KR20040003866A - Method for preparing of optically pure (R)-form or (S)-form tetrahydrofurfurylamine using heterogeneous catalysts - Google Patents

Abstract

PURPOSE: A method for preparing optically pure (R)-form or (S)-form tetrahydroperfurylamine using heterogenous catalyst is provided, thereby maintaining high optical purity, decreasing the preparation cost thereof, and increasing the productivity. CONSTITUTION: A method for preparing optically pure (R)-form or (S)-form tetrahydroperfurylamine using heterogenous catalyst comprises the steps of: continuously passing (R)-2-tetrahydrofurannitrile of the formula(1a) through a fixed bed reactor in the presence of heterogenous catalyst and an organic solvent under conditions of the temperature of 0 to 200 deg. C, pressure of 1 to 1000 psig, and WHSV of 0.1 to 10 h-1 and selectively hydrogenating the (R)-2-tetrahydrofurannitrile of the formula(1a) to obtain (R)-tetrahydroperfurylamine of the formula(2a), wherein the heterogenous catalyst is selected from Ni, Ru, Pd, Pt and Rh.

Description

Method for preparing of optically pure (R) -form or (S) -form tetrahydrofurfurylyl using heterogeneous catalysts

The present invention relates to a method for preparing optically pure (R) -form or (S) -form tetrahydroperfurylamine using a heterogeneous catalyst, and more particularly, to (R) -form or (S) -form 2 The present invention relates to a method for producing optically pure (R) -form or (S) -form tetrahydroperfurylamine through an economical and environmentally friendly process by reducing tetrahydrofurannitrile by hydrogenation using a heterogeneous catalyst.

(R) -form or (S) -form tetrahydroperfurylamine is the raw material upon which optically active drug development materials and other optically active chemicals are manufactured.

Representative examples of the method for preparing optically pure (R) -form or (S) -form tetrahydroperfurylamine in the prior art are as follows.

See, eg, US Pat. No. 3,577,409 and J. Org. Chem . 1981, 46 , 2798 (R) -forms having high optical purity by chemical optical splitting method using racemic tetrahydroperfurylamine, which can be easily prepared from perfural, as a starting material and forming salts with D-tartaric acid. A method for preparing tetrahydroperfurylamine is disclosed. However, since the method requires five recrystallization steps to obtain high optical purity, the manufacturing process is complicated and the manufacturing time is long. In addition, in order to separate (R) -form tetrahydroperfurylamine from a salt formed by reaction with D-tartaric acid, a basic aqueous solution should be used. In this process, a yield is lowered because an amine having high solubility in water must be extracted. There is.

In addition, J. Org. Chem . 1981, 46, and 2110 disclose methods for simultaneously producing (S) -form tetrahydroperfurylamine and (R) -form tetrahydroperfurylamine using L-tartaric acid, and British Patent No. 1,031,916 discloses tartaric acid. Instead, a method of preparing (R) -form tetrahydroperfurylamine using dibenzoyltartaric acid has been disclosed. However, as described above, there is a problem of separation through recrystallization and extraction from water.

Meanwhile, US Patent No. 4,129,580 discloses a method of preparing (R) -form tetrahydroperfurylamine by chemical optical splitting method by forming a salt using an expensive organic acid called lasaloside, but the organic acid used is In addition to being expensive, since (R) -form tetrahydrofurfurylamine having an optical purity of about 50% is manufactured, there is a problem that it is difficult to apply to industrial production.

As mentioned above, the existing manufacturing processes are mostly improved in optical purity through several recrystallization methods, or by adopting a batch process which is likely to generate side reactions, resulting in low productivity, large amount of waste, or manufacturing. Due to the complexity of the process, the overall yield is low, so mass production is impossible and there is a limit to industrial application.

Accordingly, in the present invention, in order to solve the above problems, (R) -form or (S) -form 2-tetrahydrofurannitrile is used as a starting material and (R) -form having high optical purity through a hydrogenation reaction. Or an effort was made to develop a continuous reaction process for obtaining (S) -form tetrahydroperfurylamine, and as a result, in the presence of a heterogeneous catalyst and an organic solvent in which a metal is supported on an inorganic oxide carrier, (R) -form or (S A method of hydrogenation of) -form 2-tetrahydrofurannitrile in a fixed bed continuous reactor has been found to continuously produce optically pure (R) -form or (S) -form tetrahydroperfurylamine in high purity and high yield. The present invention has been completed based on this.

