CN110372722A - A method of synthesis sulfur-bearing nitrogen bis-heterocyclic compound - Google Patents
A method of synthesis sulfur-bearing nitrogen bis-heterocyclic compound Download PDFInfo
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- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
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Abstract
The invention discloses a kind of methods of bis-heterocyclic compounds for synthesizing sulfur-bearing nitrogen, belong to technical field of organic chemistry.Using Benzazole compounds 1, o-bromobenzaldehye class compound 2 and sulphur simple substance as raw material, in the presence of sodium carbonate, heating reaction obtains the bis-heterocyclic compound 3 of polysubstituted sulfur-bearing nitrogen.The present invention utilize Benzazole compounds, 2- bromobenzaldehyde class compound and sulphur simple substance, under conditions of no metal one step can the polysubstituted sulfur-bearing nitrogen of constructing function bis-heterocyclic compounds, method is simple, and wide application range of substrates is general.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of side for synthesizing sulfur-bearing nitrogen bis-heterocyclic compound
Method.
Background technique
Heterocyclic compound is widely present in nature, and important compound majority related with biology is heterocyclic compound,
Such as nucleic acid, certain vitamins, antibiotic, hormone, pigment and alkaloid etc..In addition, the heterocyclic compound with various performances
It is important composition ingredient in drug, some of them can make drug, Insecticides (tech) & Herbicides (tech), dyestuff, plastics etc..
Sulfur-bearing or azacyclic molecules and sulfur-bearing nitrogen bis-heterocyclic compounds are important heterocyclic compound, can be used for producing
Various dyestuffs, fragrance, the plastics of resistance to rapid heat cycle, high activity solvent, stimulin, insecticide, brightener, cosmetics and bioactivation
The drugs such as substance and vitamin, anesthetic and antibiotic.Wherein Derivative of thiadiazole is even more to have multiple biological activities, is removed
A variety of drug effects such as antibacterial, antiviral, anti-inflammatory, hypoglycemic, anticancer activity are also gradually attract attention.Exactly
Due to its potential application foreground in each field, so as to cause the attention and concern of scientist, and this is carried out a large amount of
Research, achieves numerous valuable scientific achievements.
It is more or less in the method or technique of traditional synthesis sulfur-bearing nitrogen bis-heterocyclic compounds that there are many defects, examples
Such as: (1) it is with high costs using expensive organometallic reagent, it is unfavorable for industrialized production；(2) need high temperature, multistep anti-
It answers, condition is harsh, limits the practical application of reaction；(3) yield, selectivity are still not high enough, be further improved etc..
Therefore, the synthesis technology for developing sulfur-bearing nitrogen bis-heterocyclic compounds easy to operate, at low cost, high income, becomes
Where the target of vast researcher, not only there is urgent researching value, it may have good prospects for commercial application.
Summary of the invention
In order to overcome many defects as indicated above, and then seek the simplicity that synthesis replaces sulfur-bearing nitrogen bis-heterocyclic compounds
Method, the invention discloses a kind of methods of simple, effective, convenient synthesis sulfur-bearing nitrogen bis-heterocyclic compound.From simple and easy to get
Reagent sets out, and via easy operating procedure, under mild reaction conditions, the double heterocycles of sulfur-bearing nitrogen can be obtained by single step reaction
The method of class compound avoids the drawbacks such as prior synthesizing method raw material complexity, condition harshness, successfully synthesizes multiple functionalized contain
The bis-heterocyclic compound of sulphur nitrogen.
A method of the bis-heterocyclic compound of synthesis sulfur-bearing nitrogen, the technical solution adopted by the present invention, which is characterized in that
Including following operation: by Benzazole compounds 1, o-bromobenzaldehye class compound 2 and sulphur simple substance, in the presence of an inorganic base, in machine
Reaction is heated in solvent, obtains the bis-heterocyclic compound 3 of sulfur-bearing nitrogen, reaction equation is as follows:
Wherein: Ar1For substituted aryl, substituent group is selected from hydrogen, methyl, methoxyl group or halogen；The Ar2Substituted aryl is miscellaneous
Aryl, substituent group are selected from hydrogen, methyl, halogen or trifluoromethyl.
