CA2098277C - Preparation of formyltetrahydropyrans - Google Patents

Abstract

Disclosed is a method for the preparation of formyltetrahydropyrans (I) by dehydrogenating hydroxymethyltetrahydropy-rans (II) in the presence of a copper, silver and/or gold catalyst. The formyltetrahydropyrans (I) thus obtained are useful interme-diates in the preparation of pharmaceuticals and phytopathalogical products.

Description

l1 O.Z. 0050/42091 Preparation of formYltetrahydropvrans The present invention relates to a novel process far the preparation of formyltetrahydropyrans of the formula I
~CHO I
US-A-2,042,220 discloses that unsaturated primary and secondary alcohols can be oxidized using an excess of oxygen at from 360 to 550°C in the presence of a metal catalyst, for example a copper or silver catalyst, to give the corresponding aldehydes. The catalyst may bean alloy, a metal compound or elemental metal. Activated catalysts are preferred; the activation operations described axe surface amalgamation of the metal and _ subsequent heating of the metal surface. In addition, DE-B-20 41 976 states that considerable amounts of un-desired byproducts are formed in the process disclosed in US-A-2,042,220.
DE-A-25 17 859 describes the dehydrogenation of unsaturated alcohols on .a copper catalyst which has a specific surface area of from 0:01 to 1.5 mZ/g, essen tially in the absence of oxygen, at from 150 to 300°C. If the starting materials are «,;8-unsaturated alcohols, p, y-unsaturated aldehydes are formed, with saturated aldehydes as byproducts; the selectivity for a,p-unsaturated aldehydes is lova (page 2, final paragraph).
Mixtures of this type must be separated. into their components using complex separation operations.
DE-B-20 20 865 and DE-B-20 41 976 describe the dehydrogenation of ,e,~-unsaturated alcohols and a,,e unsaturated alcohols, respectively, to give a,~-unsatu rated aldehydes. The dehydrogenation catalysts mentioned . include mixed catalysts; far example comprising copper and silver. However, it is disadvantageous that con siderable, amounts of nucleophilic substances must be added. In the reaction of 3-methyl-3-buten-1-ol, good 2098?'~'~

- 2 - O.Z. 0050/42091 results are only achieved at incomplete conversions, which, according to DE-B-22 43 810, can result in problems in .removing unreacted starting material.
The dehydrogenation of 3-methyl-3-buten-1-of by the process of DE-B-25 17 859 without addition of oxygen on metallic copper gives considerable amounts of iso valeraldehyde, and the activity of the catalysts drops rapidly within a few days, arid must therefore frequently be regenerated.
_ FR-A-2 231 650 describes the preparation of aldehydes and ketones from the corresponding alcohols by air oxidation at from 250 to 600°C in the presence of a gold catalyst. The advantage of the gold catalyst is the greater selectivity compared with copper and silver catalysts, so that the formation of byproducts is reduced. This process has the disadvantage of high catalyst costs, since a solid gold catalyst mint be used.
DE-B-27 15 209 and EP-B-55 354 describe the oxidative dehydrogenation of 3-alkyl-buten-1-ols on catalysts comprising layers of silver crystals and/or copper crystals, with addition of molecular oxygen. This process has the disadvantage of high catalyst costs due to the use of solid silver and moreover good selPC-tivities can only be achieved if defined catalyst par-title sizes or distributions are employed in a layered structure, in Some cases even certain mixtures of layers of copper crystals and silver crystals. This means both complex filling of the reactor and complex recovery of the catalyst. In addition, the high reaction temperatures used cause sintering of the metal crystals, which. result in an increase in pressure and short catalyst lives.
JP-A-60/246 340 describes the gas-phase oxidation of 3-methyl-2-buten-1-of to give 3-methyl-2-buten-1-oI at from 300 to 600°C in the presence of ~xygen and in the presence of a supported catalyst. However, the catalyst preparation is complex. In addition, the good selectivity of 96.6 is achieved at the expense of a low conversion ' ~~~~~~~

