A kind of synthetic method of 3,5-diaryl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene derivative

Abstract

The invention discloses synthesis method of a 3,5-diaryl-2,6,6-tricyan-1-imino-2,4-cyclohexadiene derivative. The method is as below: reacting a chalcone derivative with a malononitrile dimer under the promotion of alkali at room temperature to obtain a corresponding Michael adduct; then subjecting the Michael addition product to cyclization and dehydrogenation oxidation under the promotion of alkali to obtain the 3,5-diaryl-2,6,6-tricyan-1-imino-2,4-cyclohexadiene derivative. Compared with the traditional method, the two-step synthesis of the invention uses ordinary alkali with low price as a catalyst, so as to effectively reducing the cost and reach high product yield. Especially, in the construction of cyclohexadiene derivative, the method can realize greater flexibility in the selection of a substituent in cyclohexadiene. The 3,5-diaryl-2,6, 6-tricyan-1-imino-2,4-cyclohexadiene derivative synthesized by the method can be used in the fields of synthesis of heteropolycyclic chemical and natural antibiotics, synthesis of anticancer drug, and research on structural modification of natural products.

Description

technical field

[0001] The invention belongs to the technical field of synthesis of 1-iminocyclohexadiene derivatives, in particular to a 3,5-diaryl-2,6,6-tricyano-1-imino-2,4-cyclo Synthetic methods of hexadiene derivatives. Background technique

[0002] The 1-iminocyclohexadiene molecule is an important organic synthon, from which a variety of derivatives can be formed. Therefore, this organic synthon has always been widely concerned. The synthetic method of 1-iminocyclohexadiene There have been a large number of literature reports. However, there are few synthetic methods for pentasubstituted 1-imino-2,4-cyclohexadiene derivatives. So far, there are only three cases of synthesis of 3,5-diaryl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene, and only one compound is synthesized. The first example is a three-component two-step method of 3-pyrazine carboxamidoacetophenone, 4-methoxydicyanostyrene and malononitrile to obtain 3,5-diaryl-2,6, 6-tricyano-1-imino-2,4-cyclohexadiene...

Examples

Embodiment 1

[0030] Taking the synthesis of 3,5-diphenyl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene with the following structural formula as an example, the specific synthesis method is as follows:

[0031]

[0032] 1. Add 0.4161g (2mmol) 1,3-diphenylpropenone-1, 0.2642g (2mmol) 2-amino-1,1,3-tricyanopropene, 0.4246g to a 50mL dry single-necked flask in sequence (2mmol)K 3 PO 4 , 5mL of methanol, stirred at room temperature for 2 hours, added 20mL of ethyl acetate, the mixture was washed three times with saturated brine, the organic phase was dried overnight with anhydrous sodium sulfate, filtered to remove the desiccant, concentrated under reduced pressure, the crude product was separated by silica gel column chromatography (with Petroleum ether and ethyl acetate with a volume ratio of 4:1 is the eluent), concentrated under reduced pressure, and dried in vacuo to obtain 1,3-diphenyl-3-(2-amino-1,1, 3-Tricyanoallyl)acetone-1, 95% yield.

[0033] 2. Add 0.3404g (1mmol) 1,3-diphenyl-3-(2-...

Embodiment 2

[0038] Taking the synthesis of 3-(4-fluorophenyl)-5-phenyl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene as an example, the specific synthesis method is :

[0039]

[0040] In step 1 of Example 1, the 1,3-diphenylpropenone-1 used was replaced with equimolar 1-phenyl-3-(4-fluorophenyl)-propenone-1, and the reaction time was prolonged to 5 hours, the other steps were the same as in Example 1 to obtain brick red powder 3-(4-fluorophenyl)-5-phenyl-2,6,6-tricyano-1-imino-2,4- Cyclohexadiene, the yield is 78%, the melting point>300°C (ethyl acetate), and the structural characterization data are as follows:

[0041] 1 H NMR (400MHz, DMSO) δ (ppm): 8.13 (dd, J=6.6, 3.1Hz, 2H), 7.67 (dd, J=8.7, 5.4Hz, 2H), 7.49 (d, J=1.7Hz, 1H ), 7.48 (d, J=1.9Hz, 2H), 7.36 (t, J=8.9Hz, 2H), 7.15 (s, 1H).

[0042] 13 C NMR (100MHz, DMSO) δ (ppm): 161.57, 160.94, 156.57, 154.45, 137.19, 130.88, 130.05(2), 128.56(2), 127.01(2), 122.12, 116.88, 115.54(3), 115.33( 2), 109.75, 91.99, 30.06.

[0043] H...

Embodiment 3

[0045] To synthesize 3-(4-fluorophenyl)-5-(4-methoxyphenyl)-2,6,6-tricyano-1-imino-2,4-cyclohexadiene with the following structural formula For example, the specific synthesis method is:

[0046]

[0047] In step 1 of Example 1, the 1,3-diphenylpropenone-1 used was equimolar with 1-(4-methoxyphenyl)-3-(4-fluorophenyl)-propenone -1 replacement, the reaction time was extended to 5 hours, other steps were the same as in Example 1, and brown powder 3-(4-fluorophenyl)-5-(4-methoxyphenyl)-2,6,6- Tricyano-1-imino-2,4-cyclohexadiene, the yield is 89%, the melting point is >300°C (ethyl acetate), and the structural characterization data are as follows:

[0048] 1 H NMR (400MHz, DMSO) δ (ppm): 8.14 (d, J = 8.9Hz, 2H), 7.65 (dd, J = 8.7, 5.5Hz, 2H), 7.35 (t, J = 8.8Hz, 2H), 7.09 (s, 1H), 7.03 (d, J=8.9Hz, 2H), 3.82 (s, 3H).

