FR2679554A1 - Process for the synthesis of nitroalkanes from nitroolefins - Google Patents

Abstract

Process for the selective hydrogenation of a carbon-carbon bond in a nitrated unsaturated organic compound, in a solvent, in the presence of a catalyst consisting of a ruthenium complex dissolved in the solvent; an amine, an aminophosphine, a diphosphine iminium salt or/and a mixed phosphine is preferably added to the reaction mixture.

Description

The invention relates to a process for the hydrogenation of the double bond of nitroolefins to produce the corresponding nitroalkanes. It allows obtaining these with excellent conversion rates and selected glazed
The selective reduction of nitro-olefins to nitro-alkanes, without practically reducing the NO2 group to amine, is a difficult task, which has not been achieved, so far, with a truly industrial success. Researchers have therefore explored various routes: with palladium hydrogenation supported by activated carbon (US Pat. No. 3,297,769), the disadvantages of reduction in a heterogeneous medium have been found. The search for a method in a homogeneous medium has led to TREFOUEL et al. . (INSA), Bull.

Chem. Soc. Jpm 60, 4492-4494 (1987) to study the reduction of nitrostyrene to sodium borohydride, NaBH4, which the authors find very difficult (page 4492). Better results would be obtained with NADH formed by grafting nicotinamide onto a halo-methylated copolymer of styrene with divinylbenzene, which would reduce the olefinic bond at 800C, in acetonitrile in the presence of a Mg salt; however, the method is laborious and the preparation of the catalyst alone requires 6 days (page 4493, paragraph "Experimental").

It has also been proposed to use a particular NADH together with silica gel: Masayuki FUJI,
Bull. Chem Soc. Jpn. 4029-4035 (1988). It is a "Hantzsch ester" which is used, namely bis (ethoxycarbonyl) -3,5-dimethyl-2,6-dihydro-1,4-pyridine. There again, the preparation of the reducing agent is tedious, and the presence of gelatinous silica makes the disadvantages of hydrogenations in a heterogeneous medium.

In this state, unfavorable, of the prior art, the present invention provides a significant improvement, in that it allows a hydrogenation in homogeneous medium, very effective, various compounds bearing olefinic unsaturation. These compounds can carry other functions and / or heteroatoms, and the saturated product can be obtained with a very high conversion and selectivity, the preparation of the catalyst being easy and economical. Thus, the process according to the invention makes it possible, in particular, to obtain nitroalkanes or nitroarylalkanes from nitroalkenes or nitroaryl alkenes, without practically
NO2 be affected.

Particular interesting applications of the invention include the hydrogenation of cyclic compounds carrying unsaturation and sulfur. While thio- or thia-compounds generally give rise to great difficulties, in conventional hydrogenation processes, due to the poisoning of the catalyst by sulfur, it is unexpectedly observed that this pit disappears in the process. case of the process according to the invention.

This has the remarkable advantage of allowing the efficient hydrogenation of various sulfur product derivatives, in particular cyclic compounds such as, for example, thiophene, thioxene, thiazole, thionaphthene, thioxanthene, thioxanthone and the like. Thus it became possible to reduce the nitro vinyl thiophene nitro ethyl thiophene, with excellent yield and selectivity, while conventional methods gave poor results for this reaction.

The hydrogenation process according to the invention consists in subjecting a nitrated compound bearing olefinic unsaturation to the action of hydrogen in a solvent in the presence of a catalyst consisting of a ruthenium complex, dissolved in this solvent. Various Ru complexes may be employed, and especially those (or their precursors) which have the general formula RunHCpOrTt n being 1 to 4; m = 0 to 4; Halogen; p = 0 to 2
Q denotes CO or OCOR 'where R' is C1-C4 alkyl or C6-C10 aryl; r = 1 to 12; T is a ligand, in particular phosphine, which may be PR "3 where R" denotes a C 1 to C 18 aliphatic group and / or a C 6 to C 10 aryl, while t is 0 to 3. R "may comprise a amine group.

Here are some of the complexes thus defined H4Ru4 (CO) 12; Ru3 (CO) 12-precursors.

