CN106588936A - Hexahydropyrrolo-indole compound as well as preparation method and application thereof - Google Patents
Hexahydropyrrolo-indole compound as well as preparation method and application thereof Download PDFInfo
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- CN106588936A CN106588936A CN201611113112.3A CN201611113112A CN106588936A CN 106588936 A CN106588936 A CN 106588936A CN 201611113112 A CN201611113112 A CN 201611113112A CN 106588936 A CN106588936 A CN 106588936A
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- diindyl
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- 0 CC[C@@]1C(C)C(F)=[C@@]=CC=*C(CC2C=C[C@@]3C=C=CC(CC)=CC23)CC1 Chemical compound CC[C@@]1C(C)C(F)=[C@@]=CC=*C(CC2C=C[C@@]3C=C=CC(CC)=CC23)CC1 0.000 description 3
- IOJLRMLUXLDNEM-FUVGTJSASA-N CC/C=C\N=C/C[O](C(C)=O)C(C)=O Chemical compound CC/C=C\N=C/C[O](C(C)=O)C(C)=O IOJLRMLUXLDNEM-FUVGTJSASA-N 0.000 description 1
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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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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/16—Antifouling paints; Underwater paints
- C09D5/1606—Antifouling paints; Underwater paints characterised by the anti-fouling agent
- C09D5/1612—Non-macromolecular compounds
- C09D5/1625—Non-macromolecular compounds organic
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D7/00—Features of coating compositions, not provided for in group C09D5/00; Processes for incorporating ingredients in coating compositions
- C09D7/40—Additives
- C09D7/60—Additives non-macromolecular
- C09D7/63—Additives non-macromolecular organic
Abstract
The invention belongs to the technical field of marine antifouling, and discloses a hexahydropyrrolo-indole compound of a formula (I) as shown in the specification; in the formula, R1 and R2 represent single-substituted or multi-substituted benzyl; R1 and R2 can be identical substituent groups. A synthesis route comprises that indole-3-acetonitrile is adopted as an initial synthesis raw material. A method for preparing the hexahydropyrrolo-indole compound, which is disclosed by the invention, has the advantages of being high in yield, easy to separate and the like. The compound has inhibition functions of different grades to staphylococcus aureus and escherichia coli, and can be developed as an antiflouring agent with potential application values in ship antiflouring.
Description
Technical field
The invention belongs to APollution prevention technology for ships field, is related to the new marine antifouling compound of a class, and in particular to one
Class hexahydropyrrolo diindyl class compound.The present invention gives this kind of compound synthesis method and its answering in terms of marine antifouling
With.
Background technology
Ship often suffers from the halobiontic surface attachment such as marine alga, barnacle, referred to as biodeterioration in oceanic trip.It is raw
Thing is stained the deadweight and ship resistance increase that can make naval vessel, so as to increase fuel consumption；The corruption of hull bottom steel plate can also be greatly accelerated
Erosion, reduces the service life on naval vessel.Harm is stained in order to reduce, many countries have all carried out grinding for environmental protection type ship anti-soil technology
Study carefully, wherein brushing antifouling paint becomes most widely used method.Brushing antifouling paint have good antifouling effect, feasibility it is strong,
One-time investment is few and the outstanding advantages such as need not manage.Anti-fouling agent in antifouling paint is main, maximally effective composition,
It is the core of antifouling paint.
The anti-fouling agent that traditional antifouling paint is used, such as TBT (tributyl tin), larger negative effect is caused to environment.
It is the developing direction of following anti-fouling agent and natural products active material is the main source of environmentally friendly anti-fouling agent, but carries
Natural products active material not only operating difficulties, complex steps are taken, and content is especially low, it is difficult to industrialized production.For this purpose, root
According to the design feature of natural products, can by chemical synthesis process obtain the substantial amounts of natural products with antifouling activity and its
Analog, to meet antifouling paint industrial production demand.
