One pot, one step process for the halogenation of aromatics using solid acid catalysts

Abstract

The present invention disclosed an improved one pot, one step process for halogenation of compound of formula (II) to afford corresponding halogenated compound of formula (I) having improved yield and increased selectivity under very mild conditions.

Claims

1. An improved one pot, one step process for the halogenation of substituted aromatic compound selected from hydroxy aromatic compound, aromatic aldehyde compound, halo substituted aromatics, amide substituted aromatic compound and amino aromatic compound, said process consists of: addition of halogenating agent selected from chlorine, bromine or iodine and solid acid catalyst to the mixture of substituted aromatic compound in solvent selected from ethylene dichloride, methanol, hexane, toluene, ethanol, higher alcohols, dimethylsulfoxide, dioxane, dimethylformamide, acetone, diethyl ether, butanol and benzylalcohol followed by stirring the reaction mixture at temperature in the range of 25 to 85° C. and at atmospheric pressure of 14 psig for the period in the range of 2 to 6 hrs to afford corresponding halogenated compound wherein said solid acid catalyst is selected from MoO.sub.3/TiO.sub.2, MoO.sub.3/SiO.sub.2, WO.sub.3/TiO.sub.2, WO.sub.3/SiO.sub.2, and Mo Si/Al (7.5); wherein no mixed halogenated products are produced; wherein said catalyst is recyclable.

2. The process as claimed in claim 1, wherein said aminoaromatic compound is selected from aniline, 4-Chloroaniline, 4-Bromoaniline, 2,6 dimethyl aniline, anthranilamide, 2,6 diethyl aniline.

3. The process as claimed in claim 1, wherein said hydroxy aromatic compound is selected from phenol.

4. The process as claimed in claim 1, wherein said aromatic aldehyde compound benzaldehyde.

5. The process as claimed in claim 1, wherein said corresponding halogenated compound is selected from 4-chloro-2-iodoaniline, 2-iodoaniline, 4-bromo-2-iodoaniline, 4-iodo-2,6-dimethylaniline, 3-iodobenzaldehyde, 2-iodophenol, 2-amino-3-iodobenzamide, 2,6-diethyl-4-iodoaniline, 4-chloro-2,6-dimethylaniline and 4-bromo-2,6-dimethylaniline.

6. The process as claimed in claim 1, wherein selectivity towards corresponding ortho-halogenated compound is in the range of 50 to 100%.

7. The process as claimed in claim 1, wherein said process is carried out in batch mode or continuous mode.

8. The process as claimed in claim 1, wherein aniline conversion to bromination is 100% and selectivity for 2-bromo aniline, 4-bromo aniline and 2,4-dibromo aniline is 40%, 50% and 10% respectively.

9. The process as claimed in claim 1, wherein aniline conversion to chlorination is 100% and selectivity for 4-chloro aniline and 2,4-dichloro aniline is 40% and 60% respectively.

Description

DETAILED DESCRIPTION OF THE INVENTION

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

(2) In the view of above, the present invention provides an improved one pot, one step process for the halogenation of compound of formula (II);

(3) ##STR00001##
Wherein;
R1 is selected from alkyl, amines, carbonyl containing compounds, halides, amides and acids;
R2 and R3 is selected from the hydrogen, halogen, alkyl, aryl and amine; to afford corresponding halo compound of formula (I)

(4) ##STR00002##
Wherein;
X is selected from chlorine, bromine, iodine;
R1 is selected from alkyl, amines, carbonyl containing compounds, halides, amides and acids;
R2 and R3 is selected from the hydrogen, halogen, alkyl, aryl and having improved yield and increased selectivity.

(5) In an embodiment, the present invention provides an improved one pot, one step process for iodination of aromatics of compound of formula (II) to corresponding iodo compound of formula (I) in presence of suitable catalyst and solvent using I.sub.2 as iodinating agent having improved yield and increased selectivity.

(6) In another embodiment, the present invention provides an improved one pot, one step process for the halogenation of substituted aromatic compound comprises addition of halogenating agent and solid acid catalyst to the mixture of substituted aromatic compound in solvent followed by stirring the reaction mixture at temperature in the range of 25 to 150° C. for the period in the range of 2 to 6 hrs to afford corresponding halogenated compound.