Accordingly, an object of the present invention is to provide a method for economically preparing (R) -form or (S) -form tetrahydroperfurylamine having high optical purity that is industrially available.

Another object of the present invention is to provide a method for efficiently preparing (R) -form or (S) -form tetrahydroperfurylamine having high optical purity through a simple and environmentally friendly process.

The method for preparing optically pure (R) -tetrahydroperfurylamine according to the present invention for achieving the above and other objects is (R) -2-tetra represented by the following general formula (1a) in the presence of a heterogeneous catalyst and an organic solvent. Hydrofurannitrile is continuously hydrogenated through a fixed bed reactor under reaction conditions of reaction temperature of 0 to 200 ° C, reaction pressure of 1 to 1000 psig, and weight hourly space velocity (WHSV) of 0.1 to 10 h ^-1 to be selectively hydrogenated to be represented by the following Chemical Formula 2a. Obtain (R) -tetrahydroperfurylamine:

The method for preparing optically pure (S) -tetrahydroperfurylamine according to the present invention for achieving the above and other objects is (S) -2-tetra represented by the following general formula (1b) in the presence of a heterogeneous catalyst and an organic solvent. Hydrofurannitrile is continuously hydrogenated through a fixed bed reactor under the reaction conditions of reaction temperature 0 ~ 200 ℃, reaction pressure 1 ~ 1000psig, weight hourly space velocity (WHSV) 0.1 ~ 10h ^-1 and selectively hydrogenated to be represented by the formula (2b) Obtain (S) -tetrahydroperfurylamine:

Hereinafter, the present invention will be described in more detail.

As described above, in the present invention, in the presence of a heterogeneous catalyst and an organic solvent, (R) -2-tetrahydrofurannitrile or (S) -2-tetrahydrofurannitrile is reduced to a hydrogenation reaction through an economical and environmentally friendly process. A method of preparing optically pure (R) -form or (S) -form tetrahydroperfurylamine is provided.

In general, in the preparation of optically pure (R) -2-tetrahydrofurannitrile or (S) -2-tetrahydrofurannitrile, the optical purity of the reaction product is lowered depending on the reaction conditions and the type of catalyst, or the reaction Secondary and tertiary amines, which are byproducts, may be produced, but the present inventors have selected an optimal catalyst system and reaction conditions so that the reaction such as in Scheme 1a or Scheme 1b can occur mainly.

As a result, the present invention has developed a method for obtaining a reaction product having a high optical purity through an economical and environmentally friendly process, unlike the conventional manufacturing method. Therefore, in the present invention, a batch according to the prior art through the process of hydrogenating (R) -form or (S) -form 2-tetrahydrofurannitrile while continuously passing through a fixed bed reactor filled with a catalyst supported on a metal. Compared to the optical purity improvement method by the recrystallization method, the reaction product can be obtained in high yield, and the productivity is high, the waste is minimized, it is eco-friendly, and the catalyst can be recycled and used continuously. It is possible to obtain (R) -form or (S) -form tetrahydroperfurylamine with high optical purity continuously by applying a simple manufacturing process that does not require a complicated post-treatment step such as removing a filter.

Method for producing (R) -tetrahydroperfurylamine of the present invention is a reaction temperature of 0 ~ 200 ℃, reaction pressure of (R) -2-tetrahydrofurannitrile represented by the formula (1a) in the presence of a heterogeneous catalyst and an organic solvent Under a reaction condition of ¹ to 1000 psig, hourly space-weighted velocity (WHSV) of 0.1 to 10 h ⁻¹ , continuously passing through a fixed bed reactor to selectively hydrogenate to obtain (R) -tetrahydroperfurylamine represented by the following formula (2a):

Formula 1a

Formula 2a

In addition, the method for producing (S) -tetrahydroperfurylamine of the present invention is (S) -2-tetrahydrofurannitrile represented by the following general formula (1b) in the presence of a heterogeneous catalyst and an organic solvent, the reaction temperature of 0 ~ 200 ℃, Under the reaction conditions of ¹ to 1000 psig of reaction pressure and 0.1 to 10 h ^-1 weight hourly space velocity (WHSV), the mixture was continuously hydrogenated to obtain (S) -tetrahydroperfurylamine represented by the following Chemical Formula 2b. :