At present, indoles anti-fouling agent is one of most promising anti-fouling agent.To Benzazole compounds as antifouling
The research of agent is achieved with greater advance, but the current research with regard to indoles anti-fouling agent is concentrated mainly on substituted base on 3- positions
Indole -3-formaldehyde class and giantreed alkaloid compound, and for other structures benzazolyl compounds antifouling activity study not
See detailed report.Therefore, the analog of such compound is obtained by chemical synthesis process, is conducive to developing novel antifouling
Agent, is that the research and development of environmental protection type anti-pollution paint are laid a solid foundation.
The content of the invention
It is an object of the present invention to pass through chemical synthesis process, the novel hexahydropyrrolo of various chemical constitutions and Yin are developed
Diindyl class compound, and this kind of compound is explored as the application of anti-fouling ship paint.
To achieve these goals, the present invention adopts bionic structure strategy, has designed and synthesized multiple lead compounds
Analog, using analytical technologies such as NMR the structural formula of target compound is confirmed.Further, the present invention adopts two times of test tube
Dilution method has investigated the compound of synthesis to staphylococcus aureus (staphylococcus aureus) and Escherichia coli
The bacteriostatic activity of (escherichia coli).The result of study that the present invention is presented will be follow-up hexahydropyrrolo diindyl class
Further research or initiative based theoretical of the compound as novel antifouling agent.
Hexahydropyrrolo diindyl class compound of the present invention, it has the chemical constitution of formula (I)：
Wherein, substituent R1、R2Represent monosubstituted or polysubstituted benzyl.For full and accurate description formula (I) hexahydropyrrolo diindyl
The structure of class compound, the monosubstituted benzyl of present invention definition should refer to the hydrogen of a carbon atom in benzyl on phenyl ring by other bases
Group replaces；And polysubstituted benzyl should refer to that the hydrogen of two or more carbon atoms in benzyl on phenyl ring is taken by other groups
Generation.For example, the hydrogen of a carbon atom on benzyl phenyl ring, this hydrogen can be replaced by halogen (fluorine, chlorine, bromine or iodine), formation neighbour,
Between, to halogeno-benzyl；Or replaced by methyl, form adjacent methyl-benzyl, a methyl-benzyl, to methyl-benzyl.Polysubstituted benzyl with
This is similar to, and is not described in detail here.
Preferably, the substituent R1And R2Represent any one in following substituents：
Substituent R 1 and R2 can be between methyl-benzyl, to methyl-benzyl, a Fluoro-benz rLl or to Fluoro-benz rLl in appoint
It is a kind of.
Hexahydropyrrolo diindyl class compound of the present invention, its substituent R1And R2Can be with identical, or different
Substituent.
If substituent R1And R2It is to methyl-benzyl, the hexahydropyrrolo diindyl class compound with formula (I) chemical constitution
For compound 1.
If substituent R1And R2It is to Fluoro-benz rLl, the hexahydropyrrolo diindyl class compound with formula (I) chemical constitution
For compound 2.
If substituent R1And R2Adjacent Fluoro-benz rLl is, the hexahydropyrrolo diindyl class compound with formula (I) chemical constitution
For compound 3.
If substituent R1And R2Adjacent methyl-benzyl is, the hexahydropyrrolo diindyl class compound with formula (I) chemical constitution
For compound 4.
In order to synthesize the hexahydropyrrolo diindyl class compound with formula (I) structure, The present invention gives preferred design
Synthetic route.Synthetic route comprises the steps：
Preferably, by said synthesis route, substituent R can be synthesized1And R2Identical hexahydropyrrolo diindyl class chemical combination
Thing.
