CN107141246B - A kind of preparation method of Isatine derivatives - Google Patents
A kind of preparation method of Isatine derivatives Download PDFInfo
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- CN107141246B CN107141246B CN201710422389.2A CN201710422389A CN107141246B CN 107141246 B CN107141246 B CN 107141246B CN 201710422389 A CN201710422389 A CN 201710422389A CN 107141246 B CN107141246 B CN 107141246B
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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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
Abstract
The invention discloses a kind of new method for synthesizing Isatine derivatives, this method uses nitrite tert-butyl/O2Catalytic oxidation system, do not use metal reagent, react at normal temperatures and pressures, in high yield and purity obtain Isatine derivatives, have the advantages that technological operation is simple and easy, at low cost.
Description
Technical field
It is original that the present invention relates to a kind of preparation methods of Isatine derivatives, more particularly to one kind with 2- indolone derivatives
Material, simple process, the environmental-friendly method for preparing Isatine derivatives.
Background technique
Indigo (indigo) is aoxidized since Erdmann and Laurent in 1841 passes through, has separately obtained a kind of point
Son is C8H6NO2Organic compound, and it is named as indole dione (isatin, i.e. isatin), then finally determine to Kolbe
Its structure, the chemical property and purposes of indole dione are gradually recognized by people.Today, it has been found that indole dione skeleton
Compound has extensive purposes in dyestuff, antibiotic, anticancer class drug.Therefore, synthesis contains the compound of this kind of skeleton
Also increasingly by the attention of synthetic organic chemists.
1841, by experiment, indigo (indigo) was starting material by Erdmann and Laurent, in various different oxidations
Under the conditions of agent, indole dione is separately obtained, this is that mankind's first passage chemical method is obtained and found this organic
Compound (formula one).
In recent years, some steps are simple, and the mild synthesis isatin approach of reaction condition is developed in succession.Wherein one
Important channel is then to prepare corresponding Isatine derivatives by raw material oxidation of 2- indolone derivatives.
Yong-qiang Wang etc. (Tetrahedron Letters., 56 (2015), 1575-1580.) reports substitution
2- oxindole compounds prepared under cupric, alkali, Oxygen Condition replace isatin method (formula two).
Parvathaneni Sai Prathima etc. (Tetrahedron Letters., 56 (2015), 6385-6388.)
It is then the side for reporting a kind of substituted 2- indole ketone compound oxidation under the conditions of PIDA, TEMPO and preparing Isatine derivatives
Method (formula three).
Inventor proposes a kind of substituted 2- indole ketone compound oxidation and prepares Isatine derivatives by concentrating on studies
New method, this method has not been reported.
Summary of the invention
It is an object of the invention to overcome the deficiencies of the prior art and provide a kind of simple processes, at low cost, environmental-friendly
The new method for preparing isatin-BETA-oxime derivative, using 2- indolone derivatives as raw material, under nitrite tert-butyl/Oxygen Condition
Reaction prepares Isatine derivatives.
The preparation method of Isatine derivatives provided by the invention, this method is using 2- indolone derivatives as raw material, under
Column step is prepared:
2- indolone derivatives (1a), nitrite tert-butyl (t-BuONO, 2a) and solvent are added into reactor, then
At oxygen atmosphere (1atm), reactor is placed in and is stirred to react under room temperature, reaction process is monitored through TLC or GC, until anti-
Answering raw material 2- indolone derivatives to react completely can stop reacting, post-treated to obtain target product (Isatine derivatives, I).
The preparation method of Isatine derivatives provided by the invention, process flow are summarised as (formula four):
The solvent used can be the mixed of any one or a few in tetrahydrofuran, dioxane, ethyl acetate, toluene
Object is closed, it is preferable to use any one in tetrahydrofuran or ethyl acetate.
The dosage for the nitrite tert-butyl (t-BuONO, 2a) being added be selected from 2- indolone derivatives (1a) dosage 1~
5 equivalents, preferably 2~3 equivalents.
The post-processing operation is as follows: by reaction solution saturated common salt water washing, recycling organic phase, water phase acetic acid second
Ester extraction, merges organic phase；Organic phase is dried over anhydrous sodium sulfate, filters, is evaporated under reduced pressure, by residue through column chromatography for separation
(petrol ether/ethyl acetate) obtains target product (Isatine derivatives, I).