Formula 1b

Formula 2b

On the other hand, the heterogeneous catalyst used in the hydrogenation reaction is used by supporting a metal precursor or metal on an inorganic oxide carrier, the metal is nickel (Ni), ruthenium (Ru), palladium (Pd), platinum (Pt), and One selected from the group consisting of rhodium (Rh), or a mixture of these metals may be used, of which nickel (Ni) is most preferred. In addition, the carrier may be an inorganic material such as alumina, silica, silica-alumina, zirconia, titania, zeolite, or molecular sieve. Oxides can be used, of which alumina is most preferred. On the other hand, the carrier particles may be in the form of a circular, cylindrical, granular, or any type, but have a circular or cylindrical pellet to have suitable mechanical properties. Molded in the form of pellets is preferred.

At this time, the content of the metal is preferably maintained at 1 to 50% by weight based on the total catalyst, more preferably 5 to 40% by weight, if the content of the metal is less than 1% by weight of the hydrogenation reaction activity is reduced And, if it exceeds 50% by weight has a disadvantage of lowering the economics of the process due to the high price of the metal.

As a method of supporting the metal on the carrier, any of methods such as incipient wetness impregnation, excess water impregnation, spraying, or physical mixing may be used.

Meanwhile, in the hydrogenation reaction, a specific solvent should be used, and the solvent can dissolve the (R) -form or (S) -form 2-tetrahydrofurannitrile well so that it can be smoothly supplied to the reactor, and exothermic. It also serves to easily remove the heat of reaction generated by the hydrogenation reaction, which is a reaction, and must not react with the reactants (R) -form or (S) -form 2-tetrahydrofurannitrile and hydrogen. Therefore, in the present invention, a suitable solvent for such a hydrogenation reaction, methyl alcohol (methyl alcohol), ethyl alcohol (ethyl alcohol), normal propyl alcohol (n-propyl alcohol), isopropyl alcohol (i-propyl alcohol), normal butyl alcohol ( n-butyl alcohol), secondary-butyl alcohol (sec-butyl alcohol), tert-butyl alcohol (tert-butyl alcohol) and the like can be used, and most preferably ethyl alcohol (ethyl alcohol) is preferably used. . At this time, the content of the (R) -form or (S) -form 2-tetrahydrofurannitrile in the solution when the solvent is used is preferably maintained at 1 to 50% by weight, preferably 2 to 40% by weight.

In addition, in order to make an alkaline reaction system to improve the reaction selectivity by reducing the amount of secondary or tertiary amines that can be generated during the hydrogenation reaction of the nitrile compound, ammonia, methyl as an appropriate additive to the organic solvent Amines (methylamine), dimethylamine (dimethylamine), ammonium chloride (ammoniumcloride), and ammonium acetate (ammonium acetate) may be added and used, most preferably ammonia (ammonia) is preferably used. At this time, the content of ammonia in the solvent is preferably maintained at 0.1 to 10% by weight, preferably 1 to 5% by weight. If the content of the ammonia is less than 0.1% by weight, the activity of the hydrogenation reaction and the (R) -form Alternatively, if the selectivity of the (S) -form tetrahydrofurfurylamine is reduced and exceeds 10% by weight, the reaction yield of the process is lowered due to the decrease in conversion rate.

In addition, in the present invention, by using a continuous process using a fixed bed reactor, it is possible to obtain a reaction product with a higher yield than the reaction time compared to the conventional method, and it is economical because the catalyst can be repeatedly reused without further processing. There is no need to remove the filter by a filter, which provides a method for greatly simplifying the post-reaction process. In the fixed bed reaction system, there is no limitation in the form of the reactor or the direction of the input and flow of the reactants, but in order for the contact between the reactants to occur smoothly, the reactants hydrocarbon and hydrogen flow together from the top of the reactor to the bottom and the reactants are evenly distributed throughout the reactor. It is best to use a trickle-bed reactor with facilities to disperse.

On the other hand, the production reaction of the (R) -form or (S) -form tetrahydrofurfurylamine by hydrogenation carried out in the fixed bed reactor is the reaction temperature 0 ~ 200 ℃, hydrogen partial pressure 1 ~ 1000psig, weight hourly space velocity (WHSV ) Is preferably carried out under the reaction conditions of 0.1 to 10 h ^-1 , preferably 5 to 100 ° C, ¹ to 800 psig, and the reaction conditions of WHSV 0.2 to 10 h ^-1 , and more preferably 10 to 100 ° C, respectively. , 15 to 500 psig, WHSV 0.5 to 5 h ^-1 is preferably carried out under the reaction conditions.

