CN108409732B - A kind of green synthesis method of B-carboline heterocyclic compound - Google Patents
A kind of green synthesis method of B-carboline heterocyclic compound Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract
The invention discloses the green synthesis methods of B-carboline heterocyclic compound, using alcohol compound as raw material, under catalyst TEMPO and catalyst TBN catalysis, one pot of tandem reaction that color aminated compounds and alcohol are reoxidized through oxidative condensation cyclisation under oxygen obtains B-carboline heterocyclic compound, reaction temperature is 40-120 DEG C, and the reaction time is 6-48 hours.The above method is raw material using alcohols from a wealth of sources, cheap and easy to get, stablizing low toxicity, under the conditions of the concerted catalysis of TEMPO and TBN and acetic acid solvent, realize that the aerobic oxidation condensation and cyclization of color aminated compounds and alcohol reoxidizes the green method that tandem reaction prepares B-carboline cyclics, target product selectivity is high, by-product is water, efficient pollution-free.
Description
Technical field
The present invention relates to chemosynthesis technical fields, and in particular to a kind of green syt side of B-carboline heterocyclic compound
Method.
Background technique
B-carboline heterocycle structure is the structural unit of many natural products and important drugs.Using B-carboline heterocycle as core knot
The drug molecule of structure includes eudistomins U, canthine, manzamines and a few fermentoids such as cholinesterase
(Cholinesterases), tyrosine kinase (kinases) etc., it is many kinds of.Further, it is well known that much with B-carboline
Heterocycle is that the molecule of nuclear structure has the bio-pharmaceuticals such as AntiHIV1 RT activity, antitumor, anti-malarial, antiplasmodial activity.International drugs refer to
Number search result is also shown, and having 200 reports above with respect to study medication to be related to B-carboline heterocycle is core knot
The compound of structure.Therefore the synthesis of B-carboline heterocyclic compound is always one of synthesis and Pharmaceutical Chemist focus of attention.
Known B-carboline heterocyclic compound synthetic method includes that traditional Pictet-Spengler condensation and cyclization reoxidizes
Tandem reaction, Graebe-Ullmann coupling reaction, Bischler-Napieralski reaction etc., mainly with tryptamines and its derivative
Object and aldehyde or the higher ketone of activity are raw material.It includes bronsted acid such as trifluoro that Pictet-Spengler, which reacts custom catalysts,
Acetic acid, hydrochloric acid, glacial acetic acid, trifluoromethanesulfonic acid, p-methyl benzenesulfonic acid, formic acid etc., common lewis acid such as Yb (OTf)3、AuCl3/
AgOTf etc..Since Pictet-Spengler reaction is mainly raw material using aldehyde, and aldehyde stink weight toxicity is big and active unstable
It being difficult to ensure and deposits, need to purify before each use, there are many disadvantages, and in addition some methods also use transition-metal catalyst and ligand,
Cause not being suitable for synthesizing the exigent pharmaceutical intermediate of metal residual there are heavy-metal residual in product, also limit
The further synthesis application of these methods.
Therefore, the new method pair of the efficient green synthesis B-carboline heterocyclic compound participated in without transition-metal catalyst is developed
Multi-field organic synthesis, biochemistry and pharmaceutical synthesis etc. are all significantly to study.
Summary of the invention
In view of the deficiencies of the prior art, the present invention intends to provide a kind of green of B-carboline heterocyclic compound
Synthetic method, it is raw material that this method, which is using alcohols from a wealth of sources, cheap and easy to get, stablizing low toxicity, in the association of TEMPO and TBN
Under the conditions of catalysis and acetic acid solvent, realize that the aerobic oxidation condensation and cyclization of color aminated compounds and alcohol reoxidizes tandem reaction system
The green method of standby B-carboline cyclics, target product selectivity is high, and by-product is water, efficient pollution-free.