(7) In preferred embodiment, said substituted aromatic compound is selected from aminoaromatic compound, hydroxy aromatic compound, aromatic aldehyde compound, halo substituted aromatics, amide substituted aromatic compound.

(8) In another preferred embodiment, said aminoaromatic compound is selected from aniline, 4-Chloroaniline, 4-Bromoaniline, 2,6 dimethyl aniline, anthranilamide, 2,6 diethyl aniline.

(9) In yet another preferred embodiment, wherein said hydroxy aromatic compound is selected from phenol.

(10) In still another preferred embodiment, said aromatic aldehyde compound is benzaldehyde.

(11) In yet still another preferred embodiment, said corresponding ortho-halogenated compound is selected from 4-chloro-2-iodoaniline, 2-iodoaniline, 4-bromo-2-iodoaniline, 4-iodo-2,6-dimethylaniline, 3-iodobenzaldehyde, 2-iodophenol, 2-amino-3-iodobenzamide, 2,6-diethyl-4-iodoaniline, 4-chloro-2,6-dimethylaniline and 4-bromo-2,6-dimethylaniline.

(12) In yet still another preferred embodiment, said solid acid catalyst is selected from SiO.sub.2, MoO.sub.3/TiO.sub.2, MoO.sub.3/TiO.sub.2, WO.sub.3/TiO.sub.2, WO.sub.3/TiO.sub.2 and 5% Mo Si/Al (7.5) Impr.

(13) In yet still another preferred embodiment, said solvent is selected from ethylene dichloride, methanol, hexane, toluene, dichloromethane, ethanol, higher alcohols, dimethylsulfoxide, dioxane, dimethylformamide, acetone, diethyl ether, butanol and benzylalcohol.

(14) In yet still another preferred embodiment, selectivity towards said corresponding ortho-halogenated aromatic compound is in the range of 50 to 100%.

(15) In yet still another preferred embodiment, said process is carried out in batch mode or continuous mode.

(16) The halogenation is carried out in batch mode.

(17) The halogenation is carried out in continuous mode in down-flow reactor.

(18) The improved one pot, one step process for the halogenation of compound of formula (II) is to afford corresponding halo compound of formula (I) is depicted in scheme 1 below:

(19) ##STR00003##

(20) A range of heterogeneous solid acid catalysts are used for iodination of aromatics to corresponding iodo compounds with up to 97% conversion and 100% selectivity using I.sub.2 as iodinating agent and ethylene dichloride as solvent at only 80° C.

(21) 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

(22) Following examples are given by way of illustration and therefore should not be construed to limit the scope of the invention.

Example: 1 General Procedure for the Synthesis of Halo Compound of Formula I

(23) A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g substrate (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.28 g iodine (0.001 mol) was added to the same flask followed by addition of 0.02 g catalyst. The reaction was carried out at different temperatures (Table 1) for 2-6 hrs. After completion of the reaction, 5 mL water was added to the reaction flask to stop the reaction. The reaction was monitored by GC analysis.

(24) The compounds which are used for the iodination of aromatics are listed in table 1 below:

(25) TABLE-US-00001 TABLE 1 Liquid phase iodination of aromatics Molar % ratio Catalyst of loading Ex Temp, Sub: wrt % no. Substrate Catalyst ° C. I.sub.2 Solvent substrate Conv. % Selectivity  1 SiO.sub.2 28° C. 1:0.5 Hexane 10 45  2 20% MoO.sub.3/ TiO.sub.2 65° C. 1:1 MeOH  5 91  3 0 2% WO.sub.3/ TiO.sub.2 68° C. 1:0.5 Hexane 20 48 .sup.#OP 22  4 20 wt % WO.sub.3/ SiO.sub.2 28° C. 1:1.2 EDC 10 85  5 20 mol % MoO.sub.3/ SiO.sub.2 28° C. 1:1.2 EDC 10 65  7 5% MoSi/ Al (7.5) Impr 40° C. 1:1.2 EDC  5  3  8 20 wt % WO.sub.3/ SiO.sub.2 28° C. 1:1.2 MeOH 20 11 0  9 20 wt % WO.sub.3/ SiO.sub.2 65° C. 1:1.2 MeOH 20 22 10 20 wt % MO.sub.3/ SiO.sub.2 84° C. 1:1.2 EDC 20 88 .sup.#OP 15 11 20 wt % MO.sub.3/ SiO.sub.2 84° C. 1:1.2 EDC 20 88 0 .sup.#OP = Other products

