CN114436954B - Method for cross deamination alkenyl of methyl substituted nitrogen heterocyclic compound and benzylamine compound - Google Patents
Method for cross deamination alkenyl of methyl substituted nitrogen heterocyclic compound and benzylamine compound Download PDFInfo
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Abstract
The invention belongs to an organic compound C (sp 3 ) The field of H bond alkenylation, in particular to a method for cross deamination alkenylation of methyl-substituted nitrogen heterocyclic compounds and benzylamine compounds. In the presence of iodine and organic acid, toluene is used as a solvent, and methyl-substituted nitrogen heterocyclic compound and benzylamine compound are used as substrates, so that the cross deamination alkenyl product of the methyl-substituted nitrogen heterocyclic compound and benzylamine can be obtained. The method has the advantages of cheap and easily obtained reagent, no use of metal catalyst, mild reaction condition, simple operation and high yield up to 88%.
Description
Technical Field
The invention belongs to an organic compound C (sp 3 ) -H-bond alkenylation, more specifically, to a process for cross deamination alkenylation of methyl-substituted nitrogen heterocycles with benzylamine compounds.
Background
Azacyclic compounds exist as important structural units in many molecules, drugs, materials and fine chemicals with important biological activities, and 2-or 4-methyl-substituted azacyclic compounds are good nucleophiles due to the special positions of methyl groups, thus attracting chemists to the use of such methyl-substituted azacyclic compounds C (sp 3 ) Study of H bond functionalization. Wherein, methyl-substituted nitrogen heterocyclic compound C (sp 3 ) H-bond alkenylation is considered to be a powerful method of constructing c=c bonds. The methods reported in the literature currently include the following:
(1) And the dehydroxylation alkenyl reaction is realized with benzyl alcohol. Methyl substituted azaheterocyclic compounds in Mn (CO) 5 Br(Barman,M.K.；Waiba,S.；Maji,B.Angew.Chem.Int.Ed.2018,57,9126-9130.)、Pt/Al 2 O 3 (Chaudhari,C.；Siddiki,S.M.A.H.；Ken-ichi,S.Tetrahedron Letters.2013,54,6490-6493.)、Fe(OAc) 2 (Das, j.; vellakkaran, m.; SK, m.; banerjee, d.org. lett.2019,21, 7514-7518.) or NiBr 2 (Ramalingam B.M.; ramalirishena I.; baidya M.J. org. Chem.2019,84, 9819-9825.) and the like, can realize C (sp) 3 ) Alkenylation of the H bond. For example, 2-methylpyrazine, at 140 ℃, tert-butanol as solvent, potassium tert-butoxide as base, mn (CO) 5 Br is used as a catalyst and can be subjected to cross-coupling reaction with benzyl alcohol to realize C (sp) 3 ) H-bond alkenylation, which gives higher reaction yields, but requires the addition of transition metals as catalysts and higher reaction temperatures.
(2) And (3) withThe aldehyde realizes the alkenylation reaction. Methyl-substituted nitrogen heterocyclic compounds in InCl 3 (Jamal,Z.；Teo,Y.-C.；Lim,G.S.Tetrahedron.2016,72,2132-2138.)、Fe(OAc) 2 (Pi,D.；Jiang,K.；Zhou,H.；Sui,Y.；Uozumi,Y.；Zou,K.RSC Adv.2014,4,57875-57884.)、(AcO) 2 C (E) can be achieved with aldehydes under catalysis of O (Kuz' mini, L.G., vedernikov, A.I., lobova, N.A., howard, J.A.K., strelenko, Y.A., fedin, V.P., alfimov, M.V., gromov, S.P., new J.chem.,2006,30,458-466.) or 1, 3-dimethylbarbituric acid (Liang, E., wang, J., wu, Y., huang, L., yao, X, tang, X.Adv, synthh.Catal.2019, 361, 1-6.) and the like 3 ) Alkenylation of the H bond. For example, under the catalysis of 1, 3-dimethylbarbituric acid, 2-methylquinoline and benzaldehyde can take water and 1, 4-dioxane as common solvents, acetic acid as additives, so as to realize 2-methylquinoline C (sp) 3 ) Alkenylation of the H bond. Most of these reactions require metal catalysts and methods employing non-metal catalysts have been rarely reported.