3 - O.Z. 0050/42091 rate, so that the process is scarcely suitable for industrial purposes.
JP-A-58/059 933 describes the preparation of aldehydes and ketones by oxidative dehydrogenation of alcohals in the presence of a silver catalyst which additionally contains phosphorus. In order to maintain the selectivity of the reaction, a phosphorus compound is additionally introduced into the alcohol stream, so that contamination of the product is unavoidable.
EP-A 263 385 discloses that aliphatic and arali-phatic, primary and secondary alcohols can be oxidized at elevated temperature using oxygen in the presence of a copper, silver andlor gold catalyst to give the cor-responding aldehydes and ketones. However, very specific conditions with respect to the catalyst and reactor must be observed. In addition, higher conversion rates are desirable.
The synthesis of formyltetrahydropyrans by dehydrogenating the corresponding hydroxymethyltetra hydrofurans is not mentioned in the cited literature.
The processes known hitherto for the preparation of aldehydes and ketones are also unsuitable for the industrial preparation of formyltetrahydropyraris if an uncomplicated and economical process, long catalyst lives and high selectivity of the reaction are desired.
In addition, it ig extremely doubtful whether the abovementioned oxidation processes can be applied to hydroxymethyltetrahydropyrans since, as is known, cyclic ethers react particularly rapidly with oxygen to given peroxides (cf., for example, Organzkum, 2nd reprint of the 15th Edition, VEB Deutscher Verlag der w Wissenschaften, Berlin, 1981, page 807). The continuous oxidation of, hydroxymethyltetrahydropyrans in the gas phase should accordingly not give formyltetrahydropyrans, or should only do so in very low selectivity. Further more, the possibility of the formation of explosive by-products makes an oxidation process at high temperature 2~9~2'~'~ ~ .. .

