CN104710430B - A kind of synthetic method of aminocarbazole class compound - Google Patents
A kind of synthetic method of aminocarbazole class compound Download PDFInfo
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- CN104710430B CN104710430B CN201510113421.XA CN201510113421A CN104710430B CN 104710430 B CN104710430 B CN 104710430B CN 201510113421 A CN201510113421 A CN 201510113421A CN 104710430 B CN104710430 B CN 104710430B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
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Abstract
The invention discloses the preparation method of aminocarbazole class compound, belong to organic synthesis field.The method is with Fe (acac)3It is catalyst, hydrazine hydrate is reducing agent, 100 DEG C ~ 180 DEG C reduction azido carbazole compounds prepare aminocarbazole class compound in alcohols solvent.Method is easy, and reaction relaxes easily-controllable, and catalyst amount is less, excellent catalytic effect, accessory substance are few, and reduction efficiency is high, and reduction efficiency is up to more than 86%, and Fe3O4With magnetic, it is easy to clear up；With preferable industrial application value.
Description
Technical field
The present invention relates to a kind of synthetic method of aminocarbazole class compound, belong to organic synthesis field.
Background technology
With heterocyclic chemistry and it is pharmaceutical chemical continue to develop, synthesis and the modification of aminated compounds become increasingly complex.It is folded
Nitrogen base can be incorporated into organic molecule conveniently by inorganic azido compound, be then reduced into by suitable reagent
Amine, it has also become produce a kind of important method of primary amine, be widely applied in organic synthesis.Wherein Azide carbazole chemical combination
It is the important reaction of a class in Synthetic Organic Chemistry that thing is reduced into aminocarbazole class compound.
The common method of Azide carbazole compound reduction is as follows：1. catalytic hydrogenation.Azide carbazole compound is in Pd/
Through H under C catalysis2Reduction can obtain aminocarbazole class compound, but the method has potential safety hazard, and expensive catalyst, it is difficult to
Realize industrialized production；2. sodium borohydride method.The method is gentle due to reaction condition, selectivity extensive use well, but amine
Yield is relatively low to be restricted it.In addition with lithium aluminium hydride reduction method etc., industrialized production is not suitable for, therefore, find a kind of
Convenient and simple easy to operate, the preparation method for being particularly suited for the aminocarbazole analog derivative of more large-scale industrial production seems outstanding
For important.
The content of the invention
Regarding to the issue above, present invention aim at providing, a kind of reduction efficiency is high, is adapted to the ammonia of industrial amplification production
Base carbazole derivates new synthetic method.
To achieve the above object, the present invention is adopted the following technical scheme that：
Successively by hydrazine hydrate, catalyst Fe (acac) that nitrine carbazole compound, mass percent are 80%3, alcohols it is molten
Agent is put into reaction bulb, and control temperature is reacted at 100 DEG C ~ 180 DEG C, and alcohols solvent is removed after completion of the reaction, is added after cooling
Water-insoluble solvent, after being sufficiently mixed, filters partial solvent, and residue recrystallization can obtain aminocarbazole class chemical combination produce
Product.
Reaction equation is as follows：
Wherein：R1It is H, C1-C5Direct-connected or branched alkyl；R2It is H, C1-C5Direct-connected or branched alkyl；Rn、RmRespectively H,
Cl、Br；Two R2It is identical or different.
Preferred scope：R1It is H, C1-C5Straight chained alkyl；R2It is H, C1-C2Alkyl；Rn、RmRespectively H, Cl, Br；Two R2Phase
Together.
Above-mentioned nitrine carbazole compound, hydrazine hydrate, catalyst Fe (acac)3Mol ratio is 1：1~2：0.01~0.05；On
State nitrine carbazole compound, the mass ratio of alcohols solvent is 1：1 ~10；Water-insoluble solvent is with the mass ratio of alcohols solvent
2~5：1.
Above-mentioned alcohols solvent is monohydric alcohol, dihydroxylic alcohols of C2-10 of C4-10 etc., and its boiling point is 100 DEG C ~ 200 DEG C；It is excellent
Select butanol or ethylene glycol.
Preferably 140 DEG C ~ 160 DEG C of above-mentioned reaction temperature.
Water-insoluble solvent described above is the one kind in esters, aromatic hydrocarbons, halogenated hydrocarbons, alkane；Ethyl acetate, oil
Ether.
Beneficial effects of the present invention are：（1）Selected alcohols solvent has higher, can make catalyst Fe (acac)3
Fe is decomposed at ambient pressure3O4, catalyst amount is less, excellent catalytic effect, accessory substance are few, and reduction efficiency is high, and reduction efficiency reaches
86 more than %, and Fe3O4With magnetic, it is easy to clear up；（2）The synthetic method have reaction gentle, high income, safety and environmental protection,
The advantages of not high to equipment requirement, with preferable industrial applications value.
Specific implementation method
Synthetic method of the present invention is described in further detail below by way of several preferred embodiments, but protection of the invention
Scope is not limited thereto.