More specifically, compound 1 be indoles, 4- methyl indol, 5- methyl indol, 6- methyl indol, 4- methoxy-Indole,
5- methoxy-Indole, 7- methoxy-Indole, 4- chloro-indole, 5- chloro-indole, 6- chloro-indole, 7- chloro-indole, 5- fluoro indole, 6- fluorine Yin
Diindyl, 4- bromo indole, 5- bromo indole, 7- bromo indole, etc.；Compound 2 is 2- bromobenzaldehyde, the bromo- 4- tolyl aldehyde of 2-, 2- bromo-
The bromo- 5- trifluoromethylated benzaldehyde of 5- fluorobenzaldehyde, 2-, the bromo- 3- pyridine carboxaldehyde of 2-, the bromo- 2- naphthaldehyde of 1-, etc..
Further, in the above-mentioned technical solutions, the inorganic base be selected from sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate,
Any one in sodium bicarbonate.It is preferred that inorganic base is sodium carbonate.
Further, in the above-mentioned technical solutions, when the heating is reacted, reaction temperature is 100-140 DEG C；Further
Ground, optimization temperature are 130 DEG C.
Further, in the above-mentioned technical solutions, the reaction dissolvent is selected from DMF, DMAC, DMSO；Further, excellent
Selecting solvent is DMF.
Further, in the above-mentioned technical solutions, the Benzazole compounds 1, adjacent bromine benzaldehyde compound 2, sulphur simple substance
It is 1:3:3:4 with alkali molar ratio, under the conditions of the ratio, reaction can reach optimum response effect.
Further, in the above-mentioned technical solutions, reaction preferably carries out under nitrogen protection.
Further, in order to better understand the present invention, using indoles 1a and o-bromobenzaldehye 2a as substrate, sodium carbonate is nothing
When machine alkali, DMF are solvent, for progress condition optimizing: in a nitrogen atmosphere, by 0.25mmol indoles 1a, 0.75mmol 2- bromine
Benzaldehyde 2a, 0.75mmol sulphur simple substance, 1.0mmol sodium carbonate and 2mL DMF are added sequentially in Schlenk reaction tube, in IKA
Heated at constant temperature is stirred to react 20h to 130 DEG C in (constant temperature blender with magnetic force).After reaction, it is cooled to room temperature, with distillation water quenching
It goes out.Then it is extracted with ethyl acetate (3 × 20mL).Organic layer is merged, the dry organic phase of anhydrous sodium sulfate filters and vacuum is dense
Contracting.Pass through the isolated purified product 3a of column chromatography, yield 71%.
It is as a result as follows when only changing following reaction condition when other conditions are constant:
1) when sulphur simple substance dosage being adjusted to 1.0mmol and 0.50mmol, separation yield is respectively 41% and 24%.
2) inorganic base is changed to potassium carbonate, lithium carbonate, cesium carbonate and sodium bicarbonate, separation yield is respectively 50%,
24%, 28% and 48%.
3) when using other reaction dissolvents such as DMSO, DMAC, yield is respectively 43% and 57%.
4) when reaction temperature is 110 DEG C and 140 DEG C, reaction yield is respectively corresponded as 50% and 56%.
For a further understanding of reaction mechanism, following comparative test is done, reaction equation is expressed as follows:
According to the above reaction experiment, thus it is speculated that reaction mechanism are as follows:
Invention beneficial effect
1) the method for the present invention experimental procedure is few, and technical difficulty is low, and mild condition is easily operated.Inventive process avoids
Using the process of multistep reaction, reacting a step be can be completed.
2) present invention is synthesized by the oxidative coupling reaction of Benzazole compounds, 2- bromobenzaldehyde class compound and sulphur simple substance
A kind of bis-heterocyclic compounds of novel sulfur-bearing nitrogen.
Specific embodiment:
Above content of the invention is described in further details by following instance, but this should not be interpreted as this hair
The range of bright above-mentioned theme is only limitted to following instance, and all technologies realized based on above content of the present invention belong to model of the invention
It encloses.
