Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-04-06
2002-08-13
Barts, Samuel (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S309000, C568S626000, C568S631000
Reexamination Certificate
active
06433227
ABSTRACT:
The invention relates to the use of tris(trifluoromethylsulfonyl)methane and its alkali metal salts and alkaline earth metal salts as catalysts in the reaction of Lewis-acid-activatable or Brönsted-acid-activatable electrophiles with nucleophiles or for carrying out [4+2]-cycloadditions, and to the provision of the novel Mg salt of tris(trifluoromethylsulfonyl)methane.
The Lewis-acid-induced reaction of electrophiles, for example alkyl chlorides or carbonyl compounds, with nucleophiles is a simple, widely used and long-known synthesis method for building up carbon skeletons.
The metal halides MX
n
used here as Lewis acids, for example TiCl
4
, ZnCl
2
or AlCl
3
are frequently, as in the case of Friedel-Crafts acylations, used in equimolar amounts and must be irreversibly deactivated by hydrolysis during the work-up of the reaction batches. This produces large amounts of unutilizable wastes. However, carrying out industrial-scale syntheses in which unutilizable byproducts are formed is highly problematical from the ecological and economic aspects. Reutilizable Lewis acid systems and their use in Lewis-acid-induced carbon-carbon bond formations is, if possible, to be given preference.
Reusable Lewis acid systems in carbon-carbon bond-forming syntheses are, for example, lithium perchlorate or magnesium perchlorate in strongly coordinating organic solvents, such as diethyl ether, or in non-coordinating solvents, such as dichloromethane.
In this case the solutions of lithium perchlorate or magnesium perchlorate in diethyl ether show a sufficient ionization capacity in order to partially ionize, for example trityl chloride, in order to achieve the desired reaction, the ionization capacity increasing with increasing lithium salt concentration (cf. Y. Pocker, R. F. Buchholz, J. Am. Chem. Soc. 1970, 92, 2075-2084). The strong coordinating interaction between the lithium cation and the solvent diethyl ether favour, however, the formation of etherates and therefore decrease considerably the Lewis acidity of the lithium cation (Y. Pocker et al., loc. cit.). Therefore, the pronounced Lewis acid properties of lithium perchlorate solutions are restricted in ether to highly concentrated solutions. Such solutions are used, in particular, in the catalysis of Diels-Alder reactions with substances sensitive to hydrolysis, in which case as an additional effect the formation of the endo-cycloadducts is promoted.
Although the solubility of lithium perchlorate in non-coordinating solvents such as dichloromethane is very low (solubility <<10
−3
mol/l), a suspension of lithium perchlorate in dichloromethane also has Lewis acid properties. Aldehydes are sufficiently activated in this heterogeneous medium, for example, for reactions with 1-tert-butyldimethylsiloxy-1-methoxyethene to give the corresponding &bgr;-siloxycarboxylic esters (Mukaiyama-aldol reaction), in which case lithium perchlorate is used in catalytic amounts with respect to the starting materials.
However, the use of lithium perchlorate and magnesium perchlorate as Lewis acids in the organic synthesis is a considerable hazard potential, which is due firstly to the redox instability of the perchlorates (risk of decomposition and explosion) and secondly to the formation of organic perchlorates which cannot be safely excluded in the reaction to be catalyzed (P. G. Urben, Chemtech 1991 (5), 259; A. B. Charette in Encyclopedia of Reagents for Organic Synthesis (Edited by L. A. Paquette), J. Wiley and Sons, New York 1995, Vol. 5, p. 3155). The use of perchlorates as Lewis acids in industrial synthesis is therefore a problem. Although it is possible to recover lithium perchlorate or magnesium perchlorate from the organic reaction solvents, such as ether, dichloromethane or pentane, in principle by aqueous extraction, the crystallization of the perchlorates from water is in turn associated with the above-described risks and also with a high energy consumption, so that the work-up is unfavourable for safety and economic reasons.
The object therefore underlying the present invention is to provide Lewis acid catalysts for the reaction of electrophiles with nucleophiles, which catalysts can be used safely industrially and can be recovered readily and safely without a high energy consumption.
