ELECTROCHEMICAL ORGANIC REACTION SETUP AND METHODS

Abstract

The present invention provides to a simple and efficient electrochemical organic reaction setup, particularly to carry out electrolysis reactions in chemistry laboratory and methods for performing the same with good yield and less impurity formation using the instantly presented device. Accordingly, the present invention relates to an electrochemical organic reaction setup as shown in fig. A-J comprising (a) Current source (6), (b) Reaction vessel or vial assembly set up comprising reaction vessel or vial (3), anode (1) cathode (2), Guard tube (8), alligator clip (5) and (c) Reaction mixture (4); for use in electrochemical reactions involving coupling between carbocyclic or heterocyclic rings and also in ring formation reactions between two or more moieties.

Claims

1. An electrochemical reaction setup assembly, comprising: a) Current source; b) Reaction vessel or vial assembly set up comprising reaction vial, anode, cathode, Guard tube, alligator clip; c) Reaction mixture; for use in electrochemical reactions involving coupling between carbocyclic or heterocyclic rings and also in ring formation reactions between two or more moieties.

2. The electrochemical reaction setup according to claim 1, wherein the current source used in step (a) is selected from battery, mobile charger, phone charger, adaptor.

3. The electrochemical reaction setup according to claim 1, wherein electrolyte used is selected from tetrabutylammonium iodide (TBAI), tetrabutylammonium-p-toluenesulfonate, tetrabutylammonium tetrafluoroborate, lithium perchlorate (LiClO4), sodium iodide (NaI).

4. The electrochemical reaction setup according to claim 1, wherein the solvent used is selected from acetonitrile, methanol, acetone, dichloromethane.

5. The electrochemical reaction setup according to claim 1, wherein the cathode or anode used is selected from Carbon (C), Iron (Fe), Copper (Cu), Aluminium (Al).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0030] The above and similar other objectives of the present invention are achieved by the arrangement of the electrochemical reaction setup assembly/set up (device) and developed methods for performing the electrolysis using the instantly presented device.

[0031] In general, the various terms used herein pertaining to the instantly presented invention are defined herein below:

[0032] It should be understood that the detailed description and specific examples, while indicating embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art. One skilled in the art, based upon the definitions herein, may utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

[0033] Unless otherwise defined, all the terms used herein, including the technical and scientific terms, have the meaning as that generally understood by one of ordinary skill in the art to which the present invention relates.

[0034] As used herein, the term “reaction vessel” refers to a glass container apparatus designed for optimal thermal transfer to or from a sample and for efficient optical viewing of a chemical reaction with the sample. The vessel includes a reaction chamber for holding a sample for chemical reaction. The vessel is designed for optimal thermal conductance and for efficient optical viewing of the reaction product. The thin shape of the vessel contributes to optimal thermal kinetics by providing large surfaces for thermal conduction and for contacting temperature-regulating elements. In addition, the vessel is suitable for a wide range of reaction volumes. Unlike reaction vessel instant invention uses reaction vials whenever required by the electrochemical reaction setup to perform the reaction.

[0035] As used herein, the term “batteries” refers to a source of current to carry out the reaction. In some cases these are replaced with mobile charger or adaptors to supply uninterrupted power supply. In the first attempt inventor uses 9V batteries followed by cell phone charger as an alternate source of current. This has added advantage of handling current flow in a safer way and the output is always constant. Inventor of the instant invention used either 5V adaptor or 12V adaptor depending upon the requirement and it was found that the use of 5V adaptor requires more reaction time as compared to 12V adaptor; however both gave good yields and cleaner reaction profile.

[0036] As used herein, the term “cathode or anode” refers to two different electrode terminals for in or out flow of ions in an electrochemical organic reaction set up. The electrodes used in the present study are selected from the group but not limited to Carbon (C), Iron (Fe), Copper (Cu) and Aluminium (Al). All the permutations and combinations of electrodes as anodes and cathodes are carried out to for best possible output. Carbon electrodes were purchased online while all other electrodes were gathered from the metal scrap and cleaned thoroughly before use. All electrodes were connected to the current source by alligator clips. The best combinations of electrodes (with respect to yield and reaction time) have been used in the scale up studies. Other electrodes can also be used for organic transformations.

[0037] Accordingly, the present invention relates to an electrochemical reaction setup assembly as shown in fig. A-J; comprising of:

[0038] (a) Current source (6),

[0039] (b) Reaction vessel or vial assembly set up comprising reaction vial (3) anode (1), cathode (2), Guard tube (8), alligator clip (5).

[0040] (c) Reaction mixture (4);

[0041] for use in high-yielding reactions involving coupling between carbocyclic or heterocyclic rings and also in ring formation reactions between two or more moieties.

