Catalyst – solid sorbent – or support therefor: product or process – Catalyst or precursor therefor – Organic compound containing
Reexamination Certificate
2003-01-16
2004-08-03
Bell, Mark L. (Department: 1755)
Catalyst, solid sorbent, or support therefor: product or process
Catalyst or precursor therefor
Organic compound containing
C502S171000, C502S172000, C556S118000, C556S119000, C556S120000, C556S121000, C556S122000, C556S123000, C556S124000, C556S125000, C556S126000, C556S127000, C556S128000, C556S129000, C556S130000, C556S131000, C556S132000, C556S133000, C556S134000, C556S135000
Reexamination Certificate
active
06770588
ABSTRACT:
BRIEF SUMMARY OF THE INVENTION
The present invention concerns the field of organic synthesis. It concerns, more particularly, a process for the selective reduction of carbonyl compounds, such as aldehydes, ketones, esters and lactones into the corresponding alcohols, using silanes as reducing agents, preferably polymethylhydrosiloxane (PMHS), in the presence of catalysts which comprise monomeric zinc compounds, complexed by basic ligands such as amines, polyamines, aminoalcohols, amine oxydes, amides, phosphoramides, etc.
BACKGROUND OF THE INVENTION
The selective reduction of carbonyl compounds to the corresponding alcohols in the course of which only the reaction of the C═O function is observed, is an important task in the field of organic chemistry. Until now, there were exclusively used hydride reducing agents, such as lithium aluminum hydride LiAlH
4
, sodium borohydride NaBH
4
, or sodium dihydroxybis(2-methoxyethoxy)aluminate (SDMA) of formula NaAlH
2
(OCH
2
CH
2
OCH
3
)
2
, the two latter reagents being of limited value for the reduction of esters and lactones. All the above-mentioned reagents are employed in stoichiometric amounts and show the disadvantage of releasing hydrogen in the course of the reaction or, when entering into contact with humidity, of leading to explosion risks and requiring the inertization of the reactors used. Furthermore, the use of these reagents is costly as they are required in stoichiometric amounts. Thus, there is a continuous search for other systems which are more economic and easier to use.
Several publications describe the use of silanes as reducing agents for carbonyl substrates, together with a metal catalyst. A preferred silane for this type of reductions is polymethylhydrosiloxane or PMHS, according to the general formula
U.S. Pat. No. 3,061,424 to Nitzsche and Wick describes the reduction of aldehydes and ketones with PMHS and a salt of mercury, iron, copper, titanium, nickel, zirconium, aluminum, zinc, lead, cadmium and, as the preferred embodiment, tin. This reductive system requires activation by a proton source, without which the reaction does not proceed. However, the system is not effective for the reduction of esters and lactones.
U.S. Pat. No. 5,220,020 to Buchwald et al. describes a method for the preparation of alcohols by the reduction of carbonyl compounds using a system composed of a silane reducing agent and a metal catalyst of formula M(L)(L
I
)(L
II
) to M(L)(L
I
)(L
II
)(L
III
)(L
IV
)(L
V
), in which M is a metal belonging to any of groups 3, 4, 5, or 6 of the periodical table, a lanthanide or an actinide, whereas (L
I
) to (L
V
) represent hydrogen, an alkyl group, an aryl group, a silyl group, a halogen atom, or a —OR, —SR or —NR(R′) group, R and R′ being hydrogen, an alkyl or an aryl group. Amongst the preferred catalysts, the cited patent mentions titane (IV) isopropylate or ethylate or trichlorotitane (IV) isopropylate. Such a system is said to be appropriate for the reduction of esters, lactones, amides or imines. More recently, Breedon and Lawrence (Synlett., 1994, 833) and Reding and Buchwald (J. Org. Chem., 1995, 60, 7884) have described a similar process, namely the use of non-activated titane tetraalkoxydes as catalysts for the reduction of esters by PMHS. The method described in those three mentioned references requires the use of large amounts, at least 25 mole % with respect to the substrate, of catalyst. Barr, Berk and Buchwald (J. Org. Chem., 1994, 59, 4323) have shown that the complex Cp
2
TiCl
2
, when reduced by butyllithium or ethylmagnesium bromide, could catalyze the reduction of esters into the corresponding alcohols with good yields, but this technique requires reagents which are expensive and difficult to use in a large scale, as is the case in industrial organic synthesis.