In a specific embodiment, the synthetic method of the hexahydropyrrolo diindyl class compound, it comprises the steps：
1) indole -3-acetonitrile is dissolved in DMSO, and 37%HCl is added in ice bath, stirring reaction 30min under room temperature, adjusts pH value
Between 7～8, ethyl acetate extraction, precipitation obtains Oxoindole -3- acetonitriles；
2) sodium hydride is dissolved under anhydrous tetrahydro furan, room temperature and stirs 20min, and Oxoindole -3- acetonitriles are added in ice bath
Tetrahydrofuran solution, stir 25min under room temperature, benzyl bromide a-bromotoluene is added in ice bath, under room temperature stir, add ammonium chloride be quenched instead
Should, ethyl acetate extraction, precipitation obtains 1,3- positions benzyl and replaces Oxoindole -3- acetonitriles；
3) 1,3- positions benzyl replaces Oxoindole -3- acetonitriles to be dissolved in anhydrous tetrahydro furan, adds four in batches in ice bath
Hydrogen aluminium lithium, stirring reaction 1h under room temperature is heated to reflux 1.5h, is gone out reaction with ethyl acetate and water quenching successively, ethyl acetate extraction,
Precipitation, obtains 3a, double (benzyl) -1,2,3,3a of 8-, 8,8a- hexahydropyrrolos [2,3] diindyl；
4) double (benzyl) -1,2,3,3a of 3a, 8-, 8,8a- hexahydropyrrolos [2,3] diindyl is dissolved in anhydrous pyridine, in frozen water
In bath, acetic anhydride is slowly added dropwise thereto, stirring reaction 2h under room temperature adds methanol solution that reaction, precipitation, acetic acid second is quenched
Ester is extracted, precipitation, obtains 3a, and double (benzyl) -1,2,3,3a of 8-, 8,8a- hexahydropyrrolo -5- formic acid-[2,3] diindyl are that is, described
Hexahydropyrrolo diindyl class compound.
Above-mentioned hexahydropyrrolo diindyl class compound structure is novel.The synthetic route that the present invention recommends is also to synthesize such
Successful Application in compound, the synthetic route is novel, yield is high and product is easily isolated, it may be said that be to prepare such chemical combination
The relatively major path of thing.The concrete synthetic method of the hexahydropyrrolo diindyl class compound of formula (I) structure, has in detail in embodiment
Record.
On the other hand, the present invention has investigated the compound of synthesis to staphylococcus aureus using test tube doubling dilution
(staphylococcus aureus) and the bacteriostatic activity of Escherichia coli (escherichia coli).The hexahydropyrrolo is simultaneously
Benzazole compounds can include the hexahydro pyrrole as the active ingredient of marine antifouling agent, i.e. its active ingredient of marine antifouling agent
Cough up at least one in diindyl class compound.
Further, purposes of the hexahydropyrrolo diindyl class compound of the present invention in terms of marine antifouling.
The present invention at least has the advantages that following or beneficial effect：
(1) present invention establishes the process for synthesizing the hexahydropyrrolo diindyl class compound, the process institute
The reaction being related to is more classical efficiently, and reaction condition is gentle, and synthesis step is more brief, post-processes simple.
(2) The present invention gives various hexahydropyrrolo diindyl class compounds with general character structure, such compound knot
Structure is novel, different from the existing Benzazole compounds as anti-fouling agent application.The present invention provides bar for new anti-fouling agent exploitation
Part, hexahydropyrrolo diindyl class compound can be applied to marine antifouling aspect as anti-fouling agent composition.
(3) present invention determines 1,2,3,4 pairs of staphylococcus aureuses of compound using micro-dilution method
(staphylococcus aureus) and the bacteriostatic activity of Escherichia coli (escherichia coli), antibacterial activity test card
It is bright：Target compound is respectively provided with the inhibitory action of varying degree to supplying examination bacterium.As can be seen here, the hexahydropyrrolo diindyl class
Compound has higher antifouling activity than TBT, can be developed into the anti-fouling agent with potential using value in terms of marine antifouling, this
Invention will be that the subsequent design of such compound and its extensive application study provide theoretical foundation and technical support.
The present invention is further described in the examples below, and is not intended in any form limit as indicated in claim
Protection scope of the present invention.
