WO2020104956A1

WO2020104956A1 - Electrochemical organic reaction setup and methods

Info

Publication number: WO2020104956A1
Application number: PCT/IB2019/059959
Authority: WO
Inventors: Tanay GHOSAL; Vishal NAGAR; Sharadsrikar KOTTURI; Sasikumar KUTTAAPPAN
Original assignee: Piramal Enterprises Limited
Priority date: 2018-11-21
Filing date: 2019-11-20
Publication date: 2020-05-28
Also published as: US20210371992A1

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.

Description

ELECTROCHEMICAL ORGANIC REACTION SETUP AND

METHODS

FIELD OF THE INVENTION

The present invention relates 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, particularly for use in electrochemical reactions involving coupling between carbocyclic or heterocyclic rings and also in ring formation reactions between two or more moieties.

BACKGROUND OF THE INVENTION

The following discussion of the prior art is intended to present the invention in an appropriate technical context, and allows its significance to be properly appreciated. Unless clearly indicated to the contrary, reference to any prior art in this specification should not be construed as an expressed or implied admission that such art is widely known or forms part of common general knowledge in the field.

The electrochemical organic reactions or specifically electrolysis is a widely followed technology by laboratory scientists for many years in this industry arena. The deposition of ions through an ionized solution is known as the electrolytic cell, which is used in several industries such as electroplating, Kolbe reaction, refining bauxite into aluminum, producing chlorine and caustic soda from table salt (sodium chloride), and in analytical techniques such as polarography. Basic principles of electrolysis were discovered by the UK scientist Michael Faraday (1791-1867) and were developed by the Swedish scientist Svante Arrhenius (1859-1927), winner of the 1903 Nobel Prize in chemistry.

More clearly the electrolysis of water involves the decomposition (i.e.,“splitting”) of water into oxygen and hydrogen gas by the action of an electric voltage (i.e., current) being applied to the water across electrodes of opposite polarity. Hydrogen is produced at the negative electrode (cathode) and oxygen is produced at the positive electrode (anode), as shown by the following well-known chemical equations: Cathode (reduction): 2H+(aq)+2e— >H2(g)

Anode (oxidation): 2H20(I) 02(g)+4H+(aq)+4e-

The technique of electrolyzing water in the presence of an electrolyte such as sodium hydroxide (NaOH) or potassium hydroxide (KOH) to liberate hydrogen and oxygen gas (¾, O2) is well known. The process involves applying a DC potential difference between two or more anode/cathode electrode pairs and delivering the minimum energy required to break the H— O bonds (i.e. 68.3 kcal per mole @STP). The gases are produced in the stoichiometric proportions for O2 :H _sub.2 of 1:2 liberated respectively from the anode (+) and cathode (-).

US granted patent No. 1,839,905 B 1 refers to improvements in methods of electrolysis, and especially to a method of preventing liberation of spray or acid mist from-the surface of the electrolyte in an electrolytic cell.

US granted patent No. 5,843,292 B 1 refers to the generation of hydrogen gas and oxygen gas from water, either as an admixture or as separated gases, by the process of electrolysis, and relates further to applications for the use of the liberated gas.

US granted patent No. 6,248,221 B1 refers to electrolysis systems having more improved materials, structures and methods. It further specifically discloses use of improved cathode material and improved reaction vessel for application as an electrolysis apparatus.

US granted patent No. 5,632,870 A1 refers to an electrolytic cell apparatus and methods for generating a useful energy product from a plurality of energy sources. In a preferred embodiment, hydrogen gas is produced at a cathode by transmission of electrons through a low voltage potential barrier to electron flow achieved by careful control of electrolyte constituent concentrations and surface materials on the cathode.

US patent application no. 20040084325 A1 refers to an improved method for electrolyzing water for enhanced production of oxygen, hydrogen and heat. More specifically it discloses electrochemical cell comprising an isotopic hydrogen storage cathode, an electrically conductive anode and an ionically conducting electrolyte comprising water. US granted patent No. 4,285,795 refers to an improved apparatus for the electrolysis of aqueous solutions of ionizable chemical compounds is disclosed including specifically an apparatus for the production of chlorine and caustic containing low concentrations of sodium chloride by the electrolysis of brine which comprises electrolyzing brine solutions in a cell equipped with a cathode and an anode separated by a cation-active permselective diaphragm.

It is evident from the above discussion or cited patent documents that the reported electrolysis process and/or associated apparatus involves specifically designed assembly which comprises complex apparatus assembly and methods to perform the process. Further, the reported electrolysis process involves chemical reagent which are harmful in nature and may impact final purity of the product. Thus, there exists a need for the development of a new, inexpensive, simple and efficient setup for conducting electrochemical organic chemistry reactions in a regular chemistry laboratory. Further, this new setup does not involve any harmful chemical reagent to conduct the reaction which in turn leads to a safe procedure without compromising in yield value.

As stated above inventors of the present invention have developed a new, simple and efficient setup that addresses the problems associated with the setup reported in the prior art and their practical limitations while performing the reactions. The device of the present invention does not involve use of any specialized design and/or costly instrumental parts, also does not involve use of any high cost materials. Moreover, the process does not require any chemical reagents which are harmful in nature and impact final purity of the product. Accordingly, the present invention provides an electro chemical apparatus setup and its implementation in the electrolysis or electro chemical organic reaction, which is simple, efficient, cost effective, environmentally friendly and commercially scalable.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a water electrolysis assembly set up (device) as shown in fig. A; comprising of a Battery (6) (as described herein), a Switch (7) (as described herein) and a reaction vial (3) (as described herein), Anode (Carbon) (1) (as described herein), Cathode (Iron, Copper, aluminium) (2) (as described herein), Reaction mixture (4) (as described herein). In one aspect, the present invention relates to a water electrolysis assembly set up (device) as shown in fig. B; comprising of a Mobile charger (6) (as described herein), an alligator clips (5) (as described herein), Cathode (Iron, Copper, aluminium) (2) (as described herein), Anode (Carbon) (1) (as described herein), Reaction vial (3) (as described herein), Reaction mixture (4) (as described herein).