Catalysts: RuCl2 (CO) 2 (PR3) 2; RuHCl (CO) 2 (PR3) 2 RuHCl (CO) (PR3) 3; RuH (OCOR) (CO) (PR3) 2
RuH (OCOR ') (CO) (PR3) 3; [H3Ru4 (CO) 12] [PPh3-N-PPh3] RuCl (CO) (PPh Py) and the like.

2 2 2
In these compounds R can be an aliphatic, cycloaliphatic, mainly C 1 to C 18 and / or C 6 to C 10 aryl group.
The reaction medium is preferably added with an amine, an amino-phosphine, a diphosphine iminium salt and / or a mixed phosphine.

The preferred proportion of such adjuvants in the hydrogenation medium is 1 to 100 moles per Ru atom present in the catalyst or, more preferably, 5 to 50 moles per Ru atom.

The addition of a sufficient amount of amine, phosphine, imino or amino-phosphine to the precursor of the catalyst leads to the replacement of a portion of the CO with such a T compound of the general formula given above; Catalysts similar to those of the preceding lines are thus obtained with phosphine or. amino-phosphine used instead of PR3.

Catalyst proport can vary widely, as in most catalytic reactions; however, the preferred limits. are between the amounts of catalyst containing Or005 at 0.1 Ru atom per mole of unsaturated compound to be hydrogenated, and especially between 0.01 and 0.05 Ru atom.

on utilise de préférence celles dans lesquelles R1, R2,R3, semblables ou différents, sont des groupes aliphatiques, cycloaliphatiques ou/et aryliques, principalement en C1 à C18, et aryliques, tout au plus un seul de ces symboles pouvant désigner H.Les plus courantes, parmi ces amines, et économiquement les plus accessibles sont, par exemple, les diméthylphénylamine, triéthylamine, éthylpropylamine, diméthyl éthylamine, di-isopropylamine, tripropylamine, dicyclohexylamine, diméthyl cyclohexylamine, isopropylphénylamine, triphénylamine, diméthl-1,4 éthylène diamine, N-méthyl propylène diamine etc. De préférence les groupes R1 à R3 sont en
C1 à C6.Amines, suitable according to the invention, are mono
Or poly-secondary amines or ereres res and especially the latter. By designating them by

those in which R1, R2, R3, which are alike or different, are preferably aliphatic, cycloaliphatic and / or aryl groups, mainly C 1 to C 18, and aryl groups, at most only one of these symbols which can be designated H. the most common of these amines, and economically the most accessible are, for example, dimethylphenylamine, triethylamine, ethylpropylamine, dimethylethylamine, di-isopropylamine, tripropylamine, dicyclohexylamine, dimethyl cyclohexylamine, isopropylphenylamine, triphenylamine, 1,4-dimethyl-ethylenediamine, N-methyl propylene diamine etc. Preferably, the groups R1 to R3 are in
C1 to C6.

où les groupes R1 à R4 ont la même signification 5 que les
R1 à R3 définis plus haut . Conviennent également des aminophosphines dont le P n'est pas directement lié à N,par exemple

Amino-phosphines, the addition of which has a very marked favorable effect on the rate of hydrogenation, and on the yield of nitroalkane, may be represented schematically by the formula

where groups R1 to R4 have the same meaning as
R1 to R3 defined above. Also suitable are aminophosphines whose P is not directly linked to N, for example

A remarkable example of an additive is bis (triphenylphosphine) -iminium, the salts of which
[(PPh 3) 2 N] + [X], especially those in which X is a halogen, a cyanide group or a carboxylate, strongly increase the selectivity to nitroalkane ormé and allow to work under a lower pressure of hydrogen.

A dans lesquelles les symboles R1 à R4 ont la même signification que plus haut, mais au moins deux des groupes liés à P sont différents 1' un de l'autre. De préférence, une partie de ces groupes sont des aryles, les autres étant des allyles ou des cycloalkyles. n est en général 1 à 6. il est connu, dans la technique des catalyseurs au ruthénium, d'incorporer la triphénylphosphine P(C6H5)3 dans le complexe de ce métal, mais il est surprenant que l'ac- tion activante de la phosphine soit fortement accrue, lorsque les trois groupes hydrocarbonés ne sont pas identiques. Ce fait n'a jamais été signalé à la connaissance des inventeurs du présent procédé.Or, les résultats des hydrogénations sont meilleurs siles R1 à R4 ne sont pas identiques, et particulièrement quand il y a en même temps des aryles et des groupes aliphatiques.With regard to the mixed phosphines, useful for carrying out the invention, they can be represented by formulas such as