Specific embodiment
Embodiment 1
The synthesis of hexahydropyrrolo diindyl class compound.The present embodiment provides the hexahydropyrrolo diindyl class compound
Synthesis step, it is specific as follows：
1st, the synthesis of Oxoindole -3- acetonitriles
Indole -3-acetonitrile being dried in round-bottomed flask in 250mL of 3.12g (20mmol) is weighed, 30mL DMSO are added,
15min is stirred under room temperature is completely dissolved it, then slow thereto with constant pressure funnel in placing reaction liquid into 0 DEG C of ice bath
150mL concentrated hydrochloric acid (37%HCl, V is added dropwiseDMSO:VHCl=1:5), reactant liquor is moved to after being added dropwise completely and 30min is stirred at room temperature,
TLC(PE:EA=4:1) detect that raw material reaction is complete.Under placing reaction liquid into 0 DEG C of ice bath, the dilution of 50mL water is added, with anhydrous
K2CO3Or anhydrous Na2CO3Solid adjust pH value, side stirring, frontier inspection survey solution pH value, by the pH value of solution be modulated at 7～8 it
Between.Whole system is moved under room temperature, is extracted with ethyl acetate (3 × 100mL), merge organic phase, organic phase uses respectively saturation
Sodium chloride (3 × 50mL) is washed, and anhydrous sodium sulfate drying, reduced pressure concentration obtains the compound oxidation indole -3-acetonitrile of 3.20g
(18.6mmol, 93%).
2nd, 1,3- positions benzyl replaces the synthesis of Oxoindole -3- acetonitriles
360mg NaH (15mmol) are weighed in the round-bottomed flask that 100mL is dried, and be slowly added in 5mL anhydrous four
20min is stirred under hydrogen furans, room temperature, whole system is placed in 0 DEG C of ice-water bath, with constant pressure funnel 500mg is slowly added dropwise
(3mmol) compound oxidation indole -3-acetonitrile tetrahydrofuran solution, after being added dropwise completely, whole system is put at room temperature
Stirring 25min, then whole system is placed in 0 DEG C of ice-water bath, then excessive change is slowly added dropwise thereto with constant pressure funnel
2- methyl bromobenzyl 0.9mL (6.9mmol, 2.3eq) of compound 1, or 2- fluorine bromobenzyl 0.8mL (6.9mmol, 2.3eq) of compound 2,
Or 4- methyl bromobenzyl 1.28g (6.9mmol, 2.3eq) of compound 3, or the 4- fluorine bromobenzyl 0.8mL of compound 4 (6.9mmol,
Tetrahydrofuran solution 2.3eq), waits to be added dropwise completely, reactant liquor is moved to and stir under room temperature, overnight.Next day, with TLC (oil
Ether:Ethyl acetate=4:1) detect, treat that substrate point disappears, reactant liquor is moved in 0 DEG C of ice-water bath, be slowly added dropwise thereto suitable
The saturated ammonium chloride solution of amount is quenched reaction, after stirring 10min, by rotary evaporation in vacuo the tetrahydrochysene furan in reaction system is removed
Mutter, be then extracted with ethyl acetate (3 × 50mL), washed using saturated nacl aqueous solution (2 × 20mL) respectively, anhydrous sodium sulfate
It is dried, reduced pressure concentration, crude product passes through chromatographic column quick separating (petroleum ether:Ethyl acetate=10:1 or petroleum ether:Ethyl acetate
=8:1) the compound b of 618mg, is respectively obtained1(R=compound 1,1.6mmol, 56%) or 662mg compound b2(R=ization
Compound 2,1.7mmol, 59%) or 685mg compound b3(R=compound 3,1.8mmol, 62%) or 575mg compound
b4(R=compound 4,1.5mmol, 51%).
3rd, the synthesis of indoles and pyrrole skeleton
Weigh the compound IAN of 600mg (1.6mmol)1Or the compound IAN of 600mg (1.5mmol)2Or 600mg
(1.6mmol) compound IAN3Or the compound IAN of 500mg (1.3mmol)4In the round-bottomed flask that 100mL is dried, add
The anhydrous tetrahydro furan stirring of 15mL is completely dissolved it, and whole system is placed in 0 DEG C of ice-water bath, is dividedly in some parts 460mg
Lithium Aluminium Hydride (12mmol, 7.5eq) or 420mg Lithium Aluminium Hydrides (11mmol, 7.5eq) or 460mg Lithium Aluminium Hydrides (12mmol,
7.5eq) or 380mg Lithium Aluminium Hydrides (10mmol, 7.5eq).Reactant liquor moves to and 1h is stirred at room temperature, and is then heated to reflux 1.5h.Will
Reactant liquor is cooled to after room temperature, then is moved on under 0 DEG C of ice bath, is slowly added dropwise 50mL ethyl acetate and 20mL in reactant liquor successively
Water quenching is gone out reaction.Reduce pressure suction filtration on residual solid side, and side is washed with appropriate ethyl acetate, only complete to washing.Merge organic phase, use
Saturated sodium-chloride (2 × 50mL) is washed, anhydrous sodium sulfate drying, reduced pressure concentration, and crude product passes through chromatographic column quick separating (oil
Ether:Ethyl acetate=2:1 or petroleum ether:Ethyl acetate=4:1) the compound c of 310mg, is respectively obtained1(0.84mmol,
53%), the compound c of 330mg2(0.85mmol, 57%), the compound c of 380mg3(1.03mmol, 65%), the change of 330mg
Compound c4(0.85mmol, 68%).
