PROCESS FOR THE PREPARATION OF DIHYDROPYRAN

The present invention relates to a process for the preparation of 2,3-dihydropyran (DHP, CAS [110-87-2]) and its use in industrial chemistry.

2,3-Dihydropyran is an important reagent and building block in the synthesis of pharmaceutical and agrochemical compounds. Several processes for the preparation of DHP are described in the prior art. US-A-2976299 discloses a process for producing DHP by passing vaporized tetrahydrofurfuryl alcohol (THFA, CAS [97-77-4]) through a catalyst comprising A1 ₂ 0 ₃ and Ti0 ₂ . The vaporized THFA is entrained in a carrier gas such as nitrogen or hydrogen.

US-A-3518281 discloses a process for producing DHP by conversion of vaporized THFA at a temperature from 200 to 375 °C using η-Α1 ₂ 0 ₃ as a catalyst. As above, the THFA may be entrained in a carrier gas such as nitrogen or argon when contacted with the catalyst.

If gases such as nitrogen are used, however, considerable amounts of product are lost by removal with the carrier gas, as condensation is usually not sufficient for completely separating the products from the carried gas. Moreover, the above processes suffer from the drawback that they require frequent regeneration of the catalyst resulting in interruption of the production. Since the regeneration is typically carried out at elevated temperatures in the presence of air or oxygen while the catalyst is still installed. The object of the present invention, therefore, is to provide a simple and cost efficient process for the production of DHP, wherein DHP is obtained in high yields and good recovery rates, with low amounts of by-products, and wherein the used catalyst has a long life and little regeneration is required. This object has been achieved by the present invention, which provides a process for producing 2,3-dihydropyran (DHP), comprising contacting tetrahydrofurfuryl alcohol (THFA) entrained in a carrier gas with a catalyst comprising aluminium oxide (A1 ₂ 0 ₃ ), wherein the carrier gas comprises water vapor. Scheme 1 below shows the conversion of THF A (formula I) in the presence of a solid phase A1 ₂ 0 ₃ catalyst to form DHP (formula II) and H ₂ 0, which typically takes place at elevated temperatures.

THF A (I) DHP (II)

Description of Figures:

Figure 1 shows a simple schematic representation of the production process of DHP according to the present invention with subsequent distillation. The number of heat exchangers and vaporizers before the reactor are dependent from the conditions in the industrial environment.

Water (14) is pumped through heat exchanger (1) and heated by the raw product stream leaving the reactor (79. After leaving the heat exchanger (1) the water has a temperature of about 195 to 210 °C. The water vapor then is passed through vaporizers (2) and (3) to reach a temperature of about 370 to 395 °C.

THFA (15) is pumped through heat exchanger (4) and vaporizer (5) to reach a temperature of about 300 °C. Gaseous THFA is entrained in the water vapor in a mixing device (6) and passed through reactor (7) which is the Al ₂ 0 ₃ -comprising catalyst. The temperature in the reactor is about 350 °C at the beginning of the production run and is further maintained at about 330 °C. The reactor pressure is maintained at atmospheric pressure. A small amount of nitrogen can be fed into the system, advantageously between heat exchanger (1) and vaporizer (2). The obtained crude product is cooled with the feed water (14) at heat exchanger (1) and nitrogen and other uncondensable gases were removed in a separator (not shown). The crude product (16), mainly consisting of DHP and water, is further passed into the decanter (8) and separated from water. The water was disposed (17) as it contains at room temperature only about 1.6 weight % of DHP. Following separation from water, the crude product optionally is collected in one or more tanks (9) before subjected to distillation.

For a batch distillation the crude product is filled into a distillation boiler (10) and heated to reflux over a column (11), said column optionally is packed with structured bodies. Preferably, the distillation is carried also out at atmospheric pressure. The sump (18) is periodically removed from the distillation boiler (10).

At the beginning, the reflux from the column is returned completely to the column after passing a condenser (12). After reaching steady state a constant flow of the reflux is passed through the decanter (13), which is filled with water to wash the reflux, before returning the washed reflux to the column. Azeotropes remain in the decanter and the water (19) in the decanter is replaced periodically until the organic phase meets the required specifications, particularly until the acrolein content is 20 ppm or less. Then the reflux ratio is changed and the product DHP (20) is distilled into suitable tank(s). Expediently, the distillation is interrupted when the temperature in the distillation boiler drops to 130 °C or less.

