CN103706399A

CN103706399A - Cyclometallated iridium catalyst for reducing nitrogen heterocyclic compounds under mild conditions

Info

Publication number: CN103706399A
Application number: CN201310680656.8A
Authority: CN
Inventors: 张毅; 陈钢; 唐镜杰; 王浩鑫
Original assignee: Shanxi Provincial Guoxin Energy Development Group Co Ltd
Current assignee: Shanxi Provincial Guoxin Energy Development Group Co Ltd
Priority date: 2013-12-13
Filing date: 2013-12-13
Publication date: 2014-04-09

Abstract

The invention relates to a catalyst applied to homogeneous catalytic reduction reaction of organic compounds and in particular relates to a cyclometallated iridium catalyst for reducing nitrogen heterocyclic compounds under mild conditions. A structure formula of the catalyst is shown in the specification. The cyclometallated iridium catalyst CP*Ir (N<>N)Cl is used for reducing a series of nitrogen heterocyclic compounds under normal-temperature and low-pressure condition with 1atm and H2 in a TFE (Trifluoroethanol) solution; any additives, special devices and purified solutions are not used in a reaction process.

Description

For reduce the Cyclometalated iridium catalyst of heterocyclic nitrogen compound under temperate condition

Technical field

The present invention relates to the catalyst that organic compound carries out homogeneous catalysis reduction reaction, be specially a kind of for reduce the Cyclometalated iridium catalyst of heterocyclic nitrogen compound under temperate condition.

Background technology

The homogeneous catalysis reduction reaction of organic compound is the research topic of the awfully hot door of a class.Wherein, for the compound of HanC=CHe C=O functional group, the development of its reduction reaction is very ripe.But for the compound of HanC=N functional group especially heterocyclic nitrogen compound, due to its special molecular structure and armaticity, its reduction reaction is more difficult carries out, also relatively less to its achievement in research.

In research in the past, people conventionally use and contain Rh, Ir, and Ru, Os, the catalyst of the transition metal such as Mo and Fe carries out homogeneous catalytic reaction to heterocyclic nitrogen compound.But this class reaction conventionally need to be at high temperature and high pressure (H ₂) condition under carry out.And a lot of reaction needed are used additive, such as: bronsted acid, iodine and chloro-carbonic acid etc.In 2011, Crabtree found compound [Ir (NHC) (PPh ₃) (COD)] [PF ₆] can be at room temperature and low pressure (1-5atm, H ₂) heterocyclic nitrogen compound is carried out to hydrogenation under condition.But the defect of the method is to use PPh ₃functional group guarantees the activity of catalyst, and reactant only limits to quinolines.

So, without any a kind of homogeneous catalyst, can to multiple heterocyclic nitrogen compound, carry out reduction reaction at present simultaneously.

Summary of the invention

The object of the present invention is to provide a kind of for reduce the Cyclometalated iridium catalyst of multiple heterocyclic nitrogen compound under temperate condition.

The present invention adopts following technical scheme to realize:

For reduce the Cyclometalated iridium catalyst of heterocyclic nitrogen compound under temperate condition, structural formula is as follows:

1, the preparation method of catalyst is as follows:

1.1, part is synthetic:

Corresponding ketone and amine solvent in anhydrous toluene solution, with

in the situation of molecular sieve, add hot reflux 18 hours.The mixture obtaining, by diatomite filtration, carries out wash-out with ethyl acetate.Then use vacuum rotary evaporator that mixture is dry, obtain crude product and be recrystallized and obtain sterling in hexane solution, be i.e. part.

Principle:

For example:

1.2, Cyclometalated iridium catalyst is synthetic

Part (2.05eq.), [Cp*IrCl ₂] ₂(1.0eq.) and NaOAc (20.0eq.) and a stirring rod pack in the teat glass of a thickening, a cap test tube that has diaphragm of rubber on cuvette cartridge.This test tube is inflated with nitrogen 3 times repeatedly, and reacts under nitrogen protection.Utilize syringe by dry CH ₂cl ₂(10mL) solution joins in test tube.Then, the in the situation that of room temperature, strong stirring, react 18 hours.Reacted product, by diatomite filtration, is used CH ₂cl ₂solution carries out wash-out, uses MgSO ₄solid is dried and again filters, and through rotary evaporation, obtains crude product.This crude product is recrystallized in 10:1 n-hexane/dichloromethane solution, then under vacuum condition, is dried and obtains pure product, i.e. catalyst.

Adopt different ketone and amine can synthesize following 12 kinds of Cyclometalated iridium catalyst.