To achieve the above object, the present invention provides the following technical scheme that a kind of green of B-carboline heterocyclic compound is closed
At method, using alcohol compound as raw material, under catalyst TEMPO and catalyst TBN catalysis, color aminated compounds is (unsubstituted
Tryptamines and substitution tryptamines etc.) and alcohol (such as benzylalcohol, cinnamyl alcohol, pyridinemethanol, thenyl alcohol and its substituted alcohol) is under oxygen
The one pot of tandem reaction reoxidized through oxidative condensation cyclisation obtains B-carboline heterocyclic compound, and reaction temperature is 40-120 DEG C, instead
It is 6-48 hours between seasonable, reaction equation are as follows:
Wherein:
R1 is the alkyl such as hydrogen methyl, ethyl or replaces alkyl, halogen atom, alkoxy etc. from simple to complexity
Various substituent groups；
R2 is phenyl or other substituted aryls, substituted furan, the substitution that various functional groups are substituted in 2-, 3- or 4-
The groups such as the substituted heteroaryls such as thiophene, substituted pyridines or cinnamyl, allyl, fatty alkyl.
Preferably, the catalyst TEMPO and catalyst TBN are nontransition metal catalyst, catalyst TEMPO
It is 2,2,6,6- tetramethyl piperidine nitrogen oxides, catalyst TBN is nitrite tert-butyl.
Preferably, the dosage of the catalyst TEMPO and catalyst TBN is 10~100mol%.
Preferably, the dosage of the catalyst TEMPO and catalyst TBN uses 50-100mol%.
Preferably, can be reacted in the case where there is solvent condition or under solvent-free conditions.
It is carried out under solvent condition preferably, selection has, solvent uses acetic acid solvent.
Preferably, can be reacted under air or under oxygen, the temperature for reacting progress selects 40-80 DEG C.
Preferably, the reaction time selects 12-24 hours.
The invention has the advantages that compared with prior art, TEMPO and TBN catalyst used in the present invention universal quotient
Product can be directly commercially available.Alcohol compound using cheap and easy to get, from a wealth of sources, stable low toxicity, green is raw material,
Without using any transition-metal catalyst and ligand, reaction is not necessarily to inert gas shielding, carries out under oxygen atmosphere, using cheap
It is easy to get, green acetic acid is solvent relatively, and easily operated, by-product is water, product heavy metal free residual, environmentally protective no dirt
Dye.Therefore, requirement of this method to reaction condition is lower, the scope of application is wider, with the obvious advantage compared with known method, has latent
In broad application prospect.
Specific embodiment
It will be helpful to understand the present invention by following embodiments, but be not restricted to the contents of the present invention.
Embodiment 1
Tryptamines and benzyl alcohol prepare 1- phenyl-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), benzyl alcohol (0.0621ml, 1.2equiv.),
TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute gas tube sealing three times
Oxygen stirs lower reaction for 24 hours then at 80 DEG C.After TLC monitors fully reacting, product is purified with pillar layer separation, separation yield