Listing of embodiments of Fig. 1:

1 : heat exchanger

2: vaporizer

3: vaporizer

4: heat exchanger

5: vaporizer

6: mixing device

7: reactor

8: decanter

9: tank(s)

10: distillation boiler

11 : distillation column

12: condenser

13: decanter

14: water feed

15: THFA feed 16 crude product

17 water

18 sump

19 water

20 product (DHP)

Figure 2 shows a more detailed schematic representation then Fig. 1 of the production process of DHP according to the present invention with subsequent distillation. The number of heat exchangers and vaporizers before the reactor are dependent from the conditions in the industrial environment. Construction elements are marked with plain numbers (1 to 18). Flows are marked with numbers in diamond fields (20 to 34). Only valves necessary for an improved distillation circuit and obtaining the product (13, 15, 16 and 18) are numbered to allow simple identification in the description. Water (20) is fed through a heat exchanger (1) and preheated by the crude reaction mixture (23) leaving the reactor (7). After leaving the heat exchanger (1) the water vapor (approx. 195 to 210 °C) is passed through one or more vaporizer(s) (2, 3) to reach about 370 to 395 °C.

THFA (21) is fed through a heat exchanger (4) and a vaporizer (5) to reach about 300 °C.

Gaseous THFA is entrained in the water vapor in a mixing device (6) and passed through a reactor (7) charged with the Al20 ₃ -comprising catalyst. Starting temperature in the reactor is about 350 °C and is usually further maintained at approx. 330 °C. The reactor can be operated at atmospheric pressure. A small amount of an additional purge gas (22) might be fed into the system, preferably between heat exchanger (1) and vaporizer (2).

After leaving the reactor (7), the crude reaction mixture (23) is condensed in the heat exchanger (1), and the condensed product (24) is fed to a gas-liquid separator (8), where gaseous components (25), i.e. purge gas(es) and/or other uncondensable gas(es), are removed. The crude condensate (26), mainly consisting of DHP and water, then is passed into the decanter (9) and separated from water (28), which can be disposed as it contains at room temperature only about 1.6 weight % of DHP. An azeotropic distillation of the crude product (27) can be carried out in continuous mode or in batch mode. In continuous mode the crude product (27) leaving the decanter (9) is passed continuously into the distillation boiler (1 1), whereas in batch mode the crude product is first collected for example in one or more tanks (10) and then passed into the distillation boiler (1 1). Expediently, the distillation is carried out in batch mode to obtain DHP with very low acrolein amounts. Thus, the following description only refers to a batch mode distillation.

In the distillation boiler (1 1) the crude product (27) is heated to reflux over a column (12), said column (12) might optionally be operated with separation plates or filled with a structured packing. Expediently, distillation is carried out at atmospheric pressure. The sump (29) can be periodically removed.

Regulated by a valve (13) the head product (30) is passed through a condenser (14) to obtain a condensed head product (31). The first runnings of the condensed head product (31) are returned completely to the column. After reaching steady state, a more or less constant part of the condensed head product (31), i.e. between 50 and 100% of the regulated by valves (15) and (16), is fed to a decanter (17) which is charged with water to wash the condensed head product (31) and to remove acrolein. Washed head product (32) is then returned to the column (12) as well as any condensed head product (31) passing valve (15). Expediently, about 2/3 of the condensed head product (31) is passed through said decanter (17) where azeotropes comprised in the head product remain in the decanter. The water (33) in the decanter is replaced at appropriate intervals until the organic phase in the decanter (i.e. washed head product (32)) meets the required specifications, particularly until the acrolein content is 20 ppm or less. Distilled product (34) can be removed from the circuit via valve 18. In a preferred embodiment to remove the product (DHP, 34) the ratio of the total reflux (i.e condensed head product (31) which is fed back to the column either after passing valves (15) or (16)) to removed DHP (34) is controlled to be about 3/4 and of about ¼ of the condensed head product (31), respectively. Removed DHP preferably is stored in a suitable tank. The distillation should be interrupted when the temperature in the distillation boiler drops to about 130 °C or less. Listing of embodiments of Fig. 2:

(Numbers in brackets indicate the corresponding embodiment in Fig. 1)

1 : heat exchanger (1)

2: vaporizer (2)

3: . vaporizer (3)

4: heat exchanger (4)

5: vaporizer (5)

6: mixing device (6)

7: reactor (7)

8: gas-liquid separator (not shown)

9: decanter (8)

10: tank(s) (9)

11 : distillation boiler (10)

12: distillation column (11) 13: valve (— )

14: condensor (12)

15: valve (— )

16: valve (— )

17: decanter (13) 18: valve (— )

19: valve (— )

20: water feed (14)

21 : THFA feed (15)

22: optional purge gas feed (— ) 23: crude reaction mixture (— )

24: condensed reaction mixture (— )

25: uncondensable gas(es) (— )

26: crude degassed condensed reaction mixture (16)

27: crude product (— ) 28: water (17)

29: sump (18)

30: head product (reflux) (— )

31 : condensed head product (reflux) (— ) 32 washed condensed head product (reflux)

33 water

34 product (DHP) Figure 3 shows the reactor temperature measured during a 4.5 day run of a production process according to the present invention.