4th, phase homoalkyl in 1,3- positions replaces the synthesis of half calycanthine analog
With substrate IAN1～4, reaction reagent be acetic anhydride, weigh 200mg (0.54mmol) substrate IAN1, 200mg
(0.53mmol) substrate IAN2, 200mg (0.54mmol) substrate IAN3, 200mg (0.53mmol) substrate IAN4It is placed in the dry of 50mL
In dry round-bottomed flask, the anhydrous pyridine stirring and dissolving of 5mL is added, this system is placed in 0 DEG C of ice-water bath, respectively thereto
0.06mL (0.65mmol, 1.2eq) acetic anhydride is slowly added dropwise, waits to be added dropwise completely, move to room temperature, carry out room temperature reaction 2h.TLC with
Track detection question response is complete.Proper amount of methanol is added dropwise in reactant liquor reaction is quenched, reduced pressure concentration removes methyl alcohol and a small amount of pyridine,
Extracted with ethyl acetate (3 × 20mL) again, merge organic phase, then wash with copper/saturated copper sulphate solution (3 × 10mL) (removing according to this
Remaining pyridine), saturated nacl aqueous solution (3 × 10mL) washing, finally use anhydrous sodium sulfate drying.Reduced pressure concentration, gained
Crude product separates (petroleum ether using silica gel column chromatography:Ethyl acetate=8:1) 216mg N positions acetyl derivatives 1, are obtained
(1.0mmol, 97%), 208mg N positions acetyl derivatives 2 (1.0mmol, 94%), 211mg N positions acetyl derivatives 3
(1.0mmol, 95%), 201mg N positions acetyl derivatives 4 (1.0mmol, 91%).
The appraising datum of compound 1,2,3 and 4：
Compound 1：Yellow oily,1H-NMR(CDCl3,500MHz),δ7.03-6.98(m,8H),6.89-6.88(m,
1H), 6.83-6.77 (m, 3H), 6.66-6.62 (m, 1H), 6.62-6.60 (d, 1H, J=8Hz), 5.74 (s, 1H), 4.63,
4.49 (Abq, 2H, J=16.4Hz), 3.49-3.43 (m, 1H), 3.26-3.12 (m, 1H), 2.98,2.82 (Abq, 2H, J=
12.00Hz),2.31(s,3H),2.29(s,3H),1.93(s,3H).MS-ESI m/z:411.57[M+H]+.
Compound 2：Pale yellowish oil,1H-NMR(CDCl3,500MHz),δ7.04-6.99(m,2H),6.96-6.92(m,
3H), 6.90-6.88 (m, 2H), 6.85-6.83 (m, 5H), 6.68 (t, 1H, J=12Hz), 6.14 (d, 1H, J=12Hz),
5.72 (s, 1H), 4.54,4.39 (Abq, 2H, J=16.0Hz), 3.57-353 (m, 1H), 3.28-3.21 (m, 1H), 3.07,
2.82 (Abq, 2H, J=12.00Hz), 1.99 (s, 3H) .MS-ESI m/z:419.50[M+H]+.