85%.1H NMR(500MHz,DMSO-d6): δ 11.54 (br s, 1H), 8.48 (d, J=5.0Hz, 1H), 8.27 (d, J=
8.0Hz, 1H), 8.13 (d, J=5.0Hz, 1H), 8.06 (d, J=7.5Hz, 2H), 7.68 (d, J=8.0Hz, 1H), 7.63 (t,
J=7.5Hz, 2H), 7.58-7.52 (m, 2H), 7.28 (t, J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ
142.1,141.1,138.3,138.2,132.9,129.2,128.7,128.5,128.3,128.1,121.5,120.8,
119.5,113.8,112.4。
Embodiment 2
Tryptamines and 4- methoxy benzyl alcohol prepare 1- (4- methoxyphenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- methoxy benzyl alcohol (0.0745ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 64%.1H NMR(500MHz,DMSO-d6): δ 11.51 (br s, 1H), 8.43 (d, J=5.0Hz, 1H),
8.26 (d, J=8.0Hz, 1H), 8.07 (d, J=5.0Hz, 1H), 8.01 (d, J=8.5Hz, 2H), 7.67 (d, J=8.5Hz,
1H), 7.56 (t, J=7.5Hz, 1H), 7.27 (t, J=7.5Hz, 1H), 7.18 (d, J=8.0Hz, 2H), 3.88 (s, 3H)13C
NMR(125.4MHz,DMSO-d6):δ159.6,142.1,141.0,138.2,132.7,130.9,129.6,128.9,127.9,
121.5,120.9,119.4,114.1,113.2,112.4,55.3。
Embodiment 3
Tryptamines and 4- methylbenzyl alcohol prepare 1- (4- aminomethyl phenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- methylbenzyl alcohol (0.0733g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 64%.1H NMR(500MHz,DMSO-d6): δ 11.51 (br s, 1H), 8.46 (d, J=5.0Hz, 1H),
8.26 (d, J=7.5Hz, 1H), 8.10 (d, J=5.0Hz, 1H), 7.96 (d, J=7.5Hz, 2H), 7.67 (d, J=8.0Hz,
1H), 7.56 (t, J=7.5Hz, 1H), 7.43 (d, J=7.5Hz, 2H), 7.27 (t, J=7.5Hz, 1H), 2.44 (s, 3H)13C
NMR(125.4MHz,DMSO-d6):δ142.2,141.0,138.2,137.9,135.6,132.9,129.2,129.0,128.2,
128.0,121.5,120.8,119.4,113.6,112.4,20.9。
Embodiment 4
Tryptamines and 3- methylbenzyl alcohol prepare 1- (3- aminomethyl phenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 3- methylbenzyl alcohol (0.0722ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 71%.1H NMR(500MHz,DMSO-d6): δ 11.53 (br s, 1H), 8.47 (d, J=5.0Hz, 1H),
8.27 (d, J=7.5Hz, 1H), 8.12 (d, J=5.0Hz, 1H), 7.86 (s, 1H), 7.84 (d, J=8.5Hz, 1H), 7.68
(d, J=8.5Hz, 1H), 7.57 (t, J=7.5Hz, 1H), 7.51 (t, J=7.5Hz, 1H), 7.34 (d, J=7.5Hz, 1H),
7.28 (d, J=7.5Hz, 1H), 2.48 (s, 3H)13C NMR(125.4MHz,DMSO-d6):δ142.3,141.0,138.3,
138.2,137.8,133.0,129.1,129.0,128.9,128.6,128.1,125.5,121.5,120.8,119.4,
113.7,112.4,21.2。
Embodiment 5
Tryptamines and 2- methylbenzyl alcohol prepare 1- (2- aminomethyl phenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 2- methylbenzyl alcohol (0.0733g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 74%.1H NMR(500MHz,DMSO-d6): δ 11.21 (br s, 1H), 8.44 (d, J=5.5Hz, 1H),
8.27 (d, J=7.5Hz, 1H), 8.12 (d, J=5.5Hz, 1H), 7.57 (d, J=8.0Hz, 1H), 7.53 (t, J=7.5Hz,
1H), 7.48 (d, 7.5Hz, 1H), 7.45-7.39 (m, 3H), 7.26 (t, J=7.5Hz, 1H), 7.20 (s, 3H)13C NMR
(125.4MHz,DMSO-d6):δ143.8,140.9,137.8,136.2,133.8,130.5,129.6,128.3,128.1,
127.9,125.8,121.6,120.8,119.3,113.6,112.2,19.5。
Embodiment 6
Tryptamines and 4- butyl-benzyl alcohol prepare 1- (4- tert-butyl-phenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- butyl-benzyl alcohol (0.1062ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 71%.1H NMR(500MHz,DMSO-d6): δ 11.54 (br s, 1H), 8.46 (d, J=5.0Hz, 1H),
8.26 (d, J=8.0Hz, 1H), 8.10 (d, J=5.0Hz, 1H), 7.98 (d, J=8.0,2H), 7.67 (d, J=8.0Hz,
