A ONE POT PROCESS FOR SYNTHESIS OF OXAZOLINE AND IMIDAZOLE COMPOUNDS FROM GLYCEROL

Abstract

The present invention disclose a single step one pot process for synthesis of oxazoline and imidazole derivatives from glycerol using solid acid metal catalyst with improved yield.

Claims

1. A single step, one pot process for synthesis of nitrogen containing heterocyclic compounds from glycerol or bio- glycerol using solid acid metal catalysts comprising the steps of: a. stirring the mixture of glycerol and solid acid metal catalyst at temperature in the range of 180 to 240° C. for a period in the range of 4-6 hrs to obtain acetol; b. cooling the reaction mixture of step (a) to a temperature in the range of 0° C. to 50° C. and adding ammonia solution followed by stirring the mixture for the period in the range of 1-10 hrs to obtain nitrogen containing heterocyclic compound; wherein, the selectivity of said heterocyclic compound is greater than 95%.

2. The process as claimed in claim 1, wherein said metal catalyst is selected from Cu, Al, Zr, Zn, Mg, Ba, Ru, Pd, Pt or combinations thereof.

3. The process as claimed in claim 1, wherein said metal catalyst is selected from combinations of Cu—Al, Cu—Zr or Cu—Mg, Ru—C, Ru/C, Ru/s-ZrO.sub.2Ru/γ-Al.sub.2O.sub.3.

4. The process as claimed in claim 1, wherein said nitrogen containing heterocyclic compounds are oxazoline or imidazole.

5. The process as claimed in claim 1, wherein the ratio of glycerol: ammonia is in the range of 1:1 to 1:3.

6. The process as claimed in claim 1, wherein step (a) of said process optionally comprises addition of water to a mixture of glycerol and solid acid metal catalyst.

7. The process as claimed in claim 1, wherein said stirring in step (b) is carried out at temperature in the range of 10° C. to 20° C.

8. The process as claimed in claim 1, wherein said process is carried out via reactive distillation or batch mode.

Description

BRIEF DESCRIPTION OF THE DRAWINGS:

[0031] FIG. 1: Reactive distillation set-up

[0032] FIG. 2:.sup.13C NMR of oxazoline

[0033] FIG. 3:.sup.1H NMR of oxazoline

DETAILED DESCRIPTION OF THE INVENTION:

[0034] The invention will now be described detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

[0035] In the view of above, the present invention provides a single step one pot process for synthesis of oxazoline and imidazole from glycerol using solid acid metal catalyst with high yield.

[0036] In an embodiment, the present invention provides a single step, one pot process for the synthesis of oxazoline from glycerol using metal catalysts with selectivity greater than 95%, comprising reacting glycerol in the presence of metal catalyst, cooling, adding ammonia and stirring the reaction mixture to obtain oxazoline or imidazole.

[0037] The present invention provides Scheme 1:

##STR00001##

[0038] In preferred embodiment, the present invention provides a process wherein the metal catalyst is selected from Cu, Al, Zr, Zn, Mg, Ba, Ru, Pd, Pt or combinations thereof

[0039] In more preferred embodiment, the present invention provides a process wherein the metal catalyst is a bimetallic catalyst preferably selected from combinations of Cu—Al, Cu—Zr or Cu—Mg.

[0040] In another preferred embodiment, said metal catalyst is selected from Ru/C, Ru/s-ZrO.sub.2,Ru/γ-Al.sub.2O.sub.3.

[0041] In another preferred embodiment, the present invention provides a process wherein the ratio of glycerol: ammonia is in the range of 1:1 to 1:3; reaction temperature is in the range of 180-220° C.; cooling temperature is in the range of 0-50° C.

[0042] In still another preferred embodiment, the present invention provides a process wherein the selectivity is >95% and preferably >97%.

[0043] In yet another preferred embodiment, the present invention provides a process wherein the reaction can be carried via reactive distillation or batch mode. More preferably, the reaction is carried out via reactive distillation.

[0044] In another embodiment, the present invention provides a process for the preparation of imidazole derivatives from glycerol comprising: [0045] a. carrying the dehydration reactions in a stirred autoclave of bio-glycerol and water in presence of metal catalyst at ambient pressure of nitrogen to obtain the reaction mixture; [0046] b. filtering and cooling the reaction mixture of step (a) followed by addition of ammonia, metal catalyst and stirring to obtain imidazole derivatives.

[0047] The above process of the present invention is shown below in Scheme 2

##STR00002##

[0048] In preferred embodiment, the present invention provides a process wherein the metal catalyst is selected from Cu, Al, Zr, Zn, Mg, Ba, Ru, Pd, Pt or combinations thereof

[0049] In more preferred embodiment, the present invention provides a process wherein the metal catalyst is a bimetallic catalyst preferably selected from combinations of Cu—Al, Cu—Zr or Cu—Mg.

[0050] In another preferred embodiment, the present invention provides a process wherein the reaction is carried via batch mode.