f~.
- 4 - O.Z. 0050/42091 using oxygen to appear unsuitable for industry.
Formyltetrahydropyrans are therefore usually prepared in salution, for example 1. from oxopyrans by - ~rignard reaction with alkoxymethylmagnesium halides, further reaction of the products with acetyl chloride or acid dehydration, and subsequent hydrolysis [CA 79, 66132 g: Arm. Khim. Zh. 26 (1973), 227; CA 79, 126228 e: Dokl. Vscs. Konf.
Khim. Atselinena 4th, (1972) 384; CA 76, 25029 y:
Arm. Khim. Zh. 24, (1971) 503];
- Wittig reaction with alkoxymethylenetriphenylphos-phoranes [CA 100, 68212 j: Arm. Khim. Zh. 27 (1974), 945];
- conversion into tetrahydropyranylidene glycidyl esters by the method of Darzens and alkaline hydro-lysis of the products [CA 87, 151967 t: Arm. Khim.
Zh. 30 (1977), 516; CA 94, 30479 w: Sint.
Geterotsikl. Soedin 11 (1979), 25; CA 77, 48187 k:
Arm. Khim. Zh. 25 (1972), 173; CA 87, 23051 c: SU-A
550389];
2. by hydrogenation of - 4-pyranaldehyde on a Pd/CaC03 catalyst prepared by rearrangement flf 4,8-dioxabicyclo[5.1.0]-octa-2,5 dien [Angew. Chem. 86'(1974), 742];
- tetrahydropyrancarbonyl chlorides by the method of Rosemund on a Pd/BaS04 catalyst (Collect. 7, (1935), 430];
- 2-phenoxy- and 2-alkoxy-substituted 2,3-dihydro pyrans, which can be prepared by cycloaddition of alkoxy- or aryloxy-substituted alkenes with 1-carboxy-2-formyl-substituted alkenes [EP-A
219 091];
3) by ring expansion of tetrahydro-~-pyrone using diazomethane and rearrangement of the product to °
- O.Z. 0050/42091 give 4-formyltetrahydropyran [Chem. Ber. 91 (1985), 1589];
4) by treatment of 4-hydroxy-4-hydroxymethyltetrahydro-pyrans or 1,6-dioxaspiro[2.5]octaves at elevated 5 temperature with. a catalyst [DE-A 3 630 614].
However, the abovementioned methods are unsuit-able for the synthesis of formyltetrahydropyrans on an industrial scale since the starting compounds are dif-ficult to handle or relatively expensive and the yields over several process stegs are unsatisfactory. Thus, the preparation of alkoxymethylmagnesium halide and alkoxy-methylenetriphenylphosphine requires halomethyl ethers;
but these are undesired due to their highly toxic proper-ties.
The glycidyl ester method of Darzens gives substituted 4-formyltetrahydropyrans in a maximum yield of 70$. However, the preparation of unsubstituted formyl tetrahydropyrans by this synthetic route is uneconomical since the desired products are only obtained in very low yields.
The preparation of 4-formyltetrahydropyran by hydrogenating 4-pyranaldehyde is likewise industrially uneconomical since the precursor, i.e. 4,8-dioxabicyclo-[5.1.0]octa-2,5-dien, is only accessible with great difficulty [cf. Angew. Chem. 86 (1974) ,742]. The reduc-tion of tetrahydropyrancarbonyl' chlorides by the method of Rosemund, described in Collect. 7 (1935), 430, gives a product with a melting point of 135°C, whereas 4-formyltetrahydropyran is a colorless, low-viscosity liquid at room temperature and atmospheric pressure. The solids are probably relatively high-molecular-weight adducts of 4-formyltetrahydropyran, since this compound is known to dimerize easily or to autoxidize to give 4-carboxytetrahydropyran [cf. Chem. Ber. 91 (1985), 1589]. The preparation of 4-formyltetrahydropyran by ring expansion of tetrahydro-7-pyrone using diazomethane proceeds in very unsatisfactory yields (about 42%) and is therefore just as unsuitable for industrial synthesis as the other processes mentioned.
In some cases, the synthesis of formyltetrahydro-pyrans under oxidative conditions has also been described, but these are always batch processes carried out in the presence of an inert solvent or solvent mixture:
- oxidation of 2-hydroxymethyltetrahydropyran using silver(II) picolinate in dimethylsulfoxide/water to give 2-formyltetrahydropyran, but the yield is only 59% [Canad. J. Chem. 47, (1969), 1649];
- oxidation oft-hydroxymethyl-4-methyltetrahydropyran using an oxidant such as chromic acid or pyridine chlorochromate, in, for example, methylene chloride or acetone to give 2-formyl-4-methyltetrahydropyran ~JP-A 54/055.570 published on May 2, 1979 .
Acta Chem. Scand., Ser. B 28 (1974), Tetrahedron Lett. 23 (1982), 4305, Carbohydr. Res. 150 (1986), 163 and Synthesis (1971) 70 describe processes for the oxidation of hydroxymethyl groups in sugars. However, the ketal structure of the sugars means that these methods cannot easily be transferred to hydroxymethyltetrahydro-pyrans.
It is therefore an object of the present inven-tion to provide a simple and industrially economical method for the preparation of formyltetrahydropyrans I.
We have found that this object is achieved by a process for the preparation of formyltetrahydropyrans of the formula I, which comprises dehydrogenating a hydroxy methyltetrahydropyran of the formula II
~CH ZOH I I