(3) Deamination-alkenylation reaction with benzylamine is achieved. Methyl substituted azaheterocyclic compounds in NH 4 I (Li, X.; huang, B.; wang, J.W.; zhang, Y.Y.; liao, W.B.J.chem.Res.2021, 903-910.; NBS/TBHP (Gong, L.; xing L.; J.; xu, T.; zhu, X.; P.; zhou, W.; kang, N.; wang, B.org.Biomol.chem.2014,12, 6557-6560.; 1, 10-phenanthroline-5, 6-dione (Thorve, P.R.; maji, B.org.Lett.2021,23, 542-547.;) under catalysis or ionic liquids Bmin [ BF ] 4 ]In (3) deamination-alkenylation reaction with benzylamine can be achieved. For example, under the co-catalysis of 4-methylpyrimidine and benzylamine, 1, 10-phenanthroline-5, 6-dione and trifluoromethanesulfonic acid, oxygen is taken as an oxidant, and 4-methylpyrimidine C (sp) is realized in chlorobenzene 3 ) Deamination of the H bond. The reaction uses benzylamine as a benzyl source, high-temperature reaction is mostly adopted, and the method is less researched.
Disclosure of Invention
The invention aims at overcoming the defects, and provides a method for cross deamination and alkenyl of methyl-substituted nitrogen heterocyclic compound and benzylamine compound, which takes toluene as a solvent and takes methyl-substituted nitrogen heterocyclic compound and benzylamine compound as substrates in the presence of iodine and organic acid, so that the cross deamination and alkenyl products of the methyl-substituted nitrogen heterocyclic compound and benzylamine can be efficiently obtained.
In order to achieve the above purpose, the invention is realized by the following technical scheme: a method for cross deamination alkenylation of a methyl-substituted nitrogen heterocyclic compound with a benzylamine compound, comprising the steps of:
in oxygen atmosphere, mixing methyl substituted nitrogen heterocyclic compound, benzylamine compound, iodine and organic acid in toluene solvent for reaction, and column chromatography to obtain methyl substituted nitrogen heterocyclic compound and benzylamine compound cross deamination alkenyl product.
Wherein the cross deaminated alkenylation product of the methyl-substituted nitrogen heterocyclic compound and benzylamine has the formula:
wherein:is one of quinoline, quinoxaline, pyridine, pyrazine, pyrimidine, benzothiazole and benzoxazole, R 1 Is any one of-hydrogen, -methoxy, -ethyl, -bromo, or-chloro, R 2 Is one of-hydrogen, 2-methyl, 4-methyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-chloro, 4-chloro, 2-fluoro, 4-fluoro, 2-bromo, 3, 4-dimethoxy, 4-trifluoromethyl or 4-phenyl.
The cross deamination alkenyl product of the methyl-substituted nitrogen heterocyclic compound and the benzylamine in the preparation method is any one of the following compounds:
the general formula of the methyl-substituted nitrogen heterocyclic compound is:
wherein:is one of quinoline, quinoxaline, pyridine, pyrazine, pyrimidine, benzothiazole and benzoxazole, and R is one of-hydrogen, -methoxy, -ethyl, -bromine or-chlorine.
Further, the compound can be any one of the following compounds:
further, the methyl-substituted nitrogen heterocyclic compound and benzylamine compound cross deamination alkenyl method, wherein the benzylamine compound has a general formula of
Wherein: r is R 1 Is any one of-hydrogen, 2-methyl, 4-methyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-chloro, 4-chloro, 2-fluoro, 4-fluoro, 2-bromo, 3, 4-dimethoxy, 4-trifluoromethyl or 4-phenyl.
The compound can be any one of the following compounds:
in order to further increase the yield, the following preferences may be made:
the benzylamine compound is used in an amount of 1.1 to 2.0 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound and/or the iodine is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound and/or the organic acid is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound and/or the concentration of the methyl-substituted nitrogen heterocyclic compound, benzylamine compound, iodine and the mixture of the organic acid and toluene is 0.2 to 0.8 mol/liter.
Further, in the preparation method, the organic acid is trifluoroacetic acid.
Further, in the above preparation method, the reaction time is 18 to 24 hours, and the temperature is 80 to 110 ℃.
Further, in the above preparation method, in the column chromatography step, the preferred column packing solvent is petroleum ether; the eluent is petroleum ether/ethyl acetate; the column packing used was 300-400 mesh silica gel with a specification of 2cm diameter by 30cm height.
Compared with the prior art, the invention has the beneficial effects that:
(1) The method for cross deamination and alkenylation of the methyl-substituted nitrogen heterocyclic compound and the benzylamine compound has the advantages of simple and easily obtained reagent, simple and convenient operation, no use of metal catalyst and high atom economy.