Wherein the symbols R1 to R4 have the same meaning as above, but at least two of the groups related to P are different from each other. Preferably, some of these groups are aryls, the others being allyls or cycloalkyls. n is generally 1 to 6. It is known in the ruthenium catalyst technique to incorporate triphenylphosphine P (C6H5) 3 in the complex of this metal, but it is surprising that the activating action of the phosphine is greatly increased when the three hydrocarbon groups are not identical. This fact has never been reported to the inventors of the present process. However, the results of the hydrogenations are better if R1 to R4 are not identical, and particularly when there are at the same time aryls and aliphatic groups.

Examples of mixed phosphines according to the invention are given below, without limitation, methyl diphenyl phosphine, diethyl tolyl phosphine, propyl dihexyl phosphine, dimethyl cyclohexyl phosphine, ethyl dioctyl phosphine, bis (methyl) phenyl phosphine, bis ( ethyl tolyl phosphino) ethane, bis (propyl octyl phosphino) methane, etc.

Since the process of the invention is carried out in solution in a solvent, it is chosen according to the solubility of the materials treated, among liquids which are chemically inert with respect to these materials. Solvents such as methanol, ethanol, ethyl ether, tetrahydrofuran, dioxin, benzene, toluene, dichloromethane and the like can be used most often. and various mixtures thereof. It is good to operate on solutions containing 0.05 to 3 moles of substrate to be hydrogenated per liter of solvent, and preferably 0.1 to 2 moles / liter.

The hydrogenation is carried out at hydrogen temperatures and pressures which depend on the nature of the substrate and that of the catalyst employed. Most often, the temperature is about 20 to 140 C and especially 80 to 1300C. The hydrogen pressure generally varies between 1 to 120 bar, and preferably between 20 and 100 bar.

We describe after a procedure that was practiced during work on the process according to the invention.

The catalytic solution is prepared under an inert atmosphere (nitrogen or argon) before being introduced into an autoclave which is purged beforehand by several vacuum-argon cycles. The autoclave is equipped with a double wall, for heating by circulating oil, and a magnetic bar for magnetic stirring. After introduction of the catalytic solution, the autoclave is pressurized and then heated with magnetic stirring (1000 rpm).

The catalytic reactions are monitored by regular sampling and analysis by vapor phase chromatography (VPC). The products, resulting from the reduction of nitroolefins, are identified by CPV, first by comparison with authentic samples and then by nuclear magnetic resonance (1H NMR). The nitroalkanes, obtained after reduction of the corresponding nitroolefins, are isolated from the reaction mixture by distillation under reduced pressure.

The catalyst is recovered by evaporation of a large amount of solvent and then precipitation by a suitable nonsolvent such as methanol, ethanol, ethyl ether or the like depending on the catalyst used.

According to a particular feature of the invention, following a first hydrogenation, a new substrate portion is added to the reaction medium and a second hydrogenation is carried out. This provides excellent performance and contributes to the economy of the process.

In His examples given below, we proceeded as follows. In a Schlenck apparatus, a catalytic quantity of complex was introduced under nitrogen.
RuCl 2 (CO) 2 (PPh 3) 2 C, 66 mmol (0.5 g) to which 30 ml of degassed hydrochloride solvent was added. The additive according to the invention, in particular 16.5 mmol triethylamine (2.3 ml), was then added, followed by a large excess of substrate to be hydrogenated, 33 mmol, in a large amount of solvent (150 ml). An amount of internal standard, selected from the family of alkanes, was also introduced. The homogeneous solution was placed in the autoclave under nitrogen. Then, the autoclave was pressurized with hydrogen and heated to the given temperature for a time indicated in each example.

After cooling and evacuating the excess gas, the brownish-yellow solution was removed from the reactor. Identification of the reaction mixture was by vapor phase chromatography, infrared and nuclear magnetic resonance.

In the case of the nitro vinyl thiophene, "NVT", the quantitative analysis of the nitroalkane (nitro ethyl thiophene, or thienyl nitroethane) (TNE) obtained by catalytic reduction of the nitroolefin (NVT), was carried out by quantitative determination. using an internal PVC calibration, the decane being used as an internal standard.

