Preparation of orthoesters

Details Preparation of orthoesters Preparation of orthoesters

1999-11-15

2001-08-28

Keys, Rosalynd (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C568S591000, C568S592000

Reexamination Certificate

active

06281392

ABSTRACT:

The present invention relates to a process for preparing orthoesters by reacting metal alkoxides with 1,1,1-trihaloalkanes. Orthoesters, in particular trialkylorthoesters and, among these, particularly the trialkylorthoesters of formic acid (“orthoformates”), are important synthesis building blocks in organic chemistry and are used, for example, to prepare usually complex organic structures such as pharmaceuticals or plant protection agents. The orthoesters of most economic importance are the two orthoformates trimethyl orthoformate (“TMOF”) and triethyl orthoformate (“TEOF”).
Processes for preparing orthoesters from metal alkoxides and 1,1,1-trihaloalkanes have long been known. Usually, for this purpose, three moles of a metal alkoxide MOR (M=metal, R=organic radical) are reacted with a 1,1,1-trihaloalkane R′—CHal
3
(Hal=F, Cl, Br, I, R′=H or organic radical), the orthoester R′—C(OR)
3
forming with the elimination of alkali metal halide. To prepare orthoformates, accordingly, alkali metal alkoxide MOR is reacted with trihalomethane H—CHal
3
. Generally, when orthoesters are prepared, use is made of chlorine as halogen and of sodium as alkali metal, since these are the cheapest representatives of their groups. Therefore, for the industrial preparation of TMOF or TEOF, usually sodium methoxide (M=Na, R=CH
3
) or sodium ethoxide (M=Na, R=CH
2
CH
3
) is reacted with chloroform (trichloromethane, R′=H, Hal=Cl).
Usually, the processes for preparing orthoesters are carried out in homogeneous solution (apart from alkali metal halide which precipitates out) with the corresponding alcohol as solvent; TMOF is therefore prepared in methanolic solution and TEOF in ethanolic solution. Frequently in this reaction, the alkali metal alkoxide, when a solution of alkali metal hydroxide in the alcohol is used, is not formed in equilibrium until before or during the reaction. Thus, DE-A 21 04 206 teaches a process for the continuous preparation of trialkyl orthoformates by reacting chloroform with a solution of an alkali metal alkoxide in the corresponding alcohol, the reaction being carried out in the absence of water and oxygen at from 40 to 120° C. and a pressure of from 1 to 8 bar. PL-B 125872 discloses the preparation of triethyl orthoformate by reacting chloroform with three moles of sodium ethoxide in ethanol. CN-A 1106375 discloses the preparation of triethyl orthoformate by slowly adding ethanol to a mixture of sodium hydroxide and chloroform, the pH of the reaction mixture being kept at from 7 to 10. JP-A 59-001 435 teaches preparing trialkyl orthoformates by reacting the alcohol, a solution of from 5 to 23% by weight of alkali metal hydroxide in the alcohol, and chloroform. DE-A 36 06 472 teaches a process for preparing trialkyl orthoformates by isothermic reaction of chloroform and an alcoholic solution of alkali metal alkoxide at from 1 to 6 bar, from 30 to 120° C. and a pH above 7, use being made of a stoichiometric excess of chloroform. The molar ratio of chloroform to the alkoxide is from 1 to 2:3.
These processes have the disadvantage that the alcoholic solvent must be separated off from the orthoester. When the orthoester is isolated from customary reaction mixtures, to achieve the orthoester product purity demanded by the market, distillation towers having a high number of theoretical plates and a correspondingly high energy consumption are required.
Therefore, attempts have been made with other processes to avoid the use of alcohol as solvent or at least to avoid distilling orthoester/alcohol mixtures.
Thus, DE-A 12 17 943 teaches reacting chloroform with a metal methoxide suspended in the trialkyl orthoformate to be prepared, a yield of 84 mol %, based on methoxide used, being achieved. JP-A 58-225 036 teaches extracting orthoesters from a mixture of alcohol, alkali metal hydroxide and chloroform with optionally halogen-substituted aliphatic or aromatic hydrocarbons or ethers. CN-A 10 68 103 teaches using an inert solvent in the reaction.