(2) The invention takes methyl-substituted nitrogen heterocyclic compounds with different structures as raw materials, can realize deamination alkenyl reaction of the methyl-substituted nitrogen heterocyclic compounds and benzylamine in an iodine/organic acid system under toluene solvent, and effectively synthesizes a series of methyl-substituted nitrogen heterocyclic compounds C (sp 3 ) -H-bond alkenylation products. The method has the advantages of simple and easily obtained reagent, mild reaction condition, simple operation, no use of metal catalyst, high atom economy and high yield of 88 percent.
Detailed Description
The invention is further described in detail below in connection with the examples:
a method for cross deamination of a methyl-substituted nitrogen heterocyclic compound with a benzylamine compound comprising the steps of:
in oxygen atmosphere, mixing methyl substituted nitrogen heterocyclic compound, benzylamine compound, iodine and organic acid in toluene solvent for reaction, and column chromatography to obtain methyl substituted nitrogen heterocyclic compound and benzylamine compound cross deamination alkenyl product.
Wherein the general formula of the cross deamination alkenyl product of the methyl substituted nitrogen heterocyclic compound and the benzylamine, the methyl substituted nitrogen heterocyclic compound and the benzylamine compound are as follows:
wherein:is one of quinoline, quinoxaline, pyridine, pyrazine, pyrimidine, benzothiazole and benzoxazole, R 1 And R of the general formula of methyl-substituted nitrogen heterocyclic compound is any one of-hydrogen, -methoxy, -ethyl, -bromine or-chlorine, R 2 And R in the benzylamine compound is any one of hydrogen, 2-methyl, 4-methyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-chlorine, 4-chlorine, 2-fluorine, 4-fluorine, 2-bromine, 3, 4-dimethoxy, 4-trifluoromethyl or 4-phenyl.
The cross deaminated alkenylation product of the methyl-substituted nitrogen heterocyclic compound and the benzylamine is any one of the following compounds:
in the above preparation method, the benzyl amine compound is used in an amount of 1.1 to 2.0 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound, and/or the iodine compound is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound, and/or the organic acid is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound, and/or the concentration of the methyl-substituted nitrogen heterocyclic compound, benzyl amine compound, iodine, and the mixture of the organic acid and toluene is 0.2 to 0.8 mole/liter, the organic acid is trifluoroacetic acid, the reaction time is 18 to 24 hours, and the temperature is 80 to 110 ℃.
The experiment shows that the consumption, the reaction time and the temperature of each material mainly influence the yield of the cross deamination alkenyl product of the methyl substituted nitrogen heterocyclic compound and the benzylamine compound, but basically have no influence on the selectivity of the cross deamination alkenyl product of the methyl substituted nitrogen heterocyclic compound and the benzylamine compound, and the yield of the cross deamination alkenyl product of the methyl substituted nitrogen heterocyclic compound and the benzylamine compound obtained under the conditions is more than 65 percent.
It has also been found in experiments that under the above conditions, methyl-substituted azaheterocyclic compounds C (sp 3 ) The H bond itself is deoxidised, but the reaction generally occurs at a rate of less than 10%, but when the toluene solvent is replaced by dimethyl sulfoxide, acetonitrile, methanol, dioxane and ionic liquid, the yield of the cross deaminated alkenylation product of the methyl-substituted aza ring compound and benzylamine compound is less than 50%.
Specifically, DMSO (11% yield of 4-styryl quinoline, 83% yield of 4-quinolinyl quinoline), CH 3 CN (4-styryl quinoline yield 28%, 4-quinolinyl quinoline yield 43%), CH 3 OH (4-styryl quinoline yield 23%, 4-quinolinyl quinoline yield 40%), dioxane (4-styryl quinoline yield 37%, 4-quinolinyl quinoline yield 45%), [ BMlM ]]BF 4 (4-styrylquinoline yield 45%, 4-quinolinylquinoline yield 53%), [ BMlM]PF 6 (4-styryl quinoline yield 44%, 4-quinolinyl quinoline yield 34%).
Preferred embodiments of the present invention will be described in more detail below in connection with specific examples. The methods are conventional methods unless otherwise specified. The starting materials are commercially available from the public unless otherwise specified. In the column chromatography step of the following examples, the column was packed with 300-400 mesh silica gel in a size of 2cm diameter by 30cm height.
