FORM 2,
The Patents Act 1970,
(39 of 1970)
&
The patents Rule 2003,
Complete specification
(See section 10 rule 1.3)
The Title of Invention : An improved process for the manufacture
of substituted diphenyicynoacrylate compounds
Applicant :Chemspec Chemicals Pvt. Limited
Nationality : Indian
Address : Plot No. 3, 3-C, MIDC, Taloja,, Tal Panvel,
Dist. Raigad-410208
The following specification particularly describes the invention and manner in which it is to be performed.

The field of invention;
The present invention relates to an improved process for the manufacture of substituted diphenylcynoacrylate compounds. More particularly, invention is relates to transestrification process to obtain higher alkylcyanoacetate from Sower alkylcyanoester which is key intermediate which upon condensation with ketones yields substituted diphenylcynoacrylate compounds.
Prior art and background of invention;
Prior art;
Substituted 2-cycnocinnmamic esters such as 2-cyano-3-3-diarylacrylic
esters or 2-cynanocinnamic esters are highly effective UV-absorbers which
are used as light stabilizers in plastics or as sunscreening agents in
cosmetics.
Substituted 2-cynocinnamic esters are an effective UV absorbers due to
presence of extended conjugation of acrylate portion of the molecule. The
extended conjugation of the acrylate portion of the molecule absorbs UVB
and short-wave UVA rays with wavelength from 280-320nm thereby
protecting skin form direct DNA damages.
The ethylhexanol portion is a fatty alcohol, adding emollient and oil-like
water resistant properties.
Substituted 2-cyanocinnamic esters may be prepared by Knoevenagel condensation of cyanoacetic esters and carbonyl compounds as disclosed in EP430 023, US 2623 060, US4178 303.
JP1293 982 the catalyst is preferably a mixture of glacial acetic acid and ammonium acetate; the reaction water formed being removed as an azeotrope with an organic solvent such as cyclohexane, hexane, heptane, benzene, toluene or xylene. However, for the achievement of high yields, the processes of the prior art require long reaction times, which favor the formation of unwanted bi- products.

US 5451694 disclose the use of C 3 -C6 monocarboxylic acids in the presence of ammonium ions in the absence of organic solvents in order to reduce the reaction time to about 5 hrs while achieving good yields. However,, based on the molar ratio of cyanoacetate ester to carbonyl compound employed this process yields either a low conversion based on the carbonyl compound or a low conversion based on the cyanoacetate ester.
Object of the invention;
The object of the invention is to provide an efficient process for the manufacture of substituted diphenylcynoacrylate compounds which minimizes the loss of raw materials due to bi-product formation during the course of reaction.
Another, object of the invention is to provide an efficient process for the manufacture of substituted diphenylcynoacrylate compounds by transestrification process to obtain higher alkylcyanoacetate from lower atkylcyanoacetate which is key intermediate.
Yet, another object of the invention is to provide efficient process for the manufacture of substituted diphenylcynoacrylate compounds by condensation of alkylcyanoacetate with diphenylketones in presence of solvent.
Yet, another object of the invention is to provide suitable condensation system for the condensation of alkylcynoacetate and diphenylketones.
Yet, another object of the invention is to provide continues addition of condensation system during the course of reaction, therefore, avoiding formation of undesired side product.

Summary of the invention;
The present invention discloses an improved process for manufacture of substituted diphenylcynoacrylate compounds derivatives. The process involves the transesterification process to obtain alkylcyanoacetate which is key intermediate which is further condensed with ketones to yield substituted 2-cycnocinnamic ester, in presence of the suitably formulated condensation medium of the weak acid-base system. The trans-esterififcation of the alkylcyanoacetate reduces formation of the bi-products in the process resulting in increasing efficiency of the process.
Detailed description of the invention;
Prior art process are marked with the following difficulties like, raw materials involved in the synthesis of diphenylcynoacrylate compounds are cyanoacetic acids and 'ketones', Cyanoacetic acids are susceptible to many side reactions during the course of esterification reaction under dehydrating conditions.
Furthermore, there are many such processes which utilize aqueous solutions of cyanoacetic acid during esterification, which leads to extended time cycles of dehydration during esterification involving additional utility consumption and resulting into more impurity formation.
Similarly, condensation of cyanoacetate esters with 'ketones' is reported to be taking place in presence of ammonium acetate-acetic acid systems in most of the places, where this mixture is added into lots over a period. This results into extended time cycles.
The above problem is solved by the trans-esterification of the lower alkyl cyanoacetate,
In a particular preferred embodiment of the invention relates to a process manufacture of substituted diphenylcynoacrylate compounds which involves

trans-esterification of lower alkyl cyanoacetate and alcohol, p-toluene sulphonic acid to obtain higher alkylcycanoacetate,
In a particular preferred embodiment of the invention relates to the processes that lower esters are converted into higher esters in the presence of acids or bases, known as trans-esterification reactions. The present invention makes use of trans-esterification reaction in solvent free conditions, catalyzed by acids or bases. The reaction generates lower alcohol as the only bi-product. The advantage of such reactions is reduced time cycles and volumes, both resulting into increased productivity. Another advantage of trans-esterification in the present process is that the esters thus obtained are practically free from other impurities and can directly be taken for condensation with out isolation and purification of ester.
Similarly, condensation of ester with benzophenone is carried out in the presence or absence of solvents which are cyclic/acyclic hydrocarbons. A mixture of ammonium salt of carboxylic acid and the corresponding carboxylic acid solution is slowly fed to the reaction mixture under refluxing conditions while removing water, formed in the reaction along with acetic acid.