Example 2: Catalyst Preparation

(26) a) SiO.sub.2: In a typical procedure, SiO.sub.2 catalyst was synthesized by dissolving ES-40 (50.0 g) in IPA (35 mL) with constant stirring. To this solution 3 mL dil. NH.sub.4OH (2.5%) solution was added. The solution was stirred until white gel was obtained. The resultant gel was air dried and further calcined at 500° C. in air in a muffle furnace for 5 h.

(27) b) 20% WO.sub.3/SiO.sub.2: In a typical procedure, 20 WS catalyst was synthesized by dissolving 5.31 g AMT in 10 mL distilled water. This solution was added drop wise to the dry IPA solution (35 mL) of ES-40 (50.0 g) with constant stirring. To this solution 3 mL dil. NH.sub.4OH (2.5%) solution was added. The solution was stirred until white gel was obtained. The resultant gel was air dried and further calcined at 500° C. in air in a muffle furnace for 5 h. Similarly catalysts with 1, 5, 10, 15, 25 and 30 wt % tungsten oxide loadings were prepared.

(28) c) 20 mol % MoO.sub.3/SiO.sub.2: In a typical procedure, 20 m % MoO.sub.3/SiO.sub.2 catalyst was synthesized by dissolving 14.11 g of ABM in 40 ml of water at 80° C. This hot solution was added dropwise to a dry isopropyl alcohol solution of ethyl silicate-40 (48.0 g) with constant stirring. The resultant transparent greenish gel was air-dried and calcined at 500° C. in air in a muffle furnace for 12 h. Similarly, catalysts with 1, 10 and 30 mol % molybdenum oxide loading were prepared.

(29) d) 20% MoO.sub.3/TiO.sub.2: In typical procedure Titanium(W) tetrabutoxide hydrolysed with deionized water (500 mL) and stirred vigorously for 10 min. The resulting titanium hydroxide precipitate separated by decantation and thoroughly washed with water until the alcohol generated during the hydrolysis of titanium alkoxide completely removes. Then precipitate dissolved in aqueous hydrogen peroxide (50%), which resulted in a very exothermic reaction. Additional water (200 mL) added to reduce the reaction rate and avoid the development of a highly viscous polymeric gel phase. A clear yellow solution formed within 30 min, the colour of which is characteristic of a titanium peroxo complex. To it added the aqueous solution of precursor MoO.sub.3 dropwise with stirring. Then the solution was kept overnight to form the uniform gel. After gelation air dried the gel, crushed it. The resulting powder dried in oven @ 100° C. then calcined @ 500° C. for 5 hr. (heating rate 2° C./min.).

(30) e) 2% WO.sub.3/TiO.sub.2: In typical procedure Titanium(IV) tetrabutoxide hydrolysed with deionized water (500 mL) and stirred vigorously for 10 min. The resulting titanium hydroxide precipitate separated by decantation and thoroughly washed with water until the alcohol generated during the hydrolysis of titanium alkoxide completely removes. Then precipitate dissolved in aqueous hydrogen peroxide (50%), which resulted in a very exothermic reaction. Additional water (200 mL) added to reduce the reaction rate and avoid the development of a highly viscous polymeric gel phase. A clear yellow solution formed within 30 min, the colour of which is characteristic of a titanium peroxo complex. To it added the aqueous solution (in 50% H.sub.2O.sub.2) of precursor AMT dropwise with stirring. Then the solution was kept overnight to form the uniform gel. After gelation air dried the gel, crushed it. The resulting powder dried in oven @ 100° C. then calcined @ 500° C. for 5 hr. (heating rate 2° C./min.).