Example 1
A cross deamination alkenyl product of 4-methylquinoline and benzylamine shown in the formula IV-a is prepared by the following steps:
the reaction equation above is the synthesis of the cross deaminated alkenylation product of 4-methylquinoline with benzylamine:
4-methylquinoline (74.0 g,0.5 mmol), benzylamine (82.1 g,0.75 mmol), iodine (158.1 g,0.6 mmol), a second organic solvent PhMe (2 mL) and then TFA (28.5 g,0.25 mmol) were added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, oxygen was added, and the temperature was naturally raised to 110℃overnight, and 100mL of water was added to the reaction mixture to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the white solid 4-styrylquinoline 64.39mg,87% yield as shown in formula IV-a.
Example 2
A cross deamination alkenyl product of 4-methylquinoline and benzylamine shown in the formula IV-a is prepared by the following steps:
the reaction equation above is the synthesis of the cross deaminated alkenylation product of 4-methylquinoline with benzylamine:
4-methylquinoline (72.4 g,0.5 mmol), benzylamine (83.5 g,0.75 mmol), iodine (189.3 g,0.75 mmol), a second organic solvent PhMe (2 mL) and then TFA (28.5 g,0.25 mmol) were added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, oxygen was added, and the temperature was naturally raised to 100℃overnight, and 100mL of water was added to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the white solid, 58.44mg of 4-styrylquinoline of formula IV-a, 81% yield.
Example 3
A cross deamination alkenyl product of 4-methylquinoline and benzylamine shown in the formula IV-a is prepared by the following steps:
the reaction equation above is the synthesis of the cross deaminated alkenylation product of 4-methylquinoline with benzylamine:
4-methylquinoline (72.3 g,0.5 mmol), benzylamine (82.2 g,0.75 mmol), iodine (157.6 g,0.6 mmol), a second organic solvent PhMe (2 mL) and then TFA (28.5 g,0.25 mmol) were added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, oxygen was added, and the temperature was naturally raised to 100℃overnight, and 100mL of water was added to the reaction mixture to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the white solid, 4-styrylquinoline of formula IV-a, 63.34mg,88% yield.
Example 4
A cross deamination alkenyl product of 4-methylquinoline and benzylamine shown in the formula IV-a is prepared by the following steps:
the reaction equation above is the synthesis of the cross deaminated alkenylation product of 4-methylquinoline with benzylamine:
4-methylquinoline (75.0 g,0.5 mmol), benzylamine (83.3 g,0.75 mmol), iodine (127.7 g,0.5 mmol), a second organic solvent PhMe (2 mL) and then TFA (28.5 g,0.25 mmol) were added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, oxygen was added, and the temperature was naturally raised to 110℃overnight, and 100mL of water was added to the reaction mixture to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the white solid 4-styrylquinoline of formula IV-a, 56.15mg,75% yield.
Example 5
A cross deamination alkenyl product of 4-methylquinoline and benzylamine shown in the formula IV-a is prepared by the following steps:
the reaction equation above is the synthesis of the cross deaminated alkenylation product of 4-methylquinoline with benzylamine:
4-methylquinoline (72.0 g,0.5 mmol), benzylamine (67.5 g,0.6 mmol), iodine (157.1 g,0.6 mmol), a second organic solvent PhMe (2 mL) and then TFA (28.5 g,0.25 mmol) were added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, oxygen was added, the temperature was naturally raised to 100℃overnight, and 100mL of water was added to the reaction mixture for quenching reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, extracted with a third organic solvent, ethyl acetate (3X 30.0 mL), the combined organic phases were dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the white solid, 54.57mg of 4-styrylquinoline of formula IV-a, 76% yield.
The structure validation results are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.90(d,J＝4.6Hz,1H),8.22(d,J＝8.4Hz,1H),8.14(d,J＝8.4Hz,1H),7.82(d,J＝16.1Hz,1H),7.74(t,J＝7.6Hz,1H),7.65-7.58(m,4H),7.43(t,J＝7.5Hz,2H),7.38-7.32(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ150.3,148.7,143.0,136.6,135.2,130.2,129.4,129.0,128.9,127.2,126.6,126.5,123.6,122.9,117.1。
the compound synthesized by structural identification is 4-styryl quinoline shown as a target compound IV-a.
Comparative example 1
A4-methylquinoline self-dehydroalkenylation product shown in a formula III-a is prepared by the following steps:
the above reaction equation is for the synthesis of the 4-methylquinoline self dehydroalkenylation product III-a:
4-methylquinoline (73.3 g,0.5 mmol), benzylamine (81.1 g,0.75 mmol), iodine (196.2 g,0.75 mmol), a first organic solvent DMSO (2 mL), then TFA (57.0 g,0.5 mmol) was added sequentially to the reactor, the plug was immediately plugged, allowed to stand for 2 minutes, stirred for 2 minutes, allowed to stand until white fumes in the reactor disappeared, an oxygen balloon was attached, and the temperature was naturally raised to 80℃overnight, and 100mL of water was added to the reaction mixture to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give the yellow solid, formula III-a, 4-quinolinylquinoline 65.4mg,90% yield.
