31.8 grams of 2,3-Dichloro-5,6-dicyano-1,4-benzoquinones, 600 milliliters of chlorobenzenes are heated to 85
℃.It is tracked and is reacted with thin-layer chromatography method, until reaction raw materials disappear；2. after reaction, ethyl acetate extracts product, saturation food
Salt water washing removes solvent with Rotary Evaporators after drying, obtains crude product；3. crude product chromatographs (petroleum ether: ethyl acetate with column
=50:1) purifying, obtain 18.50 grams of N, bis- (carbonamidine base) dicyanide of heterochromatic full -1, the 1- of N'- di-tert-butyl -3- phenyl,
Structural formula are as follows:Yield is 62%.Fusing point: 145 DEG C.
IR(KBr,cm-1):2975,2216,1646,1457,1367,1233,1210,1069,916,748,692；
1H NMR(CDCl3, 500MHz): δ 7.55 (d, J=7.5Hz, 2H), 7.42 (t, J=7.5Hz, 2H), 7.36-
7.30 (m, 2H), 7.22 (t, J=6.8Hz, 2H), 6.99 (d, J=7.7Hz, 1H), 4.78 (dd, J=11.6,2.6Hz, 1H),
3.31 (dd, J=16.4,11.6Hz, 1H), 3.03 (dd, J=16.4,2.6Hz, 1H), 1.44 (s, 9H), 1.37 (s, 9H)；
13C NMR(CDCl3,125MHz):140.1,139.7,139.5,135.1,129.8,129.0,128.6,128.5,
128.3,128.2,127.5,126.3,125.8,125.6,111.6,110.6,86.2,73.5,59.3,58.8,35.6,
29.1,29.0；
LC-MS(ESI)m/z:427[M+H]；
HRMS(ESI)m/z:calcd for C27H30N4O 427.2498[M+H],found 427.2493。
Claims (1)
1. a kind of synthetic method for preparing double alpha-cyano imines substituted isochroman class compounds, it is characterised in that this method has such as
Lower step: under an inert atmosphere, heterochromatic full, tert-butyl isonitrile, trifluoro-methane sulfonic acid silver, dichlorocyanobenzoquinone (DDQ) are pressed
1.0: (3.0~5.0): (0.1~0.2): the molar ratio of (1.0~3.0) is added in chloro benzene solvent, in 80~90oIt is stirred to react under C to reaction raw materials and is disappeared；After reaction, ethyl acetate extracts product, and water and saturated salt solution are washed respectively
It washs, organic phase obtains crude product after removing solvent after drying；The crude product replaces through separating-purifying to get to double alpha-cyano imines
Heterochromatic compound；The heterochromatic full structural formula are as follows:, wherein R1For
Phenyl, methyl, bromine or furyl；R2For phenyl, methyl or cyclohexyl.
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