DESC:FORM 2
THE PATENTS ACT
1970 (39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
[See section 10, Rule 13]

“NOVEL DERIVATIVES OF 2,3-DIHYDROTHIENO[3,4-B][1,4]DIOXIN-2-YL)METHANOL (HMEDOT) AND PROCESS FOR PURIFICATION OF HMEDOT”

The following specification particularly describes the invention & the manner in which it is to be performed.

FIELD OF THE INVENTION
The disclosure generally relates to a novel derivatives of 2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methanol (HMEDOT) and process for its purification.

BACKGROUND OF THE INVENTION
Poly(3,4-ethylenedioxythiophene) (PEDOT) is an important electrically conductive polymer because of both its high conductivity and temperature stability. Its monomeric unit is 3,4-ethylenedioxythiophene (EDOT). HMEDOT is a water-soluble EDOT compound known in the art.

2,3-Dihydrothieno[3,4-b][1,4]dioxin-2-yl)methanol (compound of Formula I) (HMEDOT), also known as Hydroxymethyl EDOT or EDT-methanol, is a conjugated polymer that is used as a precursor of ethylenedioxythiophene (EDOT). The hydroxymethyl groups in the EDOT monomers enhance the electro-polymerization in an aqueous solution to form an electro-active hydrophilic polymer.

Formula I

EDOT derivative is useful in preparation of functional electroactive polymers. EDT-methanol can functionalize poly(L-lactic acid) by using organometallic polymerization, which can be used to form biodegradable and conducting macromonomers for biomedical applications. It can be polymerized to form poly(hydroxymethyl EDOT) based films, which may be incorporated with silver nanoparticles to form nanocomposites on polyethylene terephthalate (PET) for flexible plastic devices.

U.S. Pat. No. 5,111,327 discloses the process for the preparation of crude HMEDOT as a viscous oil and purification of crude HMEDOT by flash chromatography. The reaction scheme disclosed in the U.S. Pat. No. 5,111,327 is as follows.

U.S. Pat. No. 7,838,688 discloses methods for preparing HMEDOT comprising contacting 3,4-dialkoxythiophene with 3-halo-1,2-propanediol in the presence of an acid to form a compound of Formula IV

Formula IV
wherein X is halogen; and subsequently contacting a compound of Formula IV with an inorganic hydroxide, ammonium or alkylammonium hydroxide, alkali metal carboxylate, alkaline earth metal carboxylate, ammonium or alkylammonium carboxylate, alkali metal alkoxide, alkaline earth metal alkoxide, ammonium or alkylammonium alkoxides, to form HMEDOT. The patent also discloses purification of HMEDOT by column chromatography.

The methods known in the art for the preparation of HMEDOT provide brown viscous oil which is subsequently purified by column chromatography. However, column purification has limitation for use on the commercial scale.

Inventors have surprisingly discovered the novel process of purification of HMEDOT without using column chromatography.

SUMMARY OF THE INVENTION
The specification discloses a process for preparation of pure HMEDOT comprising:
a. reacting a crude HMEDOT with a compound of Formula II

Formula II
wherein
A, B, E and G are selected from CH or N,
n is 1-3,
R1 and R2 are similar or different and are selected from hydrogen, nitro, halogen, alkyl, alkoxy or equivalent thereof,
X is OH, Cl, Br or equivalent thereof,
b. isolating a compound of Formula III

Formula III
wherein A, B, E, G, n, R1 and R2 are as defined above,
c. optionally, crystalizing the compound of Formula III, and
d. hydrolysing the compound of Formula III to obtain pure HMEDOT,
wherein the pure HMEDOT has GC purity of at least 90%.

The specification also discloses a compound of formula III

Formula III
wherein
A, B, E and G are selected from CH or N,
n is 1-3,
R1 and R2 are similar or different and are selected from hydrogen, nitro, halogen, alkyl, alkoxy or equivalent thereof.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1. Synthetic scheme for the crude HMEDOT
Figure 2. General scheme for the purification of HMEDOT

DETAILED DESCRIPTION
As disclosed in the specification the term “Crude HMEDOT” means HMEDOT is in the form of solid or viscous oil having GC purity of less than 98%, less than 95%, less than 90%, less than 85%, less than 80%, less than 75% or less than 70%.