Embodiment 1-16
In a nitrogen atmosphere, by 0.25mmol Benzazole compounds 1a-p, 0.75mmol o-bromobenzaldehye class compound 2a,
0.75mmol sulphur simple substance, 1.0mmol sodium carbonate and 2mLDMF are added sequentially in Schlenk reaction tube, in temperature constant magnetic stirring
In device, heated at constant temperature is stirred to react 20h to 130 DEG C.After reaction, it is cooled to room temperature, is quenched with distilled water.Then acetic acid is used
Ethyl ester (3 × 20mL) extraction.Organic layer is merged, the dry organic phase of anhydrous sodium sulfate, the crude product column chromatography for separation rotated
Obtain sterling 3a-3p.As a result as shown in the table:
Standard condition:1a (1equiv, 0.25mmol), 2a (3equiv, 0.75mmol), S8(3equiv,
0.75mmol), Na2CO3(4equiv, 1.0mmol), DMF (2mL), N2, 130 DEG C, 20h.
Compound 3a-3p characterize data is as follows:
Thiochromeno [2,3-b] indole 3a, 71%；1H NMR (600MHz, CDCl3) δ 8.20 (s, 1H), 7.92
(d, J=6.0Hz, 1H), 7.79 (d, J=6.0Hz, 1H), 7.70 (t, J=6.0Hz, 2H), 7.50 (q, J=8.0Hz, 2H),
7.43 (t, J=9.0Hz, 1H), 7.27 (t, J=9.0Hz, 1H)13C NMR (151MHz, CDCl3) δ 160.9,154.0,
132.3,131.5,130.4,130.1,128.6,128.6,125.7,125.6,125.2,124.7,121.4,119.7,
117.6.HRMS, calculated for C15H10NS(M+H+): 236.0528, found:236.0528.
10-methylthiochromeno [2,3-b] indole 3b, 57%；1H NMR (600MHz, CDCl3)δ8.28
(s, 1H), 7.86 (d, J=6.0Hz, 1H), 7.74 (d, J=12.0Hz, 1H), 7.58 (d, J=12.0Hz, 1H), 7.53 (t, J
=6.0Hz, 1H), 7.47 (t, J=9.0Hz, 1H), 7.42 (t, J=9.0Hz, 1H), 7.07 (d, J=12.0Hz, 1H), 2.76
(s,3H).13C NMR(151MHz,CDCl3)δ161.8,155.0,134.3,133.4,133.3,132.8,129.5,129.3,
127.0,126.6,126.5,126.1,124.8,123.7,116.5,20.4.HRMS,calculated for C16H12NS(M+
H+):250.0685,found:250.0685.
9-methylthiochromeno [2,3-b] indole 3c, 41%；1H NMR(600MHz,CDCl3)δ8.30(d,
J=6.0Hz, 1H), 7.88 (dd, J=12.0,6.0Hz, 1H), 7.79 (d, J=12.0Hz, 2H), 7.62 (d, J=6.0Hz,
1H), 7.57 (t, J=9.0Hz, 1H), 7.50 (t, J=6.0Hz, 1H), 7.35 (d, J=12.0Hz, 1H), 2.51 (s, 3H)
.13C NMR(151MHz,CDCl3)δ161.1,153.1,133.4,132.5,132.1,131.5,130.7,130.7,129.5,
126.7,126.7,126.1,125.9,121.2,118.2,21.5.HRMS,calculated for C16H12NS(M+H+):
250.0685,found:250.0685.
8-methylthiochromeno [2,3-b] indole 3d, 55%；1H NMR(600MHz,CDCl3)δ8.26(d,
J=12.0Hz, 1H), 7.86 (td, J=12.0,6.0Hz, 2H), 7.78 (t, J=12.0Hz, 1H), 7.57-7.48 (m, 3H),
7.12 (t, J=9.0Hz, 1H), 2.53 (d, J=6.0Hz, 3H)13C NMR(151MHz,CDCl3)δ162.1,155.4,
140.3,133.0,132.4,131.3,130.1,129.3,126.8,126.7,126.2,123.6,123.1,120.5,
119.1,22.3.HRMS,calculated for C16H12NS(M+H+):250.0685,found:250.0685.
