CN104177283A - Method for preparing bis (indolyl) methane derivative in presence of amine salt - Google Patents
Method for preparing bis (indolyl) methane derivative in presence of amine salt Download PDFInfo
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- CN104177283A CN104177283A CN201410326348.XA CN201410326348A CN104177283A CN 104177283 A CN104177283 A CN 104177283A CN 201410326348 A CN201410326348 A CN 201410326348A CN 104177283 A CN104177283 A CN 104177283A
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- 0 Bc1c(*)ccc(C=O)c1C Chemical compound Bc1c(*)ccc(C=O)c1C 0.000 description 2
- BPROMKRCUQDRIH-UHFFFAOYSA-N C(CC1)CCC1C(c1c[nH]c2ccccc12)c1c[nH]c2c1cccc2 Chemical compound C(CC1)CCC1C(c1c[nH]c2ccccc12)c1c[nH]c2c1cccc2 BPROMKRCUQDRIH-UHFFFAOYSA-N 0.000 description 1
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N O=Cc1ccc[nH]1 Chemical compound O=Cc1ccc[nH]1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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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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Abstract
The invention discloses a method for preparing a bis (indolyl) methane derivative in the presence of an amine salt. According to the method, by taking the amine salt as a catalyst, indole or an indole derivative is reacted with aldehyde to obtain the bis (indolyl) methane derivative, wherein the amine salt is aniline hydrochloride, o-chloroaniline hydrochloride, o-methoxyaniline hydrochloride, pyrrole hydrochloride, aniline trifluoromethane sulphonate or aniline trifluoroacetate. The method disclosed by the invention is simple in operation, mild in reaction condition, short in reaction time, good in substrate applicability and high in target matter yield; the catalyst is cheap and easily available, free of toxicity and stable to air and water; therefore, the method can be widely used for the preparation of the bis (indolyl) methane derivative.
Description
Technical field
The present invention relates to prepare the method for bis (indolyl) methane derivative under amine salt exists.
Background technology
Bis-indolyl alkyl compounds and derivative thereof are the metabolites that a class is extensively present in colored section plant and continent and ocean protista, and they mostly have certain physiologically active, as: antitumor, antiviral, antibacterial and anti-inflammatory etc.Bis-indolyl alkyl compounds is also the synthetic alkaloidal key intermediate of many complex structures, can be used for building dendritic macromole skeleton.Bis-indolyl alkyl compounds is also usually used in dyestuff in addition.Along with the continuous expansion of bis (indolyl) methane and derivative Application Areas thereof, its preparation enjoys organic chemist and medicine scholar extensive concern.
The preparation of bis-indolyl alkyl compounds is mainly that catalyzing indole and aldehydes or ketones obtain desired product taking Bronsted acid or Lewis acid as catalyzer.2003 B.P.Bandgar (Tetrahedron Letters44 (2003) 1959-1961) with I
2for catalyzer, under room temperature condition, prepare bis (indolyl) methane derivative, but the method catalyst levels is too much.University Of Suzhou in 2005 records and uses solid acid SO along pretty wait (CN1706829A)
4 2-/ TiO
2as catalyzer, indoles and aldehyde one step are prepared to bis (indolyl) methane derivative, this method high-efficient simple, but used catalyst preparation process is loaded down with trivial details, TiCl that need to be extremely responsive to air
4, at 100 DEG C, repeatedly process and reach 36 hours, then carry out again secondary treatment at 600 DEG C of high temperature, preparation condition harshness has limited its application greatly.Afterwards, Claudio C.Silveira was with glycerine and CeCl
3(Tetrahedron Letters50 (2009) 6060-6063) synthesizes bis (indolyl) methane derivative as catalyzer, this catalyzer reusable edible, but in catalyzer, use precious metal, and expensive, react temperature required higher.InCl in 2010
3(Carbohydr.Res.2010,345,1708), FeCl
