Description:
Field of the Invention
The present invention relates to a cost effective, green process of preparation of alkyl phosphate and salt thereof of Formula I, wherein R = C16- C22. More particularly, the present invention relates to the process of preparation of alkyl phosphates and/or salts thereof by reacting fatty alcohol with polyphosphoric acid (PPA).

Background of the Invention
The phosphoric ester salts are very well accepted as emulsifiers in skin care applications in cosmetic and pharmaceutical topical formulations. Alkyl phosphates (e.g. cetyl phosphate and its potassium salt) are widely being used as emulsifiers in leave on formulations, such as creams and lotions. They are characterised by very good detergency and high ecotoxicological compatibility. With increasing concern of ecotoxicological balance there is a need of good emulsifiers with lesser unwanted impurities in it which otherwise could be concern to formulation stability and also its cosmetic application. Widely accepted acidic phosphoric esters are generally the equimolar mixtures of a mono esters and a diester. The physical properties of both, the monoester and the diester are fairly different from each other. Alkali metal salts of a long chain alkylphosphate monoester have good foaming property, good water solubility and emulsifying property, good cleansing property and low toxicity to the skin, hence can be used as high foaming and cleansing agent and preferred in personal care applications, whereas the diester form has less foaming property and is hardly soluble in water, so may not be used as a good foaming, emulsifying and cleansing agent.

Literature reveals different methodologies to prepare cetyl phosphate with good mono:dicetyl (mono:dialkyl) phosphate ratio and claimed best conversion with control over unwanted impurities. GB 1475109 describe the synthesis of cetyl phosphate based on reacting fatty alcohol with phosphorous oxychloride. Though yielding good conversion, the process is disadvantageous due to unavoidable generation of organochlorides, the fatty alkyl halide. Also release of hydrogen chloride during the reaction may lead to corrosion of the apparatus and disposal of the hydrochloric acid is difficult. Considering the toxicity of fatty alkyl halide, the acceptance of product with such impurity, is seldom possible in leave on cosmetic products such as creams and lotions. Hence, there is a need of significantly improved manufacturing process which does not lead to organohalide impurities and yet giving quantitative conversion.

US patent 5883280 describes an alternative route to overcome the drawback of phosphorous oxychloride route. The synthesis is based on reacting polyphosphoric acid of various strengths followed by converting phosphoric acid generated during reaction into polyphosphoric acid by reacting with phosphorous pentoxide. The sequence followed involves hazardous step of handling Phosphorous pentoxide which is reported to be highly reactive and hazardous chemical and also ends up with more dialkyl phosphate, and phosphoric acid in cetyl phosphate as high as 4-5%. The attempts to convert this remnant phosphoric acid into polyphosphoric acid and desired product, leads to the generation of more dicetyl phosphate affecting the desired mono:dialkyl phosphate ratio.

The product made by PPA and P2O5 route escaping the purification step, renders formulation incompatible due to high salt content. Hence, there is a need to develop a novel, efficient and industrially viable and acceptable process for the preparation cetyl phosphate and its salt thereof which gives desired product acceptable in the topical compositions.

Recently, Duesterloh et al came up with the methodology (US 20190321277A1) to lower the inorganic phosphate. To lower the inorganic phosphate the reported methodology in US 20190321277A1, is to carry out reaction in solvents like cyclohexane followed by washing with water. But due to amphiphilic nature of cetyl phosphate, neither there is ease of separation of two phases nor removal of solvent traces from the product. Also, the quantity of solvent required and its flammability imposes limitation on effective batch size which is not viable on commercial scale. The removal of remnant solvent traces also involves energy consuming process like distillation. On the contrary, the presence of traces of remaining solvent also sometime makes utilisation of product in end formulation undesirable due to the odor.

Thus, there exists a need of a convenient, simple and energy efficient green process for the preparation alkyl phosphates and its salts that yields higher ratio of the mono alkyl phosphate ester without using any organic solvent.

Objectives of the Invention
It is an objective of the present invention to overcome the drawbacks of prior arts and develop a convenient, simple and energy efficient green process to produce more than 90:10 weight ratio of mono:dialkyl phosphate ester.