10-methoxythiochromeno [2,3-b] indole 3e, 59%；1H NMR(600MHz,CDCl3)δ8.47
(s, 1H), 7.78 (d, J=6.0Hz, 1H), 7.66 (d, J=6.0Hz, 1H), 7.42 (td, J=9.0,6.0Hz, 1H), 7.37
(q, J=8.0Hz, 2H), 7.28 (d, J=12.0Hz, 1H), 6.70 (d, J=6.0Hz, 1H), 3.97 (s, 3H)13C NMR
(151MHz,CDCl3)δ162.0,156.8,156.3,133.5,132.6,132.5,130.5,130.4,129.1,127.4,
126.6,126.1,113.6,111.8,104.5,55.5.HRMS,calculated for C16H12NOS(M+H+):
266.0634,found:266.0634.
9-methoxythiochromeno [2,3-b] indole 3f, 93%；1H NMR(600MHz,CDCl3)δ8.24
(s, 1H), 7.85 (d, J=6.0Hz, 1H), 7.75 (d, J=12.0Hz, 1H), 7.61 (d, J=6.0Hz, 1H), 7.55 (td, J
=9.0,6.0Hz, 1H), 7.48 (td, J=9.0,6.0Hz, 2H), 7.10 (dd, J=12.0,6.0Hz, 1H), 3.90 (s,
3H).13C NMR(151MHz,CDCl3)δ160.0,156.1,149.4,133.5,132.6,131.6,131.1,129.6,
126.7,126.7,126.5,126.1,119.0,116.5,105.7,56.0.HRMS,calculated for C16H12NOS(M
+H+):266.0634,found:266.0634.
7-methoxythiochromeno [2,3-b] indole 3g, 91%；1H NMR(600MHz,CDCl3)δ8.35
(s, 1H), 7.88 (d, J=6.0Hz, 1H), 7.79 (d, J=6.0Hz, 1H), 7.62 (d, J=6.0Hz, 1H), 7.56 (t, J=
9.0Hz, 1H), 7.49 (t, J=9.0Hz, 1H), 7.25 (d, J=6.0Hz, 1H), 7.05 (d, J=12.0Hz, 1H), 4.05
(s,3H).13C NMR(151MHz,CDCl3)δ160.0,149.9,143.8,133.9,132.6,132.2,131.6,129.7,
127.3,126.8,126.6,126.2,123.4,113.4,111.4,55.9.HRMS,calculated for C16H12NOS(M
+H+):266.0634,found:266.0634.
10-chlorothiochromeno [2,3-b] indole 3h, 79%；1H NMR(600MHz,CDCl3)δ8.95
(s, 1H), 7.96 (d, J=12.0Hz, 1H), 7.82 (d, J=6.0Hz, 1H), 7.65 (d, J=12.0Hz, 1H), 7.60 (t, J
=6.0Hz, 1H), 7.53 (t, J=9.0Hz, 1H), 7.46 (t, J=6.0Hz, 1H), 7.28 (d, J=6.0Hz, 1H)13C
NMR(151MHz,CDCl3)δ162.4,156.2,135.3,133.3,133.1,130.2,130.0,129.7,129.4,
126.6,126.6,126.4,123.4,122.6,117.2.HRMS,calculated for C15H9ClNS(M+H+):
270.0139,found:270.0139.
9-chlorothiochromeno [2,3-b] indole 3i, 67%；1H NMR(600MHz,CDCl3)δ8.40(s,
1H), 7.99 (s, 1H), 7.96 (d, J=6.0Hz, 1H), 7.86 (d, J=6.0Hz, 1H), 7.65 (td, J=9.0,6.0Hz,
2H), 7.57 (td, J=9.0,6.0Hz, 1H), 7.51 (dd, J=12.0,6.0Hz, 1H)13C NMR(151MHz,CDCl3)δ
162.2,153.4,133.8,132.9,132.4,130.7,130.2,129.6,128.2,127.1,126.9,126.5,
126.5,120.8,119.5.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
8-chlorothiochromeno [2,3-b] indole 3j, 62%；1H NMR(600MHz,CDCl3)δ8.32(s,
1H), 7.91 (dd, J=12.0,6.0Hz, 1H), 7.87 (d, J=12.0Hz, 1H), 7.82 (d, J=6.0Hz, 1H), 7.67
(s, 1H), 7.61 (t, J=6.0Hz, 1H), 7.54 (t, J=6.0Hz, 1H), 7.25 (s, 1H)13C NMR(151MHz,
CDCl3)δ163.3,155.7,135.3,133.4,132.8,131.9,130.5,130.0,126.9,126.6,124.1,
122.7,121.3,118.9.HRMS,calculated for C15H9ClNS(M+H+):270.0139,found:270.0139.
