Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
1999-08-31
2001-10-16
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S823000, C568S700000, C556S136000, C540S538000, C558S044000, C558S045000, C558S303000
Reexamination Certificate
active
06303837
ABSTRACT:
BACKGROUND OF THE INVENTION
The background of the invention relates to the synthesis of substituted ring systems. Using the process according to the invention, it is possible to provide, with few reaction steps, a novel route to &agr;-substituted ring systems which optionally have further substituents. Cyclohexen-3-ol is an excellent example of a compound which can be prepared according to the invention. It is an important intermediate, for example for preparing Nylon® or Dralon® (from cyclohexanone and &egr;-caprolactam) and for the synthesis of fine chemicals.
Cyclohexanone and, by hydrogenation, cyclohexanol (of so-called KA oil which is used as a precursor for polymers such as Nylon® and Dralon®) can be obtained from cyclohexen-3-ol by catalytic isomerization, i.e., free from further by-products or subsequent products. Additionally, phenol is obtainable by catalytic dehydrogenation and cyclohexadiene by catalytic dehydration.
Hitherto, cyclohexen-3-ol was obtained by selective hydrogenation of phenol. This process comprises a large number of steps or partial steps. Thus, it is first necessary to produce phenol from benzene, usually by the so-called cumene process in which, in a Friedel-Crafts alkylation, isopropylbenzene is obtained from benzene. A disadvantage of this step is the high expense since this step cannot be carried out catalytically. Correspondingly large amounts of compounds such as iron salts, which either have to be disposed of or worked up, are formed in the Friedel-Crafts alkylation. With the aid of oxygen, this product is subsequently rearranged into phenol and acetone. As a general principle, the co-product acetone is generated in this process. The phenol which has been obtained in this manner is subjected to selective hydrogenation which is stopped at the stage of the cyclohexen-3-ol. Accordingly, this process is expensive, generates large amounts of waste products which are difficult to recycle. Additionally, the process also generates the by-product acetone, which is not always desired. A review is given, for example, by K. Weissermel and H.-J. Arpe in “Industrielle Organische Chemie”, 4th Edition, 1994, VCH Verlagsgesellschaft Weinheim, pp. 375-379.
There was therefore a need to develop a process which improves the preparation of (&agr;-substituted ring systems such as cyclohexen-3-ol from easily obtainable starting materials, with a simultaneous reduction in costs.
In principle, the olefin metathesis (a description of this reaction type is given, for example, in M. Schuster, S. Blechert, Angew. Chem. 1997, 109, 2124 and S. Armstrong, J. Chem. Soc., Perkin Trans. 1, 1998, 371), could be considered to be a feasible route for the synthesis of cyclohexen-3-ol and other &agr;-substituted cycloolefins of the same or a greater ring size. The dienes required as starting materials are easily obtainable by the so-called telomerization reaction or by other reaction routes known per se.
By olefin metathesis of functionalized terminal dienes, it is easily possible to obtain various products catalytically by inducing a ring closure of the diene, and ethylene is obtained as a further product of value in this reaction. However, the prior art does not disclose any generally applicable specifications for carrying out certain syntheses.
SUMMARY OF THE INVENTION
The invention relates to a process for preparing at least &agr;-substituted ring systems of the formula (II)
in which
Y represents a component selected from hydrogen, acyl, alkyl and aryl, sulfonyl,
R represents one or more further substituents and
n represents the numbers 1, 2, 3 or 4,
and where even the double bond may be substituted by at least one radical R. The process involves subjecting a compound of the formula (I)
in which Y, R and n are each as defined above, to a metathesis reaction in the presence of a noble metal catalyst, characterized in that the reaction is carried out in a solvent selected from at least one member of a group consisting of secondary alcohols, tertiary alcohols, trihalogenomethane compounds, supercritical carbon dioxide and ethyl phenyl acetate. These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description and appended claims.
DESCRIPTION OF THE INVENTION
The process according to the invention is based on starting materials which can preferably be obtained from a telomerization reaction (T. Prinz, W. Keim, B. Drie&bgr;en-Hölscher, Angew. Chem. 1996, 108, 1835; see also, for example, K. Kaneda, H. Kurosaki, M. Terasawa, T. Imanaka, S. Teranishi, J. Org. Chem. 1981, 46, 2356; R. M. Manyik, K. E. Atkins, W. E. Walker, J. Chem. Soc. D. 1971, 7, 330. Alternative synthesis routes for these have also been described or can easily be conceived. The starting materials are easily obtainable, for example by reacting a nucleophile such as water or ammonia with optionally substituted butadienes. This also provides access to other &agr;-substituted cycloolefins besides cyclohexen-3-ol.
In the field of the cycloolefination by metathesis, the synthesis of a cyclopentenol unit in a complex precursor molecule of a natural product has already been disclosed, where the following structure was synthesized under the following conditions (M. T. Crimmins, B. W. King, J. Org. Chem. 1996, 4192):
However, the stated reaction conditions cannot be applied to the synthesis of 2-olefins having larger rings. It was found that for the synthesis of cyclohexenol building blocks as precursors for the synthesis of optically pure amino acids other conditions were required. Moreover, the conditions differ in the reaction time required when changing from the S to the R enantiomer (K. Hammer, K. Undheim, Tetrahedron 1997, 53, 5925). To achieve the stated Yield (88 and 89%, respectively), the solvent benzene which was used had to be added in large amounts. Thus, the reaction was carried out at very high dilution using a solvent which can no longer be commercially employed in these amounts. The dilution used in this process is 5- to 10-times higher than that used in the process according to the invention.
It was found that benzene was not suitable anyway for the synthesis of cyclohexenol since the conversion is not complete. Using the conditions described, the maximum yield was 60%. A rearrangement to the ketone (isomerization allyl alcohol-ketone) was observed as a side reaction. This took place increasingly under the conditions and in the solvents which were given at the very place for formation of the five-membered ring (in dichloromethane) or seven-membered ring (dichloroethane).
Thus, it is not possible to apply the above example to the synthesis of six-membered or larger rings which are not of the same type as those above.
With respect to compounds having unprotected functional groups, such as in the above case of the 3-hydroxy-1,7-octadiene, the reaction conditions known from the literature do not allow the reaction conditions which are suitable for the reaction described above to be inferred.
It was therefore also an object of the present invention to provide a universally applicable process which also provides, in addition to cyclohexen-3-ol, access to other, optionally larger, &agr;-functionalized unsaturated ring systems of the formula (II):
Here, in each case independently of one another,
Y represents a component selected from hydrogen, acyl, alkyl, aryl and sulfonyl,
R represents one or more further substituents, preferably a component selected from hydrogen, optionally fused aryl, alkyl, —CN, —COOR
1
,
in which
R
1
represents a component selected from alkyl, aryl, hydrogen,
R
2
represents formyl, acetyl, acyl, sulfonyl, carboxyalkyl or -aryl,
R
3
represents a component selected from alkyl, phenyl and
n represents the numbers 1, 2, 3 or 4, preferably 1 or 2, and most preferably 1.
The double bond in the compound (II) may likewise be substituted by at least one radical R.
The nature of the substituent R is not essential for the invention. In principle, all radicals which are customary in organic chemistr
Gürtler Christoph
Jautelat Manfred
Bayer Aktiengesellschaft
Eyl Diderico van
Geist Gary
Gil Joseph C.
Oh Taylor V.
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