[0049] 13 C NMR (100MHz, DMSO) δ (ppm): 163.36, 161.66, 161.16, 160.60, 156.25, 154.02, 134.26, 130.82(2), 129.83, 128.66, 122.49, 117.13(3), 115.42(2), 113...

technical field

[0001] The invention belongs to the technical field of synthesis of 1-iminocyclohexadiene derivatives, in particular to a 3,5-diaryl-2,6,6-tricyano-1-imino-2,4-cyclo Synthetic methods of hexadiene derivatives. Background technique

[0002] The 1-iminocyclohexadiene molecule is an important organic synthon, from which a variety of derivatives can be formed. Therefore, this organic synthon has always been widely concerned. The synthetic method of 1-iminocyclohexadiene There have been a large number of literature reports. However, there are few synthetic methods for pentasubstituted 1-imino-2,4-cyclohexadiene derivatives. So far, there are only three cases of synthesis of 3,5-diaryl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene, and only one compound is synthesized. The first example is a three-component two-step method of 3-pyrazine carboxamidoacetophenone, 4-methoxydicyanostyrene and malononitrile to obtain 3,5-diaryl-2,6, 6-tricyano-1-imino-2,4-cyclohexadiene...

Examples

Embodiment 1

[0030] Taking the synthesis of 3,5-diphenyl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene with the following structural formula as an example, the specific synthesis method is as follows:

[0031]

[0032] 1. Add 0.4161g (2mmol) 1,3-diphenylpropenone-1, 0.2642g (2mmol) 2-amino-1,1,3-tricyanopropene, 0.4246g to a 50mL dry single-necked flask in sequence (2mmol)K 3 PO 4 , 5mL of methanol, stirred at room temperature for 2 hours, added 20mL of ethyl acetate, the mixture was washed three times with saturated brine, the organic phase was dried overnight with anhydrous sodium sulfate, filtered to remove the desiccant, concentrated under reduced pressure, the crude product was separated by silica gel column chromatography (with Petroleum ether and ethyl acetate with a volume ratio of 4:1 is the eluent), concentrated under reduced pressure, and dried in vacuo to obtain 1,3-diphenyl-3-(2-amino-1,1, 3-Tricyanoallyl)acetone-1, 95% yield.

[0033] 2. Add 0.3404g (1mmol) 1,3-diphenyl-3-(2-...

Embodiment 2

[0038] Taking the synthesis of 3-(4-fluorophenyl)-5-phenyl-2,6,6-tricyano-1-imino-2,4-cyclohexadiene as an example, the specific synthesis method is :

[0039]

[0040] In step 1 of Example 1, the 1,3-diphenylpropenone-1 used was replaced with equimolar 1-phenyl-3-(4-fluorophenyl)-propenone-1, and the reaction time was prolonged to 5 hours, the other steps were the same as in Example 1 to obtain brick red powder 3-(4-fluorophenyl)-5-phenyl-2,6,6-tricyano-1-imino-2,4- Cyclohexadiene, the yield is 78%, the melting point>300°C (ethyl acetate), and the structural characterization data are as follows:

[0041] 1 H NMR (400MHz, DMSO) δ (ppm): 8.13 (dd, J=6.6, 3.1Hz, 2H), 7.67 (dd, J=8.7, 5.4Hz, 2H), 7.49 (d, J=1.7Hz, 1H ), 7.48 (d, J=1.9Hz, 2H), 7.36 (t, J=8.9Hz, 2H), 7.15 (s, 1H).

[0042] 13 C NMR (100MHz, DMSO) δ (ppm): 161.57, 160.94, 156.57, 154.45, 137.19, 130.88, 130.05(2), 128.56(2), 127.01(2), 122.12, 116.88, 115.54(3), 115.33( 2), 109.75, 91.99, 30.06.

[0043] H...

Embodiment 3

[0045] To synthesize 3-(4-fluorophenyl)-5-(4-methoxyphenyl)-2,6,6-tricyano-1-imino-2,4-cyclohexadiene with the following structural formula For example, the specific synthesis method is:

[0046]

[0047] In step 1 of Example 1, the 1,3-diphenylpropenone-1 used was equimolar with 1-(4-methoxyphenyl)-3-(4-fluorophenyl)-propenone -1 replacement, the reaction time was extended to 5 hours, other steps were the same as in Example 1, and brown powder 3-(4-fluorophenyl)-5-(4-methoxyphenyl)-2,6,6- Tricyano-1-imino-2,4-cyclohexadiene, the yield is 89%, the melting point is >300°C (ethyl acetate), and the structural characterization data are as follows:

[0048] 1 H NMR (400MHz, DMSO) δ (ppm): 8.14 (d, J = 8.9Hz, 2H), 7.65 (dd, J = 8.7, 5.5Hz, 2H), 7.35 (t, J = 8.8Hz, 2H), 7.09 (s, 1H), 7.03 (d, J=8.9Hz, 2H), 3.82 (s, 3H).

[0049] 13 C NMR (100MHz, DMSO) δ (ppm): 163.36, 161.66, 161.16, 160.60, 156.25, 154.02, 134.26, 130.82(2), 129.83, 128.66, 122.49, 117.13(3), 115.42(2), 113...

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