1H), 7.63 (d, J=8.0,2H), 7.56 (t, J=7.5Hz, 1H), 7.27 (t, J=7.5Hz, 1H), 1.38 (s, 9H)13C
NMR(125.4MHz,DMSO-d6):δ150.9,142.2,141.1,138.3,135.7,132.9,129.0,128.1,125.4,
121.5,120.8,119.4,113.6,112.4,34.4,31.1。
Embodiment 7
Tryptamines and 4- fluorophenyl methanol prepare 1- (4- fluorophenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- fluorophenyl methanol (0.0655ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 84%.1H NMR(500MHz,DMSO-d6): δ 11.57 (br s, 1H), 8.46 (d, J=5.0Hz, 1H),
8.28 (d, J=7.5Hz, 1H), 8.13 (d, J=5.0Hz, 1H), 8.09 (q, J=6.0Hz, 2H), 7.66 (d, J=8.5Hz,
1H), 7.57 (t, J=7.5Hz, 1H), 7.45 (t, J=8.5Hz, 2H), 7.28 (d, J=7.5Hz, 1H)13C NMR
(125.4MHz,DMSO-d6): δ 162.3 (d, J=244.7Hz), 141.1 (d, J=6.5Hz), 138.3,134.8 (d, J=
3.0Hz), 132.9,130.5 (d, J=8.4Hz), 129.2,128.2,121.6,120.8,119.5,115.6,115.4,
113.9,112.3。
Embodiment 8
Tryptamines and 4- chlorobenzene methanol prepare 1- (4- chlorphenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- chlorobenzene methanol (0.0855g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 61%.1H NMR(500MHz,DMSO-d6): δ 11.59 (br s, 1H), 8.48 (d, J=5.0Hz, 1H),
8.28 (d, J=8.0Hz, 1H), 8.15 (d, J=5.0Hz, 1H), 8.08 (d, J=8.0Hz, 2H), 7.68-7.66 (m, 3H),
7.58 (t, J=7.5Hz, 1H), 7.28 (t, J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ141.1,
140.8,138.4,137.1,133.2,132.9,130.1,129.4,128.7,128.2,121.6,120.8,119.6,
114.2,112.3。
Embodiment 9
Tryptamines and 4- bromobenzene methanol prepare 1- (4- bromophenyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- bromobenzene methanol (0.1122g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 74%.1H NMR(500MHz,DMSO-d6): δ 11.59 (br s, 1H), 8.48 (d, J=5.5Hz, 1H),
8.28 (d, J=7.5Hz, 1H), 8.15 (d, J=5.5Hz, 1H), 8.01 (d, J=8.5Hz, 2H), 7.81 (d, J=8.5Hz,
2H), 7.67 (d, J=8.0Hz, 1H), 7.58 (t, J=7.5Hz, 1H), 7.29 (t, J=7.5Hz, 1H)13C NMR
(125.4MHz,DMSO-d6):δ141.1,140.9,138.4,137.5,132.9,131.6,130.4,129.4,128.3,
121.9,121.6,120.8,119.6,114.2,112.3。
Embodiment 10
Tryptamines and 3- nitrobenzyl alcohol prepare 1- (3- nitrobenzophenone)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 3- nitrobenzyl alcohol (0.0712ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 90%.1H NMR(500MHz,DMSO-d6): δ 11.76 (br s, 1H), 8.83 (s, 1H), 8.54 (d, J=
5.0Hz, 1H), 8.50 (d, J=8.0Hz, 1H), 8.38 (d, J=8.0Hz, 1H), 8.31 (d, J=8.0Hz, 1H), 8.22 (d,
J=5.0Hz, 1H), 7.92 (t, J=8.0Hz, 1H), 7.68 (d, J=8.5Hz, 1H), 7.61 (t, J=7.5Hz, 1H), 7.31
(t, J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ148.2,141.2,139.8,139.4,138.6,
134.6,133.2,130.3,129.8,128.5,122.9,121.7,120.8,119.7,114.8,112.3。
Embodiment 11
Tryptamines and 4- trifluoromethyl benzyl alcohol prepare 1- (4- trifluoromethyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 4- trifluoromethyl benzyl alcohol (0.0821ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 83%.1H NMR(500MHz,DMSO-d6): δ 11.69 (br s, 1H), 8.52 (d, J=5.5Hz, 1H),
8.30 (d, J=8.0Hz, 1H), 8.27 (d, J=8.0Hz, 2H), 8.20 (d, J=5.5Hz, 1H), 7.98 (d, J=8.0Hz,
2H), 7.68 (d, J=8.5Hz, 1H), 7.60 (t, J=7.5Hz, 1H), 7.30 (t, J=7.5Hz, 1H)13C NMR
(125.4MHz,DMSO-d6): δ 142.3,141.2,140.4,138.5,133.2,129.6,129.1,128.6 (d, J=
31.9Hz), 128.4,125.5 (q, J=3.6Hz), 124.3 (d, J=271.1), 121.6,120.7,119.6,114.6,