Compound 3：Yellow oily,1H-NMR(CDCl3,500MHz),δ7.22-7.14(m,3H),7.07-6.90(m,
8H), 6.82-6.78 (m, 1H), 6.66 (t, 1H, J=16Hz), 6.23 (d, 1H, J=20Hz), 5.79 (s, 1H), 4.79,
4.63 (Abq, 2H, J=16.0Hz), 3.55-3.49 (m, 1H), 3.28-3.21 (m, 1H), 3.10,2.96 (Abq, 2H, J=
13.00Hz),1.94(s,3H).MS-ESI m/z:419.50[M+H]+.
Compound 4：Pale yellowish oil,1H-NMR(CDCl3,500MHz),δ7.17-7.05(m,8H),7.05-6.97(m,
3H), 6.63-6.61 (m, 1H), 6.59-6.55 (m, 1H), 6.18 (d, 1H, J=8Hz), 5.73 (s, 1H), 4.82,4.54
(Abq, 2H, J=16.4Hz), 3.56-3.52 (m, 1H), 3.28-3.21 (m, 1H), 3.15,2.92 (Abq, 2H, J=
12.00Hz),2.33(s,3H),2.00(s,3H),1.93(s,3H).MS-ESI m/z:411.57[M+H]+.
Embodiment 2
The bactericidal activity of hexahydropyrrolo diindyl class compound is determined.
N- methyl formates hexahydropyrrolo -5- methyl formates-[2,3] and-N- triazoles (N- fourths are determined using micro-dilution method
Base)-indoles is to staphylococcus aureus (staphylococcus aureus) and Escherichia coli (escherichia coli)
Bacteriostatic activity.Bacterial classification used is purchased from China General Microbiological DSMZ.
Using test tube doubling dilution, the sterilizing test tubes added with 2mL fluid nutrient mediums are taken, connect with being not added with test-compound
The test tube for planting bacterium is positive control, and the test tube of bacterium is not inoculated with yet as negative control to be not added with test-compound.Medicine initial mass
Concentration is 1g/L, successively doubling dilution, is well mixed.Add the μ L of bacteria suspension 200 of certain mass concentration in each test tube respectively,
Final bacterial concentration is set to be 104～105(cfu is CFU to cfu/mL, and 1cfu is referred to Jing after culture on agar plate
The single bacterium colony for being formed).After shaken cultivation 24h, minimum-bacteriostat mass concentration is judged according to the growing state of bacterium in test tube.
Judge accordingly, the MIC value (unit of hexahydropyrrolo diindyl class 1,2,3 and 4 pairs of two kinds of bacteriums of compound：G/L), examine
Survey the results are shown in Table 1.The result explanation of table 1, compound 1-4 is respectively provided with very strong suppression to Escherichia coli and staphylococcus aureus
Effect.
Table 1, compound 1,2,3 and 4 pairs of Escherichia coli, the MIC values of staphylococcus aureus
Further narration has been done to the present invention above in conjunction with embodiment, but the present invention is not limited to above-mentioned embodiment,
In the ken that one skilled in the relevant art possesses, can be making on the premise of without departing from present inventive concept
Various change.
Claims (8)
1. hexahydropyrrolo diindyl class compound, it is characterised in that the chemical constitution with formula (I)：
Wherein, substituent R1、R2Represent monosubstituted or polysubstituted benzyl.
2. hexahydropyrrolo diindyl class compound according to claim 1, it is characterised in that the substituent R1And R2Represent
Any one in following substituents：
3. hexahydropyrrolo diindyl class compound according to claim 2, it is characterised in that the substituent R1And R2It is identical,
Compound with formula (I) chemical constitution be it is following in any one：
4. the synthetic method of hexahydropyrrolo diindyl class compound, it adopts following reaction scheme：
5. the synthetic method of hexahydropyrrolo diindyl class compound according to claim 4, it is characterised in that the substituent
R1And R2It is identical.