Comparative example 2
A2, 6-dimethylquinoline self-dehydroalkenylation product shown in a formula III-b is prepared by the following steps:
the reaction equation is the synthesis of the self dehydroalkenylation product III-b of 2, 6-dimethylquinoline:
to the reactor was added 2, 6-dimethylquinoline (77.4 g,0.5 mmol), benzylamine (81.1 g,0.75 mmol), iodine (196.2 g,0.75 mmol), first organic solvent DMSO (2 mL), then TFA (57.0 g,0.5 mmol), immediately stoppered, allowed to stand for 2 minutes, stirred for 2 minutes again, allowed to stand until white fumes in the reactor disappeared, oxygen balloon was attached, and naturally warmed to 80℃overnight, and 100mL of water was added to quench the reaction. The remaining iodine was removed with saturated aqueous sodium thiosulfate, and the organic phases were combined by extraction with ethyl acetate (3X 30.0 mL), dried over anhydrous sodium sulfate, filtered, and column chromatographed after spin-drying to give 39.8mg of 1, 2-bis (6-methylquinolin-2-yl) ethylene of the yellow solid formula III-a, 52% yield.
The foregoing description of embodiments of the invention has been presented for purposes of illustration and description, and is not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the various embodiments described, and these modifications and variations should also be considered as being within the scope of the invention.
Claims (6)
1. A method for cross deamination alkenylation of methyl-substituted nitrogen heterocyclic compounds and benzylamine compounds, characterized in that: the method comprises the following steps:
in oxygen atmosphere, mixing methyl substituted nitrogen heterocyclic compound, benzylamine compound, iodine and organic acid in toluene solvent for reaction, and performing column chromatography after the reaction is finished to obtain methyl substituted nitrogen heterocyclic compound and benzylamine compound cross deamination alkenyl product;
wherein the cross deaminated alkenylation product of the methyl-substituted nitrogen heterocyclic compound and benzylamine has the formula:
wherein:is one of quinoline, quinoxaline, pyridine, pyrazine, pyrimidine, benzothiazole and benzoxazole, R 1 Is one of-hydrogen, -methoxy, -ethyl, -bromo, or-chloro, R 2 Is any one of-hydrogen, 2-methyl, 4-methyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-chloro, 4-chloro, 2-fluoro, 4-fluoro, 2-bromo, 3, 4-dimethoxy, 4-trifluoromethyl or 4-phenyl;
the general formula of the methyl substituted nitrogen heterocyclic compound is
Wherein:is one of quinoline, quinoxaline, pyridine, pyrazine, pyrimidine, benzothiazole and benzoxazole, and R is one of-hydrogen, -methoxy, -ethyl, -bromine or-chlorine; the general formula of the benzylamine is as follows:
wherein: r is R 1 Is one of-hydrogen, 2-methyl, 4-methyl, 2-methoxy, 3-methoxy, 4-methoxy, 2-chloro, 4-chloro, 2-fluoro, 4-fluoro, 2-bromo, 3, 4-dimethoxy, 4-trifluoromethyl or 4-phenyl;
the organic acid is trifluoroacetic acid.
2. The method for cross deamination of methyl-substituted nitrogen heterocycle compound and benzylamine compound according to claim 1, wherein: the cross deaminated alkenylation product of the methyl-substituted nitrogen heterocyclic compound and the benzylamine is any one of the following compounds:
3. the method for cross deamination of methyl-substituted nitrogen heterocycle compound and benzylamine compound according to claim 1, wherein: the methyl-substituted nitrogen heterocyclic compound is any one of the following compounds:
4. the method for cross deamination of methyl-substituted nitrogen heterocycle compound and benzylamine compound according to claim 1, wherein: the benzylamine compound is any one of the following compounds:
5. the method for cross deamination of methyl-substituted nitrogen heterocycle compound and benzylamine compound according to claim 1, wherein: the reaction conditions are as follows: the reaction time is 18 to 24 hours under the stirring condition of 80 to 110 ℃.
6. The method for cross deamination of methyl-substituted nitrogen heterocycle compound and benzylamine compound according to claim 1, wherein: the benzyl amine compound is used in an amount of 1.1 to 2.0 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound, the iodine compound is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound, and the organic acid compound is used in an amount of 0.5 to 1.5 times by mole ratio of the methyl-substituted nitrogen heterocyclic compound.
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