CN108358893A - A kind of method of one pot process tetrahydro benzo-[1,4]-diazepan derivatives - Google Patents
A kind of method of one pot process tetrahydro benzo-[1,4]-diazepan derivatives Download PDFInfo
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- CN108358893A CN108358893A CN201810138302.3A CN201810138302A CN108358893A CN 108358893 A CN108358893 A CN 108358893A CN 201810138302 A CN201810138302 A CN 201810138302A CN 108358893 A CN108358893 A CN 108358893A
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- RXPVBHIKMWUBCR-UHFFFAOYSA-N Cc1cc(NC(C(C2=NC=[I]C=C2)NC2OC22)c3ncccc3)c2cc1 Chemical compound Cc1cc(NC(C(C2=NC=[I]C=C2)NC2OC22)c3ncccc3)c2cc1 RXPVBHIKMWUBCR-UHFFFAOYSA-N 0.000 description 1
- UUTMUXXIVDNGJI-UHFFFAOYSA-N NC1=CCC=CC=C1C#N Chemical compound NC1=CCC=CC=C1C#N UUTMUXXIVDNGJI-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention discloses a kind of one pot process tetrahydro benzos [1,4] method of diazepan derivatives, using methylene primary alconol class substrate, Gas chromatography and water as raw material, by borrowing hydrogen reaction to generate N alkylates and making catalyst regeneration under ruthenium catalysis, it is subsequently added into water the reaction was continued and can be obtained target product tetrahydro benzo [1,4] diazepan derivatives, it is intermediate without purification or transfer reaction liquid, one pot of synthesis that target product can be realized；This method is easy to operate, and substrate spectrum is wide, and catalyst can be recycled and byproduct of reaction only has water generation, it is environmentally protective, Atom economy is high, the synthetic reaction of seven yuan of azacyclo-s is enriched, for for finding that new bioactive compound provides important evidence.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of one pot process tetrahydro benzo-[Isosorbide-5-Nitrae]-diaza
The method of cycloheptane derivative.
Background technology
Compound containing seven yuan of azepine ring structures often has important bioactivity, is commonly applied to medicine, pesticide, table
The fields such as face activating agent and functional material, but at present the method for seven yuan of azacyclo-s of synthesis be not it is very much, this may be due to
General middle ring reaction is all relatively difficult.
2001, Dawei Ma seminars were using CuI as catalyst aryl halide and amino acid or amino-acid ester
Coupling reaction, reaction temperature completes in 100 DEG C, 48 hours, this shows the structure containing a-amino acid for Liv Ullmann type
Aryl amination reaction has acceleration；This coupling reaction can be used for preparing N- aryl beta-amino acids enantiomers, be a kind of effective
Approach synthesize SB214857, it can be used as potent glycoprotein IIB/IIIa receptor antagonists.
2012, LamiaW.Mohamed et al. synthesized the Diazesuberane (such as formula A, B, C) of a series of new,
And ability of such noval chemical compound to internal and external acetylcholine esterase inhibition is had detected, and find that they have by force reversible
Property anticholinesterase activity；In the past few years, it opens and treats Alzheimer's with acetylcholine and similar recognize
Know obstacle；
In recent years, by completing being alkylated into for nitrogen by means of hydrogen methods polysubstituted amine is directly synthesized in order to which one kind is very important
Method, the advantage of such method is that the by-product of reaction process only has water, and selects a large amount of sustainable alcohol to replace
In generation, has the alkyl halide of pollution as alkylating reagent environment, improves the Atom economy of reaction.Diazesuberane derives
Object is biologically active seven yuan of azacyclo-s, and synthesis step is more in the method for existing synthesis Diazesuberane, yield
It is low, and seven yuan of azacyclo- biological respinse types of synthesis are less, and hydrogen reaction principle, one pot process diazacyclo are borrowed using green
The report of heptane derivative is even more to rarely have.