3(J.Org.Chem.2010,75 (15): 5240-5249) etc. simple Lewis acid catalyst is used to catalyzing indole and imines is also prepared bis (indolyl) methane derivative efficiently, but reaction desired raw material is the sulfimide that active higher N-replaces, its preparation process complexity and imines have certain toxicity.Within 2011, Tomasz M.Kubczyk obtains bis (indolyl) methane derivative with nanoporous silico-aluminate (Green Chem., 2011,13,2320-2325) catalyzing indole and aldehyde, and this catalyzer is to water, thermally-stabilised, but the process complexity of Kaolinite Preparation of Catalyst.2012 Lee of Taizhou University one hundred woods (CN102766081A) a kind of use ionic liquid [(HSO is disclosed
3-p)
2im] [CF
3sO
3] prepare the method for bis (indolyl) methane derivative for catalyzer, this method reaction is efficient gentle, but the preparation of two alkylsulphonic acid type ionic liquid is complicated, expensive.[Ir (COD) (SnCl in 2013
3) Cl (m-Cl)]
2title complex (Tetrahedron, 2013,69:2816-2826) is found to realize catalyzing N-sulfimide and indole reaction prepares bis (indolyl) methane derivative, but it is expensive, and raw material obtains same being difficult for.There is TPPMS/CBr the same year
4(ACS Sustainable Chem.Eng.2013,1,549-553) obtains bis-indolyl alkyl compounds for catalyst indoles and carbonyl compound and acetal, this catalyzer is stable to be easy to get, and does not need anhydrous and oxygen-free condition, catalysis capable of circulation 10 times, but it is high that substrate requires, catalyst system complexity.In addition, xanthogenic acid, LiClO
4, In (OTf)
3, Y (OTf)
3, Dy (OTf)
3preparing this compounds Deng also for catalysis, all there is certain deficiency in these methods, as long in the reaction times, use expensive metal catalyst, substrate activity to require high, severe reaction conditions, operating process safe not etc.
Summary of the invention
Technical problem to be solved by this invention is to overcome the shortcoming that existing bis (indolyl) methane derivative preparation method exists, a kind of simple preparation method of bis (indolyl) methane derivative is provided, the method catalyzer used is cheap and easy to get, nontoxic, stable to empty G&W, reaction conditions gentleness, reaction times are short, target substance productive rate is high, simple to operate, good substrate applicability.
Solving the problems of the technologies described above adopted technical scheme is: aldehyde and indoles or indole derivatives are dissolved in organic solvent for 1:2～4 in molar ratio, add amine salt, the add-on of amine salt is 5%～15% of aldehyde molar weight, and room temperature reaction 5～30 minutes, obtains bis (indolyl) methane derivative.
Above-mentioned amine salt is any one in anilinechloride, o-chloroaniline hydrochloride, ORTHO ANISIDINE hydrochloride, pyrroles's hydrochloride, aniline trifluoro-methanyl sulfonate, aniline trifluoroacetate, preferably anilinechloride or o-chloroaniline hydrochloride; Organic solvent is any one in tetrahydrofuran (THF), methyl-sulphoxide, ethyl acetate, acetonitrile, methylene dichloride, chloroform, benzene, toluene.
Above-mentioned aldehyde is further preferred
any one in hexahydrobenzaldehyde, isovaleric aldehyde, in formula, A, B, C independently represent H, C separately
1～C
3alkyl, C
1～C
3alkoxyl group, CN, F, Cl, Br, NO
2in any one, M represents any one in N, O, S: further preferably 5-bromo indoles or N-skatole of described indole derivatives.
The present invention is under the existence of amine salt, make indoles or indole derivatives and aldehyde reaction obtain bis (indolyl) methane derivative, the method is simple to operate, react efficient, gentle, amine salt is cheap and easy to get, nontoxic, stable to empty G&W, good substrate applicability, can be widely used in the preparation of bis (indolyl) methane derivative.
Embodiment
Below in conjunction with embodiment, the present invention is described in more detail, but invention which is intended to be protected is not limited only to these embodiment.
