CN107082771B - Bis-alpha-cyanoimine substituted isochroman compounds and synthesis method thereof - Google Patents

Abstract

The present invention relates to a kind of double α-cyanoimine substituted isochroman compound, the structural formula of this compound is: The inventive method raw material is simple and easy to get, and under the effect of dichlorodicyanobenzoquinone, adopts tert-butyl isonitrile as the cyano group source of reaction, shows higher reactivity under the catalysis of silver trifluoromethanesulfonate; In the reaction process, the operation is simple, the conditions are mild, the environment is friendly, and the yield is generally to moderate. The generated product has a relatively special double α-cyanoimine substituent skeleton, which can undergo a series of chemical transformations to generate various substituted isochroman derivatives. Therefore, it has a good development prospect in industrial production.

Description

Bis-alpha-cyanoimine substituted isochroman compounds and synthesis method thereof

technical field

The invention relates to a bis-alpha-cyanoimine substituted isochroman compound and a synthesis method thereof.

Background technique

Heterochroman is a class of heterocyclic compounds that have attracted much attention, and it exists widely in nature as the basic ring system of some antibiotics. Among them, the isochromans that are substituted simultaneously in the aromatic ring and the dihydropyran ring are widely used. These compounds have the effects of anti-inflammatory, analgesic, hypotensive and anti-tumor properties, which have aroused people's strong interest ( See references: Andrieux, J. et al Bull. Soc. chim. Fr. 1973, 3421). Many spices with a heterochromatic ring structure are called heterochromatic spices. The most outstanding representative is Jiale musk; cannabinol, which is clinically used for pain relief, also has a heterochromatic ring. It is derived from the female flower strain of cannabis and extracted from flower spikes. In recent years, the synthesis of isochroman derivatives with various pharmacological activities has aroused great interest, and isochroman compounds with anticoagulant, hypotensive and antitumor activities have been synthesized one after another (see reference : Croston, G.E. et al R.J. Med. Chem. 2002, 45, 4950). Therefore, it is of great significance to efficiently construct isochroman derivatives with various substitutions.

α-cyanoimine compounds are a class of very useful intermediates in organic synthesis, which can be used to quickly construct other organic compounds with more complex and variable structures. For example, the Jursic research group realized the hydrolysis reaction of the α-cyanoimine skeleton in a certain concentration of hydrochloric acid solution to obtain α-carbonyl carboxylic acid compounds (see references: Jursic, B.S.etal.Tetrahedron Lett., 2002,43 ,5361). The Levov group used sodium azide in the DMF solution of ammonium chloride to realize the cyclization reaction of the α-cyanoimine skeleton to obtain substituted triazole compounds (see references: Levov, A.N.etal.Chem.Heterocycle. Compd., 2005, 41, 7). In addition, α-cyanoimine compounds can also be used as precursors for the synthesis of amides, amidines, aminopyrazoles, N-alkylketene amines, etc. (see references: 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). In addition to the application in organic transformation, the α-cyanoimine-like framework can be used as a cyano source under metal catalysis to realize the direct cyanation reaction of C–H bond. For example, Shen's group synthesized substituted benzonitrile compounds using 2-phenylpyridines as substrates in a palladium-copper system (see reference: Shen, J.K. et al., RSCAdv., 2016, 6, 64234) . In addition, α-cyanoimine compounds also exhibit a variety of biological activities and have attracted widespread attention. For example, the inhibitory function of contractions induced by histamine or acetylcholine is shown in the ileum of rats (see reference: Fichtner, K. et. al, Pharmazie, 1983, 38, 449).

The method of the synthetic α-cyano imine compound that has been reported in the literature mainly contains the following several kinds:

(1) Yoshihiko et al. used tert-butyl isonitrile as a substrate to undergo a cationic reaction in 15 mol% boron trifluoride ether solution at 0°C to obtain N-tert-butyl-α-tert-butyliminonitrile. However, the conditions of this method are harsh and the by-products are relatively complicated (see references: Ito, Y. et al. J. Org. Chem., 1969, 34, 4040).

(2) Yamamoto et al. used oxime compounds as substrates, first converted them into mesylate, and then completed intramolecular migration and molecular N-pentyl-alpha-hexyl iminonitrile has been synthesized, but the method is cumbersome to operate (seeing references: Yamamoto, H.et.al, J.Am.Chem.Soc., 1983,105,2831 ).

(3) Toshihiko et al., under the catalysis of Pd, used benzene as a solvent to break the C-X bond. At the same time, the isocyanide insertion reaction and the tri-tert-butylcyanostannane provided the cyano source to complete the nucleophilic substitution, and synthesized N-tert Butyl-α-phenyliminonitrile. However, this method is poor in atom economy and has environmental pollution problems (see references: Migita, T. et al., Chem. Lett., 1986, 15, 1197-1200).