EXAMPLES 1 TO 6
Reduction of NVT in TNE by RuCl2 (CO) 2 (PPh3) 2 in the presence of triethylamine.

<Tb>

<SEP> 11 <SEP> S
<tb> / e <SEP> MCIrT = CH.No <SEP> t <SEP> 07r <SEP> The,
<tb> 2 <SEP> 2 <SEP> nu2
<tb>"NVT"<SEP>"TNE"
<Tb>
According to the method and apparatus described above, the effect exerted by triethylamine in the reaction medium is studied. Example 1 is carried out in the absence of amine whereas the tests 2 to 6 are carried out in the presence of 5 to 50 molar equivalents of N (C 2 H 5) 3 with respect to the catalyst.

It is evident from Table I that, for a generally total conversion, the presence of NEt3 increases the activity of the catalyst. Indeed, the total duration goes from 24 to 8 hours maximum, while the selectivity remains substantially constant. This increase in activity therefore makes it possible to increase the substrate-to-catalyst molar ratio. Another remarkable fact in these tests is that the initial precursor becomes more active in reducing a new amount of NVT. Indeed, for an equivalent quantity of substrate (50 Eq), the total duration passes
From 6 to 4 hours (tests 3 and 4). At the same time, the selectivity is significantly improved since it becomes practically total, 98%. This proves that the catalytically active species is not deactivated at the end of reduction.

TABLE I.

Reduction of vinyl thiophene
Tests Molar Report Duration Conversion Selectivity
substrate / NEt3 / in
N catal. 9d hours
1 50/0/1 24 l00 87
0/5/1
3 50/25/1 6 98 72
4 * + 50Eq from NVT 4 100 98
5 100/25/1 7 95 88
6 100/50/1 7 89 60 (*) Essa 4: a new quantity of NVT (50
Equivalents) at the end of the test 3, which amounts overall to a ratio substrate / NEt3 / catalyst: 100/25/1.

EXAMPLES 7 TO 10 (TABLE II)
Selective reduction of NVT in TNE using RuCl2 (CO) 2 (PPh3) 2 in various solvents.

According to the technique and with the aid of the apparatus used in the preceding examples, the effect of the nature of the solvent on the activity of the catalyst is studied. We work with a molar ratio Substrate / NEt3 / Catalyst: 50/5/1. The results obtained show that the best selectivity for nitroalkane is obtained in this solvent.

TABLE II
Testing of various solvents
Tests Solvents Duration Conversion Selectivity
N hour%%
7 CH2C12 8 95 78
8 THF 9 73 52
9 Benzene 9 95 65
10 Benzene / 9 95 63
EtOH 1/1
EXAMPLES 11 TO 14 (TABLE III)
Reduction of Yv'T with RuCl2 (CO) 2 (pPh3) 2 under different temperature and pressure conditions
Using the technique and the apparatus of the preceding examples, the effects exerted by the temperature and the hydrogen pressure on the various parameters of the reaction are studied. The ratios substrate / NEt3 / ca catalyst are 100/25/1. The solvent used is dichloromethane. The temperature and pressure domains that allow the reduction of NVT are very wide. However, only the sensitive zones are described, which offer the best efficiency of the catalyst. From Table III it can be seen that there is a net effect of temperature and hydrogen pressure on the duration of the reaction. When one goes from 100 C to 1200C and from 40 to 80 bars in hydrogen, the reaction time required for a total conversion of the substrate decreases.

TABLE III
Temp. Pressure (H2) Duration Conversion Selectivity
NC bars hours%%
11 100 40 9 100 93
12 120 40 7 95 88
13 120 80 5 99 81
14 120 60 6 100 85
EXAMPLES 15 TO 19 (TABLE I)
Reduction of Nv'T with different mononuclear ruthenium (II) catalysts.

According to the previous technique and apparatus, the effect of different ruthenium (II) catalysts on the transformation of the substrate is investigated for the same duration of 24 hours, using THF as the solvent (Table IV). Note that in this series of tests, we work in the absence of amine.

this comparative study shows that RuCl2 (PPh3) 2 is by far the most effective for reducing NVT in
TNE.