Embodiment 1
To prepare following formula: compound 3,3'-(Phenylmethylene)bis[1H-indole] as example, raw materials used and preparation method thereof as follows:
0.106g (1.0mmol) phenyl aldehyde, 0.234g (2.0mmol) indoles, 0.0165g (0.1mmol) o-chloroaniline hydrochloride are added in 1mL acetonitrile, room temperature reaction 10 minutes, stopped reaction, mixed solution taking the volume ratio of ethyl acetate and sherwood oil as 3:1 is as moving phase column chromatography for separation, obtain bright pink solid 3,3'-(Phenylmethylene)bis[1H-indole], its productive rate is 99%.Products therefrom characterizes with Bruker Avance type superconduction fourier numeralization nuclear magnetic resonance spectrometer, and characterization data is:
1h NMR (400MHz, DMSO) δ: 10.83 (d, J=1.3Hz, 2H), 7.46-7.20 (m, 8H), 7.15 (d, J=7.3Hz, 1H), 7.04 (dd, J=11.1,4.0Hz, 2H), 6.92-6.78 (m, 4H), 5.86 (s, 1H);
13c NMR (101MHz, DMSO) δ: 144.98,136.63,128.32,128.01,126.67,125.76,123.56,120.89,119.14,118.19,118.10,111.45.
Embodiment 2
In embodiment 1, o-chloroaniline hydrochloride is replaced with equimolar anilinechloride, room temperature reaction 30 minutes, other steps are identical with embodiment 1, are prepared into pink solid 3,3'-(Phenylmethylene)bis[1H-indole], and its productive rate is 98%.
Embodiment 3
In embodiment 1, o-chloroaniline hydrochloride is replaced with equimolar aniline trifluoroacetate, room temperature reaction 30 minutes, other steps are identical with embodiment 1, are prepared into pink solid 3,3'-(Phenylmethylene)bis[1H-indole], and its productive rate is 99%.
Embodiment 4
In embodiment 1, o-chloroaniline hydrochloride is replaced with equimolar ORTHO ANISIDINE hydrochloride, room temperature reaction 30 minutes, other steps are identical with embodiment 1, are prepared into pink solid 3,3'-(Phenylmethylene)bis[1H-indole], and its productive rate is 90%.
Embodiment 5
In embodiment 1, o-chloroaniline hydrochloride is replaced with equimolar pyrroles's hydrochloride, room temperature reaction 30 minutes, other steps are identical with embodiment 1, are prepared into pink solid 3,3'-(Phenylmethylene)bis[1H-indole], and its productive rate is 80%.
Embodiment 6
In embodiment 1, o-chloroaniline hydrochloride is replaced with equimolar aniline trifluoro-methanyl sulfonate, room temperature reaction 30 minutes, other steps are identical with embodiment 1, are prepared into pink solid 3,3'-(Phenylmethylene)bis[1H-indole], and its productive rate is 85%.
Embodiment 7
To prepare two (5-bromo indoles) the m-methoxyphenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced by equimolar NSC 43794, and indoles is replaced with equimolar 5-bromo indoles, other steps are identical with embodiment 1, be prepared into the two 5-bromo indoles m-methoxyphenyl methane of dark red solid, its productive rate is 99%, and characterization data is:
1h NMR (400MHz, DMSO) δ: 11.12 (s, 2H), 7.51 (s, 2H), 7.40 (s, 2H), 7.22 (s, 4H), 6.97 (s, 4H), 5.88 (s, 1H), 3.69 (s, 3H);
13c NMR (101MHz, DMSO) δ: 159.19,145.94,135.27,129.19,128.40,125.23,123.47,121.21,120.59,117.53,114.46,113.58,110.97,110.93,54.83.
Embodiment 8
To prepare the two N-skatole phenylmethanes of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, indoles used is replaced with equimolar N-skatole, and other steps are identical with embodiment 1, is prepared into the two N-skatole phenylmethanes of pink solid, and its productive rate is 90%, and characterization data is:
1h NMR (400MHz, DMSO) δ: 7.36 (d, J=8.3Hz, 4H), 7.28 (dd, J=17.5,7.8Hz, 4H), 7.13 (dt, J=27.4,7.4Hz, 3H), (6.90 t, J=7.4Hz, 2H), 6.82 (s, 2H), 5.83 (s, 1H), 3.69 (s, 6H);
13c NMR (101MHz, DMSO) δ: 150.04,142.26,133.45,133.31,133.07,132.05,131.07,126.14,124.33,123.53,122.58,114.80,37.47.