Invention content
The purpose of the present invention is to provide a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives
Method, this method is easy to operate, and catalyst can be recycled and byproduct of reaction only has water generation, green non-pollution.
The purpose of the present invention can be achieved through the following technical solutions：
The method of one pot process tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives, specifically comprises the following steps：
It is added in reaction tube the methylene primary alconol class substrate of 1 structure of formula, Gas chromatography, the catalyst system and catalyzing of 2 structure of formula
And solvent, nitrogen filled protection close valve seal, after reacting a period of time, valve is opened in cooling, and adding water, the reaction was continued, reaction knot
Shu Hou, reacting coarse product obtain tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives through isolating and purifying；
Above-mentioned synthetic reaction is shown below:
Further, R in the formula 11Including pyridyl group, phenyl, thienyl, furyl or linear paraffin base.
Further, the linear paraffin base is preferably the linear paraffin base of 3 carbochains.
Further, RuCl is used in the catalyst system and catalyzing3For metallic catalyst, alkali selects sodium methoxide, and ligand is triphen
Base phosphine；
The ligand triphenylphosphine structural formula is as shown in Equation 8：
Further, the methylene primary alconol class substrate, Gas chromatography, metallic catalyst, ligand, alkali molar ratio be
5-8:1:0.01:0.03:0.05。
Further, the solvent is acetonitrile, and the amount of solvent is to react the 1%-2% of pipe volume.
Further, described plus water the amount is to react the 0.5%-2% of pipe volume.
Further, the reaction is that 6-10h is reacted at 110-120 DEG C for a period of time；
The temperature of the cooling is 50-60 DEG C；
The reaction was continued for described plus water to react 4-6h at 85-90 DEG C.
Further, the purification procedures are after reaction, reaction mixture to be sucked out, ethyl acetate washer bottle
Bottom merges reaction mixture and washing lotion, removes solvent by rotary evaporation, then crude product purifies to obtain by column chromatography for separation
Tetrahydro benzo-[1,4]-diazepan derivatives；
The column chromatography refers to that the mixed solvent of n-hexane and ethyl acetate is the column chromatography of eluent；
The volume ratio of n-hexane/ethyl acetate is 2-4:1.
Further, the tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives include 2,3- bis- (2- pyridyl groups)-
3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one, 2,3- diphenyl -3,4- dihydro -1H- benzos
[e] [1,4]-Diazesuberane -5 (2H) -one, (2- the thienyls) -3,4- dihydro -1H- benzos of 2,3- bis- [e] [1,4]-two
Azepan -5 (2H) -one, 2,3- bis- (2- furyls) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5
(2H) -one and 2,3- di-n-butyl -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one.
The reaction mechanism of tetrahydrobiopterin synthesis benzo-[1,4]-diazepan derivatives of the present invention is：
Methylene primary alconol class substrate is catalyzed by ruthenium, and by taking pyridinemethanol as an example, ruthenium catalyst system and catalyzing is borrowed and taken on pyridinemethanol 1a
Hydrogen, make substrate is upper in situ to generate intermediate aldehydes 1-1, intermediate aldehydes 1-1, which reacts to be dehydrated with Gas chromatography, generates imines
Intermediate 3, imine intermediate 3 generates N alkylates 4 by hydrogenation and makes catalyst regeneration, without addition in reaction
Hydrogen source, N alkylates 4 are reacted with water generates amide intermediate 5, and amide intermediate 5 and intermediate aldehydes 1-1 is obtained by the reaction
Intermediate state 6, the condensation dehydration that intermediate state 6 carries out intramolecular have obtained target product 7a；Specific reaction process is shown below：
Beneficial effects of the present invention：
A kind of method of one pot process tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives provided by the invention,
Using methylene primary alconol class substrate, Gas chromatography and water as raw material, by borrowing hydrogen reaction to generate N alkylation productions under ruthenium catalysis
Object is subsequently added into water the reaction was continued and can be obtained target product tetrahydro benzo-[Isosorbide-5-Nitrae]-diaza simultaneously so that catalyst regeneration
Cycloheptane derivative, it is intermediate without purification or transfer reaction liquid, one pot of synthesis that target product can be realized, and yield is up to
81%, this method is easy to operate, and substrate spectrum is wide, has good tolerance, and catalyst can be recycled and react secondary
Product only has water generation, environmentally protective, and Atom economy is high, enriches the synthetic reaction of seven yuan of azacyclo-s, new to be used to find
Bioactive compound provide important evidence.