In particular, when the reaction temperature exceeds 200 ℃ can not obtain the desired optical purity due to the racemization of the raw material, if the reaction temperature is less than 0 ℃ does not occur. Therefore, when the reaction conditions deviate from the above range, the hydrogenation reactivity of (R) -form or (S) -form tetrahydroperfurylamine is lowered, so that the production yield is lowered and the optical purity is lowered. The advantages of the continuous manufacturing process using heterogeneous catalysts are lost.

In addition, in order to completely convert the (R) -form or (S) -form 2-tetrahydrofurannitrile by hydrogenation, the molar ratio of hydrogen to the (R) -form or (S) -form 2-tetrahydrofurannitrile is Although it is preferable that it is 2.0 or more and there is no restriction | limiting about the numerical value beyond that, in consideration of process economics, the molar ratio of hydrogen to said (R) -form or (S) -form 2-tetrahydrofurannitrile is maintained between 2.0-10. It is good. At this time, hydrogen not used in the reaction and passed through the reactor is recompressed and circulated to the reactor.

On the other hand, the reaction product flowing out of the reactor is sent to a device for recovering the solvent, where at least some solvent is separated from the rest of the reaction product. Such a recovery device may use any type of device such as a distillation column or a flash vaporizer. In addition, the product, or the concentrate flowing out from the lower end of the solvent recovery device is transferred to a vacuum distillation apparatus.

As described above, according to the present invention, (R) -form or (S) -form 2-tetrahydrofurannitrile in a fixed bed continuous reactor in the presence of a heterogeneous catalyst having a metal supported on an inorganic oxide carrier, and an organic solvent. Through hydrogenation and economical and environmentally friendly processes, optically pure (R)-or (S) -form tetrahydroperfurylamine can be continuously produced in high purity and high yield.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited thereto.

Examples 1-4

Continuous Production Reaction of (R) -form Tetrahydroperfurylamine

10 g of a nickel (Ni / Al ₂ O ₃ ) catalyst was charged in a continuous high pressure reactor made of 316 stainless steel. Then, the catalyst in the reactor was raised to 300 ° C. at a temperature increase rate of 2 ° C. per minute in a hydrogen atmosphere, followed by a reduction process for 6 hours, and then the reactor was cooled and blown with nitrogen. Then, hydrogen was flowed at 100 ° C. at 15 ° C. in the reactor. Then, the injection amount of hydrogen was doubled than necessary for the reaction, and (R) -form 2-tetrahydrofurannitrile was dissolved in ethanol to be 10% by weight and injected into the continuous reactor. At this time, the reaction results according to the injection amount of the reactants and the reaction conditions inside the reactor are shown in Table 1 below. The reaction product was collected every 4 hours and analyzed by FID of gas chromatograph (50m × 0.2mm × 0.5m, HP-5 column).

Example ¹ Temperature (℃) Pressure (psig) WHSV (h ^-1 ) % Conversion Selectivity (%) ²⁾ Optical purity (%) ³⁾ One 15 150 1.0 100 91.0 99.50 2 50 150 1.0 100 80.4 98.21 3 15 100 1.0 86 90.5 99.21 4 15 150 2.0 72 91.0 99.14

¹⁾ Catalyst Manufacturer: CRI Kataleuna

²⁾ Reaction Selectivity of (R) -form Tetrahydroperfurylamine

³⁾ Optical Purity of (R) -form Tetrahydroperfurylamine

Example 5

Continuous Production Reaction of (S) -form Tetrahydroperfurylamine

10 g of a nickel (Ni / Al ₂ O ₃ ) catalyst (CRI Kataleuna) was charged to a continuous high pressure reactor made of 316 stainless steel. Then, the catalyst in the reactor was raised to 300 ° C. at a temperature increase rate of 2 ° C. per minute in a hydrogen atmosphere, followed by a reduction process for 6 hours, and then the reactor was cooled and blown with nitrogen. Then, hydrogen was flowed at 100 ° C. at 15 ° C. in the reactor. Then, the amount of hydrogen injected was increased twice as much as necessary for the reaction, and (S) -form 2-tetrahydrofurannitrile was dissolved in ethanol to be 10% by weight and injected into a continuous reactor. At this time, (S) -form tetrahydroperfurylamine of 100% of conversion, 91% of selectivity, and 99.5% of optical purity was obtained under reaction conditions of a reaction temperature of 15 ° C., a pressure of 154 psig, and a WHSV 1.0 h ⁻¹ . The reaction product was analyzed by FID of gas chromatograph (50m × 0.2mm × 0.5m, HP-5 column).