[0042] In an embodiment, the electrolytes used in the present study are selected from the group but not limited to tetrabutylammonium iodide (TBAI), tetrabutylammonium-p-toluenesulfonate, tetrabutylammonium tetrafluoroborate, lithium perchlorate (LiClO4), sodium iodide (NaI) and the like. Other electrolytes can also be used for organic transformations.

[0043] In an embodiment, the solvents used in the present study are selected from the group but not limited to acetonitrile, methanol, acetone, dichloromethane and the like.

[0044] The electrochemical reaction setup assembly of the present invention is extended to use in the process comprising the below electrochemical experimental condition and it is illustrated in the following Scheme-I,

##STR00001##

[0045] The process of the present invention as illustrated in the above Scheme-I comprise reaction of a typical electrochemical experimental condition as shown below:

[0046] A 20 mL screw capped vial with a septum was taken and two carbon pencil leads were inserted as anode and cathode. The electrodes were connected to a 9V battery purchased locally. To the reaction vial were added benzoxazole 1 (1 mmol), amine 2a (2 mmol), acetic acid (5 mmol) and TBAI (10 mole %) and the mixture was dissolved in 10 mL of acetonitrile and stirred gently at room temperature. The electric current was passed through the reaction vial at room temperature for 2-8 hours. The progress of the reaction was monitored by TLC and LC-MS. After the completion of the reaction, the solvent was removed in vacuo and the crude material was dissolved in ethyl acetate (25 mL) and then washed with saturated aqueous sodium carbonate solution (3×10 ml). The organic layer was separated, washed with water and then dried over sodium sulfate. The product was purified by column chromatography using hexane and ethyl acetate as eluent to afford compound 3a in 85% yield.

[0047] In an embodiment, inventor of the instant invention developed a new set up comprising multiple USB ports to divert the current to different reactor vessels as shown in the following figure (Fig.C). This parallel assembly gave fantastic results and it was possible to carry out multiple reactions at the same time. Since the multiple USB port has individual switches, one could independently switch off any of the reactions without disturbing the others. This method can be extended to any number of ports in the USB adaptor (4 reactions shown in the following diagram; but it is not limited to four). The same concept has been successfully used in the scale up (1 g, 10 g) of the reaction shown in Scheme 1 and the diagram illustrated in Fig. D and Fig. E. It has been found that the scale up reaction can be carried out faster using 12V adaptor (Fig. E) rather performing the reaction by using 5 V adaptor as illustrated in the set up Fig.D.

Role of Acetic Acid in the Present Electrochemical Reactions:

[0048] The invention is further illustrated by the following examples which are provided to be exemplary of the invention, and do not limit the scope of the invention. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Examples of Coupling Reactions

[0049] ##STR00002##

Analytical Data of Newly Synthesized Compounds.

[0050]

TABLE-US-00001 Comp Isolated No. Analytical data (Mass/1H NMR) Yield 3a LCMS (m/z): 205.1 [M + 1].sup.+ .sup.1H NMR (400 MHz, 85% CDCl3) δ 7.41-7.42 (d, J = 7.6 Hz, 1H), 7.30-7.32 (d, J = 7.6 Hz, 1H), 7.20-7.24 (t, 1H), 7.07-7.10 (t, 1H), 3.85-3.88 (t, 4H), 3.72-3.75 (t, 4H). 3b LCMS (m/z): 304.7 [M + 1].sup.+ .sup.1H NMR (400 MHz, 80% CDCl3) δ 7.40-7.42 (d, J = 8 Hz, 1H), 7.30-7.32 (d, J = 8 Hz, 1H), 7.20-7.24 (t, 1H), 7.06-7.10 (t, 1H), 3.70-3.73 (t, 4H), 3.59-3.62 (t, 4H), 1.62 (s, 9H). 3c LCMS (m/z): 261.7 [M + 1].sup.+ .sup.1H NMR (400 MHz, 50% CDCl3) δ 7.39-7.41 (d, J = 7.6 Hz, 1H), 7.28-7.30 (d, J = 7.6 Hz, 1H), 7.08-7.20 (t, 1H), 7.04-7.08 (t, 1H), 4.39-4.43 (m, 1H), 4.17-4.20 (m, 1H), 3.75 (s, 3H), 3.35-3.41 (m, 1H), 2.17-2.21 (m, 1H), 1.88-1.92 (m, 1H), 1.68-1.87 (m, 2H).

[0051] Effect of voltage on reaction time (5V vs 12V):

[0052] Scale of the reaction: 1 g-10 g

[0053] Experimental procedure: Same as in scheme 1.