Embodiment 9
To prepare the two indoles o-methoxyphenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar o-methoxybenzaldehyde, and other steps are identical with embodiment 1, is prepared into the two indoles o-methoxyphenyl methane of faint yellow solid, and its productive rate is 94%, and characterization data is:
1h NMR (400MHz, DMSO) δ: 10.75 (s, 2H), 7.34 (d, J=8.1Hz, 2H), 7.22 (d, J=7.9Hz, 2H), 7.19-7.10 (m, 2H), 7.01 (dt, J=9.0,6.2Hz, 3H), 6.89-6.70 (m, 6H), 6.22 (s, 1H), 3.87-3.74 (m, 3H);
13c NMR (101MHz, DMSO) δ: 156.26,136.57,132.63,129.11,126.97,126.74,123.55,120.77,120.01,118.89,118.08,117.80,111.39,110.81,55.53,40.12,39.91,39.70,39.50,39.29,39.08,38.87,31.44.
Embodiment 10
To prepare the two indoles m-methoxyphenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced by equimolar NSC 43794, and other steps are identical with embodiment 1, is prepared into the two indoles m-methoxyphenyl methane of tangerine pink solid, and its productive rate is 96%, and characterization data is:
1h NMR (400MHz, CDCl
3) δ: 7.81 (s, 2H), 7.33 (d, J=7.9Hz, 2H), 7.27 (d, J=8.1Hz, 2H), 7.15-7.06 (m, 3H), 6.96-6.83 (m, 4H), 6.68 (dd, J=8.1,2.2Hz, 1H), 6.59 (d, J=1.4Hz, 2H), 5.78 (s, 1H), 3.66 (s, 3H);
13c NMR (101MHz, CDCl
3) δ: 158.55,144.71,135.66,128.08,126.07,122.53,120.89,120.27,118.88,118.55,118.21,113.73,110.24,109.96,54.08,39.21.
Embodiment 11
To prepare the two indoles p-methoxyphenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar aubepine, and other steps are identical with embodiment 1, is prepared into the two indoles p-methoxyphenyl methane of pink solid, and its productive rate is 99%, and characterization data is:
1h NMR (400MHz, DMSO) δ: 7.89 (s, 2H), 7.37 (dd, J=16.7,7.9Hz, 4H), 7.25 (m, 2H), 7.16 (t, J=7.2Hz, 2H), 7.01 (d, J=7.0Hz, 2H), 6.82 (m, 2H), 6.65 (s, 2H), 5.84 (s, 1H), (3.78 d, J=2.1Hz, 3H);
13c NMR (101MHz, DMSO) δ: 157.93,136.73,136.23,129.60,127.10,123.49,121.90,120.11,120.00,119.20,113.58,110.98,55.21,39.36.
Embodiment 12
To prepare the two indoles Chloro-O-Phenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar o-chlorobenzaldehyde, and other steps are identical with embodiment 1, is prepared into the two indoles p-nitrophenyl methylmethanes of white solid, and its productive rate is 85%, and characterization data is:
1h NMR (400MHz, DMSO) δ: 10.86 (s, 2H), 7.45 (m, 1H), 7.36 (s, 1H), 7.25 (m, 6H), 7.04 (t, J=7.4Hz, 2H), 6.87 (t, J=7.3Hz, 2H), 6.75 (s, 2H), 6.20 (s, 1H), 3.33 (s, 1H), 2.49 (s, 3H);
13c NMR (101MHz, DMSO) δ: 141.81,136.59,132.64,130.17,129.19,127.70,126.94,126.46,123.96,120.98,118.62,118.35,116.46,111.54,36.09.