Figures 4 to 8 show the contents of different compounds in the crude product during a 4.5 day run of a production process according to the present invention (measured by gas chromatography with FID detection, column Type DB-1701 of dimensions 10 m x 0.18 mm x 0.4 μιη, and expressed as % area of the peak of the respective compound in the chromatogram what corresponds with the weight % of the respective compound in the crude product), wherein

Figure 4 shows the content of generated DHP in % area vs. running time in days,

Figure 5 shows the content of the by-product THP in % area vs. running time in days,

Figure 6 shows the content of the by-product cyclopentanone in % area vs. running time in days, Figure 7 shows the content of the by-product acrolein in % area vs. running time in days, and Figure 8 shows the content of unconverted THFA in % area vs. running time in days.

A surprising feature of the present invention is that the catalyst is continuously regenerated in the presence of the water vapor. Thus, the catalyst has a long life and little regeneration, if ever, is required.

Typically, at the beginning of the process of the invention, THFA and water are fed separately through different lines for vaporization. At industrial scale, conveniently, waste heat may be used for preheating the starting compounds. In case waste heat is not sufficient to heat the starting compounds to the desired temperature, additional vaporizers may be used. Typically, the vaporized THFA is entrained in the water vapor immediately before entering the reactor in a mixing device (see Figure 1 and Example below). The weight ratio between THFA and water in the vapor phase when contacting the A1 ₂ 0 ₃ - comprising catalyst is at least 1 :10. Typically, the weight ratio of THFA to water vapor is in the range of 1 : 10 to 10: 1. In another preferred embodiment the weight ratio of THFA to water vapor is in the range of 1 :5 to 5 : 1 , more preferably 1 :2 to 2: 1 , in the latter case for example about 1 : 1. Typically, the THFA is contacted with the solid phase catalyst by passing the THFA entrained in the carrier gas over/through the catalyst. In the Al ₂ 03-comprising catalyst used according to the instant process, the A1 ₂ 0 ₃ may be used as the sole catalytically active component, or A1 ₂ 0 ₃ may be used in combination with one or more further catalytically active components. Examples of catalytically active components include further oxides such as Ti0 ₂ , V ₂ 0 ₅ or Mo0 ₃ . The content of A1 ₂ 0 ₃ in the solid phase catalyst is typically within a range of from 50 to 100 weight % and preferably is at least 75 weight %, more preferably at least 90 weight %. Most preferably, the catalyst is essentially composed of A1 ₂ 0 ₃ . Preferably, the η -modification of A1 ₂ 0 ₃ , i.e. η-Α1 ₂ 0 ₃ , is used.

The THFA entrained in the water vapor typically is continuously passed through a heated reactor containing the A1 ₂ 0 ₃ catalyst. The residence time in the reactor is typically from 0.5 to 20 sec, preferably from 1 to 10 sec, more preferably from 1 to 5 sec, and most preferably from 1 to 2 sec.

The process of the present invention, i.e. conversion of THFA on the Al ₂ 0 ₃ -comprising catalyst, is typically carried out at a temperature of 280 to 380 °C, preferably of 300 to 350 °C, for example at 330 °C. According to the present invention, a small amount of an inert gas such as nitrogen, argon, hydrogen, helium, carbon dioxide or a mixture thereof, may be optionally used in the conversion reaction. Nitrogen is the preferred additional gas in view of availability and price. Such additional gas may be used for example for safety reasons and/or to control the contact time of the reactants with the catalyst. In a preferred embodiment, the amount of nitrogen is typically in the range of 0.1 to 3 weight %, preferably of 0.5 to 2 weight % relative to the THF A/water vapor mixture passed over the catalyst.

In the reactor, the THFA vapor is converted to DHP vapor and water vapor. The obtained DHP and water vapors, together with the water vapor of the carrier gas, leaving the reactor are condensed and are typically passed through a separator or decanter where the water is removed from DHP. The DHP obtained according to the invention may be subjected to further purification, to meet the standards required for the production of pharmaceutical compounds or agrochemicals. The most common by-products generated in DHP production are tetrahydropyran (THP),

cyclopentanone and acrolein. Also some unreacted THFA is typically contained in the crude product. Further purification steps typically include distillation.