(4) Erick et al. used substituted imine compounds as raw materials to obtain the target product in one pot by gradually reacting with bromine, potassium cyanide and sodium hydride (see references: Alonso, E.R.et.al, Tetrahedron Lett ., 2001, 42, 3921–3923). The highly toxic potassium cyanide was used in the reaction.

(5) Zhu et al. used aldehydes, amines, and trimethylsilyl cyanide as substrates to obtain α-cyanoimine skeletons at room temperature through a three-component reaction. Add IBX/TBAB to the unseparated system, and α-cyanoimine compounds can be obtained through oxidation reaction. The method is simple to operate, with mild conditions and moderate to excellent yields, but poor substrate adaptability (see references: Zhu, J.P.et.al, Org. Lett., 2008, 10, 1509).

(6) Shen et al. used halogenated hydrocarbons as substrates to obtain α-cyanoimine compounds through two consecutive insertion reactions of isonitriles under palladium catalysis. However, this method requires the use of more expensive aryl halides as well as palladium catalysts and phosphorus-containing ligands (see references: Shen, J.K.et.al, J.Org.Chem., 2016, 81, 1610).

In summary, there are mainly the above methods for the synthesis of α-cyanoimine compounds, but most of them are multi-step reactions, complex substrates and involve toxic cyanide, or use relatively harsh conditions. However, there are no reports on bis-cyanoimine substituted compounds and synthetic methods in the literature, and there is a lack of efficient synthetic methods.

Contents of the invention

One of the objectives of the present invention is to provide a bis-cyanoimine substituted isochroman compound.

The second object of the present invention is to provide a synthetic method of the compound.

For achieving the above object, the reaction mechanism that the inventive method adopts is:

Wherein: R ¹ is phenyl, methyl, bromine, furyl;

R ² is phenyl, methyl, cyclohexyl.

According to above-mentioned reaction mechanism, the present invention has adopted following technical scheme:

A double α-cyanoimine substituted isochroman compound is characterized in that the structural formula of the compound is:

Wherein: R is phenyl, methyl, bromine or furyl ^;

R ² is phenyl, methyl or cyclohexyl.

A preparation of the above-mentioned bis-cyanoimine substituted isochroman compounds, characterized in that the method has the following steps: under an inert atmosphere, isochroman, tert-butyl isonitrile, silver trifluoromethanesulfonate, di Chlorodicyanobenzoquinone (DDQ) is added to the chlorobenzene solvent at a molar ratio of 1.0:(3.0~5.0):(0.1~0.2):(1.0~3.0), and stirred at 80~90°C until the reaction The raw materials disappeared; after the reaction, the product was extracted with ethyl acetate, washed with water and saturated brine respectively, the organic phase was dried and the solvent was removed to obtain a crude product; the crude product was separated and purified to obtain bis-α-cyanoimine substituted Isochroman compounds; the structural formula of the isochroman is:

The raw material of the method of the present invention is simple and easy to obtain, under the action of dichlorodicyanobenzoquinone, tert-butyl isonitrile is used as the cyano source of the reaction, and under the catalysis of silver trifluoromethanesulfonate, it exhibits higher reactivity; the reaction The operation is simple, the conditions are mild, the environment is friendly, and the yield is generally to moderate.

The resulting product has a special double α-cyanoimine substituent skeleton, which can undergo a series of chemical transformations to generate various substituted isochroman derivatives, for example, double α-cyanoimine substituted isochroman The product can be reacted with phenylpyrimidine under palladium catalysis, and the important bisamide-substituted isochroman and cyanoarylpyrimidine can be simultaneously produced in high yield. However, there is no effective synthesis method for this bisamide-substituted isochroman in the current literature, and it has a good development prospect in industrial production.

Detailed ways

Example 1: N, N'-di-tert-butylisochroman-1,1-bis(formamimidino) dicyanide

N, N'-di-tert-butylisochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: 1. add 9.4 grams of isochroman, 17.4 grams of tert-butyl isocyanide, 1.8 g of silver trifluoromethanesulfonate, 15.9 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and 700 ml of chlorobenzene, heated to 80°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ② After the reaction, extract the product with ethyl acetate, wash with saturated brine, and remove the solvent with a rotary evaporator after drying to obtain a crude product; ③ Use a column layer for the crude product Analyze (petroleum ether: ethyl acetate=100:1) purify, obtain 14.71 grams of N, N'-di-tert-butylisochroman-1,1-bis(formamidinyl) dicyanide, its structural formula is: The yield was 60%. Melting point: 114°C.