Specific implementation mode
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
All other embodiment that technical staff is obtained without creative efforts belongs to the model that the present invention protects
It encloses.
Embodiment 1
The conjunction of 2,3- bis- (2- pyridyl groups) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one
At：
Reaction equation is：
The specific steps are：Magneton, the sodium methoxide of 0.05mmol, 0.03mmol are added in the 100mL Schlenk pipes to match
Body triphenylphosphine, the catalyst RuCl of 0.01mmol3, the 2- pyridinemethanols of 5mmol, the 2- aminobenzonitriles of 1mmol, 1.5ml's
Solvent acetonitrile is then filled with nitrogen into Schlenk pipes, and Schlenk pipes are put into the oil bath pan for filling silicone oil, beat by sealing
Magnetic stirring apparatus is opened, it is 120 DEG C of reaction 6h to be heated to temperature, is cooled to 50 DEG C, slowly opens the breather valve of Schlenk pipes, add
Enter 2ml water, close valve, is warming up to 85 DEG C of reaction 5h and is cooled to room temperature after reaction, slowly open the logical of Schlenk pipes
Reaction mixture is sucked out air valve, ethyl acetate washer bottle bottom, merges reaction mixture and washing lotion, is removed by rotary evaporation
Solvent, then crude product purified by column chromatography for separation, eluant, eluent is n-hexane:Ethyl acetate=3.5:1, to be consolidated
Body target product 7a, yield 77%；
The nucleus magnetic hydrogen spectrum result of gained target product 7a is：1H NMR(400MHz,CDCl3):δ 8.52 (d, J=4.4Hz,
1H), 7.83 (d, J=7.7Hz, 1H), 7.53 (t, J=7.6Hz, 1H), 7.46 (s, 1H), 7.24 (t, J=8.8Hz, 3H),
7.18 (d, J=7.8Hz, 2H), 7.12-7.04 (m, 1H), 6.79 (t, J=7.4Hz, 1H), 6.54 (d, J=8.5Hz, 1H),
5.63 (s, 1H), 4.52 (d, J=17.2Hz, 1H), 4.28 (d, J=17.2Hz, 1H), 2.03 (s, 1H)；
The mass spectral results of gained target product 7a are：HRMS m/z(ESI+)calcd for C19H16N4O([M]+),
316.1308,found 316.119。
Embodiment 2
The synthesis of 2,3- diphenyl -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one：
Reaction equation is：
The specific steps are：Magneton, the sodium methoxide of 0.05mmol, 0.03mmol are added in the 100mL Schlenk pipes to match
Body triphenylphosphine, the catalyst RuCl of 0.01mmol3, the benzyl alcohol of 6mmol, the 2- aminobenzonitriles of 1mmol, the solvent second of 1ml
Nitrile is then filled with nitrogen into Schlenk pipes, and Schlenk pipes are put into the oil bath pan for filling silicone oil by sealing, open magnetic force
Blender, it is 112 DEG C of reaction 7h to be heated to temperature, is cooled to 60 DEG C, slowly opens the breather valve of Schlenk pipes, 1.1ml is added
Water closes valve, is warming up to 90 DEG C of reaction 6h and is cooled to room temperature after reaction, slowly opens the ventilation of Schlenk pipes
Reaction mixture is sucked out valve, ethyl acetate washer bottle bottom, merges reaction mixture and washing lotion, is removed by rotary evaporation molten