It is an objective of the present invention to render the industry a green and solvent free process for preparation of mono: dialkyl phosphate ester and salts thereof.

It is yet another objective of the present invention to provide a cost-effective process for the industrial manufacture of mono: dialkyl phosphate ester in more than 90:10 ratio, reducing the content of phosphoric acid < 0.7% and fatty alcohol <1.5%.

Another objective of the present invention is to ensure the weight percent ratio of mono:dialkyl phosphate ester salt more than 89:11 and inorganic phosphate < 0.9%.

Summary of the Invention
The present invention relates to an environmentally benign and solvent free process for the preparation of alkyl phosphates with minimum 90:10 ratio of monoalkyl phosphate: dialkyl phosphate with reduced impurities such as free phosphoric acid < 0.7% & free fatty alcohol < 1.5%, ensuring that surfactant mixture contains no organochloride impurities.

In an aspect, the present invention relates to a process of producing alkyl phosphate and/ or salt thereof of Formula I,

Formula I

wherein R= C16-22 and the product obtained contains more than 90:10 ratio of mono: dialkyl phosphate ester, free phosphoric acid <0.7% and free fatty alcohol < 1.5% and upon neutralization the composition contains more than 89:11 ratio of monoalkyl: dialkyl phosphate salt, inorganic phosphate < 0.9%, and free fatty alcohol < 1.5% and the said process comprising steps of:
A) reacting a fatty alcohol of Formula II with polyphosphoric acid (PPA) of 115 - 120% of Formula III;
B) converting the product of step A) into granules;
C) ageing the granules of alkyl phosphate for maximum 10 days;
D) wetting the granules with chilled water after ageing; and
E) filtering the granules and treating with aqueous solution of alkali metal hydroxide followed by drying under reduced pressure.

The present invention renders the process for the preparation alkyl phosphates and salts thereof which gives desired product which meets the quality requirement of the topical compositions.

Detailed description of the invention
The present invention provides the sustainable process wherein the desired quality of the product is achieved through an eco-friendly, sustainable process which is devoid of solvent. The inventors of the present invention have designed an industrial friendly process for the preparation of alkyl phosphate and have surprisingly found that alkyl phosphate formed undergoes morphological changes during the course of further operations which surprisingly gives the desired results which was never possible through the processes mentioned in the prior arts.

The inventors of present invention have come up with a process of preparation of alkyl phosphate with green and sustainable route. The process of the present invention ensures good mono/dialkyl ester ratio, phosphoric acid < 0.7%, and free fatty alcohol < 1.5% rendering potassium alkyl phosphate with the desired quality which is compatible in all topical compositions. Advantageously, the process of the present invention does not involve any organic solvent and is cost effective, operationally simple, exploits commercially available raw material, yields good conversion and results in control over impurities.

The said process is devoid of organic solvents and achieves more than 90:10 weight ratio of monoalkyl:dialkyl phosphate ester and more than 89:11 weight ratio of monoalkyl: dialkyl phosphate ester salt.

The present invention provides an eco-friendly and cost-effective process for the preparation of alkyl phosphate and salt thereof (Formula I),

Formula I

According to an embodiment of the present invention, there is provided a process for the preparation of alkyl phosphate and salt thereof of Formula I, comprising reaction of fatty alcohol (Formula II) with polyphosphoric acid of 115- 120% (Formula III) without employing any organic solvent.

The amounts in percentage (115-120%) refers to the number of phosphoric acid (H3PO4) units involved for the formation of PPA.

The process for the preparation of monoalkyl phosphate ester is depicted in Scheme 1.

SCHEME 1

According to another embodiment of the present invention, the PPA is used 2 to 6 mole % excess w.r.t fatty alcohol. The ratio is critical to ensure at least 90:10 mono:di alkyl phosphate and the temperature is maintained below 100ºC, preferably between 80-90ºC, most preferably between 70-80 ºC.

According to another embodiment of the present invention, the fatty alkyl phosphate obtained is converted into granules of particle size < 800 micron, more preferably < 500 micron and most preferably < 300 micron using granulation technique.