2, the screening to catalyst and reaction solution:

With reductase 12-methylquinoline (2a), above-mentioned catalyst is screened, as table 1:

Table 1

As shown in Table 1, use catalyst 1a-1f at TFE(ethapon) under room temperature, 2-methylquinoline (2a) is reduced in solution, the omnidistance hydrogen balloon (1atm) that uses of experiment is originated as hydrogen.From experimental result, in catalyst 1a-1f, only have 3 of electron rich, the catalyst 1f that 4-methylene-dioxy replaces has strong activity, as reaction 1-8.Although all the other catalyst 1g-1l also have activity, its activity is to be less than 1f, as reaction 9-14.When using [CP*IrCl2] 2 as catalyst or not using catalyst, not reaction, as reaction 1-7.Aspect solution selection, TFE solution is than the solution of other types, such as alcohol, ester, water etc. are more favourable to reduction reaction as can be seen from Table 1.This may be because TFE solution is more conducive to Cl ^-1the dissolving of ion, so catalyst is more easily sloughed Cl ^-1ion and form an activated room and come in conjunction with H Ir (III) is upper ₂molecule; In addition, the acidity of TFE solution higher (pKa=12.4), this makes this solution more easily and reactant or product generation hydrogen bond, stops these materials and H ₂molecule competition and Ir (III) room combine.Further experiment shows, is adding Cl ^-1ion (adds 10%NBu ₄cl) and PPh ₃(add 1%PPh ₃) situation under, the hydrogenation in TFE solution can be obstructed, conversion ratio reduces six times.Conclusion: through experiment, best reaction condition is: use catalyst 1f, react in TFE solution in the absence of additive.

3, catalyst of the present invention is as follows to the catalytic effect of multiple heterocyclic nitrogen compound:

3.1 hydrogenated quinoline compounds, as table 2:

Table 2

From table 2, can find out, under the condition of optimizing.It is corresponding 1,2,3 that a series of quinolines (comprise 2-, 3-, 4-, has the quinoline of substituent on 6-and 8-position) can be effectively reduced into, 4-tetrahydroquinoline.Meanwhile, with this understanding, other some functional compounds, such as, the quinoline that halogen, fat, hydroxy etc. (reaction 10 and reaction 12-14) replace also can effectively be reduced.It should be noted that especially material that 3-and this class of 4-methylquinoline be difficult to reduction also can obtain Restore All under higher temperature and longer reaction time.The luxuriant and rich with fragrance reaction of coughing up of reduction can obtain 1,2,3 of partial reduction, and 4-tetrahydrochysene phenanthrene is coughed up (reaction 8,9).Reaction 6 is successfully 2,2 '-diquinoline to be realized to homogeneous hydrogenation for the first time.Benzo pyridine can be reduced into the two hydrogen class products of 9,10-(reaction 7).

3.2, hydrogenation is containing C=N compounds, as table 3:

Table 3

As can be seen from Table 3: quinoxaline compound is with this understanding by reduction completely (reaction 1-3), and this is that this type of material can carry out homogeneous phase reduction for the first time at ambient temperature.Imine compound also has good reduction effect (reaction 4-10).The compound that contains nitrogen groups also has good reaction result (reaction 10).Benzazole compounds with protecting group is normally difficult to the material of homogeneous phase reduction, but under this condition, this type of substance accesses good reduction result (reaction 11-13).But, for the also not reaction of principle under this condition of ketone and vinyl compound, this explanation catalyst 1f for C=N selectively higher than C=O and C=C.

The beneficial effect of catalyst of the present invention is as follows:

1, under temperate condition (room temperature, 1atm hydrogen) and do not use and in the situation of any additive, realize the reduction to multiple heterocyclic nitrogen compound.

2, result by experiment, finds to compare with the homogeneous catalytic reaction to this compounds in the past, and the reducing activity of the catalyst 1f Rh/C catalyst more best than known activity is high more than 14 times.With catalyst [IrCl (COD)] best in other homogeneous catalytic reactions ₂/ P-Phos/I ₂compare, 1f catalyst activity is its 6 times.

In the present invention, utilize Cyclometalated iridium (III) catalyst Cp*Ir (N^C) Cl (room temperature under gentle condition, 1atm hydrogen) in TFE solution (ethapon), to a series of heterocyclic nitrogen compounds (such as quinoline, 3,4-dihydro-isoquinoline, quinoxaline and indoles etc.) carry out selective reduction.In reduction process, do not use additive, the solution of special device and purification.The technical problem that just can carry out the in the situation that of having solved former this type of reaction needed at HTHP or had additive, and solved the too narrow problem of catalyst applicability in the past.These heterocyclic nitrogen compounds after being reduced, are widely used in medicine synthetic, and natural material is synthetic, and organic dyestuff is synthetic, in perfume materials and hydrogen storage material.