As disclosed in the specification the term “Pure HMEDOT” means HMEDOT is in solid form having GC purity of at least 90%, at least 95%, preferably at least 97%, most preferably at least 98%, at least 99%, at least 99.5% or at least 99.9%.

The term “halogen” refers to chlorine, bromine, fluorine, and iodine.

The term “alkyl” refers to C1-C8 alkyl, for example methyl, ethyl, propyl or isopropyl.

The term “alkoxy” refers to C1-C8 alkoxy, for example methoxy, ethoxy, propoxy or isoproxy.

One embodiment discloses a process for preparation of pure HMEDOT comprising:
a. reacting crude HMEDOT with a compound of Formula II

Formula II
wherein
A, B, E and G are selected from CH or N,
n is 1-3,
R1 and R2 are similar or different and are selected from hydrogen, nitro, halogen, alkyl, alkoxy or equivalent thereof,
X is OH, Cl, Br or equivalent thereof,
b. isolating a compound of Formula III

Formula III
wherein A, B, E, G, n, R1 and R2 are as defined above;
c. optionally, crystalizing the compound of Formula III, and,
d. hydrolysing the compound of Formula III to obtain pure HMEDOT.

Another embodiment discloses a process for preparation of HMEDOT comprising:
a. reacting crude HMEDOT with a compound of Formula IIz

Formula IIz
wherein
R is nitro, halogen, alkyl, alkoxy or equivalent thereof,
X is OH, Cl, Br or equivalent thereof,
b. isolating a compound of Formula IIIz

Formula IIIz
wherein R is as defined above.
c. optionally, crystalizing the compound of Formula IIIz, and,
d. hydrolysing the compound of Formula IIIz to obtain pure HMEDOT.

Further embodiment discloses a process for the preparation of compound of Formula III

Formula III
wherein A, B, E, G, n, R1 and R2 are as defined above;
comprising:
a. reacting HMEDOT with a compound of Formula II

Formula II
wherein X, A, B, E, G, n, R1 and R2are as defined above, and
b. isolating the compound of Formula III and
c. optionally, crystalizing the compound of Formula III.

The crude HMEDOT used for the purification can be obtained according to the methods disclosed in U.S. Pat. No. 7,838,688 or any other suitable method known in the art. The GC purity of the crude HMEDOT may be about 70%. Synthetic scheme for the crude HMEDOT is provided in Figure 1.

Step (a) disclosed in the detailed description of the specification i.e. reaction of crude HMEDOT with a compound of Formula II may be performed in a suitable coupling agent such as 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), benzimidazole, carbonyldiimidazole (CDI) and in a suitable solvent such as tetrahydrofuran (THF), dichloromethane (DCM), dimethylformamide (DMF), toluene, ethylacetate.

Step (a) may be performed at a temperature from about 0-40° C, preferably at 0-30° C.

The crystallization of the compound of Formula III may be performed in suitable solvent such as ethylacetate, methyl tertiary-butyl ether (MTBE), dichloromethane (DCM), n-hexane, n-heptane and mixtures thereof.

Step (d) disclosed in the detailed description of the specification i.e. hydrolysis the compound of Formula III may be performed using a suitable base such as sodium hydroxide, potassium hydroxide and in a suitable solvent such as water, THF, methanol, ethanol or mixtures thereof.

Step (d) may be performed at a temperature from about 0-100° C, preferably at 40-50° C.

Another embodiment discloses the compound of Formula III

Formula III
wherein A, B, E, G, n, R1 and R2 are as defined above.

Another embodiment discloses the compound of Formula IIIz

Formula IIIz
wherein
R is nitro, halogen, alkyl or alkoxy.

In another embodiment, the compound of Formula IIIa is disclosed.

Formula IIIa

In another embodiment, the compound of Formula IIIb is disclosed.

Formula IIIb

In another embodiment, the compound of Formula IIIc is disclosed.

Formula IIIc

In yet another embodiment, the compound of Formula IIId is disclosed.

Formula IIId

In another embodiment, the compound of Formula IIIe is disclosed.

Formula IIIe

In an alternative embodiment the use of compound of Formula III as an intermediate for the purification of HMEDOT to obtain pure HMEDOT is disclosed.