Embodiment 1
Successively by 21g 3- nitrine carbazole, the hydrazine hydrate that 5 mL mass percents are 80%, 0.13 g catalyst Fes
(acac)3, 50 mL n-butanols be put into reaction bulb, be heated to reflux reacting after 3h finishing, remove n-butanol, cooling, mixture adds
Enter 100 mL ethyl acetate, be sufficiently mixed, filter, remove part ethyl acetate solvent, residue recrystallization obtains 16 g
White solid 3- aminocarbazole products（Purity 97%, yield 89%）.
1H NMR (400 MHz, CDCl3): δ (ppm) 8.14-8.11 (m, 1H), 7.64–7.62(m, 1H),
7.53-7.51 (m, 1H), 7.39-7.37 (m, 1H), 7.31-7.28 (m, 1H), 6.79-6.77(m, 1H),
6.76-6.75 (m, 1H); 13C NMR (400 MHz, CDCl3): δ (ppm) 145.36, 143.93, 129.96,
123.33, 121.74, 121.49, 119.85, 113.41, 111.16, 107.37, 104.68, 103.06. MS
(EI, m/z) 183。
3- amino -9- amyl group the carbazoles of embodiment 2
Successively by 28 g 3- nitrine -9- amyl groups carbazoles, the hydrazine hydrate that 7 mL mass percents are 80%, 0.16 g catalysis
Agent Fe (acac)3, 40 mL ethylene glycol be put into reaction bulb, control 150 DEG C of temperature, reaction is finished after 3h, removes ethylene glycol, cold
But, mixture adds 100 mL ethyl acetate, is sufficiently mixed, and filters, and removes most of ethyl acetate solvent, residue weight
Crystallization, obtains 23 g white solid 3- amino -9- amyl group carbazole products（Purity 98%, the % of yield 89）.
1H NMR (400 MHz, CDCl3): δ (ppm) 8.19-8.17 (m 1H), 7.61-7.57(m 1H),
7.42-7.38(m 3H), 6.77-6.75(m 2H), 4.16(t 2H), 1,77-1,74(m 2H), 1.31-1.29(m
4H), 0.9(t 3H) ; 13C NMR (400 MHz, CDCl3): δ (ppm)
143.92, 139.85, 128.41, 125.13, 121.47, 119.83, 109.16, 107.37,
104.62, 103.35, 58.31, 29.15, 22.43, 14.17. MS (EI, m/z) 253。
2- amino -7- bromine the carbazoles of embodiment 3
Successively by 29 g 2- nitrine -7- bromines carbazoles, the hydrazine hydrate that 6 mL mass percents are 80%, 0.15 g catalyst
Fe(acac)3, 60 mL ethylene glycol be put into reaction bulb, control 150 DEG C of temperature, reaction is finished after 3h, removes ethylene glycol, cooling,
Mixture adds 100 mL ethyl acetate, is sufficiently mixed, and filters, and removes most of ethyl acetate solvent, and residue is tied again
Crystalline substance, obtains 24 g white solid 2- amino -7- bromine carbazole products（Purity 96%, the % of yield 91）.
1H NMR (400 MHz, CDCl3): δ (ppm) 8.13-8.11 (m, 1H), 7.65-7.63 (m, 1H),
7.51-7.49 (m, 1H), 7.39-7.37 (m, 1H), 7.29-7.28 (m, 2H); 6.77-6.75 (m 2H) 13C
NMR (400 MHz, CDCl3): δ (ppm) 143.91, 141.33, 129.92, 128.53, 125.86, 124.13,
123.04, 1221.47, 119.85, 113.46, 111.01, 109.13, 107.38, 104.61, 103.07,
102.17. MS (EI, m/z) 262。
2- amino indoles-the 6- of embodiment 4 [3,2B] carbazoles chloro- simultaneously
Successively by 33 g 2- nitrine indoles -6- [3,2B] carbazoles chloro- simultaneously, the hydrazine hydrate that 6 mL mass percents are 80%,
0.12g catalyst Fes (acac)3, 50mL ethylene glycol be put into reaction bulb, 155 DEG C, reaction is finished after 6 h, removes ethylene glycol, cold
But, 100 mL ethyl acetate are added in mixture, is sufficiently mixed, filtered, remove most of ethyl acetate solvent, residue is tied again
Crystalline substance, obtains 27 g white solid 2- amino indoles -6- [3,2B] carbazole products chloro- simultaneously（Purity 97%, yield 86%）.
1H NMR (400 MHz, CDCl3): δ (ppm) 8.12-8.09(m, 1H), 7.55-7.63 (m, 2H),
7.50–7.48 (m, 1H), 7.40-7.38 (m, 2H), 7.29-7.27 (m, 1H), 6.77- 6.75 (m, 2H);13C NMR (400 MHz, CDCl3): δ (ppm) 145.36, 143.91, 131.35, 129.31, 124.18,
123.36, 121.72, 120.56, 119.82, 113.49, 111.01, 107.32, 104.61,103.07. MS
(EI, m/z) 307。
2- amino-N, the N- diethyl indoles of embodiment 5 simultaneously [3,2B] carbazole
Successively by 35g 2- nitrine-N, N- diethyl indoles simultaneously [3,2B] carbazole, the water that 8 mL mass percents are 80%
Close hydrazine, 0.17g catalyst Fes (acac)3, 50mL ethylene glycol be put into reaction bulb, reacted after being heated to reflux 4h under 155 DEG C of reactions
Finish, remove ethylene glycol, cooling adds 100mL ethyl acetate, is sufficiently mixed, filters in mixture, remove most of acetic acid second
Ester solvent, residue recrystallization, simultaneously [3,2B] carbazole is produced to obtain 29 g pale solid shape 2- amino-N, N- diethyl indoles
Product（Purity 97%, yield 88%）.