6. the synthetic method of hexahydropyrrolo diindyl class compound according to claim 4, it is characterised in that including following steps
Suddenly：
1) indole -3-acetonitrile is dissolved in DMSO, and 37%HCl is added in ice bath, stirring reaction 30min under room temperature, adjust pH value 7～
Between 8, ethyl acetate extraction, precipitation obtains Oxoindole -3- acetonitriles；
2) sodium hydride is dissolved under anhydrous tetrahydro furan, room temperature and stirs 20min, and the four of Oxoindole -3- acetonitriles is added in ice bath
25min is stirred under hydrogen tetrahydrofuran solution, room temperature, benzyl bromide a-bromotoluene is added in ice bath, stirred under room temperature, add ammonium chloride that reaction is quenched,
Ethyl acetate is extracted, precipitation, is obtained 1,3- positions benzyl and is replaced Oxoindole -3- acetonitriles；
3) 1,3- positions benzyl replaces Oxoindole -3- acetonitriles to be dissolved in anhydrous tetrahydro furan, adds tetrahydrochysene aluminium in batches in ice bath
Lithium, stirring reaction 1h under room temperature is heated to reflux 1.5h, is gone out reaction with ethyl acetate and water quenching successively, ethyl acetate extraction, takes off
It is molten, obtain 3a, double (benzyl) -1,2,3,3a of 8-, 8,8a- hexahydropyrrolos [2,3] diindyl；
4) double (benzyl) -1,2,3,3a of 3a, 8-, 8,8a- hexahydropyrrolos [2,3] diindyl is dissolved in anhydrous pyridine, in ice-water bath,
Acetic anhydride is slowly added dropwise thereto, and stirring reaction 2h under room temperature adds methanol solution that reaction is quenched, and precipitation, ethyl acetate is extracted,
Precipitation, obtains 3a, double (benzyl) -1,2,3,3a of 8-, 8,8a- hexahydropyrrolo -5- formic acid-[2,3] diindyl, i.e., described hexahydropyrrolo
Diindyl class compound.
7. purposes of the hexahydropyrrolo diindyl class compound in terms of marine antifouling.
8. marine antifouling agent, its active ingredient includes hexahydropyrrolo diindyl class chemical combination any one of claims 1 to 3
Thing.
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| CN107522702A (en) * | 2017-10-16 | 2017-12-29 | 江苏科技大学 | A kind of new indole class compound and preparation method thereof |
| CN109438442A (en) * | 2018-12-03 | 2019-03-08 | 江苏科技大学 | A kind of Benzazole compounds, its synthetic method and its application |
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| CN113845524A (en) * | 2021-10-29 | 2021-12-28 | 四川农业大学 | Spiropyrrole indolone compound and preparation method and application thereof |
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| CN107417132A (en) * | 2017-06-07 | 2017-12-01 | 常州琨瑶纺织品有限公司 | A kind of preparation method of the antifouling antifog film of glass |
| CN107522702A (en) * | 2017-10-16 | 2017-12-29 | 江苏科技大学 | A kind of new indole class compound and preparation method thereof |
| CN109438442A (en) * | 2018-12-03 | 2019-03-08 | 江苏科技大学 | A kind of Benzazole compounds, its synthetic method and its application |
| CN109627240A (en) * | 2018-12-03 | 2019-04-16 | 江苏科技大学 | A kind of Benzazole compounds, its synthetic method and its antifouling purposes |
| CN109438442B (en) * | 2018-12-03 | 2021-12-17 | 江苏科技大学 | Indole compound, and synthesis method and application thereof |
| CN110256327A (en) * | 2019-06-20 | 2019-09-20 | 南京师范大学 | A kind of method of iron catalysis oxidation Benzazole compounds synthesis 2- indole ketone compound |
| CN112724146A (en) * | 2020-12-22 | 2021-04-30 | 江苏科技大学 | Chiral indole compound, preparation method thereof and ship antifouling application |
| CN112724146B (en) * | 2020-12-22 | 2022-04-15 | 江苏科技大学 | Chiral indole compound, preparation method thereof and ship antifouling application |
| WO2022135397A1 (en) * | 2020-12-22 | 2022-06-30 | 江苏科技大学 | Chiral indole compound, preparation method therefor and ship anti-fouling use thereof |
| CN113845524A (en) * | 2021-10-29 | 2021-12-28 | 四川农业大学 | Spiropyrrole indolone compound and preparation method and application thereof |
| CN113845524B (en) * | 2021-10-29 | 2023-11-07 | 四川农业大学 | Spiropyrrolindolone compound and preparation method and application thereof |
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