As THP, acrolein and cyclopentanone, typical and dominating by-products of the reaction, form azeotropic mixtures with the residual water of the crude product obtained after the decanter (no. 8 in Fig. 1, no. 9 in Fig. 2), said by-products may be removed from the raw product by azeotropic distillation. The azeotropic distillation may be carried out according to methods known in the art. In a further embodiment THP can be obtained in the inventive process by further purification of the waste water (33) from decanter (17).

For more efficient separation, the distillation is typically carried out by rectification. To remove the azeotropic mixtures, the reflux (not specified in Fig. 1, no. 28/29 and 30 of Fig. 2) may be passed partly or completely through a decanter (no. 13 in Fig. 1, no. 17 in Fig. 2) filled with water (i.e. washed), and where the azeotropic mixtures and the contaminants accumulate in said water, which is removed an replaced with fresh at suitable intervals. The use of water vapor as carrier gas in the catalyzed production of DHP has the advantage that water and water vapor are abundantly available in industrial facilities. Moreover, after completion of the reaction, the water is easily condensed and separated from the crude DHP. The easy condensation and separation of the water also circumvents the problem of product loss. As the condensed water and the crude organic DHP are both in the liquid phase, their separation in a decanter is straightforward. Although the disposed water may still contain some DHP, the DHP loss is reduced compared to a process using large volumes of nitrogen as entrainer gas also which entrains a considerable amount of product.

Moreover, use of water vapor as a carrier gas requires less regeneration steps of the A1 ₂ 0 ₃ - comprising catalyst compared to the state of the art. Without wishing to be bound by theory, it is believed that running the catalytic conversion with water vapor avoids catalyst regeneration to a large extent, as steam has similar effects as air and oxygen. The catalyst is thus continuously regenerated in the presence of water vapor. To run a DHP production truly continuous in the art it is recommended to have two catalytic reactor columns in parallel, thus, while one reactor is in use, the catalyst in the other reactor can be recycled. The present invention allows operating with only one reactor to be truly continuous. Furthermore, no waste products (such as organics, tar, carbon black) from regenerating the catalyst need to be released to the atmosphere without regenerating with an oxygen containing gas. A further advantage of the "continuous

regeneration" is that there is no induction phase while restarting the reaction after regeneration. In the art such "induction phase" is a further reason for loss of product.

Since 2,3-Dihydropyran is an important building block in the synthesis of pharmaceutical and agrochemical compounds we further claim DHP obtained by the present process as well as the use of said DHP in industrial chemistry. Dihydropyran is commonly used to prepare

tetrahydropyran (THP, CAS [142-68-7]) by hydrogenation in the presence of a catalyst, preferably a metal catalyst, for example Raney-Nickel, Raney-Cobalt, palladium or platinum. Thus, we also claim a process for the preparation of TFP, comprising hydrogenation of DHP in the presence of a catalyst, wherein the DHP is obtained by the instant process.

The present invention is illustrated in more detail by the following non-limiting examples.

Example

Production of DHP using H ₂ 0 vapor as carrier gas

In this specific embodiment, the conversion of THFA to DHP was carried out in continuous mode and run for four days. References to Fig. 1 and Fig. 2 are indicated in brackets, such as (14/20) for water feed according to no. 14 in Fig. 1 and no. 20 in Fig. 2. Indications without a corresponding number are indicated with a two dashes, such as (— /8) for the gas-liquid separator which is not shown in Fig. 1. The reaction has been carried out in a ring-gap reactor of about 80 L internal volume, which has a treatable reaction tube having an internal length 1 of about 1700 mm, an internal diameter d ¹ of about 436 mm in the interior of which is situated in an, if appropriate, rotatable cylindrical displacement body which extends over the entire length of the reaction tube, and is arranged axially symmetrically while having an outer diameter d of about 500 mm. Water (14/20) was pumped through heat exchanger (1/1) and preheated by the raw product stream leaving the reactor. After leaving the heat exchanger (1/1) the water had a temperature of about 195 to 210 °C. The water vapor was further passed through vaporizers (2/2) and (3/3) to reach a temperature of about 370 to 395 °C.