9-fluorothiochromeno [2,3-b] indole 3k, 49%；1H NMR(600MHz,CDCl3)δ8.34(s,
1H), 7.92 (dd, J=12.0,6.0Hz, 1H), 7.83 (d, J=6.0Hz, 1H), 7.68-7.64 (m, 2H), 7.62 (td, J=
9.0,6.0Hz, 1H), 7.54 (td, J=9.0,6.0Hz, 1H), 7.25 (d, J=6.0Hz, 1H)13C NMR(151MHz,
CDCl3)δ161.6,160.2,158.6,151.2,133.8,132.8,132.2,131.1,131.1,130.1,126.9,
126.4,126.4,119.3,119.2,116.8,116.7,107.6,107.4.HRMS,calculated for C15H9FNS(M
+H+):254.0434,found:254.0434.
8-fluorothiochromeno [2,3-b] indole 3l, 67%；1H NMR(600MHz,CDCl3)δ8.35(s,
1H), 7.95 (t, J=6.0Hz, 2H), 7.85 (d, J=12.0Hz, 1H), 7.63 (t, J=9.0Hz, 1H), 7.56 (t, J=
6.0Hz, 1H), 7.41 (dd, J=12.0,6.0Hz, 1H), 7.04 (td, J=9.0,6.0Hz, 1H)13C NMR(151MHz,
CDCl3)δ165.0,163.7,163.3,156.5,156.4,133.0,132.6,130.9,130.6,129.7,126.8,
126.6,126.5,121.8,121.6,121.5,110.0,109.9,105.9,105.8.HRMS,calculated for
C15H9FNS(M+H+):254.0434,found:254.0434.7-chlorothiochromeno[2,3-b]indole 3m,
84%；1H NMR(600MHz,CDCl3) δ 8.30 (s, 1H), 7.92 (t, J=9.0Hz, 2H), 7.82 (d, J=6.0Hz, 1H),
7.60 (t, J=6.0Hz, 1H), 7.54 (t, J=9.0Hz, 1H), 7.39 (dd, J=12.0,6.0Hz, 1H), 7.02 (t, J=
9.0Hz,1H).13C NMR(151MHz,CDCl3)δ162.7,151.5,134.0,132.9,131.4,130.2,129.6,
127.6,127.0,126.5,126.5,123.6,123.1,119.2.HRMS,calculated for C15H9ClNS(M+H+):
270.0139,found:270.0139.
10-bromothiochromeno [2,3-b] indole 3n, 51%；1H NMR(600MHz,CDCl3)δ9.09(s,
1H), 7.94 (d, J=6.0Hz, 1H), 7.78 (d, J=12.0Hz, 1H), 7.68 (d, J=6.0Hz, 1H), 7.57 (td, J=
9.0,6.0Hz, 1H), 7.49 (td, J=9.0,6.0Hz, 1H), 7.44 (d, J=6.0Hz, 1H), 7.38 (t, J=9.0Hz,
1H),13C NMR(151MHz,CDCl3)δ162.4,156.5,135.1,133.5,133.1,130.9,130.1,129.9,
126.6,126.6,126.4,126.4,124.3,117.8,117.5.HRMS,calculated for C15H9BrNS(M+H+):
313.9634,found:313.9634.
9-bromothiochromeno [2,3-b] indole 3o, 52%；1H NMR(600MHz,CDCl3)δ8.43(s,
1H), 8.16 (s, 1H), 7.98 (d, J=6.0Hz, 1H), 7.88 (d, J=6.0Hz, 1H), 7.66 (td, J=9.0,6.0Hz,
2H), 7.62 (d, J=12.0Hz, 1H), 7.58 (t, J=6.0Hz, 1H)13C NMR(151MHz,CDCl3)δ134.8,
133.9,132.9,132.5,132.4,130.6,130.2,127.6,126.9,126.5,126.0,125.4,123.8,
120.0,115.8.HRMS,calculated for C15H9BrNS(M+H+):313.9634,found:313.9634.