TABLE-US-00002 Sr No Cathode Anode Electrolyte 5 V 12 V Time 1 Aluminium Carbon TBAI 76% 92% 3 h 2 Aluminium Carbon TBAI 90% 93% 6 h

Selection of Electrodes:

[0054] We have carried out different experiments to get good electrode combinations which would make reactions go faster and cleaner. Other electrodes can also be used for organic transformations.

TABLE-US-00003 Sr Electro- Cur- No Cathode Anode lyte rent Conversion Time 1 Copper Carbon TBAI 5 V 50% 1 h 2 Aluminium Carbon TBAI 5 V 47% 1 h 3 Iron Carbon TBAI 5 V  7% 1 h 4 Carbon Carbon TBAI 5 V SM present. No 3 h reaction 5 Aluminium Iron TBAI 5 V No product formed 3 h Compound degraded 6 Carbon Alumi- TBAI 5 V No reaction. SM 3 h nium present

[0055] It has been found that the copper and aluminum electrodes give faster reactions as compared to Iron electrodes. This could be due to that aluminum and copper have lower resistance as compared to Iron and therefore increases the amount of current in the electrical circuit.

Selection of Electrolyte:

[0056] The number of electrolytes for optimum reaction output has been given in the below table. However these are not limited to the listed one and may be vary as desired for the organic transformations.

TABLE-US-00004 Sr Cur- Con- No Cathode Anode Electrolyte rent version Time 1 Aluminium Carbon LiClO.sub.4 5 V  5% 16 h 2 Aluminium Carbon NaI 5 V  3% 16 h 3 Aluminium Carbon Tetraethylammonium- 5 V 60% 16 h p-toluenesulphonate 4 Aluminium Carbon Tetrabutylamonium 5 V 35% 16 h tetrafluoroborate 5 Aluminium Carbon TBAI 5 V 90% 16 h

Selection of Reaction Solvent:

[0057] The following solvents were screened for optimum reaction output. However, these are not limited to the listed one and other compatible solvents can also be used for organic transformations.

TABLE-US-00005 Sr Electro- No Cathode Anode lyte Solvent Conversion Time 1 Aluminium Carbon TBAI Acetone 14% to 64% 3 h-16 h 2 Aluminium Carbon TBAI Dichloro- 5%-8% 3 h-16 h methane 3 Aluminium Carbon TBAI Methanol 5%-9% 3 h-16 h 4 Aluminium Carbon TBAI Acetonitrile 90% 3 h

Examples of Cyclisation or Ring Formation Reactions

[0058]

TABLE-US-00006 TABLE 1 [00003] [00004] R.sub.1 and R.sub.2 each independently selected from H, halo, alkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, cyclo-alkyl, nitro, ester or any reactive functional group. (P.sub.1-23) (Q.sub.1-23) Product (S.sub.1-23) Yield % [00005] P.sub.1 [00006] Q.sub.1 [00007] S.sub.1 70% [00008] P.sub.2 [00009] Q.sub.2 [00010] S.sub.2 85% [00011] P.sub.3 [00012] Q.sub.3 [00013] S.sub.3 80% [00014] P.sub.4 [00015] Q.sub.4 [00016] S.sub.4 90% [00017] P.sub.5 [00018] Q.sub.5 [00019] S.sub.5 85% [00020] P.sub.6 [00021] Q.sub.6 [00022] S.sub.6 90% [00023] P.sub.7 [00024] Q.sub.7 [00025] S.sub.7 90% [00026] P.sub.8 [00027] Q.sub.8 [00028] S.sub.8 75% [00029] P.sub.9 [00030] Q.sub.9 [00031] S.sub.9 85% [00032] P.sub.10 [00033] Q.sub.10 [00034] S.sub.10 90% [00035] P.sub.11 [00036] Q.sub.11 [00037] S.sub.11 85% [00038] P.sub.12 [00039] Q.sub.12 [00040] S.sub.12 80% [00041] P.sub.13 [00042] Q.sub.13 [00043] S.sub.13 80% [00044] P.sub.14 [00045] Q.sub.14 [00046] S.sub.14 80% [00047] P.sub.15 [00048] Q.sub.15 [00049] S.sub.15 80% [00050] P.sub.16 [00051] Q.sub.16 [00052] S.sub.16 78% [00053] P.sub.17 [00054] Q.sub.17 [00055] S.sub.17 65% [00056] P.sub.18 [00057] Q.sub.18 [00058] S.sub.18 78% [00059] P.sub.19 [00060] Q.sub.19 [00061] S.sub.19 82% [00062] P.sub.20 [00063] Q.sub.20 [00064] S.sub.20 80% [00065] P.sub.21 [00066] Q.sub.21 [00067] S.sub.21 80% [00068] P.sub.22 [00069] Q.sub.22 [00070] S.sub.22 72% [00071] P.sub.23 [00072] Q.sub.23 [00073] S.sub.23 78%

Example-1: Preparation of 2-phenyl-1H-benzo[d]imidazole (S.SUB.1.)