Examples 6-9

The hydrogenation of (S) -form 2-tetrahydrofurannitrile was carried out using methanol as a solvent in the method illustrated in Example 1 under the conditions of temperature 15 ° C., hydrogen pressure 150 psig, weight hourly space velocity (WHSV) 1.0 h ⁻¹ . The reaction results according to the type of catalyst used were shown in Table 2 below. The catalysts are commercially available catalysts and catalysts prepared by the present invention.

Example catalyst manufacture company % Conversion Selectivity (%) ¹⁾ Optical purity (%) ²⁾ 6 25% Ni / Al ₂ O ₃ CRIKataleuna 100.0 91.0 99.50 7 10% Ru / C Degussa 98.0 85.2 96.83 8 10% Pd / Al ₂ O ₃ Self-manufacture 99.0 10.0 83.13 9 10% Ru / Al ₂ O ₃ Self-manufacture 78.2 80.5 96.31

¹⁾ Reaction Selectivity of (S) -form Tetrahydroperfurylamine

²⁾ Optical Purity of (S) -form Tetrahydroperfurylamine

Examples 10-13

The hydrogenation of (S) -form 2-tetrahydrofurannitrile was carried out by the method illustrated in Example 1 under the conditions of temperature 15 ° C., hydrogen pressure 150 psig, and weight hourly space velocity (WHSV) 1.0 h ⁻¹ using ethanol as a solvent. The reaction results according to the type of additive used were shown in Table 3 below.

Example additive % Conversion Selectivity (%) Optical purity (%) 10 NH ₃ 100 91.0 99.41 11 NH ₄ OAc 99 84.5 99.20 12 CH ₃ NH ₂ 100 27.2 97.94 13 No 99 62.8 98.80

Example 14

Continuous reaction and recovery of (S) -tetrahydroperfurylamine

The reaction was carried out in a reactor similar to the reactor illustrated above using 50 g of nickel (Ni / Al ₂ O ₃ ) catalyst in the same manner as in Example 1. The pressure was maintained at 150 psig during the reaction, and after the reaction was conducted for 100 hours under the same conditions, 5 liters of a solution containing 89% by weight of (S) -tetrahydroperfurylamine was obtained. The solution was injected into a 10 liter glass reactor equipped with a reduced pressure distillation unit to recover (S) -tetrahydroperfurylamine. The glass reactor was distilled under reduced pressure at 55 ° C. and 100 mbar at a temperature increase rate of 5 ° C. per minute to evaporate about 90% of the ethanol in the solution, and then the temperature of the glass reactor at 90 ° C. and 1 mbar at a temperature increase rate of 5 ° C. per minute. Distillation under reduced pressure was carried out to obtain (S) -tetrahydroperfurylamine having an optical purity of 99.4%, a total yield of 80%, and a chemical purity of 99.2%.

Example 15

Continuous reaction and recovery of (R) -tetrahydroperfurylamine

The reaction was carried out in a reactor similar to the reactor illustrated above using 50 g of nickel (Ni / Al ₂ O ₃ ) catalyst in the same manner as in Example 5. The pressure was maintained at 150 psig during the reaction, and after the reaction was conducted for 100 hours under the same conditions, 5 liters of a solution containing 89% by weight of (R) -tetrahydroperfurylamine was obtained. The solution was poured into a 10 liter glass reactor equipped with a reduced pressure distillation unit to recover (R) -tetrahydroperfurylamine from. The glass reactor was distilled under reduced pressure at 55 ° C. and 100 mbar at a temperature increase rate of 5 ° C. per minute to evaporate about 90% of the methanol in the solution, and then the temperature of the glass reactor at 90 ° C. and 1 mbar at a temperature increase rate of 5 ° C. per minute. Distillation under reduced pressure was carried out to obtain (R) -tetrahydroperfurylamine having an optical purity of 99.4%, a total yield of 80%, and a chemical purity of 99.2%.