In the Isatine derivatives that the 2- indolone derivatives and Formulas I that above-mentioned formula 1a is indicated indicate, R1Indicate what it was connected
One or more substituent groups on phenyl ring, each R1It is independently from each other hydrogen, C1-C6Alkyl, C1-C6Alkoxy, C1-C6Acyl group, C1-
C6Ester group, halogen, cyano, C3-C6Naphthenic base, C5-C14Aryl, C5-C14Heteroaryl ,-NRaRb.Wherein, Ra, RbIndependently of one another
Selected from C1-C6Alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N.
R2Indicate hydrogen, tertbutyloxycarbonyl (Boc), C1-C6Alkyl, C1-C6Acyl group, C3-C6Naphthenic base, C5-C14Aryl, C5-
C14Aryl-C1-C6Alkyl, C5-C14The hetero atom of heteroaryl, the heteroaryl is selected from O, S or N.The wherein C5-C14Aryl-
C1-C6Alkyl is preferably benzyl.
Wherein, alkyl, alkoxy, naphthenic base, aryl and heteroaryl can be further substituted with a substituent, and described takes
Dai Ji is selected from halogen or C1-C6Alkyl.
Preferably, R1Indicate one or more substituent groups on phenyl ring that it is connected, each R1Be independently from each other hydrogen,
C1-C6Alkyl, halogen；R2Indicate hydrogen, tertbutyloxycarbonyl (Boc), phenyl or benzyl.
The beneficial effects of the present invention are: proposing a kind of new method for synthesizing Isatine derivatives, this method uses nitrous acid
The tert-butyl ester/O2Catalytic oxidation system, do not use metal reagent, react at normal temperatures and pressures, in high yield and purity obtain indigo
Red derivative has the advantages that technological operation is simple and easy, at low cost.
Specific embodiment
Below in conjunction with specific embodiment, further detailed description is carried out to the present invention.
Embodiment 1-12 reaction condition optimization
With 2- indolone (1a) for reaction raw materials, is reacted with nitrite tert-butyl (2a) and prepare isatin (I-1), explored not
Wherein representative embodiment 1-12 is selected in the reaction condition of influence with to(for) reaction, as a result as shown in Table 1:
Table one:
| Embodiment | Auxiliary agent (equivalent) | Solvent | Separate yield |
| 1 | TBHP(2) | THF | 0 |
| 2 | DTBP(2) | THF | 0 |
| 3 | t-BuONO(2) | THF | 77 |
| 4 | K2S2O8(2) | THF | 5 |
| 5 | t-BuONO(1.2) | THF | 61 |
| 6 | t-BuONO(3) | THF | 76 |
| 7a | t-BuONO(2) | THF | 28 |
| 8b | t-BuONO(2) | THF | 0 |
| 9 | t-BuONO(2) | Isosorbide-5-Nitrae-dioxane | 12 |
| 10 | t-BuONO(2) | EtOAc | 75 |
| 11 | t-BuONO(2) | toluene | 5 |
| 12c | t-BuONO(2) | THF | 70 |
By taking embodiment 3 as an example, concrete operations are as follows: in schlenk bottles of 10mL be added 2- indolone (1a,
0.3mmol), nitrite tert-butyl (t-BuONO, 2a, 0.6mmol) and THF (2mL) will then at oxygen atmosphere (1atm)
Reactor is stirred to react under the conditions of being placed in 25 DEG C, reaction process is monitored through TLC or GC, until reaction raw materials 2- indoles reactive ketone is complete
Entirely, stop reaction, by reaction solution saturated common salt water washing, recycle organic phase, water phase is extracted with ethyl acetate, and merges organic
Phase；Organic phase is dried over anhydrous sodium sulfate, filters, is evaporated under reduced pressure, by residue through column chromatography for separation (petrol ether/ethyl acetate)
Obtain target product isatin, I-1,1H NMR (400MHz, DMSO-d6) δ: 11.07 (s, 1H), 7.59 (t, J=8.0Hz, 1H),
7.50 (d, J=7.6Hz, 1H), 7.07 (t, J=7.6Hz, 1H), 6.92 (d, J=8.0Hz, 1H)；13C NMR (100MHz,
DMSO-d6) δ: 184.8,159.8,151.2,138.8,125.1,123.2,118.2,112.7；LRMS (EI, 70eV) m/z
(%): 147 (M+, 61), 119 (100), 92 (74)
Each embodiment basic operation process of remaining in table one is same as Example 3, in which:
" a " indicates that reaction carries out under the conditions of air atmosphere (1atm) in embodiment 7；
" b " indicates that reaction carries out under the conditions of nitrogen atmosphere in embodiment 8；
It is 1g (7.52mmol) that " c " expression reaction scale, which is raw material 2- indolone (1a) inventory used, in embodiment 12
Grade.