1H NMR (400 MHz, CDCl3): δ (ppm) 8.17-8.16(m, 1H), 7.59-7.54 (m, 2H),
7.42–7.40 (m, 3H), 7.25-7.23 (m, 2H), 6.88-6.86 (m, 1H), 4.55-4.51 (m, 4H),
1.31-1.28 ppm (t, 6H); 13C NMR (400 MHz, CDCl3): δ (ppm) 143.92, 129.71,
126.24, 125.13, 121.55, 120.51, 119.45, 111.03, 109.35, 107.38, 104.62,
103.37, 40.38, 14.62. MS (EI, m/z) 329。
Claims (6)
1. the synthetic method of the aminocarbazole class compound of structure such as formula 2, it is characterised in that：Synthesize by the following method：Successively
By hydrazine hydrate, catalyst Fe (acac) that nitrine carbazole compound, mass percent are 80%3, alcohols solvent be put into reaction
Bottle, control temperature is reacted at 100 DEG C ~ 180 DEG C, and alcohols solvent is removed after completion of the reaction, is added after cooling water-insoluble molten
Agent, after being sufficiently mixed, filters partial solvent, and residue is recrystallized to give aminocarbazole class compound；
Above-mentioned alcohols solvent is the monohydric alcohol of C4-10 or the dihydroxylic alcohols of C2-10, and its boiling point is 100 DEG C ~ 200 DEG C；
Above-mentioned water-insoluble solvent is the one kind in esters, aromatic hydrocarbons, halogenated hydrocarbons, alkane；
In formula： R2It is H, C1-C5Straight or branched alkyl； RmIt is H, Cl or Br；Two R2It is identical or different.
2. aminocarbazole class compound synthesis method as claimed in claim 1, it is characterised in that R2It is H, C1-C2Alkyl； RmFor
H, Cl or Br；Two R2It is identical.
3. aminocarbazole class compound synthesis method as claimed in claim 1 or 2, it is characterised in that nitrine carbazole compound,
Hydrazine hydrate, catalyst Fe (acac)3Mol ratio is 1：1~2：0.01~0.05；The quality of nitrine carbazole compound, alcohols solvent
Than being 1：1 ~10；Water-insoluble solvent is 2 ~ 5 with the mass ratio of alcohols solvent：1.
4. aminocarbazole class compound synthesis method as claimed in claim 1 or 2, it is characterised in that alcohols solvent select butanol or
Ethylene glycol.
5. aminocarbazole class compound synthesis method as claimed in claim 1 or 2, it is characterised in that reaction temperature select 140 DEG C ~
160℃。
6. aminocarbazole class compound synthesis method as claimed in claim 1 or 2, it is characterised in that water-insoluble solvent selects second
Acetoacetic ester or petroleum ether.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102026973A (en) * | 2008-05-14 | 2011-04-20 | 方济各安吉利克化学联合股份有限公司 | 3-aminocarbazole compound, pharmaceutical composition containing it and preparation method therefor |
| CN102659666A (en) * | 2012-05-04 | 2012-09-12 | 新乡医学院 | Novel carbazole derivatives and preparation method and application thereof |
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2015
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102026973A (en) * | 2008-05-14 | 2011-04-20 | 方济各安吉利克化学联合股份有限公司 | 3-aminocarbazole compound, pharmaceutical composition containing it and preparation method therefor |
| CN102659666A (en) * | 2012-05-04 | 2012-09-12 | 新乡医学院 | Novel carbazole derivatives and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| Carbazole N-substituent effect upon DTMA: stabilizing and photochromic modulating;Zhiming Huo等;《Tetrahedron》;20130726;第69 卷;8964-8973 * |
| Hydrazine-mediated Reduction of Nitro and Azide Functionalities Catalyzed by Highly Active and Reusable Magnetic Iron Oxide Nanocrystals;David Cantillo等;《The Journal of Organic Chemistry》;20130405;第78卷;4530-4542 * |
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Inventor after: Li Xu Inventor after: Wang Jinliang Inventor after: Li Yujiang Inventor after: Wang Jianli Inventor after: Li Yuning Inventor after: Yuan Mengqi Inventor after: Zhou Xiaonan Inventor after: Xing Yanjun Inventor before: Wang Jinliang Inventor before: Li Yujiang Inventor before: Wang Jianli Inventor before: Li Yuning Inventor before: Yuan Mengqi Inventor before: Zhou Xiaonan Inventor before: Xing Yanjun |
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