7-bromothiochromeno [2,3-b] indole 3p, 88%；1H NMR(600MHz,DMSO-d6)δ9.13
(s, 1H), 8.23 (t, J=12.0Hz, 2H), 8.16 (d, J=6.0Hz, 1H), 7.81 (t, J=9.0Hz, 1H), 7.77 (d, J
=6.0Hz, 1H), 7.72 (t, J=9.0Hz, 1H), 7.30 (t, J=6.0Hz, 1H),13C NMR(151MHz,DMSO-d6)δ
162.1,152.6,135.5,134.0,133.2,132.4,131.4,131.0,128.0,127.6,127.5,126.7,
124.3,121.3,111.9.HRMS,calculated for C15H9BrNS(M+H+):313.9634,found:313.9634.
The present embodiment 1-14 has studied a variety of phenyl ring and is replaced and the indoles of heterocyclic substituted by electron-withdrawing group and electron-donating group
The coupling reaction of class compound, 2- bromobenzaldehyde and sulphur simple substance.According to the above experiment it can be found that the reaction is to the alkane of phenyl ring
The substituent groups such as base, methoxyl group, chloro, bromo, fluoro and heterocycle have extensive substrate adaptability, have obtained higher yields
Corresponding target product.
Embodiment 17-21
In a nitrogen atmosphere, by 0.25mmol indoles 1a, 0.75mmol o-bromobenzaldehye class compound 2b-g, 1.0mmol
Sulphur simple substance, 1.0mmol sodium carbonate and 2mLDMF are added sequentially in Schlenk reaction tube, in constant temperature blender with magnetic force, constant temperature
It is heated to 130 DEG C and is stirred to react 20h.After reaction, it is cooled to room temperature, is quenched with distilled water.Then with ethyl acetate (3 ×
20mL) extract.Organic layer is merged, the dry organic phase of anhydrous sodium sulfate, the crude product column chromatography for separation rotated obtains sterling
3q-3u.As a result as shown in the table:
Reaction condition:1a (1equiv, 0.25mmol), 2b-2g (3equiv, 0.75mmol), S8
(4equiv, 1.0mmol), Na2CO3(4equiv, 1.0mmol), DMF (2mL), 130 DEG C, 12h.
Compound 3q-3u characterize data is as follows:
Benzo [7,8] thiochromeno [2,3-b] indole 3q, 33%；1H NMR(600MHz,CDCl3)δ8.49
(t, J=9.0Hz, 2H), 8.06 (d, J=12.0Hz, 1H), 7.92 (d, J=6.0Hz, 1H), 7.86 (d, J=12.0Hz,
1H), 7.80 (q, J=8.0Hz, 2H), 7.70-7.64 (m, 2H), 7.58 (t, J=6.0Hz, 1H), 7.34 (t, J=6.0Hz,
1H).13C NMR(151MHz,CDCl3)δ161.0,154.9,133.1,132.6,132.1,131.1,129.7,129.0,
128.9,128.6,127.6,126.8,125.3,124.6,123.1,122.4,121.0,118.7.HRMS,calculated
for C19H12NS(M+H+):286.0685,found:286.0685.
Thiochromeno [2,3-b] indole 3r, 26%；1H NMR(600MHz,CDCl3)δ8.38(s,1H),8.03
(d, J=6.0Hz, 1H), 7.84 (d, J=6.0Hz, 1H), 7.75 (d, J=6.0Hz, 1H), 7.66 (s, 1H), 7.55 (t, J=
6.0Hz,1H),7.36-7.31(m,2H),2.54(s,3H).13C NMR(151MHz,CDCl3)δ161.9,154.9,140.8,
133.7,132.4,131.3,130.7,129.4,127.8,126.9,125.9,122.4,120.6,118.6,21.8.HRMS,
calculated for C16H12NS(M+H+):250.0685,found:250.0685.