In one aspect, the present invention relates to a water electrolysis assembly set up (device) as shown in fig. C; comprising of a Mobile charger (6) (as described herein), Multiple USB hub

(9) (as described herein), Switch (7) (as described herein), Light Indicator (10) (as described herein), alligator clips (5), Cathode (Iron, Copper, aluminium) (2) (as described herein), Anode (Carbon) (1) (as described herein), Reaction vial (3) (as described herein), USB wire (11) (as described herein) and reaction mixture (4).

In another aspect, the present invention relates to a electrochemical reaction setup assembly/ set up (device) as shown in fig. D; comprising of a Mobile charger (6) (as described herein), Multiple USB hub (9) (as described herein), Switch (7) (as described herein), Light Indicator

(10) (as described herein), alligator clips (5), Cathode (Iron, Copper, aluminium) (2) (as described herein), Anode (Carbon) (1) (as described herein), Guard tube (8) (as described herein), USB wire (11) (as described herein), reaction vessel (3) and reaction mixture (4).

In another aspect, the present invention relates to a electrochemical reaction setup assembly/ set up (device) as shown in fig. E; comprising of an adaptor (6) (as described herein), Anode (Carbon) (1), Cathode (Iron, Copper, aluminium) (2), alligator clips (5), reaction vessel (3), Guard tube (8) (as described herein) and reaction mixture (4).

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of the invention will be further explained with reference to embodiments shown in the drawings wherein:

Figure: A - is a schematic diagram of the electrochemical reaction setup using 9V battery; constructed and arranged in accordance with the present invention. Figure: B - is a schematic diagram of the electrochemical reaction setup using 5V cell phone charger; constructed and arranged in accordance with the present invention.

Figure: C - is a schematic diagram of the Parallel electrochemical reaction setup using 5V cell phone charger; constructed and arranged in accordance with the present invention.

Figure: D - is a schematic diagram of the electrochemical reaction setup using 5V cell phone charger (lg scale up); constructed and arranged in accordance with the present invention.

Figure: E - is a schematic diagram of the electrochemical reaction setup using 12V cell phone charger (10 g scales up); constructed and arranged in accordance with the present invention.

Figure: F - is an actual view of the electrochemical reaction setup using 9V battery; constructed and arranged in accordance with the present invention.

Figure: G - is an actual view of the electrochemical reaction setup using 5V cell phone charger; constructed and arranged in accordance with the present invention.

Figure: H - is an actual view of the Parallel electrochemical reaction setup using 5V cell phone charger; constructed and arranged in accordance with the present invention.

Figure: I - is an actual view of the electrochemical reaction setup using 5V cell phone charger (lg scale up); constructed and arranged in accordance with the present invention.

Figure: J - is an actual view of the electrochemical reaction setup using 12V cell phone charger (10 g scales up); constructed and arranged in accordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

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.

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

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.

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.

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.

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.

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

(a) Current source (6),

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

(c) Reaction mixture (4);

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

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 (LiC104), sodium iodide (Nal) and the like. Other electrolytes can also be used for organic transformations.

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.

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, BU₄NI (10 mol%), AcOH (5 equiv)

CH₃CN, C anode, C cathode

undivided cell

Scheme 1

Scheme-I

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

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 (3X10ml). 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.

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 (lg, lOg) 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:

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:

BU₄NI (10 mol%), AcOH (5 equiv)

CH₃CN, C anode, Fe/AI/Cu cathode

undivided cell

BU₄NI (10 mol%), AcOH (5 equiv)

CH₃CN, C anode, Cu/AI/Fe cathode

NBoc-

undivided cell

BU NI (10 mol%) AcOH (5 e uiv)

Analytical data of newly synthesized compounds.

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

Scale of the reaction: lg-lOg Experimental procedure: Same as in scheme 1.

Selection of Electrodes: 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.

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:

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.

Selection of Reaction Solvent:

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.

EXAMPLES OF CYCLISATION OR RING FORMATION REACTIONS:

Table-1

Example- 1: Preparation of 2-phenyl-lH-benzo[d]imidazole (Si)

(Pi)

electrochemical setup (Sd

device (undivided cell)

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 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 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 (Si) (126 mg, 70% yield).

Example-2: Preparation of 2-(4-chlorophenyl)-lH-benzo[d]imidazole (S2) electrochemical setup

(P ) (Q₂) (S₂)

device (undivided cell)

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

2

battery, capable of supplying constant current of -5 mA/cm for the electrochemical reaction.

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 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 (S2) (180 mg, 85% yield). Example-3: Preparation of 2-(lH-indol-6-yl)-lH-benzo[d]imidazole (S10)

(P10) electrochemical setup

(Q10) (S10)

device (undivided cell)

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 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 2

mA/cm 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 (Sio) (195 mg, 90% yield). Example-4: Preparation of 5,6-dichloro-2-phenyl-lH-benzo[d]imidazole (Sis)

Ql8 electrochemical setup

(Pie) device (undivided cell) (Sis)

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 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 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 (Sis) (116 mg, 78% yield).

Claims

We Claim:

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 (LiC104), sodium iodide (Nal).

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).