112.3。
Embodiment 12
Tryptamines and 2- naphthalene methanol prepare 1- (2- naphthalene)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 2- naphthalene methanol (0.0949g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 69%.1H NMR(500MHz,DMSO-d6): δ 11.73 (br s, 1H), 8.61 (s, 1H), 8.54 (d, J=
5.5Hz, 1H), 8.31 (d, J=8.0Hz, 1H), 8.22 (d, J=8.5Hz, 1H), 8.17 (d, J=5.5Hz, 1H), 8.14 (d,
J=8.5Hz, 2H), 8.04 (d, J=9.0Hz, 1H), 7.71 (d, J=8.0Hz, 1H), 7.64-7.59 (m, 3H), 7.30 (t, J
=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ142.0,141.1,138.4,135.7,133.3,132.9,
132.8,129.3,128.7,128.2,128.1,127.55,127.5,126.6,126.4,126.3.121.6,120.9,
119.5,113.9,112.4。
Embodiment 13
Tryptamines and 1- naphthalene methanol prepare 1- (1- naphthalene)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 1- naphthalene methanol (0.0949g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 64%.1H NMR(500MHz,DMSO-d6): δ 11.19 (br s, 1H), 8.54 (d, J=5.0Hz, 1H),
8.31 (d, J=8.0Hz, 1H), 8.22 (d, J=5.0Hz, 1H), 8.12 (d, J=8.5Hz, 1H), 8.08 (d, J=8.5Hz,
1H), 7.78 (d, J=7.0Hz, 1H), 7.72 (dd, J1=7.5Hz, J2=13.0Hz, 2H), 7.57 (t, J=7.5Hz, 1H),
7.52 (t, J=6.5Hz, 2H), 7.45 (t, J=7.5Hz, 1H), 7.27 (t, J=6.5Hz, 1H)13C NMR(125.4MHz,
DMSO-d6):δ142.7,140.9,137.9,135.6,134.6,133.6,131.2,128.6,128.5,128.3,128.1,
127.5,126.3,126.0,125.6,125.5,121.7,120.8,119.4,113.9,112.2。
Embodiment 14
Tryptamines and 3- pyridinemethanol prepare 1- (3- pyridine)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 3- pyridinemethanol (0.0655g,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 80%.1H NMR(500MHz,DMSO-d6): δ 11.78 (br s, 1H), 9.29 (s, 1H), 8.76 (d, J=
3.0Hz, 1H), 8.54 (d, J=5.0Hz, 1H), 8.45 (d, J=7.5Hz, 1H), 8.30 (d, J=8.0Hz, 1H), 8.19 (d,
J=5.0Hz, 1H), 7.70 (d, J=8.5Hz, 1H), 7.66 (dd, J1=4.5Hz, J2=8.0Hz, 1H), 7.61 (t, J=
7.5Hz, 1H), 7.31 (t, J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ149.3,149.0,141.2,
139.3,138.5,135.8,133.9,133.3,129.4,128.3,123.8,121.6,120.7,119.6,114.4,
112.4。
Embodiment 15
Tryptamines and 2- pyridinemethanol prepare 1- (2- pyridine)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 2- pyridinemethanol (0.0579ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 65%.1H NMR(500MHz,DMSO-d6): δ 11.98 (br s, 1H), 8.91 (d, J=5.0Hz, 1H),
8.66 (d, J=8.0Hz, 1H), 8.52 (d, J=5.0Hz, 1H), 8.30 (d, J=8.0Hz, 1H), 8.25 (d, J=5.0Hz,
1H), 8.05 (t, J=7.5Hz, 1H), 7.91 (d, J=8.0Hz, 1H), 7.61 (t, J=7.5Hz, 1H), 7.53 (t, J=
6.5Hz, 1H), 7.30 (t, J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ157.1,148.7,140.9,
138.1,137.7,137.2,133.5,129.9,128.3,123.3,121.6,120.8,120.3,119.5,115.6,
112.8。
Embodiment 16
Tryptamines and 2- thenyl alcohol prepare 1- (2- thiophene)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), 2- thenyl alcohol (0.0568ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 70%.1H NMR(500MHz,DMSO-d6): δ 11.53 (br s, 1H), 8.38 (d, J=5.0Hz, 1H),
8.27 (d, J=7.5Hz, 1H), 8.14 (d, J=3.5Hz, 1H), 8.10 (d, J=5.0Hz, 1H), 7.77-7.74 (m, 2H),
7.61 (t, J=7.5Hz, 1H), 7.36 (t, J=3.5Hz, 1H), 7.30 (t, J=7.5Hz, 1H)13C NMR(125.4MHz,
DMSO-d6):δ143.6,141.2,138.0,136.5,130.8,129.7,128.4,128.3,128.0,125.7,121.5,
120.7,119.9,113.9,112.6。
Embodiment 17