2-fluorothiochromeno [2,3-b] indole 3s, 33%；1H NMR(600MHz,CDCl3)δ8.31(s,
1H), 8.03 (d, J=6.0Hz, 1H), 7.80 (t, J=6.0Hz, 1H), 7.74 (d, J=12.0Hz, 1H), 7.63 (dd, J=
12.0,6.0Hz, 1H), 7.58 (t, J=9.0Hz, 1H), 7.39-7.33 (m, 2H)13C NMR(151MHz,CDCl3)δ
162.0,161.5,159.9,155.4,132.4,130.3,129.8,129.7,128.5,128.4,128.3,128.1,
128.1,125.4,122.7,121.1,118.8,118.1,118.0,117.8,117.7.HRMS,calculated for
C15H9FNS(M+H+):254.0434,found:254.0434.
2- (trifluoromethyl) thiochromeno [2,3-b] indole 3t, 33%；1H NMR(600MHz,
CDCl3) δ 8.41 (s, 1H), 8.19 (s, 1H), 8.05 (d, J=12.0Hz, 1H), 7.96 (d, J=6.0Hz, 1H), 7.81 (d,
J=12.0Hz, 1H), 7.77 (d, J=6.0Hz, 1H), 7.60 (t, J=6.0Hz, 1H), 7.38 (t, J=9.0Hz, 1H)13C
NMR(151MHz,CDCl3)δ161.1,155.2,136.9,132.8,130.5,129.8,129.2,129.2,129.2,
127.5,126.7,125.5,125.5,125.4,123.1,121.2,119.0.HRMS,calculated forC16H9F3NS(M
+H+):304.0402,found:304.0402.pyrido[3',2':5,6]thiopyrano[2,3-b]indole 3u,
55%；1H NMR(600MHz,DMSO-d6) δ 8.94 (s, 1H), 8.85 (d, J=6.0Hz, 1H), 8.54 (d, J=12.0Hz,
1H), 8.23 (d, J=6.0Hz, 1H), 7.70 (td, J=12.0,6.0Hz, 2H), 7.59 (t, J=6.0Hz, 1H), 7.40
(td, J=9.0,6.0Hz, 1H),13C NMR(151MHz,DMSO-d6)δ162.4,155.3,154.5,151.3,140.9,
131.6,131.3,130.4,126.0,124.0,123.5,122.6,122.3,119.0.HRMS,calculated for
C16H9F3NS(M+H+):237.0481,found:237.0481.
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (9)
1. a kind of method for synthesizing sulfur-bearing nitrogen bis-heterocyclic compound, which is characterized in that including following operation: by indoles chemical combination
Object 1, o-bromobenzaldehye class compound 2 and sulphur simple substance, in the presence of an inorganic base, heating reaction obtains sulfur-bearing nitrogen in solvent
Bis-heterocyclic compound 3, reaction equation is as follows:
2. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: Ar1To replace virtue
Base, substituent group are selected from hydrogen, methyl, methoxyl group or halogen；The Ar2Substituted aryl or heteroaryl, substituent group be selected from hydrogen, methyl,
Halogen or trifluoromethyl.
3. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: the inorganic base choosing
From any one in sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate, sodium bicarbonate.
4. according to claim 1 or 3 it is described synthesis sulfur-bearing nitrogen bis-heterocyclic compounds methods, it is characterised in that: it is described inorganic
Alkali is selected from sodium carbonate.
5. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: the organic solvent
Selected from DMSO, DMF or DMAC.
6. according to claim 1 or 5 it is described synthesis sulfur-bearing nitrogen bis-heterocyclic compounds methods, it is characterised in that: it is described organic
Solvent is selected from DMF.
7. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: the indoles
Closing object 1, adjacent bromine benzaldehyde compound 2, sulphur simple substance and inorganic base molar ratio is 1:2-4:3-4:4.
8. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: the heating reaction
When, temperature is 100-140 DEG C.
9. synthesizing the method for sulfur-bearing nitrogen bis-heterocyclic compound according to claim 1, it is characterised in that: reaction is protected in nitrogen
Shield is lower to be carried out.
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| JIANMING LIU，等: "Elemental sulfur accelerated the reactivity of the 3-position of indole for the construction of chromeno[2,3-b]indoles", 《ORGANIC CHEMISTRY FRONTIERS》 * |
| 张晓旭，等: "6，11-二氢苯并噻喃并［4，3-b］吲哚类化合物的合成及其抗肿瘤活性", 《合成化学》 * |
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