[0059] ##STR00074##

[0060] A 20 mL screw capped vial with a septum was equipped with the carbon pencil lead inserted as anode and aluminium cathode. Further the electrodes were connected to a 9V ordinary battery, capable of supplying constant current of 5 mA/cm.sup.2 for the electrochemical reaction. To the reaction vial was charged with benzene-1,2-diamine (0.91 mmol) and benzaldehyde (0.91 mmol) in 10 mL of methanol. The reaction mixture was stirred for 5 minutes at room temperature, followed by the addition of tetrabutylammonium iodide (TBAI) (0.047 mmole); and stirred gently at room temperature. The reaction setup cell was equipped with carbon as anode and aluminum as cathode and the mixture was electrolyzed at a constant current of ˜5 mA/cm.sup.2 at room temperature while stirring for 6 h. The progress of the reaction was monitored by TLC, after the completion of the reaction, the solvent was removed in vacuo and the crude material was purified by flash chromatography using hexane and ethyl acetate as eluent to afford compound (S.sub.1) (126 mg, 70% yield).

Example-2: Preparation of 2-(4-chlorophenyl)-1H-benzo[d]imidazole (S.SUB.2.)

[0061] ##STR00075##

[0062] A 20 mL screw capped vial with a septum was equipped with the carbon pencil lead inserted as anode and aluminium cathode. Further the electrodes were connected to a 9V ordinary battery, capable of supplying constant current of ˜5 mA/cm.sup.2 for the electrochemical reaction.

[0063] To the reaction vial was charged with benzene-1,2-diamine (0.91 mmol) and 4-chlorobenzaldehyde (0.91 mmol) in 10 mL of methanol. The reaction mixture was stirred for 5 minutes at room temperature, followed by the addition of tetrabutylammonium iodide (TBAI) (0.047 mmole); and stirred gently at room temperature. The reaction setup cell was equipped with carbon as anode and aluminum as cathode and the mixture was electrolyzed at a constant current of ˜5 mA/cm.sup.2 at room temperature while stirring for 6 h. The progress of the reaction was monitored by TLC, after the completion of the reaction, the solvent was removed in vacuo and the crude material was purified by flash chromatography using hexane and ethyl acetate as eluent to afford compound (S.sub.2) (180 mg, 85% yield).

Example-3: Preparation of 2-(1H-indol-6-yl)-1H-benzo[d]imidazole (S.SUB.10.)

[0064] ##STR00076##

[0065] A 20 mL screw capped vial with a septum was equipped with the carbon pencil lead inserted as anode and aluminium cathode. Further the electrodes were connected to a 9V ordinary battery, capable of supplying constant current of ˜5 mA/cm.sup.2 for the electrochemical reaction. To the reaction vial was charged with benzene-1,2-diamine (0.91 mmol) and 6-Formylindole (0.91 mmol) in 10 mL of methanol. The reaction mixture was stirred for 5 minutes at room temperature, followed by the addition of tetrabutylammonium iodide (TBAI) (0.047 mmole); and stirred gently at room temperature. The reaction setup cell was equipped with carbon as anode and aluminum as cathode and the mixture was electrolyzed at a constant current of ˜5 mA/cm.sup.2 at room temperature while stirring for 6 h. The progress of the reaction was monitored by TLC, after the completion of the reaction, the solvent was removed in vacuo and the crude material was purified by flash chromatography using hexane and ethyl acetate as eluent to afford compound (S.sub.10) (195 mg, 90% yield).

Example-4: Preparation of 5,6-dichloro-2-phenyl-1H-benzo[d]imidazole (S.SUB.18.)

[0066] ##STR00077##

[0067] A 20 mL screw capped vial with a septum was equipped with the carbon pencil lead inserted as anode and aluminium cathode. Further the electrodes were connected to a 9V ordinary battery, capable of supplying constant current of 5 mA/cm.sup.2 for the electrochemical reaction. To the reaction vial was charged with 4,5-dichlorobenzene-1,2-diamine (0.56 mmol) and benzaldehyde (0.56 mmol) in 10 mL of methanol. The reaction mixture was stirred for 5 minutes at room temperature, followed by the addition of tetrabutylammonium iodide (TBAI) (0.028 mmole); and stirred gently at room temperature. The reaction setup cell was equipped with carbon as anode and aluminum as cathode and the mixture was electrolyzed at a constant current of ˜5 mA/cm.sup.2 at room temperature while stirring for 6 h. The progress of the reaction was monitored by TLC, after the completion of the reaction, the solvent was removed in vacuo and the crude material was purified by flash chromatography using hexane and ethyl acetate as eluent to afford compound (S.sub.18) (116 mg, 78% yield).