IR(KBr, cm ^-1 ): 2979, 2216, 1643, 1476, 1464, 1208, 914, 754;

¹ H NMR (CDCl ₃ , 500MHz): δ7.28(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);

¹³ C NMR (CDCl ₃ , 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 .

Example 2: N, N'-di-tert-butyl-5-methylisochroman-1,1-bis(formamimidino) dicyanide

N, N'-di-tert-butyl-5-methylisochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: 1. add 10.4 grams of 5-methanol in a 1000 ml reaction kettle Isochroman, 17.4 g tert-butylisonitrile, 3.6 g silver triflate, 15.9 g 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 700 ml chlorobenzene, Heat to 80°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ② After the reaction, extract the product with ethyl acetate, wash with saturated brine, and remove the solvent with a rotary evaporator after drying to obtain a crude product; ③ Use a column layer for the crude product Analysis (petroleum ether: ethyl acetate = 100:1) purified to obtain 19.12 grams of N, N'-di-tert-butyl-5-methylisochroman-1,1-bis(formamimidino) dicyanide , whose structure is: The yield was 75%. Melting point: 104°C.

IR(KBr, cm ^-1 ): 2976, 2220, 1643, 1467, 1367, 1211, 1096, 1028, 782;

¹ H NMR (CDCl ₃ , 500MHz): δ7.14(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);

¹³ C NMR (CDCl ₃ , 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 C ₂₂ H ₂₈ N ₄ O 365.2341[M+H],found 365.2332.

Example 3: N, N'-di-tert-butyl-7-phenylisochroman-1,1-bis(formamimidino) dicyanide

N, N'-di-tert-butyl-7-phenylisochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: 1. add 14.7 grams of 7- Phenylisochroman, 17.4 g tert-butylisonitrile, 2.7 g silver triflate, 15.9 g 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 700 ml chlorobenzene , heated to 80°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ② After the reaction, extract the product with ethyl acetate, wash with saturated brine, and remove the solvent with a rotary evaporator after drying to obtain a crude product; ③ Use a column layer for the crude product Analysis (petroleum ether: ethyl acetate = 100:1) purified to obtain 23.87 grams of N, N'-di-tert-butyl-7-phenylisochroman-1,1-bis(formamimidino) dicyanide compound, its structural formula is: The yield was 80%. Melting point: 125°C.

IR(KBr,cm ^-1 ):2977,2216,1638,1475,1364,1202,1108,762,693;

¹ H NMR (CDCl ₃ , 500MHz): δ7.53-7.51(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);

¹³ C NMR (CDCl ₃ , 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 C ₂₇ H ₃₀ N ₄ O 427.2498[M+H],found 427.2489.

Example 4: N, N'-di-tert-butyl-1,2-dihydro-4H-benzo[f]isochroman-4,4-bis(carboxamidino)dicyanide

N, N'-di-tert-butyl-1,2-dihydro-4H-benzo[f]isochroman-4,4-bis(carboxamidino)dicyanide adopts the following steps: ①In 1000 ml Add 12.9 grams of 1,4-dihydro-2H-benzo[f]isochroman, 17.4 grams of tert-butyl isocyanide, 1.8 grams of silver trifluoromethanesulfonate, 15.9 grams of 2,3-dichloro-5, 6-dicyano-1,4-benzoquinone, 700 ml of chlorobenzene, heated to 90°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ②After the reaction, the product is extracted with ethyl acetate, washed with saturated brine, and dried with a rotary evaporator to remove the solvent to obtain a crude product; ③The crude product is purified by column chromatography (Petroleum ether: ethyl acetate = 80:1) purified to obtain 19.61 grams of N, N'-di-tert-butyl-1,2-dihydro-4H-benzo[f]isochroman-4,4-bis (Formamimidino) dicyanide, its structural formula is: The yield was 70%. Melting point: 140°C

IR(KBr, cm ^-1 ): 2978, 2220, 1643, 1464, 1367, 1209, 1099, 1062, 810;

¹ H NMR (CDCl ₃ , 500MHz): δ7.99(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);

¹³ C NMR (CDCl ₃ , 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 C ₂₅ H ₂₈ N ₄ O 401.2342[M ⁺ H], found 401.2335.