[0051] In yet another preferred embodiment, the present invention provides a process wherein the ratio of glycerol: ammonia is in the range of 1:1 to 1:3; reaction temperature is in the range of 180-220° C.; cooling temperature is in the range of 0-50° C.

[0052] In still another preferred embodiment, the present invention provides a process wherein the selectivity is >95% and preferably >97%.

[0053] In an aspect, the present invention provides a process for the preparation of the metal catalyst.

[0054] In a preferred aspect, the invention provides copper catalysts with various metals such as Zr and Al which are prepared by co-precipitation method with simultaneous addition of equimolar (0.05 M) mixture of aqueous solution of Cu (NO.sub.3).sub.2.3H.sub.2O, nitrate precursor of a respective metal and 0.2 M aqueous K.sub.2CO.sub.3 in a round bottom flask having 5-10 mL of water at room temperature. The obtained precipitate is digested for 4-5 h and then filtered and washed with deionized water to remove the traces of potassium. The precipitate is dried in an oven at 100° C. for 5-8 h and calcined at 400° C. for 3 h followed by its activation at 200° C. under H.sub.2 flow for 12 h.

[0055] The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

EXAMPLES

[0056] The experiments with reactive distillation were carried out in a glass reactor capacity of 100 mL. A magnetic stirrer with an agitation speed of 600 rpm was used to create a slurry reaction mixture. A condenser was attached to the top of a glass reactor, through which chilled water was circulated. In a typical procedure, the glass reactor was immersed in a constant temperature silicon oil batch, the temperature of which was maintained at 220° C. In the glass reactor, the catalyst and reaction mixture were first heated to the reaction temperature of 220° C. The distillate was continuously collected in a glass receiver connected to the condenser which was maintained at 0° C. using ice bath. All the experiments were conducted under vacuum by using a vacuum pump.

Example 1

Preparation of Catalyst: (Catalyst Preparation Repeated Twice)

[0057] a) Copper catalysts with various metals such as Zr and Al were prepared by co-precipitation method with simultaneous addition of equimolar (0.05 M) mixture of aqueous solution of Cu (NO.sub.3).sub.2.3H.sub.2O, nitrate precursor of a respective metal and 0.2 M aqueous K.sub.2CO.sub.3 in a round bottom flask having 5-10 mL of water at room temperature. The obtained precipitate was digested for 4-5 h and then filtered and washed with deionized water to remove the traces of potassium. The precipitate was dried in an oven at 100° C. for 5-8 h and calcined at 400° C. for 3 h followed by its activation at 200° C. under H.sub.2 flow for 12 h. [0058] b) Supported Ru, Pd, Pt catalysts were prepared by impregnation method. The synthesis was performed by suspending 2 g of activated carbon in aqueous medium using calculated amount of the respective metal precursors and then suspension was stirred for 2 h. It was then subsequently reduced using 5 mL of NaBH.sub.4 (1 mol) as a reducing agent. The catalyst was filtered and dried at 110° C. for 12 h.

Example 2

Preparation of oxazoline [2,4-dimethyl-2,5-dihydrooxazol-2-yl)methanol]from Glycerol

[0059] ##STR00003##

[0060] The reaction was carried out in reactive distillation set up (FIG. 1) in which round bottom flask having 100 mL capacity was taken to which 50 g of pure bio-glycerol and 0.8 g of Cu—Al catalyst were added (FIG. 1). This reaction mixture was stirred by a magnetic stirrer at an agitation speed of 600 rpm and temperature was maintained at 220° C. by using silicon oil bath. The reaction was continued for about 6 h and acetol formed was continuously distilled out during the reaction. The obtained distillate mainly containing acetol and 1,2-propanediol, was analyzed by GC (Model Shimadzu GC-2025) equipped with an auto sampler (Model AOC-20i) and a capillary FFAP (Free Fatty Acid Phase) (30 m length×0.53 mm i.d.×1 μm film thickness) column connected to the flame ionization (FID) detector. The distillate was cooled to 0-10° C. and then 30% aqueous ammonia solution (1:3 ratio) was added drop wise with stirring in the presence of 0.05 g Cu—Al catalyst,

[0061] The reaction mixture was stirred for 1 h at 50° C. and reaction progress was monitored by GC. (FIGS. 2 and 3)

[0062] 13C NMR (200 MHz, CHLOROFORM-d) δ ppm: 14.89, 21. 40, 66.6, 76.26, 110.40, 169.14. 1HMR (200 MHz, CHOLOROFORM-d) δ ppm: 1.39(CH.sub.3,s,3H), 2.08 (CH.sub.3,s,3H), 3.02(OH,s,1H), 3.64(CH.sub.2,d,2H), 4.58(CH.sub.2,s,2H).

[0063] Table 1 depicts glycerol dehydration to acetol by reactive distillation and its amination to oxazoline.