THFA (15/21) was pumped through heat exchanger (4/4) and then through vaporizer (5/5) to reach a temperature of 300 °C. The gaseous THFA was entrained in the water vapor in a mixing device (6/6) and passed through a ring gap-reactor (7/7) charged with 49.3 kg of A1 ₂ 0 ₃ (NorPro ^® Saint-Gobain, SA 3X77). The temperature in the reactor was 350 °C at the beginning of the production run and was further maintained at 330 °C. The reactor pressure was maintained at atmospheric pressure. A small amount of nitrogen (1 kg/h) as a purge gas (~/22) was fed into the system between heat exchanger (1/1) and vaporizer (2/2). The feed of the THFA was 60 kg/h and the feed of the water was about 54 kg/h respectively (total THFA feed: 5.3 tons). The residence time of the heated mixture in the reactor was approx. 1.3 sec and the WHSV (weight hourly space velocity, i.e. weight of feed flowing per unit weight of the catalyst per hour) was 2.3 h ^"1 .

The obtained crude reaction mixture (~/23) was condensed in the heat exchanger (1/1) and nitrogen and other uncondensable gases were removed in a separator (~/8). The crude degassed reaction mixture (16/26), mainly consisting of DHP and water, was further passed into a decanter (8/9) and separated from water. The water (17/28) was disposed as it contains at room

temperature only about 1.6 weight % of DHP. Following separation from water, the crude product (~/27) contained 94 weight % of DHP, 1.8 weight % of THP, 1 weight % of THFA, 0.6 weight % of H ₂ 0, 0.035 weight % of acrolein and 0.06 weight % of cyclopentanone.

and the yield was 82 %.

An azeotropic distillation was carried out in batch mode. About 4.2 m of crude product were collected in tanks (9/10) after separation of water in the decanter before the crude product was subjected to distillation in two portions. A first part of the crude product was filled into a 3.2 m distillation boiler (10/11) and heated to reflux over a column (11/12) with a structured packing (Sulzer Mellapack 250 Y) having 11 theoretical plates. The distillation was carried out at atmospheric pressure. The sump (18/29) was periodically removed. The second part of the crude product was filled was filled in the distillation boiler (10/11) when a respective amount from the first filling was distilled of.

At the beginning, the condensed head product (31) (reflux) was returned completely to column (11/12) with a rate of 900 L/h after passing a condenser (12/14). The decanter (13/17) was charged 2/3 with water, and 2/3 of the reflux was passed through the decanter before returning it to the column. The azeotropes remained in the decanter (13/17) and the water (19/33) in the decanter was replaced every 30 min until the organic phase met the required specifications, particularly until the acrolein content was 20 ppm or less. At that point, the ratio of reflux (i.e about 600 L/h) and DHP removal (i.e. about 200 L/h) was set to about 3 : 1. The DHP (20/34) was distilled into one or more suitable tank(s). The distillation was interrupted when the temperature in the distillation boiler dropped to 130 °C.

The purified DHP (20/34) thus obtained consisted of 97.77 weight % of DHP, 1.64 weight % of THP, 0.2 weight % of H ₂ 0 and 0.0017 weight % of acrolein as determined by gas

chromatography. Cyclopentanone was below detection limits after distillation. DHP yield after distillation was 74%. It must be noted that in some distillation batches we obtained a very low acrolein level of only 6 to 9 ppm. As can be seen from Figures 3 to 8, the conversion rate of THFA to DHP was consistently quantitative over four days. The amounts of generated by-products were low and did not increase over time. This demonstrates stable conversion with excellent yields when using water vapor as carrier gas. It is also evident that the process of the present invention may be carried out over long periods of time before regeneration of the catalyst is required. In the state of the art the life time of the catalyst in production corresponds to the recycle time of the catalyst. Under the conditions of the present invention even after 4.5 days of production the catalyst revealed no tendency of inactivation. Also, after 4.5 days by optical control the catalyst looked like fresh prepared catalyst and no deterioration of the catalyst could be observed. Except for the start-up phase, the content of DHP in the crude product turned out to be very high and at least 94 weight % when using water vapor as carrier gas. On the other hand, the amounts of the by-products THP, cyclopentanone and acrolein in the crude product are surprisingly low. Typically, the amount of THP is below 2.0 weight %, the amount of acrolein is below 0.05 weight % and the amount of cyclopentanone is below 0.1 weight %. Further, the amount of unreacted THFA is typically below 1.5 weight % and the amount of residual water is typically below 1.0 weight %. Specifically, the amounts of cyclopentanone and acrolein are considerably lower than in industrial processes using nitrogen as carrier gas. Using water vapor as entrainer also leads to unexpectedly low content of acrolein in the DHP product.