As described above, according to the present invention, the (R) -form or (S) -form 2- is substituted for the racemic tetrahydroperfurylamine used in the conventional chemical optical splitting technique in the presence of a heterogeneous catalyst on which a metal is supported on a carrier. Tetrahydrofurannitrile can be hydrogenated to provide high optical purity and pure (R) -form or (S) -form tetrahydroperfurylamine in high yield. In addition, the manufacturing method of the present invention is a relatively simple and environmentally friendly process, it is expected to be widely used in the industrial field because the industrial added value is very high because the industrial mass production is possible because it is economical to improve productivity.

Claims (12)

(R) -2-tetrahydrofurannitrile represented by the following Chemical Formula 1a in the presence of a heterogeneous catalyst and an organic solvent: reaction temperature of 0 to 200 ° C, reaction pressure of 1 to 1000 psig, and weight hourly space velocity (WHSV) of 0.1 to 10 h ^-1 Preparation of optically pure (R) -tetrahydroperfurylamine characterized by continuously passing through a fixed bed reactor under phosphorus reaction conditions to selectively hydrogenate to obtain (R) -tetrahydroperfurylamine represented by the following Chemical Formula 2a. Way: Formula 1a Formula 2a (S) -2-tetrahydrofurannitrile represented by the following Chemical Formula 1b in the presence of a heterogeneous catalyst and an organic solvent was reacted with a reaction temperature of 0 to 200 ° C., a reaction pressure of 1 to 1000 psig, and a weight space velocity per hour (WHSV) of 0.1 to 10 h ⁻¹ Preparation of optically pure (S) -tetrahydroperfurylamine characterized by continuously passing through a fixed bed reactor under phosphorus reaction conditions to selectively hydrogenate to obtain (S) -tetrahydroperfurylamine represented by the following Chemical Formula 2b. Way: Formula 1b Formula 2b The molar ratio of hydrogen to (R) -2-tetrahydrofurannitrile is 2.0 to 10, and the content of (R) -2-tetrahydrofurannitrile is 1 to 50% by weight based on the solvent. A process for producing optically pure (R) -tetrahydroperfurylamine, characterized in that. The molar ratio of hydrogen to (S) -2-tetrahydrofurannitrile is 2.0 to 10, and the content of (S) -2-tetrahydrofurannitrile is 1 to 50% by weight based on the solvent. Method for producing optically pure (S) -tetrahydroperfurylamine, characterized in that. The inorganic heterogeneous catalyst of claim 1 or 2, wherein the heterogeneous catalyst comprises at least one metal selected from the group consisting of nickel (Ni), ruthenium (Ru), palladium (Pd), platinum (Pt), and rhodium (Rh). A catalyst supported on an oxide carrier, wherein the content of the metal is 1 to 50% by weight relative to the catalyst. The method of claim 5, wherein the metal is nickel, and the content of nickel is 5 to 40% by weight based on the catalyst. The method of claim 5, wherein the inorganic oxide is alumina, silica, silica-alumina, zirconia, titania, zeolite, or molecular sieve. The method for producing optically pure (R) -tetrahydroperfurylamine according to claim 3, wherein the content of (R) -2-tetrahydrofurannitrile is 2 to 40% by weight based on the solvent. The method for producing optically pure (S) -tetrahydrofurfurylamine according to claim 4, wherein the content of (S) -2-tetrahydrofurannitrile is 2 to 40% by weight based on the solvent. The method according to claim 1 or 2, wherein the reaction temperature of the fixed bed reactor is 5 to 100 ° C, the reaction pressure is 1 to 800 psig, and the weight space velocity per hour is 0.2 to 10 h ^-1 . The method of claim 1 or 2, wherein the organic solvent is methyl alcohol (ethyl alcohol), ethyl alcohol (ethyl alcohol), normal propyl alcohol (n-propyl alcohol), isopropyl alcohol (i-propyl alcohol), normal butyl At least one selected from the group consisting of alcohol (n-butyl alcohol), secondary-butyl alcohol (sec-butyl alcohol), and tert-butyl alcohol (tert-butyl alcohol). The method of claim 1 or 2, wherein the reactant further comprises at least one additive selected from the group consisting of ammonia, methylamine, dimethylamine, ammonium chloride and ammonium acetate.