Example 5: N, N'-di-tert-butyl-(5-furan-3-yl)isochroman-1,1-bis(formamimidino)dicyanide

N, N'-di-tert-butyl-(5-furan-3-yl) isochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: ①Add in 1000 ml reaction kettle 14.0 g 5-(furan-3-yl)isochroman, 17.4 g tert-butylisocyanide, 1.8 g silver triflate, 15.9 g 2,3-dichloro-5,6-dicyano-1,4 - Benzoquinone, 700 ml of chlorobenzene, heated to 80°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ②After the reaction, the product is extracted with ethyl acetate, washed with saturated brine, and dried with a rotary evaporator to remove the solvent to obtain a crude product; ③The crude product is purified by column chromatography (Petroleum ether: ethyl acetate = 100:1) purification to obtain 23.89 grams of N, N'-di-tert-butyl-5-furan-3-yl)isochroman-1,1-bis(formamidoyl) Dicyanide, its structural formula is: The yield was 82%. Melting point: 114°C.

IR(KBr, cm ^-1 ): 3130, 2977, 2216, 1641, 1506, 1466, 1364, 1234, 1210, 1108, 1055, 951, 791, 749;

¹ H NMR (CDCl ₃ , 500MHz): δ7.51(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);

¹³ C NMR (CDCl ₃ , 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 .

Example 6: N, N'-di-tert-butyl-6H-benzo[c]chromene-6,6-bis(formamimidino)dicyanide

N, N'-di-tert-butyl 6H benzo[c] chromene-6,6-bis(formamimidino) dicyanide adopts the following steps: 1. add 12.7 grams of 6H-benzo in 1000 ml reaction kettle [c] Isochroman, 23.2 g tert-butylisonitrile, 1.8 g silver triflate, 31.8 g 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 600 ml chlorinated Benzene, heated to 85°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ②After the reaction, the product is extracted with ethyl acetate, washed with saturated brine, and dried with a rotary evaporator to remove the solvent to obtain a crude product; ③The crude product is purified by column chromatography (petroleum ether: ethyl acetate = 50:1) purification to obtain 25.09 grams of N, N'-di-tert-butyl-6H-benzo[c]chromene-6,6-bis(formamimidino) dicyanide , whose structural formula is: The yield was 90%. Melting point: 158°C.

IR(KBr, cm ^-1 ): 2978, 2216, 1645, 1471, 1446, 1364, 1236, 1204, 1059, 1035, 752;

¹ H NMR (CDCl ₃ , 500MHz): δ7.81(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);

¹³ C NMR (CDCl ₃ , 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 .

Example 7: N, N'-di-tert-butyl-3,3-dimethylisochroman-1,1-bis(carboxamidino) dicyanide

N, N'-di-tert-butyl-3,3-dimethylisochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: 1. add 11.3 grams of 3 in 1000 milliliters of reaction kettle ,3-Dimethylisochroman, 23.2 g tert-butylisocyanide, 1.8 g silver triflate, 31.8 g 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 600 mL of chlorobenzene, heated to 90°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ②After the reaction, the product is extracted with ethyl acetate, washed with saturated brine, and dried with a rotary evaporator to remove the solvent to obtain a crude product; ③The crude product is purified by column chromatography (Petroleum ether: ethyl acetate = 50:1) purified to obtain 15.09 g of N,N'-di-tert-butyl-3,3-dimethylisochroman-1,1-bis(methylamidine) di Cyanide, whose structural formula is The yield was 57%. Melting point: 102°C.

IR(KBr,cm ^-1 ):2979,2212,1646,1465,1371,1208,1076,921,758;

¹ H NMR (CDCl ₃ , 500MHz): δ7.26(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);

¹³ C NMR (CDCl ₃ , 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 .

Example 8: N, N'-di-tert-butyl-3-phenylisochroman-1,1-bis(carboxamidino) dicyanide

N, N'-di-tert-butyl-3-phenylisochroman-1,1-bis(formamimidino) dicyanide adopts the following steps: 1. add 14.7 grams of 3- Phenylisochroman, 44.4 g n-butyl acrylate, 23.2 g tert-butylisocyanide, 1.8 g silver triflate, 31.8 g 2,3-dichloro-5,6-dicyano-1,4-benzene Quinone, 600ml chlorobenzene, heated to 85°C. Use thin layer chromatography to track the reaction until the reaction raw materials disappear; ②After the reaction, the product is extracted with ethyl acetate, washed with saturated brine, and dried with a rotary evaporator to remove the solvent to obtain a crude product; ③The crude product is purified by column chromatography (petroleum ether: ethyl acetate = 50:1) purification to obtain 18.50 grams of N, N'-di-tert-butyl-3-phenylisochroman-1,1-bis(carboxamidino) dicyanide , whose structural formula is: The yield was 62%. Melting point: 145°C.

IR(KBr, cm ^-1 ): 2975, 2216, 1646, 1457, 1367, 1233, 1210, 1069, 916, 748, 692;

¹ H NMR (CDCl ₃ , 500MHz): δ7.55(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);

¹³ C NMR (CDCl ₃ , 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, 58.59 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 80~90^oIt 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.