(31) f) 5% Mo Si/Al (7.5) Impr: In typical procedure aluminium isopropoxide was taken in a beaker to this IPA was added, kept for stirring. To dissolve aluminium isopropoxide HNO.sub.3 was added ml by ml till it dissolves. In a separate beaker TEOS+IPA was taken, kept for stirring. To the clear solution of aluminium isopropoxide, TEOS+IPA mixture was added drop wise with stirring. The homogeneous mixture was stirred for 2 hrs then NH.sub.3 (1% NH.sub.3 in IPA) was added drop wise for gelation. The viscous liquid kept for gelation. Formed gel was oven dried at 60° C. The dried, grinded gel kept for calcination for 5 hr at 500° C. Then aqueous solution of ammonium heptamolybdate added to silica alumina support in an impregnation method. This mixture was stirred on hot plate to dry with stirring. The dried catalyst was calcined at 500° C. for 5 hr.

Example 3: Recycle Study for Liquid Phase Iodination of Aromatics

(32) A 250 mL two-necked round bottom flask fitted with condenser was charged 1 g 2,6 Dimethyl aniline (0.01 mol), 2.5 g iodine (0.01 mol), 100 mL 1,2-dichloroethane, and 0.2 g catalyst. The flask was flushed with argon. The reaction was carried out at room temperature (Table 2) for 1 hr. The reaction was monitored by GC analysis. The reaction mixture decanted leaving catalyst in the RB. The RB was charged with fresh reactants and it was stirred for 1 hr. The cycle was repeated 3 times.

(33) TABLE-US-00002 TABLE 2 Recycle study Sr. No. Recycle no. % conversion 1 0 77 2 1 74 3 2 78 4 3 76

Example 4: Continuous Flow Iodination

(34) In 10 cm fixed bed reactor 2 g 20% WO.sub.3/SiO.sub.2 was loaded. Reaction mixture containing 1 g aniline (0.01 mol), 2.8 g Iodine (0.01 mol) dissolved in 50 mL ethylene dichloride passed through the reactor at the flow rate of 3.5 ml/hr. Samples were collected at regular intervals and analyzed with GC. (Table 3)

(35) TABLE-US-00003 TABLE 3 Continuous flow iodination Sr. No. Sample (hrs) % conversion 1 0.25 69 2 0.5 68 3 0.75 68 4 1 70 5 3.5 69 6 7 68 7 18 70

Example 5: Bromination of Aniline

(36) A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g aniline (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.1 g bromine (0.0012 mol) was added to the same flask followed by addition of 0.02 g 20% WO.sub.3/SiO.sub.2 catalyst. The reaction was carried out at room temperature (25° C.) for 10 mins. The reaction was monitored by GC analysis. There was 100% aniline conversion observed with 40, 50 and 10% selectivity for 2-bromo aniline, 4-bromo aniline and 2,4-dibromo aniline respectively.

Example 6: Chlorination of Aniline

(37) A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g aniline (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.02 g of catalyst 20% WO.sub.3/SiO.sub.2 added. Later 0.027 g of chlorine (0.001 mol) gas was passed through the reaction flask. The reaction was carried out at room temperature (25° C.) for 10 mins. The reaction was monitored by GC analysis. There was 40% aniline conversion observed with 40 and 60% selectivity for 2-chloro aniline and 4-chloro aniline respectively.

Example 7: Chlorination of Aniline

(38) A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g aniline (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.02 g of catalyst 20% WO.sub.3/SiO.sub.2 added. Later 0.04 g of chlorine (0.0015 mol) gas was passed through the reaction flask. The reaction was carried out at room temperature (25° C.) for 60 mins. The reaction was monitored by GC analysis. There was 100% aniline conversion observed with 40 and 60% selectivity for 4-chloro aniline and 2,4-dichloro aniline respectively.

ADVANTAGES OF THE INVENTION

(39) 1. Halogenation of anilines can be carried out with >90% conversion in only 30 mins. 2. Very mild reaction conditions, No harmful or hazardous reagents needed for the reaction. 3. Ease of catalyst handling due to heterogeneous catalyst working at mild reaction conditions, Catalysts could be recycled very easily by just filtration or decantation. 4. No decrease in the conversion as well as selectivity in recycle runs. 5. No need to regenerate the catalyst or activate the catalyst for next cycles. 6. The iodination carried out in continuous mode in down-flow reactor at room temperature (at 25-28° C.).