This object is achieved by using at least one compound of formula (1)
M
+x
[C(SO
2
CF
3
)
3
]
x
(1)
where x is 1 or 2,
M is a hydrogen atom or alkali metal atom when x is 1, or an
alkaline earth metal atom when x is 2, as catalyst.
The preparation of tris(trifluoromethylsulfonyl)methane and also of certain alkali metal and alkaline earth metal tris(trifluoromethylsulfonyl)methanides of the formula (1) is known and described in L. Turowski, K. Seppelt, Inorg. Chem. 1988, 27, 2135-2137; K. Seppelt, Angew. Chem. 1993, 105, 1074-1076 and in J. Org. Chem. Vol. 38, No. 19, pages 3358 ff. Tris(trifluoromethylsulfonyl)methane and its lithium salt and potassium salt are also disclosed by (Beilstein Registry Nos. 4767561, 5899593,. WO 92/FR1024).
The compounds of the formula (1) may, because of their low solubility in non-coordinating solvents, be removed simply by filtration from the reaction batches. Since the compounds of the formula (1) are distinguished by high redox stability and thermal stability, syntheses using these salts and their recovery from the reaction batches have a markedly lower hazard potential than analogous reactions using inorganic perchlorates.
The compound of the formula (1) preferably used is the acid itself (M=H), the lithium, potassium, magnesium or calcium salts, and in particular the lithium and magnesium salts.
The compounds of the formula (1) are used in homogeneous solution in a coordinating organic solvent, for example diethyl ether, THF or dioxane. The concentration of the compound (1) is in this case in catalytic amounts, preferably in the range from 0.01 to 0.1 mol/l, in particular 0.02-0.04 mol/l.
It is also possible to use the compounds of the formula (1) as a suspension in non-coordinating organic solvents, for example dichloromethane, chloroform, carbon tetrachloride or hydrocarbons, such as n-hexane, n-pentane, preferably dichloromethane.
Based on electrophile, 0.01-10 mol %, preferably 0.5-6 mol %, of a compound of the formula (1) can be used.
Using the compounds of the formula (1), Lewis-acid-induced or Brönsted-acid-induced carbon-carbon bond-forming syntheses and [4+2] cycloadditions of any type can be catalysed.
In order to obtain the resultant products at a sufficiently high yield and reasonable reaction rates, it is advantageous if not only the relative reactivity of the reacting electrophilic compounds towards the nucleophilic compounds but also the nucleophilicity N of the nucleophilic compounds used do not fall below certain minimum values.
The parameter N for the nucleophilicity of a compound was introduced by Mayr and Patz, Angew. Chem. 1994, 106, 990-1010.
For numerous nucleophilic compounds, the value N can be taken from this publication, in particular pages 1003-1004. Table 1 also contains a number of N values.
The relative reactivity of electrophilic compounds can be specified, inter alia, by using the ethanolysis rate constant k
EtOH
, i.e. the solvolysis rate constant in 100% ethanol at 25° C.
This fundamental quantity can be used in particular for specifying the relative reactivity of alkyl halides, in particular alkyl chlorides or alkyl bromides. The corresponding values for k
EtOH
(25° C.) for numerous alkyl halides can be taken from, for example, the publication by J. P. Dau-Schmidt and H. Mayr in Chem. Ber. 1994, 127, pages 205-212, or the dissertation by J. P. Dau-Schmidt, Lübeck Medical University 1992.
Alkyl halides which are suitable here for a reaction of alkyl halides, in particular alkyl chlorides or alkyl bromides, induced by the lithium salt according to formula (1) in a suspension in non-coordinating organic solvents, preferably in dichloromethane, are those having a k
EtOH
(25° C.) value of ≧5×10
−5
s
&
Buchholz Herwig
Franz Klaus-Dieter
Funke Marcus-Alexander
Mayr Herbert
Zehetner Andrea
Barts Samuel
Merck Patent Gesellschaft mit beschraenkter Haftung
Millen White Zelano & Branigan P.C.
Price Elvis O.
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