Reaction can not obtain when adding others oxidisability auxiliary agent such as TBHP, DTBP it can be seen from embodiment 1-12
Obtain target product；Use K2S2O8When as oxidisability auxiliary agent, target product yield is only 5%；Use nitrite tert-butyl (t-
BuONO, 2a) it is used as reaction promoter that can obtain highest yield, optimum initial charge is 2 equivalents (the embodiment 1- of compound 1a
6).When carrying out under reaction is placed in nitrogen atmosphere, reaction can not occur；It is carried out under the conditions of reaction is placed in air atmosphere
When, the yield of target product reduces (embodiment 7-8) significantly.Using ethyl acetate can obtain and tetrahydro as reaction dissolvent
Furans makees substantially comparable target product yield when solvent, but other reaction dissolvents such as toluene, dioxane etc. are then
Very low yield does not occur or only obtains for reaction.Inventors have found that reaction scale is that the raw material 2- indolone (1a) used is thrown
When doses is 1g (7.52mmol) grade, the yield of target product is still up to 70%, illustrates present invention process suitable for big rule
Mould production.
Best based on reaction effect under conditions of embodiment 3, inventor selects the raw material of different substituents on this basis
To prepare various Isatine derivatives.
The synthesis of 13 N-methyl-isatin of embodiment
To addition N- methyl -2- indolone (1a, 0.3mmol), nitrite tert-butyl (t- in schlenk bottles of 10mL
BuONO, 2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred then at oxygen atmosphere (1atm)
Reaction monitors reaction process through TLC or GC, until reaction raw materials N- methyl -2- indolone fully reacting, stops reaction, will react
Liquid saturated common salt water washing recycles organic phase, and water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is through anhydrous slufuric acid
Sodium is dry, filtering, is evaporated under reduced pressure, and residue is obtained target product N- methyl through column chromatography for separation (petrol ether/ethyl acetate)
Isatin, I-2 separate yield 73%,1H NMR (300MHz, CDCl3) δ: 7.65-7.58 (m, 2H), 7.14 (t, J=7.5Hz,
1H), 6.91 (d, J=8.1Hz, 1H), 3.26 (s, 3H)；13C NMR (75MHz, CDCl3) δ: 183.4,158.3,151.5,
138.5,125.3,123.9,117.5,110.0,26.3；LRMS (EI, 70eV) m/z (%): 161 (M+, 82), 133 (40),
104(100).
The synthesis of 14 N- benzyl isatin of embodiment
To addition N- benzyl -2- indolone (1a, 0.3mmol), nitrite tert-butyl (t- in schlenk bottles of 10mL
BuONO, 2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred then at oxygen atmosphere (1atm)
Reaction monitors reaction process through TLC or GC, until reaction raw materials N- benzyl -2- indolone fully reacting, stops reaction, will react
Liquid saturated common salt water washing recycles organic phase, and water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is through anhydrous slufuric acid
Sodium is dry, filtering, is evaporated under reduced pressure, and residue is obtained target product N- benzyl through column chromatography for separation (petrol ether/ethyl acetate)
Isatin, I-3 separate yield 55%,1H NMR (300MHz, CDCl3) δ: 7.58 (d, J=7.2Hz, 1H), 7.47 (t, J=
7.5Hz, 1H), 7.30 (t, J=13.5Hz, 5H), 7.08 (t, J=7.8Hz, 1H), 6.78 (t, J=7.8Hz, 1H), 4.92
(s, 2H)；13C NMR (75MHz, CDCl3) δ: 183.3,158.3,150.7,138.4,134.6,129.1,128.2,127.5,
125.4,123.9,117.7,111.1,44.1；LRMS (EI, 70eV) m/z (%): 237 (M+, 79), 180 (58), 146
(100).