Other processes are carried out in the presence of a phase-transfer catalyst. RU-A 20 72 978 and SU-A 1781203 teach reacting an alkanol and an alkali metal hydroxide with chloroform in the presence of phase-transfer catalysts.
However, a characteristic of these known processes using heterogeneous reaction mixtures (not considering the alkali metal halide precipitating out) is the disadvantage of forming by-products in comparatively high amount; the selectivity of the reaction is unsatisfactory. The extraction processes, in addition to unsatisfactory selectivity of the reaction, usually have the disadvantage of an additional process step.
SU-A 16 71 656 teaches another process for preparing orthoesters by reacting chloroform with the corresponding tetraalkoxisilane in pseudocumene as solvent in the presence of alkali metal hydroxide and triethylbenzylammonium chloride. This process is unsatisfactory economically because of the use of comparatively expensive chemicals.
It is an object of the present invention, therefore, to find an economically satisfactory process for preparing orthoesters having high selectivity, high space-time yield and a low product purification requirement.
We have found that this object is achieved by a process for preparing orthoesters by reacting 1,1,1-trihaloalkanes with alkali metal alkoxides in the presence of the corresponding alcohol, which comprises using a slurry of the alkali metal alkoxide in the corresponding alcohol.
The process according to the invention avoids separating off large amounts of alcohol, and the expenditure for isolating the pure product is therefore substantially lower than with known processes. At the same time, despite the presence of solid alkali metal alkoxide in the reaction medium, surprisingly, no impairment in selectivity with respect to the use of a pure solution of the alkoxide in the alcohol occurs.
By means of the process according to the invention, orthoesters of the formula R′—C(OR)
3
are prepared by reacting an alkali metal alkoxide MOR with a 1,1,1-trihaloalkane R′—CHal
3
. It is equally possible, using the process according to the invention, to prepare mixed orthoesters, that is those which do not bear the same three radicals R, but two or three different radicals, that is orthoesters of the formulae R′—C(OR
1
)
2
(OR
2
) or R′—C(OR
1
)(OR
2
)(OR
3
). R
1
, R
2
and R
3
each independently of one another correspond to a radical R. To prepare them, the corresponding alkoxides MOR
1
, MOR
2
and/or MOR
3
and the corresponding alcohols HOR
1
, HOR
2
and/or HOR
3
must be used in the desired ratio.
M is alkali metal, that is to say lithium, sodium, potassium, rubidium and/or cesium. It is possible to use a single alkali metal or a mixture of various alkali metals. Preference is given to the use of sodium or potassium, particular preference is given to the use of sodium.
Hal is halogen, that is to say fluorine, chlorine, bromine and/or iodine. A single halogen or a mixture of halogens can be used. Preference is given to the use of chlorine.
R is an organic radical, such as alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkenyl, aryl, alkaryl or aralkyl. The radical R can be substituted with further organic radicals and can also contain heteroatoms.
Examples of radicals R which are usable in the process according to the invention are unbranched saturated alkyls having from one to 18 carbons, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl or decyl, saturated cyclic alkyls having from three to 12 carbons, such as cyclopentyl, cyclohexyl or cycloheptyl, or branched saturated alkyls such as 2-propyl, 2-butyl, 2-methyl-1-propyl, 1,1-dimethylethyl or all branched isomeric pentyl, hexyl, heptyl, octyl, nonyl or decyl radicals. R can likewise be an aromatic radical, for example phenyl or 1- or 2-naphthyl. Preferably, R is an unbranched alkyl, in particular methyl, ethyl, 1-propyl or 1-butyl. Particularly preferably, R is methyl or ethyl.
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