Embodiment 13
To prepare the two indoles p-nitrophenyl methylmethanes of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar paranitrobenzaldehyde, room temperature reaction 10 minutes, and other steps are identical with embodiment 1, are prepared into the two indoles isopentyl methane of white solid, and its productive rate is 87%, and characterization data is:
1h NMR (400MHz, DMSO) δ 11.05 (s, 1H), 8.41 (s, 1H), 8.09 (d, J=8.1Hz, 1H), 8.01 (d, J=7.6Hz, 1H), 7.60 (dd, J=13.4,7.9Hz, 2H), (7.39 d, J=8.1Hz, 1H), 7.14 – 6.95 (m, 5H), 6.74 (d, J=8.0Hz, 2H), 6.53 (t, J=8.2Hz, 2H), 6.08 (d, J=6.9Hz, 1H);
13c NMR (101MHz, DMSO) δ 147.94,147.80,146.60,136.52,133.95,129.66,128.74,125.73,123.65,121.67,121.56,121.37,119.00,118.74,116.62,116.19,113.04,111.62,53.39.
Embodiment 14
To prepare the two indoles-α-furyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar furaldehyde, and other steps are identical with embodiment 1, is prepared into the two indoles-α-furyl methane of pink solid, and its productive rate is 81%, and characterization data is:
1h NMR (400MHz, CDCl
3) δ: 7.92 (s, 2H), 7.50 (d, J=8.0Hz, 2H), 7.40-7.33 (m, 3H), 7.23-7.16 (m, 2H), 7.10-7.04 (m, 2H), 6.87 (d, J=1.9Hz, 2H), 6.32 (dd, J=3.1,1.9Hz, 1H), 6.08 (d, J=3.2Hz, 1H), 5.96 (s, 1H);
13c NMR (101MHz, CDCl
3) δ: 157.15,141.14,136.37,126.67,123.07,121.98,119.73,119.33,117.18,111.14,110.16,106.57,33.78.
Embodiment 15
To prepare the two indoles cyclohexyl-methanes of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar hexahydrobenzaldehyde, and other steps are identical with embodiment 1, is prepared into the two indoles cyclohexyl-methanes of pink solid, and its productive rate is 70%, and characterization data is:
1h NMR (400MHz, CDCl
3) δ: 8.15 (s, 2H), 7.61 (d, J=8.1Hz, 2H), 7.26 (d, J=8.0Hz, 2H), 7.16 (s, 2H), 7.11 (t, J=7.2Hz, 2H), 7.10 (d, J=7.2Hz, 2H), 4.15 (s, 1H), 2.21-2.23 (m, 1H), 1.79-1.82 (m, 2H), 1.70-1.75 (m, 2H), 1.68-1.69 (m, 2H);
13c NMR (101MHz, CDCl
3) δ: 140.82,137.45,124.22,122.08,121.77,120.45,119.89,111.98,42.7,40.6,32.4,29.8,26.7.
Embodiment 16
To prepare the two indoles isopentyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar isovaleric aldehyde, room temperature reaction 30 minutes, and other steps are identical with embodiment 1, are prepared into the two indoles isopentyl methane of white solid, and its productive rate is 52%, and characterization data is:
1h NMR (400MHz, CDCl
3) δ: 7.63-7.47 (m, 4H), 7.15 (d, J=8.1Hz, 2H), 7.07-7.01 (m, 2H), 6.95 (td, J=7.6,0.9Hz, 2H), 6.75 (d, J=2.0Hz, 2H), 4.49 (t, J=7.7Hz, 1H), 1.98 (dd, J=14.1,6.9Hz, 2H), 1.54 (dt, J=13.3,6.7Hz, 1H), 0.88 (d, J=6.6Hz, 6H);
13c NMR (101MHz, CDCl
3) δ: 136.64,127.17,121.76,121.52,120.53,119.66,119.06,111.20,45.28,31.71,26.01,22.94.