Agent, then crude product purified by column chromatography for separation, eluant, eluent is n-hexane:Ethyl acetate=3:1, to obtain solid mesh
Mark product 7b, yield 81%；
The nucleus magnetic hydrogen spectrum result of gained target product 7b is：1H NMR(400MHz,CDCl3):δ 8.42 (d, J=4.6Hz,
1H), 7.89 (d, J=7.7Hz, 1H), 7.56 (t, J=7.5Hz, 1H), 7.26 (d, J=7.7Hz, 1H), 7.22 (d, J=
8.6Hz, 1H), 7.17 (d, J=7.7Hz, 2H), 7.10-7.04 (m, 1H), 6.92 (d, J=7.7Hz, 2H), 6.80 (d, J=
7.2Hz, 2H), 6.72 (s, 1H), 6.50 (d, J=8.2Hz, 1H), 5.83 (s, 1H), 4.49 (d, J=17.2Hz, 1H),
4.28 (d, J=17.3Hz, 1H), 2.05 (s, 1H)；
The mass spectral results of gained target product 7b are：HRMS m/z(ESI+)calcd for C21H18N2O ([M]+),
314.1426,found 314.152。
Embodiment 3
The conjunction of 2,3- bis- (2- thienyls) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one
At：
Reaction equation is：
The specific steps are：Magneton, the sodium methoxide of 0.05mmol, 0.03mmol are added in the 100mL Schlenk pipes to match
Body triphenylphosphine, the catalyst RuCl of 0.01mmol3, the thenyl alcohol of 6mmol, the 2- aminobenzonitriles of 1mmol, the solvent of 2ml
Acetonitrile is then filled with nitrogen into Schlenk pipes, and Schlenk pipes are put into the oil bath pan for filling silicone oil by sealing, open magnetic
Power blender, it is 111 DEG C of reaction 10h to be heated to temperature, is cooled to 59 DEG C, slowly opens the breather valve of Schlenk pipes, is added
1.8ml water closes valve, is warming up to 86 DEG C of reaction 5.5h and is cooled to room temperature after reaction, slowly opens Schlenk pipes
Breather valve, reaction mixture is sucked out, ethyl acetate washer bottle bottom, merges reaction mixture and washing lotion, pass through rotary evaporation
Solvent is removed, then crude product is purified by column chromatography for separation, and eluant, eluent is n-hexane:Ethyl acetate=2:1, to obtain
Solid target compound 7c, yield 68%；
The nucleus magnetic hydrogen spectrum result of gained target product 7c is：1H NMR(400MHz,CDCl3):δ 8.51 (d, J=4.2Hz,
1H), 7.86 (t, J=7.3Hz, 1H), 7.68 (d, J=7.6Hz, 1H), 7.45 (d, J=8.6Hz, 1H), 7.23 (d, J=
7.7Hz, 2H), 7.10-7.04 (m, 1H), 6.96 (d, J=7.8Hz, 1H), 6.82 (d, J=7.7Hz, 2H), 5.62 (s,
1H), 4.81 (d, J=17.2Hz, 1H), 4.16 (d, J=17.3Hz, 1H), 1.98 (s, 1H)；
The mass spectral results of gained target product 7c are：HRMS m/z(ESI+)calcd for C17H14N2OS2 ([M]+),
326.0556,found 325.991。
Embodiment 4
The conjunction of 2,3- bis- (2- furyls) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one
At：
Reaction equation is：
The specific steps are：Magneton, the sodium methoxide of 0.05mmol, 0.03mmol are added in the 100mL Schlenk pipes to match
Body triphenylphosphine, the catalyst RuCl of 0.01mmol3, the furancarbinol of 6mmol, the 2- aminobenzonitriles of 1mmol, the solvent of 1ml
Acetonitrile is then filled with nitrogen into Schlenk pipes, and Schlenk pipes are put into the oil bath pan for filling silicone oil by sealing, open magnetic
Power blender, it is 117 DEG C of reaction 9h to be heated to temperature, is cooled to 58 DEG C, slowly opens the breather valve of Schlenk pipes, is added