BOARD
Catalysts Tests Conversion Selectivity
N ~~~~~~~~~~~~~~~~~~~~~~~~%%
RuCl2 (CO) 2 (pPh3) 2 100 87
RuHCl (CO) 2 (PPh 3) 2 100 73
RuHCl (CO) (PPh 3) 3 70 60
RuH2 (CO) (PPh3) 3 80 64
19 * RuH (OCOR) (CO) (PPh 3) 3 70 49 (*) R = alkyl (Me, Bu)
EXAMPLES 20 TO 27 (TABLE V)
Catalytic reduction of NVT with Ru3 (CO) 12 as catalytic precursor
According to the previous technique and apparatus, the action of the trinuclear ruthenium catalyst, with various additives, on the transformation of the substrate is studied.
NVT. It is noted that, despite the existence of several reactive centers in the complex, the reduction of
NVT remains essentially selective in NET.However, there are secondary products in small quantities, derived from secondary reactions on NVT. This reduction can be improved at optimized temperatures and pressures. The most remarkable fact is that the presence of an equivalent of phosphine phosphine "PPNCl" significantly increases the nitroalkane selectivity (compare N 22 with 24). This whole series of catalytic tests is carried out in THF for 24 hours.

TABLE V
Reduction using the Ru3 (CO) 12 catalytic precursor
Additive tests s PH, Temp. Selectivity Conversion
equivalent
N Molars bars C%%
20 no 40 100 68 31
21 no 100 100 80 50
22 no 40 120 92 60
23 no 100 120 100 80
24 (a) PPNCl 40 12.0 100 91
25 (a) PPNC1 100 120 96 92
26 (b) PPh3 40 120 67 46
27 (c) DPPM 100 120 100 72 - (a): tests 24 and 25: carried out with 1 equivalent of
[(PPh3) 2N] [Cl], bis (triphenylphosphine) chloride
iminium per mole of catalyst, - (b): test 26: 3 equivalents are added
of PPh3 per mole of catalyst - (C): test 27: "DPPM" bis (diphenyl phosphino) methane-3
equivalent per mole of catalyst
EXAMPLES 28 TO 32 (TABLE VI)
Catalytic reduction of NVT with, as precursor,
H4Ru4 (CO) 12
According to the previous technique and apparatus, the influence of the H4Ru4 (CO) 12 complex is studied in the same way as for Ru3 (CO) 12. The solvent used is THF. The substrate / catalyst ratio is 100.

after the results it is found that in the absence of any additive H4Ru4 (CO) 12 itself suitably reduces NVT to TNE. IE. Catalyst offers better selectivity than Ru3 (CO) 12. It becomes much more effective when it is added a phosphine (31,32) or an aminophosphine (30).

TABLE VI
Catalytic reduction of NVT using H4Ru4 (CO) 12
Additives tests PH Temp. Conversion Equivalents
N Molars bars C%%
28 no 40 120 100 68
29 no 100 120 100 72
30 PPNC1 100 100 100 93
31 (a) PPh3 100 100 100 95
32 (b) PPh3 100 100 100 93 (a): This is H4Ru4 (CO) 11 (PPh3) (b) This is 4 4 (00) 11 (PPh3) 2 (a) and (b) ): These two species are synthesized by
substitution of one or two molecules of CO by
PPh3 phosphines.

EXAMPLES 33 and 34 (TABLE VII)
Catalytic reduction of> -nitrostyrene by RuCl2 (CO) 2 EPPh3j
comparison with NVT
The apparatus and the technique are those of the preceding examples; we study the effect exerted by the nature of the group carried by the nitroolefin in &alpha; of the double bond. For this, we chose the 3-nitrostyrene which most closely resembles the NVT substrate The substrate / NEt3 / catalyst ratio is here 100/25/1 and a better TNE selectivity for the reduction of NVT is noted.

TABLE VII
Tests Substrate Duration Conversion Selectivity
(hour) in
nitroalkane% ~~~~~~~~~~~~~~~ ~~~~~~~% o
33 t ssnitrostyene 7 99 78
34 NVT 7 95 88 - solvent used: CH2Cl2.

EXAMPLES 35 to 38 (TABLE VIII)
Reduction of nitrovinyl thiophene - (NVT) on Ru mono-nuclear catalysts with amine phosphine ligands.