According to another embodiment of the present invention, the granules of fatty alkyl phosphate is subjected to ageing at preferably 0-50ºC, more preferably 10-50 ºC and most preferably between 20-50 ºC for minimum one day to 10 days. The ageing of micronized granules is carried out preferably for 1- 9 days, more preferably for 3-8 days, most preferably for 5-7 days.

According to another embodiment of the present invention, the granules of alkyl phosphate so obtained are subjected to water treatment at solids to water ratio of 10:80 to 40:80.

According to another embodiment of the present invention, the treatment of alkyl phosphate granules with water is done at temperature < 30 ºC, more preferably < 20 ºC and most preferably or < 5 ºC.

According to another embodiment of the present invention, the treatment with water is done with minimum or intermittent stirring for < 2 minute, more preferably < 1 minute and most preferably <30 second.

The mass is then filtered using known techniques to remove phosphoric acid and obtaining alkyl phosphate with monoalkyl phosphate: dialkyl phosphate ester ratio of at least 90:10 and free phosphoric acid < 0.7%. The product obtained is then neutralised with potassium hydroxide or sodium hydroxide, followed by drying, using techniques known in the arts to give the final product with mono: dialkyl phosphate salt ratio of at least 89:11 with inorganic salt < 0.9% and fatty alcohol < 1.5%. The final composition thus obtained is compatible with most of the topical compositions.

It is observed that wetting of aged granules lead to better separation of phosphoric acid in matrix. The process of the present invention employs the temperature condition < 30 ºC, more preferably < 20 ºC and most preferably or < 5 ºC during the water treatment along with the control over the duration of treatment. It has been observed that alkyl phosphate has tendency to form dispersion and optimization of wetting process, temperature and time is important for the effective removal of phosphoric acid.

The critical parameters of the process as described herein is the PPA is used 2 to 6 mole % excess w.r.t fatty alcohol; ageing of granules with temperature and number of days; and wetting time of the granules with chilled water after ageing.

Thus, according to the invention to ensure better ratio of mono alkyl phosphate: dialkyl phosphate, it is necessary to carry out reaction between fatty alcohol with polyphosphoric acid (115 - 120%) preferably PPA is used in 5 mole % excess w.r.t fatty alcohol and without using any solvent. This is followed by granulation ensuring the particle size < 800 micron, more preferably < 500 micron and most preferably < 300 micron using suitable granulation technique and ageing preferably 0-50 ºC, more preferably 10-50 ºC and most preferably between 20-50 ºC for minimum a day to 10 days, followed by treatment with water at < 30 ºC, more preferably < 20 ºC and most preferably < 5 ºC. The product obtained on filtration is then neutralised using alkali metal hydroxides followed by drying, meets the requirement of all topical composition.

Advantages of the invention:
The process is efficiently producing alkyl phosphate containing at least 90:10 ratio of mono:dialkyl phosphate ester while at least 89:11 ratio of mono:dialkyl phosphate ester salt.

The process is simple and cost effective and can be carried out using optimum amount of polyphosphoric acid.

The process produces product with very less amount of free phosphoric acid (< 0.7%) with residual free fatty alcohol is < 1.5%.

The process avoids the use of any organic solvent during preparation of alkyl phosphate and salt thereof.

The invention may ensure close loop process by recycling generated phosphoric acid into the stream of polyphosphoric acid.

EXAMPLES:
The present invention is now described by way of working on limiting illustrative examples. The detail of the invention provided in the following examples is given by the way of illustration only and should not be construed to limit the scope of the present invention.

Cetyl alcohol was procured from Godrej Industries Ltd. and Polyphosphoric acid was procured from Prasol Chemical Pvt. Ltd.

Reactive units of PPA is calculated as taught by Huhti et al., Canadian Journal of Chemistry, 34, 785-397, 1956; Toy et al., Phosphorus Chemistry in Everyday Living, American Chemical Society, 1976; and J-F. Masson, Energy Fuels, 22, 2637–2640, 2008.