TABLE-US-00001 TABLE 1 Acetol to Oxazoline Selectivity Glycerol to Acetol 1,2- Selectivity 5-methyl dimethyl Sr. No. Cata. Conv. Acetol 1-2,PDO Solketal Conv. Oxazoline imidazole imidazole 1 Cu—Al 20 80 7 13 99 95 3 2 2 Cu—Zr 22 82 8 10 99 95 3 2 3 Cu—Mg 25 75 10 15 99 95 3 2 Reaction conditions: Glycerol to Acetol - 50 g bio glycerol, T = 220° C., catalyst = 0.8 g, reaction time = 6 h; Acetol to oxazoline - 10 g distillate, T = 50, catalyst = 0.01 g, reaction time = 2 h.

Example 3

Preparation of Imidazole Derivatives from Glycerol

[0064] ##STR00004##

[0065] The dehydration reactions were carried out in a 300 mL capacity stirred autoclave supplied by Parr Instruments Co.USA., in which 5% W/w of bio-glycerol and 95 ml of water is added along with 0.8 gm of catalyst at ambient pressure of nitrogen. The reactions were carried out for 3 h and then catalyst is filtered out by using filter paper. The filtrate was cooled to 0-10° C. and then 30% aqueous ammonia solution (15 mL) was added drop wise with stirring,

[0066] and then the reaction mixture was stirred for 2 h at 50° C. and reaction progress was monitored by GC.

[0067] Table 2 depicts glycerol dehydration to acetol in batch reactor followed by its amination to imidazole.

TABLE-US-00002 TABLE 2 Acetol to imidazole Selectivity (%) Glycerol to acetol 1,2- Sr. Conv. Selectivity (%) Conv. 5-methyl dimethyl No. Cata. (%) Acetol 1-2,PDO other (%) imidazole imidazole oxzoline 1 Cu—Al 26 91 8 1 100 50 47 3 2 Cu—Zr 22 89 10 1 100 49 45 6 3 Cu—Mg 24 75 20 5 100 49 46 5 Reaction conditions: Glycerol to Acetol - 5 wt. % aq. bio glycerol, T = 220° C., catalyst = 0.8 g, reaction time = 3 h; Acetol to imidazole - T = 50° C., reaction time = 2 h.

Example 4

Glycerol to Oxazoline

[0068] ##STR00005##

[0069] The reactions were carried out in a 300 mL capacity stirred autoclave supplied by Parr Instruments Co.USA., in which 20% W/w of bio-glycerol and 80 ml of water is added along with 0.8 gm of catalyst. The reactions were carried out for 3 h at 220° C. After completion of reaction; reactor is cool down to the 0-10° C. by ice chilling water and then 30% Aq. Ammonia solution (10m1) was pumped into the reactor by applying the vacuum. After complete addition of ammonia, the reaction was carried out at 50° C. for 1 hr at 1000 rpm. The intermittent liquid samples were analyzed by GC (Model Shimadzu GC-2025) equipped with an auto sampler (Model AOC-20i) and FID detector on a capillary FFAP (Free Fatty Acid Phase) (30 m length×0.53 mm i d.>1 μm film thickness) column. The result of one pot synthesis of oxazoline from glycerol with different catalyst is given in table 3.

[0070] Table 3 depicts one pot synthesis of oxazoline from glycerol.

TABLE-US-00003 TABLE 3 Selectivity (%) Sr. Con. 1,2 No Catalyst (%) Oxazoline PDO Acetol Ethanol EG Imidazole Oth 1 1% Ru/C 18 85 3 2 2 1 2 5 2 3% Ru/C 26 91 2 1 2 1 2 1 3 5% Ru/C 29 78 7 2 4 4 3 2 4 10% Ru/C 33 73 10 2 5 5 3 2 5 3% Pd/C 14 5 3 3 40 5 40 4 6 3% Pt/C 15 5 40 3 20 4 20 4 7 3% Ru/s-ZrO.sub.2 22 70 10 2 10 0 2 5 8 3% Ru/γ- 20 80 5 3 3 0 4 3 Al.sub.2O.sub.3 Reaction conditions: Glycerol to Acetol - 20 wt. % aq. bio glycerol, T = 220° C., catalyst = 0.8 g, reaction time = 3 h; Acetol to Oxazoline - T = 50° C., reaction time = 2 h.

ADVANTAGES OF INVENTION

[0071] 1) A catalytic, single step one pot process for oxazoline preparation with high yields. [0072] 2) The process uses the renewable, cheapest bio-glycerol feed stock. [0073] 3) Oxazoline is used as surface active agents (lubricant, dispersing pigments), gasoline and lube oil additives (antiknock and anti-icing), corrosion inhibitors, antifoam agents, textile chemicals, pharmaceuticals (Central nervous system regulators are the substituted 2- amino-2-oxazolines. Aminooxazolines, such as 2-amino-5-phenyl-2-oxazoline, have been tested and found very potent in suppressing appetite. Raising blood sugar levels, and exhibit local aesthetic, sedative, vasoconstrictor, blood pressure depressant, and gastric fluid secretion), adhesives and binders, stabilizers for chlorinated hydrocarbons, stabilizers for aqueous formaldehyde solutions, protective films in polish formulations, foam stabilizers, photography and polymer.