The specific embodiment

Below specific embodiments of the invention are elaborated.

Concrete preparation method is as follows:

1, part is synthetic:

1-benzo [1,3] dioxole-5-ethyl ketone and 4-aminoanisole are dissolved in anhydrous toluene solution, with

in the situation of molecular sieve, add hot reflux 18 hours.The mixture obtaining, by diatomite filtration, carries out wash-out with ethyl acetate.Then use vacuum rotary evaporator that mixture is dry.The crude product obtaining, in n-hexane, recrystallization obtains white solid, i.e. ligand L 1f.Nuclear-magnetism result: 1H NMR (400MHz, CDCl3): 7.57 (d, J=2.0Hz, 1H), 7.44 (dd, J=8.0,2.0Hz, 1H), 6.90 (d, J=9.0Hz, 2H), 6.84 (d, J=8.0Hz, 1H), 6.74 (d, J=9.0Hz, 2H), 6.01 (s, 2H) 3.81 (s, 3H), 2.20 (s, 3H).

2, catalyst 1f's is synthetic

Above-mentioned synthetic ligand L 1f (2.05eq.), [Cp*IrCl ₂] ₂(1.0eq.) pack in the teat glass of a thickening cap test tube that has diaphragm of rubber on cuvette cartridge into together with NaOAc (20.0eq.) and a stirring rod.This test tube is inflated with nitrogen 3 times repeatedly, and reacts under nitrogen protection.Utilize syringe by dry CH ₂cl ₂(10mL) solution joins in test tube.Then, the in the situation that of room temperature, strong stirring, react 18 hours.Reacted product, by diatomite filtration, is used CH ₂cl ₂solution carries out wash-out, uses MgSO ₄solid is dried and again filters, and through rotary evaporation, obtains crude product.This crude product is recrystallized in n-hexane/dichloromethane solution of 10:1, then under vacuum condition, is dried and obtains yellow solid, i.e. catalyst 1f.Nuclear-magnetism result: 1H NMR (400MHz, CDCl3): 7.18 (d, J=8.0Hz, 1H) 6.92 (s, br2.2H), 6.56 (d, J=8.0Hz, 1H), 6.06 (d, J=1.5Hz, 1H), 5.99 (d, J=8.0Hz, 1H), 3.84 (s, 3H), 2.35 (s, 3H), 1.48 (s, 15H).

Above-mentioned Cyclometalated iridium catalyst Cp*Ir (N^C) Cl is (23 ℃ ± 2 ℃ of room temperatures under gentle condition, 1atm hydrogen) in TFE solution (ethapon), to a series of heterocyclic nitrogen compounds (such as quinoline, 3,4-dihydro-isoquinoline, quinoxaline and indoles etc.) carry out selective reduction.

Claims

1. for reduce the Cyclometalated iridium catalyst of heterocyclic nitrogen compound under temperate condition, it is characterized in that: structural formula is as follows:

2. Cyclometalated iridium catalyst claimed in claim 1 under temperate condition, carry out the application in catalytic reduction reaction to heterocyclic nitrogen compound in TFE solution, and described temperate condition is: temperature is 23 ℃ ± 2 ℃, H ₂pressure is a standard atmospheric pressure.

3. a preparation method for Cyclometalated iridium catalyst claimed in claim 1, is characterized in that: comprise the steps:

(1), part is synthetic:

in the situation of molecular sieve, add hot reflux 18 hours, the mixture obtaining passes through diatomite filtration, with ethyl acetate, carry out wash-out, then use vacuum rotary evaporator that mixture is dry, the crude product obtaining, in n-hexane, recrystallization obtains white solid, i.e. ligand L 1f;

(2), catalyst 1f's is synthetic

Above-mentioned synthetic ligand L 1f, [Cp*IrCl ₂] ₂pack in the teat glass of a thickening together with NaOAc and a stirring rod, a cap test tube that has diaphragm of rubber on cuvette cartridge, this test tube is inflated with nitrogen 3 times repeatedly, and reacts under nitrogen protection, utilizes syringe by dry CH ₂cl ₂(10mL) solution joins in test tube; Then, the in the situation that of room temperature, strong stirring, react 18 hours, reacted product, by diatomite filtration, is used CH ₂cl ₂solution carries out wash-out, uses MgSO ₄solid is dried and again filters, and through rotary evaporation, obtains crude product, and this crude product is recrystallized in n-hexane/dichloromethane solution of 10:1, then under vacuum condition, is dried and obtains yellow solid, i.e. catalyst 1f.