Tryptamines and cinnamyl alcohol prepare 1- (cinnamyl)-B-carboline
It is sequentially added in tubular reactor tryptamines (0.0801g, 0.5mmol), cinnamyl alcohol (0.0808g, 1.2equiv.),
TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute gas tube sealing three times
Oxygen stirs lower reaction for 24 hours then at 80 DEG C.After TLC monitors fully reacting, product is purified with pillar layer separation, separation yield
58%.1H NMR(500MHz,DMSO-d6): δ 11.92 (br s, 1H), 8.40 (d, J=5.0Hz, 1H), 8.25 (d, J=
8.0Hz, 1H), 8.06-8.03 (m, 2H), 7.91 (d, J=15.5Hz, 1H), 7.81 (d, J=8.0Hz, 1H), 7.68 (d, J=
8.0Hz, 1H), 7.59 (t, J=7.5Hz, 1H), 7.49 (t, J=7.5Hz, 2H), 7.37 (t, J=7.5Hz, 1H), 7.28 (t,
J=7.5Hz, 1H)13C NMR(125.4MHz,DMSO-d6):δ140.5,139.0,138.3,136.8,134.1,131.5,
128.8,128.5,128.2,127.0,123.3,121.8,120.9,119.4,113.7,111.8。
Embodiment 18
5- methoxytryptamine and benzyl alcohol prepare 1- phenyl -6- methoxy-p-carboline
It is sequentially added in tubular reactor 5- methoxytryptamine (0.0951g, 0.5mmol), benzyl alcohol (0.0621ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 82%.1H NMR(500MHz,DMSO-d6): δ 11.38 (br s, 1H), 8.45 (d, J=5.0Hz, 1H),
8.11 (d, J=5.5Hz, 1H), 8.07 (d, J=8.0Hz, 2H), 7.83 (d, J=2.5Hz, 1H), 7.64-7.59 (m, 3H),
7.53 (t, J=7.5Hz, 1H), 7.23 (dd, J1=2.5Hz, J2=8.5Hz, 1H), 3.90 (s, 3H)13C NMR
(125.4MHz,DMSO-d6):δ153.5,142.2,138.5,137.7,135.9,133.5,129.0,128.6,128.4,
128.3,121.1,118.2,113.9,113.2,103.3,55.6。
Embodiment 19
6- methoxytryptamine and benzyl alcohol prepare 1- phenyl -7- methoxy-p-carboline
It is sequentially added in tubular reactor 6- methoxytryptamine (0.0951g, 0.5mmol), benzyl alcohol (0.0621ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 73%.1H NMR(500MHz,DMSO-d6): δ 11.43 (br s, 1H), 8.42 (d, J=5.5Hz, 1H),
8.13 (d, J=8.5Hz, 1H), 8.04-7.98 (m, 3H), 7.62 (t, J=7.5Hz, 2H), 7.52 (t, J=7.5Hz, 1H),
7.12(s,1H),6.89(dd,J1=2.5Hz, J2=9.0Hz, 1H), 3.88 (s, 3H)13C NMR(125.4MHz,DMSO-
d6):δ160.2,142.7,141.4,138.6,138.5,133.1,129.4,128.6,128.3,128.2,122.4,114.5,
113.1,109.3,95.1,55.2。
Embodiment 20
5-methyltryptamine hydrochloride and benzyl alcohol prepare 1- phenyl -6- methyl-ss-carboline
5-methyltryptamine hydrochloride (0.1054g, 0.5mmol), benzyl alcohol are sequentially added in tubular reactor
(0.0621ml, 1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid
(0.5ml) substitutes gas tube sealing oxygen three times, then at 80 DEG C, stirs lower reaction for 24 hours.After TLC monitors fully reacting, product is used
Pillar layer separation purification, separation yield 75%.1H NMR(500MHz,DMSO-d6): δ 11.41 (br s, 1H), 8.44 (d, J=
5.0Hz, 1H), 8.07-8.03 (m, 4H), 7.61 (t, J=7.5Hz, 2H), 7.56-7.51 (m, 2H), 7.38 (d, J=
8.5Hz,1H),2.49(s,3H).13C NMR(125.4MHz,DMSO-d6):δ142.0,139.4,138.4,138.1,133.2,
129.6,128.9,128.6,128.4,128.3,128.2,121.0,120.9,113.7,112.1,21.0。
Embodiment 21
6- flutamine and benzyl alcohol prepare the fluoro- B-carboline of 1- phenyl -7-
It is sequentially added in tubular reactor 6- flutamine (0.0891g, 0.5mmol), benzyl alcohol (0.0621ml,
1.2equiv.), TEMPO (0.0790g, 100mol%), TBN (0.0586ml, 100mol%) and glacial acetic acid (0.5ml), substitute
Tube sealing oxygen reacts for 24 hours under stirring gas then at 80 DEG C three times.After TLC monitors fully reacting, product is mentioned with pillar layer separation