The following examples illustrate specific embodiments; however, the full scope of the disclosure is not limited to the examples described below.

Example 1
Preparation of compound of Formula IIIa

Formula IIIa
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (2 kg) and triethyl amine (TEA) (0.585 kg) were added to round bottom flask and the reaction mass was cooled to 0-5° C. 4-nitrobenzoylchloride (785g) was added to the reaction mixture over a period of 10 minutes at 0-5° C. HMEDOT (664g; GC purity 70%) was added slowly into reaction mass and after complete addition, the reaction mass was stirred at 25-30° C for 5 hours. Solid was filtered and washed with chilled EDC and the resulting solid was dried the material at 60-65° C for 12 hours. Yield: 1.2kg, GC Purity: 97.75%. Melting Point: 115° C -118° C.
1H NMR (300 MHz, DMSO-d6): d 8.36-8.34 (d, 2H), 8.22-8.19 (d, 2H), 6.65-6.63 (S, 2H), 4.64-4.58 (m, 3H), 4.42-4.39 (m, 1H), 4.22-4.17 (m, 2H).
LC-MS (m/z): 322.2 (M+H)+.

Example 2
Preparation of pure HMEDOT
Compound of Formula IIIa (1.2kg) was added to THF (2.4 lit.) in a round bottom flask. Aqueous sodium hydroxide solution (350g in 6 lit. water) was added at 25-30° C and the reaction mass stirred at 45-50° C for 4 hours. Water (2.4 lit.) and MTBE (2.4 lit.) were added at 25-30° C. The layers were separated and the MTBE solution was washed with 10% sodium bicarbonate solution for 3 times. Power carbon (60g) was added to the organic layer and stirred at 40-45° C for an hour. The solution was filtered and distilled off completely under vacuum at below 45° C. The obtained product was dissolved in MTBE (450 mL) and then chilled n-heptane (2.1 lit.) was added and stirred at 0-5° C for 2 hours. Solid was filtered and washed with chilled mixture of MTBE and n-heptane, and the resulting solid was dried at 25° C under high vacuum. Yield: 320 g, GC Purity: 99.0%.
,CLAIMS:We claim:

1. A process for preparation of pure HMEDOT comprising:
a. reacting a crude HMEDOT with a compound of Formula II

Formula II
wherein
A, B, E and G are selected from CH or N,
n is 1-3,
R1 and R2 are similar or different and are selected from hydrogen, nitro, halogen, alkyl, alkoxy or equivalent thereof,
X is OH, Cl, Br or equivalent thereof,
b. isolating a compound of Formula III

Formula III
wherein A, B, E, G, n, R1 and R2 are as defined above,
c. optionally, crystalizing the compound of Formula III, and
d. hydrolysing the compound of Formula III to obtain pure HMEDOT,
wherein the pure HMEDOT has GC purity of at least 90%.

2. The process according to claim 1 wherein the step a) is performed in the presence of a coupling agent.

3. The process according to claim 1 wherein the step d) is performed in the presence of a base.

4. The process according to claim 1 wherein compound of Formula II is a compound of Formula IIz

Formula IIz
wherein
R is nitro, halogen, alkyl, alkoxy or equivalent thereof,
X is OH, Cl, Br or equivalent thereof.

5. The process according to claim 4 wherein the compound of Formula II is a compound of Formula IIz

Formula IIz
wherein
R is nitro.

6. The process according to claim 1 wherein the pure HMEDOT has GC purity of at least 95%.

7. The process according to claim 6 wherein the pure HMEDOT has GC purity of at least 98%.

8. A compound of formula III

Formula III
wherein
A, B, E and G are selected from CH or N,
n is 1-3,
R1 and R2 are similar or different and are selected from hydrogen, nitro, halogen, alkyl, alkoxy or equivalent thereof.

9. The compound of Formula III according to claim 8 wherein the compound of Formula III is a compound of Formula IIIz

Formula IIIz
wherein
R is nitro, halogen, alkyl or alkoxy.

10. The compound of Formula IIIz according to claim 9 wherein the compound is selected from

Formula IIIa,

Formula IIIb,

Formula IIIc,

Formula IIId
or

Formula IIIe.