The synthesis of 15 N- phenylisatin of embodiment
To addition N- phenyl -2- indolone (1a, 0.3mmol), nitrite tert-butyl (t- in schlenk bottles of 10mL
BuONO, 2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred then at oxygen atmosphere (1atm)
Reaction monitors reaction process through TLC or GC, until reaction raw materials N- phenyl -2- indolone fully reacting, stops reaction, will react
Liquid saturated common salt water washing recycles organic phase, and water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is through anhydrous slufuric acid
Sodium is dry, filtering, is evaporated under reduced pressure, and residue is obtained target product N- phenyl through column chromatography for separation (petrol ether/ethyl acetate)
Isatin, I-4 separate yield 66%,1H NMR (300MHz, CDCl3) δ: 7.68 (d, J=7.5Hz, 1H), 7.58-7.52 (m,
3H), 7.48-7.41 (m, 3H), 7.17 (t, J=7.5Hz, 1H), 6.90 (d, J=8.1Hz, 1H)；13C NMR (75MHz,
CDCl3) δ: 183.0,157.4,151.7,138.5,132.9,130.0,128.9,126.0 (2), 124.4,117.5,111.4；
LRMS (EI, 70eV) m/z (%): 223 (M+, 18), 195 (100), 167 (42)
The synthesis of 16 N-Boc isatin of embodiment
To addition N-Boc-2- indolone (1a, 0.3mmol), nitrite tert-butyl (t- in schlenk bottles of 10mL
BuONO, 2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred then at oxygen atmosphere (1atm)
Reaction monitors reaction process through TLC or GC, until reaction raw materials N-Boc-2- indolone fully reacting, stops reaction, by reaction solution
With saturated common salt water washing, organic phase is recycled, water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is through anhydrous sodium sulfate
Dry, filtering, vacuum distillation, obtain target product N-Boc indigo through column chromatography for separation (petrol ether/ethyl acetate) for residue
Red, I-5 separates yield 57%,1H NMR (300MHz, CDCl3) δ: 8.23 (d, J=6.9Hz, 1H), 7.89 (d, J=8.4Hz,
1H), 7.44 (t, J=7.8Hz, 1H), 7.21 (t, J=7.5,1H), 1.67 (s, 9H)；13C NMR (75MHz, CDCl3) δ:
184.1,162.3,148.8,142.9,140.3,132.6,127.9,125.0,115.3,85.1,28.1；LRMS (EI, 70eV)
M/z (%): 247 (M+, 1), 146 (100), 118 (52)
The synthesis of 17 5- chlorisatide of embodiment
To be added in schlenk bottles of 10mL the chloro- 2- indolone (1a, 0.3mmol) of 5-, nitrite tert-butyl (t-BuONO,
2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred to react then at oxygen atmosphere (1atm),
Reaction process is monitored through TLC or GC, until the chloro- 2- indolone fully reacting of reaction raw materials 5-, stops reaction, reaction solution is saturated
Brine It recycles organic phase, and water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is dried over anhydrous sodium sulfate, mistake
Residue is obtained target product 5- chlorisatide through column chromatography for separation (petrol ether/ethyl acetate) by filter, vacuum distillation, and I-6 divides
From yield 74%,1H NMR (400MHz, DMSO-d6) δ: 11.15 (s, 1H), 7.61 (d, J=8.4Hz, 1H), 7.54 (s,
1H), 6.92 (d, J=8.4Hz, 1H)；13C NMR (100MHz, DMSO-d6) δ: 183.8,159.6,149.6,137.7,
127.3,124.6,119.6,114.3；LRMS (EI, 70eV) m/z (%): 183 (M+2,16), 181 (M+, 49), 153 (100),
125(39).