It is pure, separation yield 70%.1H NMR(500MHz,DMSO-d6): δ 11.66 (br s, 1H), 8.48 (d, J=5.0Hz, 1H),
8.30(dd,J1=6.0Hz, J2=9.0Hz, 1H), 8.10 (d, J=5.0Hz, 1H), 8.02 (d, J=7.0Hz, 2H), 7.62
(t, J=7.5Hz, 2H), 7.53 (t, J=7.0Hz, 1H), 7.36 (dd, J1=2.0Hz, J2=9.5Hz, 1H), 7.21 (td, J1
=9.5Hz, J2=2.0Hz, 1H)13C NMR(125.4MHz,DMSO-d6): δ 162.5 (d, J=241.3Hz), 142.1,
141.8 (d, J=13.3Hz), 138.6,138.2,133.6 (d, J=1.9Hz), 128.9,128.7,128.5,128.3,
123.3 (d, J=10.9Hz), 117.6,113.6,107.9 (d, J=24.6Hz), 98.4 (d, J=26.1Hz).
Embodiment 22
5- chloramine and benzyl alcohol prepare the chloro- B-carboline of 1- phenyl -6-
It is sequentially added in tubular reactor 5- chloramine (0.1156g, 0.5mmol), benzyl alcohol (0.0621ml,
1.2equiv.), TEMPO (0.0395g, 50mol%), TBN (0.0293ml, 50mol%) and glacial acetic acid (0.5ml), substitute gas
Tube sealing oxygen three times stirs lower reaction for 24 hours then at 80 DEG C.After TLC monitors fully reacting, product is purified with pillar layer separation,
Separation yield 47%.1H NMR(500MHz,DMSO-d6): δ 11.67 (br s, 1H), 8.49 (d, J=5.0Hz, 1H), 8.41
(d, J=2.0Hz, 1H), 8.18 (d, J=5.0Hz, 1H), 8.03 (d, J=7.0Hz, 1H), 7.67 (d, J=9.0Hz, 1H),
7.63 (t, J=7.0Hz, 1H), 7.58-7.52 (m, 2H)13C NMR(125.4MHz,DMSO-d6):δ142.6,139.5,
138.6,138.1,133.5,128.7,128.6,128.3,128.0,123.8,122.1,121.1,114.1,113.9。
Above-described embodiment is served only for that invention is further explained to specific descriptions of the invention, should not be understood as
Limiting the scope of the present invention, the technician of this field make the present invention according to the content of foregoing invention some non-
The modifications and adaptations of essence are fallen within the scope of protection of the present invention.
Claims (4)
1. a kind of green synthesis method of B-carboline heterocyclic compound, using alcohol compound as raw material, it is characterised in that:
100mol% catalyst TEMPO and 100mol% catalyst TBN catalysis under, using acetic acid as solvent, color aminated compounds and alcohol exist
The one pot of tandem reaction reoxidized under oxygen through oxidative condensation cyclisation obtains B-carboline heterocyclic compound, reaction temperature 40-120
DEG C, the reaction time is 6-48 hours, reaction equation are as follows:
Wherein:
R1It is hydrogen；
R2It is phenyl, cinnamyl, allyl or the fatty alkyl that functional group is substituted in 2-, 3- or 4-.
2. a kind of green synthesis method of B-carboline heterocyclic compound according to claim 1, it is characterised in that: described to urge
Agent TEMPO and catalyst TBN is nontransition metal catalyst, and catalyst TEMPO is 2,2,6,6- tetramethyl piperidine nitrogen oxygen
Compound, catalyst TBN are nitrite tert-butyls.
3. a kind of green synthesis method of B-carboline heterocyclic compound according to claim 1, it is characterised in that: in oxygen
The temperature that reaction carries out selects 40-80 DEG C.
4. a kind of green synthesis method of B-carboline heterocyclic compound according to claim 1, it is characterised in that: when reaction
Between select 12-24 hours.
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