1.5ml water closes valve, is warming up to 86 DEG C of reaction 6h and is cooled to room temperature after reaction, slowly opens Schlenk pipes
Reaction mixture is sucked out breather valve, ethyl acetate washer bottle bottom, merges reaction mixture and washing lotion, is removed by rotary evaporation
Solvent is removed, then crude product is purified by column chromatography for separation, and eluant, eluent is n-hexane:Ethyl acetate=2.5:1, to obtain
Solid target compound 7d, yield 71%；
The nucleus magnetic hydrogen spectrum result of gained target product 7d is：1H NMR(400MHz,CDCl3):δ 8.49 (d, J=4.0Hz,
1H), 7.77 (t, J=7.2Hz, 1H), 7.69 (d, J=7.4Hz, 1H), 7.46 (d, J=8.1Hz, 1H), 7.23 (d, J=
7.7Hz, 2H), 7.12-7.04 (m, 1H), 6.95 (d, J=7.5Hz, 1H), 6.83 (d, J=7.7 Hz, 2H), 5.47 (s,
1H), 4.79 (d, J=17.5Hz, 1H), 4.22 (d, J=17.3Hz, 1H), 1.99 (s, 1H)；
The mass spectral results of gained target product 7d are：HRMS m/z(ESI+)calcd for C17H14N2O3 ([M]+),
294.1041,found 294.118。
Embodiment 5
The synthesis of 2,3- di-n-butyl -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one：
Reaction equation is：
The specific steps are：Magneton, the sodium methoxide of 0.05mmol, 0.03mmol are added in the 100mL Schlenk pipes to match
Body triphenylphosphine, the catalyst RuCl of 0.01mmol3, the n-butanol of 8mmol, the 2- aminobenzonitriles of 1mmol, the solvent of 1.2ml
Acetonitrile is then filled with nitrogen into Schlenk pipes, and Schlenk pipes are put into the oil bath pan for filling silicone oil by sealing, open magnetic
Power blender, it is 115 DEG C of reaction 8h to be heated to temperature, is cooled to 55 DEG C, slowly opens the breather valve of Schlenk pipes, is added
0.5ml water closes valve, is warming up to 88 DEG C of reaction 4h and is cooled to room temperature after reaction, slowly opens Schlenk pipes
Reaction mixture is sucked out breather valve, ethyl acetate washer bottle bottom, merges reaction mixture and washing lotion, is removed by rotary evaporation
Solvent is removed, then crude product is purified by column chromatography for separation, and eluant, eluent is n-hexane:Ethyl acetate=4:1, to be consolidated
Body target product 7e, yield 60%；
The nucleus magnetic hydrogen spectrum result of gained target product 7e is：1H NMR(400MHz,CDCl3):δ 8.55 (d, J=4.2Hz,
1H), 7.87 (t, J=7.4Hz, 1H), 7.11 (d, J=7.7Hz, 1H), 7.03 (d, J=8.1Hz, 1H), 6.89 (d, J=
7.7Hz, 1H), 5.69 (s, 1H), 4.79 (dd, J=17.5Hz, 1H), 4.22 (dd, J=17.3 Hz, 1H), 2.26 (m, 2H),
2.05(m,2H),1.53(m,4H),1.12(t,6H)；
The mass spectral results of gained target product 7e are：HRMS m/z(ESI+)calcd for C15H22N2O([M]+),
246.1755,found 246.212。
The above content is just an example and description of the concept of the present invention, affiliated those skilled in the art
It makes various modifications or additions to the described embodiments or substitutes by a similar method, without departing from invention
Design or beyond the scope defined by this claim, be within the scope of protection of the invention.