Formula A
Where R represents streight/branched aliphatic alkyl group containing C3-C10 carbon
R1 & R2 represents H, Alkyl {C1-C1), Cyno or Halogens.
Thus, in a further embodiment of the invention relates to a process for the manufacture of substituted diphenylcynoacrylate compounds according the invention, wherein the alkyl cyanoacetate is reacted with the alcohol and p-toluene sulphonic acid, which is heated up to 120 °C under reduced pressure

of 50m of Hg in phased manner over 18-24 hrs, the reaction mass is further heated with the aromatic solvent or mixture of aromatic solvents and mixture of acid-base added in different lots under reflux for 5-6 hrs after addition of each lot, product formed is isolated by treating reaction mixture with water and aromatic solvent followed by high vacuum distillation results in formation of compound of formula A having 65% yield.
In all the embodiments of the invention, suitable C5-C10 straight or branched alcohols are for example pentanol, hexanol, and 2-ethyhexanol, in particular 2-ethylhexyalcohol.
In all embodiments of the invention preferred lower cyanoacetic esters include, for example, methyl cyanoacetate or ethyl cyanoacetate.
In all embodiments of the invention preferred carbonyl compounds are various (un) substituted ketones like benzophenone derivatives.
In all embodiments of the invention preferred C1-C6 monocarboxylic acids include, for example, methonic acid (acetic acid), ethonic acid, propionic acid, n-butyric acid, iso-butyric acid, n-valeric acid, iso-valeric acid and n-caproic acid, in particular n-propionic acid.
In all embodiments of the invention, the ammonium compound include compounds capable of forming ammonia ions such as ammonia and ammonium salts. Preferably ammonium salts of monocarboxylic acids, such as ammonium acetate. In case ammonia is used for the generation of ammonium ions, it can, for example, be used in the form of an aqueous solution or it may be introduced via addition of gaseous ammonia to the solvent/acid medium of the reaction or via dewatering of aqueous solutions of ammonia in the solvent/acid medium. Thus, the invention also relates to a process according to the invention, wherein an ammonium salt is formed via addition of ammonia to the corresponding C3-C6 monocarboxylic acid used in the reaction.

In all embodiments of the invention the organic solvent is preferably chosen from aliphatic solvents or aromatic solvents or mixtures thereof, most preferably from aromatic solvents. The term aliphatic solvent includes cyclic or acyclic hydrocarbon solvents which may be linear or branched and/ or optionally substituted such as for example pentane, hexane, cydohexane, heptane, octane, isooctane, methyl cydohexane or dekalin or mixtures thereof. The term aromatic solvent includes solvents such as benzene, toluene, and xylene.
In all embodiments of the invention preferably an aliphatic solvent is used (or mixtures thereof), even more preferably hexane, cydohexane, heptane, isooctane or methyl cydohexane or mixtures thereof and in particular hexane or cydohexane or mixtures thereof.
In all processes for the manufacture of substituted diphenylcynoacrylate compounds according to the invention the reaction temperature may vary from about 70°C to 130°C. Preferably, the reaction temperature ranges from about 90°C to 120°C. Preferably, the temperature is chosen in order to maintain the reaction at reflux. The reaction may be conducted above atmospheric pressure or under partial vacuum in order to achieve the desired temperature condition. The monocarboxylic acid/ solvent/ water mixture can be distilled off at atmospheric pressure or at reduced pressure, for example from about 20 to 400 mbar e.g. using a Dean-Stark water separator, As soon as no more water separates out, the reaction can be regarded as being terminated. This is generally the case after from about 3 to 8 hours. The reaction product is worked up in a usual manner by separating the organic and the aqueous phase, optionally washed and finally distilled for further purification. The non converted starting materials such as the carbonyl compound and/ or the cyanoacetate ester as well as the solvent and the C3-C6 monocarboxylic acid can be recycled by conventional methods such as via distillation or crystallization. Preferred processes according to the invention include the recycling of unreacted starting materials.