Example 1
Preparation of cetyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with cetyl alcohol (2.06 gmol), polyphosphoric acid (115%, 2.16 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free cetyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen for cetyl alcohol content. The mass obtained was flaked and converted into granules of particle size <500 micron using Comil granulator and kept for ageing at 42°C for 7 days. After ageing, to another open flask, equipped with mechanical stirrer and thermometer, water (1757 g) was charged and cooled to <5°C, followed by addition of granules (753 g) of cetyl phosphate with intermittent stirring for 1 minute. The material is quickly filtered, washed with water (1255 g) of temperature <5°C. The residue thus obtained is treated with aqueous solution of potassium hydroxide (85%, 142 g, 2.15 gmol in 2337 g water) followed by drying under reduced pressure (160 mmHg) yielding potassium cetyl phosphate with mono:dicetyl phosphate ratio more than 89:11, free inorganic phosphate 0.86 % and free cetyl alcohol content 1.34%.

Example 2
Preparation of cetyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with Cetyl alcohol (2.06 gmol), polyphosphoric acid (118%, 2.14 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free cetyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen in cetyl alcohol content. The mass obtained was flaked and converted into granules of particle size <500 micron using Comil granulator and kept for ageing at 45°C for 5 days. After 5 days, to the open flask, equipped with mechanical stirrer and thermometer, water (1670 g) was charged and cooled to <5°C, followed by addition of (716 g) of granules of cetyl phosphate with intermittent stirring for 30 sec. The material is quickly filtered, washed with water (1194 g) of temperature <5°C. The residue thus obtained is treated with aqueous solution of potassium hydroxide (85%, 140 g, 2.12 gmol in 2300 g water) followed by drying under reduced pressure (160 mmHg) yielding potassium cetyl phosphate with mono: dicetyl phosphate ratio of 89:11, free inorganic phosphate 0.79 % and free cetyl alcohol content 1.43%.

Example 3
Preparation of Behenyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with behenyl alcohol (1.56 gmol), polyphosphoric acid (118 %, 1.64 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free behenyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen for behenyl alcohol content. The mass obtained was flaked and converted into granules of particle size <500 micron using Comil granulator and kept for ageing at 40°C for 9 days. After ageing, to another open flask, equipped with mechanical stirrer and thermometer, water (1542 g) was charged and cooled to <5°C, followed by addition of (660 g) of granules of behenyl phosphate with intermittent stirring for 1 minute. The material is quickly filtered, washed with water (1100 g) of temperature <5°C. The residue thus obtained is treated with aqueous solution of potassium hydroxide (85%, 132 g, 2.0 gmol in 2167 g water) followed by drying under reduced pressure (160 mmHg) yielding potassium behenyl phosphate with mono:dibehenyl phosphate ratio more than 90:10, free inorganic phosphate 0.75 % and free behenyl alcohol content 1.45 %.
Comparative Example 1

Preparation of cetyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with cetyl alcohol (2.06 gmol), polyphosphoric acid (115%, 2.16 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free cetyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen for cetyl alcohol content. The mass obtained was flaked and converted into granules of particle 1000 micron using Comil granulator and kept for ageing at 40°C for 8 days. After ageing, to another open flask, equipped with mechanical stirrer and thermometer, water (1757 g) was charged and cooled to <5°C, followed by addition of granules (753 g) of cetyl phosphate with intermittent stirring for 1 minute. The material is quickly filtered, washed with water (1255 g) of temperature <5°C. The residue thus obtained is treated with aqueous solution of potassium hydroxide (85%, 145 g, 2.20 gmol in 2337 g water) followed by drying under reduced pressure (160 mmHg) yielding potassium cetyl phosphate with mono:dicetyl phosphate ratio more than 89:11, free inorganic phosphate 3.30 % and free cetyl alcohol content 1.34 %.
Comparative Example 2

Preparation of Behenyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with behenyl alcohol (1.56 gmol), polyphosphoric acid (118 %, 1.64 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free behenyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen for behenyl alcohol content. The mass obtained was flaked and converted into granules of particle size <500 micron using Comil granulator and kept for ageing at 45°C for 5 days. After ageing, to another open flask, equipped with mechanical stirrer and thermometer, water (1542 g) was charged and cooled to <5°C, followed by addition of (660 g) of granules of behenyl phosphate with intermittent stirring for 4 minutes. The longer time spent during stirring resulted into formation of stable dispersion which was difficult to handle and made the filtration step non- viable. This resulted in arresting the further steps and the desired product was not obtained.
Comparative Example 3