Claims (10)
1. a kind of method of one pot process tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives, it is characterised in that：Specifically
Include the following steps：
It is added in reaction tube the methylene primary alconol class substrate of 1 structure of formula, the Gas chromatography of 2 structure of formula, catalyst system and catalyzing and molten
Agent, nitrogen filled protection close valve seal, and after reacting a period of time, valve is opened in cooling, and adding water, the reaction was continued, and reaction terminates
Afterwards, reacting coarse product obtains tetrahydro benzo-[Isosorbide-5-Nitrae]-diazepan derivatives through isolating and purifying；
Above-mentioned synthetic reaction is shown below:
2. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：R in the formula 11Including pyridyl group, phenyl, thienyl, furyl or linear paraffin base.
3. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 2
Method, it is characterised in that：The linear paraffin base is preferably the linear paraffin base of 3 carbochains.
4. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：RuCl is used in the catalyst system and catalyzing3For metallic catalyst, alkali selects sodium methoxide, and ligand is triphen
Base phosphine；
The ligand triphenylphosphine structural formula is as shown in Equation 8：
5. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：The molar ratio of the methylene primary alconol class substrate, Gas chromatography, metallic catalyst, ligand, alkali
For 5-8:1:0.01:0.03:0.05.
6. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：The solvent is acetonitrile, and the amount of solvent is to react the 1%-2% of pipe volume.
7. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：Described plus water amount is to react the 0.5%-2% of pipe volume.
8. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：
The reaction is that 6-10h is reacted at 110-120 DEG C for a period of time；
The temperature of the cooling is 50-60 DEG C；
The reaction was continued for described plus water to react 4-6h at 85-90 DEG C.
9. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：The purification procedures are that after reaction, reaction mixture is sucked out, ethyl acetate cleaning
Bottom of bottle merges reaction mixture and washing lotion, removes solvent by rotary evaporation, then crude product is purified by column chromatography for separation
To tetrahydro benzo-[1,4]-diazepan derivatives；
The column chromatography refers to that the mixed solvent of n-hexane and ethyl acetate is the column chromatography of eluent；
The volume ratio of n-hexane/ethyl acetate is 2-4:1.
10. a kind of one pot process tetrahydro benzo-[1,4]-diazepan derivatives according to claim 1
Method, it is characterised in that：Tetrahydro benzo-[the 1,4]-diazepan derivatives include (the 2- pyridines of 2,3- bis-
Base) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one, 2,3- diphenyl -3,4- dihydro -1H- benzene
And [e] [1,4]-Diazesuberane -5 (2H) -one, (2- the thienyls) -3,4- dihydro -1H- benzos of 2,3- bis- [e] [1,4]-two
Azepan -5 (2H) -one, 2,3- bis- (2- furyls) -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5
(2H) -one and 2,3- di-n-butyl -3,4- dihydro -1H- benzos [e] [1,4]-Diazesuberane -5 (2H) -one.
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Cited By (2)
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|---|---|---|---|---|
| CN111995576A (en) * | 2020-08-31 | 2020-11-27 | 三峡大学 | Process for preparing polysubstituted nitrogen-containing heterocyclic compound |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111995576A (en) * | 2020-08-31 | 2020-11-27 | 三峡大学 | Process for preparing polysubstituted nitrogen-containing heterocyclic compound |
| CN115368363A (en) * | 2021-05-17 | 2022-11-22 | 中山大学 | Chiral or racemic pyrimido-diazacycloheptanone compound and preparation method and application thereof |
| WO2022242558A1 (en) * | 2021-05-17 | 2022-11-24 | 中山大学 | Chiral or racemic pyrimidodiazepanone compound, and preparation method therefor and use thereof |
| CN115368363B (en) * | 2021-05-17 | 2024-02-20 | 中山大学 | Chiral or racemized pyrimidodiazepinone compound and preparation method and application thereof |
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