2Q98~7'~

- 7 - O.Z. 0050/42091 in the presence of a copper, silver and/or gold catalyst.
The 2-hydroxymethyl-, 3-hydroxymethyl- and 4-hydroxymethyltetrahydropyrans II used as starting materials can be prepared, for example, by reducing the corresponding tetrahydropyrancarboxylic acid esters by known methods.
The dehydrogenation can be carried out under reductive conditions or preferably under oxidative conditions. Particularly suitable oxidants are oxygen, in pure form or preferably as a mixture with inert gases, such as nitrogen, argon and carbon dioxide, a mixing ratio of from 5 to 50 mol-~ of oxygen per mole of inert gas being advisable. In order to increase the selec-tivity, it may be advantageous to use steam as the inert gas or as the constituent of the inert gas.
The oxidant is particularly preferably atmos-pheric oxygen.
The amount of oxidant is not crucial; complete reaction requires at least 0.5 mol of oxygen (OZ) per mole of hydroxymethyltetrahydropgran II. From 50 to 400 mol-~
of oxygen are preferably used, so long as a smaller amount of from about 20 to 50 mot-~ is not recommended in order to increase the selectivity.
Tf the process is carried out under reductive conditions without oxygen, the presence of small amounts of hydrogen, up to about 0.6 mol per mole of II, is advisable in .order to prevent deactivation of the catalyst.
Catalysts which are suitable for the dehydrogena tion are copper, silver, gold or alloys or mixtures of these metals. Particular preference is given to silver containing catalysts, in particular catalysts comprising steatite having a silver surface. Mixtures of said metals with other substances which are inert for the hydrog~na tion are also possible.
The catalyst can be either in metallic form or bonded to ~n inert carrier, such as silica gel, alumina f or clay.
The catalyst carrier may also contain inert additives or a weak base, for example basic constituents such as alkali metal and alkaline earth metal oxides, in particular sodium oxide and potassium oxide, alkali metal and alkaline earth metal bicarbonates, acetates and benzoates. A catalyst carrier principally comprising silica is preferred.
The metallic catalysts are expediently used in to the form of electrolytically precipitated crystals, the particle size of the crystals preferably being from 0.1 to 10 mm.
In the case of catalysts bonded to an inert carrier, layer thicknesses of from 5 to 25 ~m of catalyst material are recommended, the mean particle diameter particularly preferably being from 1.6 to 2.0 mm.
The process is generally carried out from 180 to 750°C, particularly from 200 to 600°C. Temperatures of from 200 to 280°C are preferred. under reductive condi-tions, while temperatures of from 350 to 600°C are particularly advantageous for the oxidative variant.
2o There is no need for particular conditions with respect to the pressure, and the reaction is therefore normally carried out at atmospheric pressure.
The process according to the invention can be carried out either batchwise or continuously. In the continuous procedure, the reactants are passed over a fluidized bed comprising very finely divided catalyst or preferably over a fixed catalyst bed with a depth of from to 30 cm, in particular from 10 to 20 cm.
In a preferred embodiment, the hydroxymethyl tetrahydropyran II is evaporated in a stream of inert 30 gas, for example nitrogen, argon or carbon dioxide, and the gas mixture is heated to a temperature from about 100 to 250°C below the reaction temperature and subsequently passed into the reaction zone, with the contact time advantageously being from 0.001 to 5 seconds, in - 9 - o.z. 0050/42091 particular from 0.01 to 0.2 seconds.
The gaseous reaction product can be cooled and condensed by spraying in solvents or diluents, for example hydrocarbons such as n-hexane and toluene, ethers such as methyl tert-butyl ether, or formamides such as dimethylformamide.
In order to prevent dimerization of the formyl-tetrahydropyrans it is advantageous to pass the gaseous reaction product over a weak, if desired solid base or to pass it into a stabilizing medium, for example water, a water-miscible organic solvent or preferably an aqueous solution of a weak base.
Suitable weak bases here are, in particular, alkaline earth metal bicarbonates, such as sodium bi.car bonate and potassium bicarbonate, alkaline earth metal acetates, such as sodium acetate and potassium acetate, and alkaline earth metal.benzoates, such as sodium benzoate and potassium benzoate.
The reaction mixture is worked up in the usual manner, and further details on this are thus superfluous.
Small amounts of impurities in the crude products result principally from the formation of byproducts, for example due to elimination of water with formation of methylenetetrahydropyrans or due to opening of the tetra hydropyran ring.
The formyltetrahydropyrans I to be prepared in a simple manner in high yields and good selectivity by the process according to the invention are valuable inter-mediates in the synthesis of crop-protection agents and pharmaceuticals. In particular they are important start-ing materials for the synthesis of herbicidal or plant growth-regulating cyclohexane-1,3-diones, as described, for example, in EP-A-070 370 and EP-A-142 741. A
synthetic route which can be used to obtain 5-tetra-hydropyranylcyclohexane-1,3-diones, starting from the formyltetrahydropyrans I, is disclosed in, for example, EP-A-352 465 and. EP-A-124 041.