Embodiment 17
To prepare the two indoles p-methylphenyl methane of following formula: compound as example, raw materials used and preparation method thereof as follows:
In embodiment 1, phenyl aldehyde used is replaced with equimolar p-tolyl aldehyde, room temperature reaction 10 minutes, and other steps are identical with embodiment 1, are prepared into the two indoles p-methylphenyl methane of white solid, and its productive rate is 95%, and characterization data is:
1h NMR (400MHz, CDCl
3) δ: 7.85 (s, 2H), 7.41 (d, J=8.1Hz, 2H), 7.20-7.33 (m, 6H), 7.10 (d, J=8.0Hz, 2H), 7.06 (t, J=8.1Hz, 2H), 6.70 (d, J=2.5Hz, 2H), 5.85 (s, 1H), 2.38 (s, 3H);
13c NMR (101MHz, CDCl
3) δ: 157.11,135.73,135.23,129.10,126.99,123.19,121.55,119.81,119.20,118.60,113.43,110.62,54.19,23.36.
Acetonitrile in above embodiment also can be replaced with isopyknic methylene dichloride, tetrahydrofuran (THF), methyl-sulphoxide, ethyl acetate, chloroform, benzene or toluene.
Claims (4)
1. under existing, prepares in amine salt the method for bis (indolyl) methane derivative for one kind, it is characterized in that: aldehyde and indoles or indole derivatives are dissolved in organic solvent for 1:2～4 in molar ratio, add amine salt, the add-on of amine salt is 5%～15% of aldehyde molar weight, room temperature reaction 5～30 minutes, obtains bis (indolyl) methane derivative;
Above-mentioned amine salt is any one in anilinechloride, o-chloroaniline hydrochloride, ORTHO ANISIDINE hydrochloride, pyrroles's hydrochloride, aniline trifluoro-methanyl sulfonate, aniline trifluoroacetate; Organic solvent is any one in tetrahydrofuran (THF), methyl-sulphoxide, ethyl acetate, acetonitrile, methylene dichloride, chloroform, benzene, toluene.
2. the method for preparing bis (indolyl) methane derivative under amine salt exists according to claim 1, is characterized in that: described amine salt is anilinechloride or o-chloroaniline hydrochloride.
3. the method for preparing bis (indolyl) methane derivative under amine salt exists according to claim 1 and 2, is characterized in that: described aldehyde is
any one in hexahydrobenzaldehyde, isovaleric aldehyde, in formula, A, B, C independently represent H, C separately
1～C
3alkyl, C
1～C
3alkoxyl group, CN, F, Cl, Br, NO
2in any one, M represents any one in N, O, S.
4. the method for preparing bis (indolyl) methane derivative under amine salt exists according to claim 3, is characterized in that: described indole derivatives is 5-bromo indoles or N-skatole.
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| CN101935297A (en) * | 2010-07-27 | 2011-01-05 | 浙江大学 | 3,3- diindolyl derivative and preparation method thereof |
| CN102617442A (en) * | 2011-01-27 | 2012-08-01 | 桂林商源植物制品有限公司 | Preparation method and use of 3,3'-methylenebis(1H-Indole) |
| CN103467354A (en) * | 2013-09-16 | 2013-12-25 | 陕西师范大学 | Method for preparing diindolyl methane derivatives |
-
2014
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| JPH09110831A (en) * | 1995-10-23 | 1997-04-28 | Kissei Pharmaceut Co Ltd | Production of 2,2'-bisindole derivative |
| WO2000053313A2 (en) * | 1999-03-09 | 2000-09-14 | Arqule, Inc. | Lanthanide catalysts for synthesis of compounds and combinatorial libraries |
| CN1837193A (en) * | 2006-04-26 | 2006-09-27 | 浙江大学 | Process for preparing diindolylmethane derivatives |
| CN101935297A (en) * | 2010-07-27 | 2011-01-05 | 浙江大学 | 3,3- diindolyl derivative and preparation method thereof |
| CN102617442A (en) * | 2011-01-27 | 2012-08-01 | 桂林商源植物制品有限公司 | Preparation method and use of 3,3'-methylenebis(1H-Indole) |
| CN103467354A (en) * | 2013-09-16 | 2013-12-25 | 陕西师范大学 | Method for preparing diindolyl methane derivatives |
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| Title |
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| GIUSEPPE GIANNINI，等: "Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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