The term catalyst used in trans esterification process refers to pure p-tolunesulfonic acid as well to the monohydrate/ sodium alkoxide.
In one of the most preferred embodiment of the invention mixture of the acid-base is formed for the condensation process, the acid is the carboxylic acid as defined above most preferably acid is acetic acid, and base is ammonium salt most preferably ammonium acetate, The most preferable molar ratio of the acetic acid-ammonium acetate is 1:0.5,
In all embodiments of the invention preferably pressure at trans esterification step is the 40-60mm of Hg.
The following examples are provided to further illustrate the process of the present invention. These examples are illustrative only and not intend to limit the scope of the invention in any manner,
Examplel,
To a stirred vessel provided with heating arrangement and having distillation set up, suitable to operate under vacuum charged with 1 mole of alkyl cyanoacetate and 1.02 moles of C3-C10 straight chain or branched alcohol and 5 gms p-toluene sulphonic acid. Contents of reaction are heated unto 120 °C under reduced pressure of 50 mm of Hg in a phase manner over certain period ranging from 18 hrs to 24 hrs; bi-products formed in the reaction are distilled out simultaneously. Reaction mixture is analyzed on GC, formation of higher alkylcyanoacetate to the extent of 93-95%.
To the same mass then added 500 ml cyclohexane, 1.01 moles of 'ketone' and reaction mixture heated to reflux. A mixture of ammonium acetate, 0.826 moles and acetic acid 2.09 moles added continuously over 15-20 hrs Reaction mixture is held under reflux for 10-15 hrs. Product isolated by treating reaction mixture with water and cyclohexane removal, followed

by high vacuum distillation gave title compound as described in formula A in 65% yield & having purity not less than 98% by GC.
Example 2
Example 1 repeated with all above parameters unchanged except ammonium
acetate and acetic acid mixture (as a solution) is added over 20-25 hrs under
reflux and maintained further at reflux for 35 hrs obtained the same yield
and quality of the title compound as described in formula A
Example 3
Example 2 is repeated with all parameters unchanged except using hexane in
place of cyclohexane to get the title compound as described in formula A in
58% yield.
Example 4
Example 2 is repeated with all parameters unchanged except reaction system
is operated under reduced pressure in absence of any solvent to get 55%
yield of the title compound as described in formula A,
Examples 5
Example 1 is repeated, except sodium methoxide is used as a catalyst during
trans-esterification with all other parameters unchanged, yielded 53% title
compound as described in formula A.
Example 6-11
Example 1 is repeated with following changes and the results are tabulated
as below,
All quantities are mentioned in gm moles

Example No Alkyl Cyano acetate 2-EH Solvent reflux ketone Acetic acid Ammonium acetate Yield %
6 1 1.01 Cyclo-hexane 1.1 2.25 1.1 60
7 1 1.01 Hexane 1.1 2.25 1.1 57
62
58
58
8 1 1.01 cyclohexane 1.236 2.5 1.1

9 1 1.01 toluene 1.02 2.08 0.89

10 1 1.01 Nil 1.1 2.25 1.1 52
11 1 1.01 Nil 1.236 2.5 1.1 50.

Example 12;
To a stirred vessel provided with heating arrangement and having distillation set up, suitable to operate under vacuum charged with 1 mole of ethyl cyanoacetate and 1.02 moles of 2-ethyl hexanol and 5 gms p-toluene sulphonic acid. Contents of reaction heated unto 120 deg under reduced pressure of 50 mm of Hg in a phased manner over 18 hrs to 24 hrs. ethanol formed in the reaction distilled out simultaneously. Reaction mixture is analyzed on GC, formation of 2-ethy!hexyl cyanoacetate to the extent of 93-95%.
To the same mass then added 500 ml cyclohexane, 1.01 moles of benzophenone and reaction mixture heated to reflux. A mixture of ammonium acetate, 0.826 moles and acetic acid 2.09 moles added continuously over 15-20 hrs Reaction mixture is held under reflux for 10-15 hrs to ensure complete water removal. Reaction mixture is held under reflux for 5-6 hrs after every lot. Product isolated by treating reaction mixture with water and cyclohexane removal, followed by high vacuum distillation give compound as described in formula A in 60% yield and having purity not less than 98% by GC.

Claims;
1. An improved process for the manufacture of diphenylcynoacrylate compounds comprising trans esterification of lower alkyl cyano esters by reacting with higher alcohols in presence of catalysts under reduced pressure and at higher temperature to obtain higher alkyl cyanoacetate which is further condensed with ketones in condensation system in presence solvent to obtain compound of formula A.

Formula A
Where R represents streight/branched aliphatic alkyl group containing C3-C1Q carbon
R1 & R2 represents H, Alkyl (C1-C4), Cyno or Halogens,
2. An improved process for the manufacture of diphenylcynoacrylate
compounds according to claim 1 wherein lower alkyl cyano esters is methyl
or ethyl.
3. An improved process for the manufacture of diphenylcynoacrylate
compounds according to claim 1 wherein higher alcohol is 2-ethyl hexyl
alcohol or pentanol.

4. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 wherein catalyst for trans esterification is p-toluene sulphonic acid or sodium alkoxide.
5. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 wherein ketone is benzophenone or its derivatives.
6. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 wherein solvent for condensation is hexane, cyclohexane or toluene or mixture thereof.
7. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 wherein pressure is 40-60mm of Hg.
8. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 temperature is 110-120 °C.
9. An improved process for the manufacture of diphenylcynoacrylate compounds according to claim 1 condensation system is mixture of acetic acid; ammonium acetate.
10. An improved process for the manufacture of diphenylcynoacrylate
compounds according to claim 1 molar ratio of acetic acid; ammonium
acetate is 1:0.5.