The reaction is carried out in dichloromethane as a solvent, on 3.5 mmol of NVT with 0.07 mmol of catalyst, under a pressure of 40 bar H 2. Catalyst / NEt3 / NVT molar ratios are 1/5/50 for Examples 36 to 38, while 35 is performed without triethylamine.

In examples 36 and 37 of 14 hours of total duration, a sample only takes place at the 7th hour.

TABLE VIII
Ex. Catalyst Duration. Selectivity Conversion
n0 H%%
RuCI 2 (CO) (PPh 2 P y) 2 7 46 20
36 RuCl2 (CO) (PPh2Py) 2 7 68 47
14 96 71
RuCl 2 (CO) 2 (PP 2 P y) 2 7 68 47
14 81 60
RuCl2 (CO) 2 (PPh2Py) 7 45 26
EXAMPLES 39-43
Reduction of nitrovinyl thiophene with the catalyst
RuCl 2 (CO) 2 (PPh 3) 2 (same as in Examples 1 to 15) in the presence of different amines.

Operated under a pressure of 40 bars of H2, at 1200C, in 30 ml of CH2Cl2, on 1 g NVT (6.45 mmol) with 0.05 g (0.065 mmol) of catalyst precursor.

Table IX gives the results obtained by the addition of various amines.

TABLE IX
Example Amines Duration Conversion Selectivity
in tine
n H%%
39 without 24 100 80
40 NMt2 and 7 98 85
41 NEt3 7 95 80
42 NBu3 7 60 50
43 Pyridine 7 52 45

Claims (13)

1. A process for selectively hydrogenating a carbon-carbon bond in an unsaturated organic compound, nitrated, in a solvent, characterized in that the hydrogenation takes place in the presence of a catalyst consisting of a dissolved ruthenium complex in this solvent. 2. Method according to claim 1, characterized in that the solution is supplemented with an amine, amino-phosphine, diphosphine iminium salt and / or mixed phosphine, preferably in a proportion of 1 to 100 moles per Ru atom present in the catalyst. 3. A process according to claim 2, characterized in that the amine is a secondary mono- or poly-amine, and preferably tertiary, bearing aliphatic groups, cyclo-aliphatic and / or aryl C1 to C18. 4. Process according to claim 3, characterized in that the amine being of the type

 The groups R, R, R which are similar or different are at C 1 to C 6. 5.Procédé according to one of the preceding claims, characterized in that the amino-phosphine has hydrocarbon groups aliphatic, cycloaliphatic and / or aryl, C1 to C18. 6. Process according to one of the preceding claims, characterized in that the diphosphine iminium salt provides an anion, in particular halogen, cyanide or carboxylate. 7. Process according to claim 6, characterized in that the diphosphine iminium salt is bis (triphenyliosphino) iminium chloride, [P (C6H5) 3] 7 2NCl. 8. Process according to one of the preceding claims, characterized in that the mixed phosphine carries C1-C18 aliphatic, cycloaliphatic and / or aryl hydrocarbon groups and that at least two of them are different from each other. . 9. The method of claim 8, characterized in that the mixed phosphine comprises both aliphatic and aryl groups and in particular, it is bis (diphenyl phosphino) methane. 10. Process according to one of the preceding claims, applied to the reduction of nitro vinyl thiophene to thienyl nitroethane. 11. Process according to one of the preceding claims, characterized in that the catalyst or its precursor is chosen from complexes of the RunHmXpOrTt type where n is 1 to 4, m is 0 to 4, X is a halogen, p = 0 to 2 , Q is CO or OCOR ', R' is C 1 -C 12 alkyl or C 6 -C 10 aryl, r is 1 to 12, T is a phosphine ligand, in particular PR "3 where R" is an aliphatic group C1 to C18 or / and a C6 to C10 aryl, while t is 0 to 3. 12. Method according to one of the preceding claims, characterized in that the amount of catalyst employed comprises 0.005 to 0.1 atom of Ru, and preferably 0.01 to 0.05 Ru atom per mole of compound to be hydrogenated, the temperature being from about 200C to 1400C and the hydrogen pressure from 1 to 120 bar. 13. Process according to one of the preceding claims, characterized in that after a first hydrogenation operation, a new portion of unsaturated substrate is added to the reaction medium and the second hydrogenation is carried out.