As closest prior art, there should be cited the international application WO 96/12694 of the applicant, describing the reduction of aldehydes, ketones, esters and lactones by a reductive system composed of silanes and a metal hydride, leading to the corresponding alcohols with good yields. This systems requires only very low amounts of catalyst, i.e. the metal hydride, in the order of 1 mol % with respect to the substrate. The hydride is formed by the reaction of a salt of the respective metal with an appropriate reducing agent, preferably NaBH
4
. Besides zinc salts, cobalt, manganese and iron salts are used as precursors for the generation of metal hydrides. According to another preferred embodiment, PMHS is used as silane reducing agent.
DETAILED DESCRIPTION OF THE INVENTION
We have now successfully developed a process for the reduction of carbonyl compounds with silanes, catalyzed by metal derivatives which are not hydrides and which, in consequence, do not require the use of a reducing agent like, for example, NaBH
4
.
The object of the invention is a process for the preparation of alcohols by reduction of the carbonyl function in substrates belonging to the class of aldehydes, ketones, esters or lactones, which substrates may contain unsaturated functions other than the carbonyl group, wherein
a) said carbonyl substrate is reacted with an effective amount of a silane, preferably PMHS, in the presence of catalytic amounts of an active zinc compound which is monomeric and not a hydride, to form a siloxane,
b) the thus-obtained siloxane is hydrolyzed with a basic agent to form an alcohol, and
c) the resulting alcohol is separated and purified, if necessary.
Another object of the invention is a reductive system comprising
a) a silane, preferably PMHS, and
b) an active zinc compound which is monomeric and not a hydride.
The present invention is based on the surprising fact that the use of a monomeric species of zinc considerably enhances the reactivity of a reductive system for carbonyl compounds comprising a silane and a zinc compound. Thus, reductive systems comprising a zinc salt and a silane, as described in U.S patent U.S. Pat. No. 3,061,424 to Nitzsche and Wick which has been cited beforehand, are by far less reactive than the system according to the present application. In particular, the system as described in the prior art is not capable of reducing esters and lactones, in contrast to the reductive system of the present invention.
On the other hand, although the above-cited document WO 96/12694 of the applicant shows that it is possible to enhance the reactivity of a silane for the reduction of carbonyl substrates by adding zinc salts or complexes, the latter require the activation by a reducing agent. As reducing agent, compounds like NaBH
4
, LiAlH
4
, lithium or aluminum alkyls or Grignard compounds were used to generate a highly reactive species, namely a hydride.
The present invention, however, uses zinc compounds such as salts or complexes which do not require the activation by a reducing agent and which, when employed in stoichiometric amounts and together with a silane, catalyze the reduction of all sorts of carbonyl compounds.
The chemistry of zinc is in general characterized by the tendency of the metal to reach a coordination number higher than 2 which is a consequence of its valence state +2. The zinc can reach the higher coordination number it desires to attain by oligo- or polymerization, after which in general a tetra- or hexacoordination is observed. For those reasons, zinc salts or complexes are in most cases oligo- or polymeric, and as examples, there are mentioned here zinc carboxylates and halides.
However, an electronically unsaturated class of compounds are dialkyl- and diaryl zinc compounds. They are not capable of reaching a higher coordination number than 2 by oligo- or polymerization because alkyl and aryl groups cannot act as bridging ligands. Dialkyl- and diaryl zinc compounds are therefore monomeric, and they show a linear structure.
We have established that all the above-mentioned compounds show either no activity or a very low activity when used for the reduction of carbonyl compounds. However, these poly- or oligomeric species as well as dialkyl- or diar
Bell Mark L.
Brown Jennine M.
Firmenich SA
Winston & Strawn LLP
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