The synthesis of 18 5-bromoisatin of embodiment
To be added in schlenk bottles of 10mL the bromo- 2- indolone (1a, 0.3mmol) of 5-, nitrite tert-butyl (t-BuONO,
2a, 0.6mmol) and THF (2mL) reactor is placed under the conditions of 25 DEG C and is stirred to react then at oxygen atmosphere (1atm),
Reaction process is monitored through TLC or GC, until the bromo- 2- indolone fully reacting of reaction raw materials 5-, stops reaction, reaction solution is saturated
Brine It recycles organic phase, and water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is dried over anhydrous sodium sulfate, mistake
Residue is obtained target product 5-bromoisatin through column chromatography for separation (petrol ether/ethyl acetate) by filter, vacuum distillation, and I-6 divides
From yield 76%,1H NMR (300MHz, DMSO-d6) δ: 11.15 (s, 1H), 7.71 (d, J=8.4Hz, 1H), 7.62 (s,
1H), 6.88 (d, J=8.4Hz, 1H)；13C NMR (75MHz, DMSO-d6) δ: 183.7,159.4,150.1,140.5,127.4,
119.9,114.8 (2)；LRMS (EI, 70eV) m/z (%): 227 (M+2,35), 225 (M+, 36), 197 (100), 153 (78)
The Applicant declares that the present invention is explained by the above embodiments synthetic method of the invention, but the present invention not office
It is limited to above-described embodiment, those skilled in the art is it will be clearly understood that carry out preparation method of the invention and operation various
Conventional replacement, selection and/or adjustment, all of which fall within the scope of protection and disclosure of the present invention.
Claims (4)
1. a kind of preparation method of Isatine derivatives shown in Formulas I, which is characterized in that 2- Yin shown in formula 1a is added into reactor
Nitrite tert-butyl (t-BuONO) and solvent shown in diindyl ketone derivatives, formula 2a set reactor then under oxygen atmosphere
In being stirred to react under room temperature, reaction process is monitored through TLC or GC, until reaction raw materials 2- indolone derivatives react completely,
Stop reaction, it is post-treated to obtain target product shown in Formulas I；Its reaction equation are as follows:
In the Isatine derivatives that the 2- indolone derivatives and Formulas I that above-mentioned formula 1a is indicated indicate, R1It indicates on phenyl ring that it is connected
One or more substituent groups, each R1It is independently from each other hydrogen, C1-C6Alkyl, halogen；R2Indicate hydrogen, tertbutyloxycarbonyl
(Boc), phenyl or benzyl；
And wherein, any one of the solvent in tetrahydrofuran or ethyl acetate.
2. preparation method according to claim 1, it is characterised in that the use for the nitrite tert-butyl (t-BuONO) being added
Amount is 1~5 equivalent of 2- indolone derivatives dosage.
3. preparation method according to claim 2, it is characterised in that the use for the nitrite tert-butyl (t-BuONO) being added
Amount is 2~3 equivalents of 2- indolone derivatives dosage.
4. preparation method according to claim 1, it is characterised in that the post-processing operation is as follows: reaction solution being used full
And brine It, organic phase is recycled, water phase is extracted with ethyl acetate, and merges organic phase；Organic phase is dried over anhydrous sodium sulfate,
Filtering, vacuum distillation, obtain target product shown in Formulas I through column chromatography for separation for residue.
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| CN108409630B (en) * | 2018-02-07 | 2021-01-15 | 宁波大学 | Preparation method of 3-hydroxy-2-indolone derivative in aqueous phase |
| CN108440378B (en) * | 2018-03-27 | 2021-03-12 | 宁波大学 | Preparation method of iodine-hydrogen peroxide promoted 3-amino-2-indolone derivative at room temperature |
| CN108658836B (en) * | 2018-05-15 | 2021-04-20 | 宁波大学 | Preparation method of 3-substituted-3-azidoindole-2-ketone compound |
| CN109810043B (en) * | 2018-11-13 | 2021-08-27 | 宁波大学 | Preparation method of isatin derivative |
| CN109734645B (en) * | 2019-02-21 | 2021-02-02 | 南京金浩医药科技有限公司 | Synthetic process of isatin |
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Non-Patent Citations (3)
| Title |
|---|
| "HBr/t-BuONO催化活化分子氧选择性氧化硫醚";陈春玉等;《有机化学》;20081231(第11期);第1978～1981页 |
| "Synthesis of isatin derivatives under metal free conditions using hypervalent iodine";Parvathaneni Sai Prathima et al.,;《Tetrahedron Letters》;20150928;第56卷;第6385-6388页 |
| "亚硝酸叔丁酯参与C—N 键构建的研究进展";魏文廷等;《有机化学》;20170510;第37卷;全文 |
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