Preparation of cetyl phosphate and its potassium salt
A 1000 mL four neck round bottom flask, equipped with a mechanical stirrer, a thermometer and a condenser, was charged with Cetyl alcohol (2.06 gmol), polyphosphoric acid (118%, 2.14 gmol). The stirred reaction mass was then heated to 80-90°C. The reaction was continued till free cetyl alcohol found to be <1.5% by gas chromatographic analysis and no further decrease is seen in cetyl alcohol content. The mass obtained was flaked and converted into granules of particle size <500 micron using Comil granulator and kept for ageing at 40°C for 20 days. After 20 days, to the open flask, equipped with mechanical stirrer and thermometer, water (1670 g) was charged and cooled to <5°C, followed by addition of (716 g) of granules of cetyl phosphate with intermittent stirring for 30 sec. The material is quickly filtered, washed with water (1194 g) of temperature <5°C. The residue thus obtained is treated with aqueous solution of potassium hydroxide (85%, 140 g, 2.12 gmol in 2300 g water) followed by drying under reduced pressure (160 mmHg) yielding potassium cetyl phosphate with mono: dicetyl phosphate ratio of 89:11, free inorganic phosphate 0.86 % and free cetyl alcohol content 1.43%.

It was observed that ageing of cetyl phosphate for a longer period did not result in enhancing the quality of the product ie. getting rid of the inorganic phosphate impurity to further extent.
, Claims:
1. A process of producing alkyl phosphate and salt thereof of Formula I

Formula I

Wherein the product obtained contains at least 90:10 ratio of mono: dialkyl phosphate ester, free phosphoric acid < 0.7% and free fatty alcohol < 1.5% and upon neutralization the composition contains at least 89:11 ratio of monoalkyl:dialkyl phosphate salt, inorganic phosphate < 0.9%, and free fatty alcohol < 1.5% and the said process comprising steps of:
A) reacting a fatty alcohol of Formula II with polyphosphoric acid (PPA) of 115- 120% of Formula III;
B) converting the product of step A) into granules;
C) ageing the granules of alkyl phosphates for maximum 10 days;
D) wetting the granules with chilled water after ageing; and
E) filtering the granules and treating with aqueous solution of alkali metal hydroxides followed by drying under reduced pressure.

2. The process for preparation of alkyl phosphate and its salt as claimed in claim 1, wherein PPA is used 2 to 6 mole % excess with respect to fatty alcohol.

3. The process for preparation of alkyl phosphate and its salt as claimed in claim 1, wherein alkyl phosphate is converted into granules of particle size < 800 micron, preferably particles of size < 500 micron and more preferably particles of size < 300 micron.

4. The process for preparation of alkyl phosphate and its salt as claimed in claim1, wherein ageing of micronized granules is carried out at temperature at between 0- 50°C, more preferably 10-50°C and most preferably 20-50°C.

5. The process for preparation of alkyl phosphate and its salt as claimed in claim 1, wherein ageing of micronized granules is carried out preferably for 1- 9 days, more preferably for 3-8 days, most preferably for 5-7 days.

6. The process for preparation of alkyl phosphate and its salt as claimed in claim1, wherein the wetting of micronized granules is carried out with water at 0 to 50°C, preferably less than 30°C, most preferably less than 5°C.

7. The process for preparation of alkyl phosphate and its potassium salt as claimed in claim 1, wherein wetting time with water is less than 2 minute, preferably less than 1 minute, most preferably less than 30 seconds.

8. The process for preparation of alkyl phosphate and its potassium salt as claimed in claim 1, wherein the micronized granules are subjected to water treatment at solids to water ratio of 10:80 to 40:80.

9. The process for preparation of alkyl phosphate and its potassium salt as claimed in claim 1, wherein the alkali metal hydroxides is selected from potassium hydroxide or sodium hydroxide.