200~2~7 A w'.
I ''.:).: .i '"';,'v - 10 - O.Z. 0050/42091 A 10 cm thick catalyst layer of steatite spheres coated with 4.2$ by weight of silver were introduced into ~a 1.2 cm diameter tube. A gas mixture comprising 33.2 g (0.286 molj per hour of 4-hydroxymethyltetrahydropyran, 46 1 {S.T.P.) (2.05 mol) per hour of nitrogen and 46 1 (S.T.P.) per hour of air was passed continuously through this catalyst bed at 450°C at atmospheric pressure. After passing through the reaction zone, the gaseous reaction mixture was cooled to from 20 to 25°C and passed into water containing 1~ by weight of sodium bicarbonate for stabilization of the product. The aqueous phase was worked up in the usual manner. Conversion: >99~; aldehyde selectivity: 80$.
EXAMPLE Z
A gas mixture having a composition of 55.5 g (0.478 mol) per hour of 4-hydroxymethyltetrahydropyran, ? 8 1 ( S . T . P . ) ( 3 . 4 8 mol ) per hour of nitrogen and 7 8 1 (S.T.P.) per hour of air was reacted by a method similar to that of Example 1. Conversion: >99~; aldehyde selec-tivitya 83~.

A gas mixture having a composition of 33.7 g (0.290 mol) per hour of 3-hydroxymethyltetrahydropyran, 45.5 1 (S.T.P.) (2.03 mol) per hour of nitrogen and 45.5 1 (S.T.P:) per hour of air was reacted by a method similar to that of Example 1. Conversions >94$; aldehyde selectivity: 90~.

A continuous gas stream composed of 24 g (0.21 mol) per hour of 4-hydroxymethyltetrahydropyran, 90 1 (S.T.P.) (4:02 mol) per hour of nitrogen and 30 1 (S.T..P.) per hour of air was passed at 380°C at atmos-pheric pressure through a cylindrical reaction tube 209~27~
.5'X:;:;.
- 11 - O.Z. 0050/42091 (volume 0.1 1) packed with copper Raschig rings. After passing through the reaction zone, the gaseous reaction mixture was cooled to from 20 to 25°C and worked up in the usual manner to give the product: Conversion: 54~;
aldehyde selectivity: 89~:

For this experiment, a pellet-form catalyst was used which comprised silica gel with a coating of l5~ by weight of copper and 1.2$ by weight of sodium oxide.: A
continuous gas stream composed of 100 g (0.86 mol) per hour of 4-hydroxymethyltetrahydropyran, 200 1 (S.T.P.) (8.93 mol) per hour of nitrogen and 10 1 (S.T.P.) (0.45 mol) per hour of hydrogen was passed at 220°C at atmospheric pressure through a cylindrical reaction tube (volume 1.0 1) packed with pellets (length 10 mm, dia-meter 4 mm) of the catalyst. After passing through the reaction zone, the gaseous reaction mixture Was cooled to from 20 to 25°C and passed into a 1$ strength by weight aqueous potassium acetate solution. The aqueous phase was subsequently worked up in the usual manner to give the product. Conversion: 53~; aldehyde selectivity: 94~.
No ageing of the catalyst with respect to conver-sion and aldehyde selectivity was observed after an operating time of 240 hours:

Claims (9)

We claim:

1. A process for the preparation of a formyltetrahydro-pyran of the formula I
which comprises dehydrogenating a hydroxymethyl-tetrahydropyran of the formula II
in the presence of a copper, silver and/or gold catalyst.

2. A process as claimed in claim 1, wherein the dehydrogenation is carried out under reductive conditions.

3. A process as claimed in claim 1, wherein the dehydrogenation is carried out under oxidative conditions.

4. A process as claimed in claim 3, wherein the oxidant used is oxygen or air.

5. A process as claimed in claim 1 or 2 or 3 or 4, wherein the dehydrogenation is carried out at from 180 to 750ÀC.

6. A process as claimed in claim 1 or 2 or 3 or 4 or 5, wherein the product is stabilized by being passed into water, if desired in the presence of a weak base.

7. A process as claimed in claim 1 or 2 or 3 or 4 or 5 or 6, wherein the catalyst is in metallic form or is bonded to an inert carrier.

8 . A process as claimed in claim 1 or 2 , or 3 , or 4 , or 5, or 6, or 7, wherein the catalyst contains a silica-containing carrier.

9. A process as claimed in claims 7 or 8, wherein the catalyst carrier contains a basic constituent selected from alkali metal and alkaline earth metal oxides, alkali metal and alkaline earth metal bicarbonates, alkali metal and alkaline earth metal acetates and alkali metal and alkaline earth metal benzoates