Title of Invention	"NOVEL SUBSTITUTED ARYL ALKENOIC ACID HETEROCYCLIC AMIDES"
Abstract	A novel aryl alkenoic acid heterocyclic amide and a process for the preparation of novel aryl alkenoic acid heterocyclic amides. The present invention also relates to the process of the preparation of novel substituted aryl alkenoic acid heterocyclic amides. These compounds are useful as food additives and anti-oxidants.

Full Text

The present invention relates to novel substituted aryl alkenoic acid heterocyclic amides. The invention particularly relates to the novel substituted aryl alkenoic acid heterocyclic amides of formula I shown in the drawings accompanying the specification where n= 1 or 2, x= O or N-CH3 and Ar represents:- 4-substituted phenyl moiety where R= C 1.5 alkyl group, Ar also represents heterobicyclic 3,4- disubstituted phenyl group such as 3', 4'- dihydro-2', 2'-dimethyl benzopyran-61-yl, 3',4'- methylenedioxy or 3',4' - ethylenedioxyphenyl. The present invention also relates to the process of the preparation of novel substituted aryl alkenoic acid heterocyclic amides of formula 1 where n=l or 2, x=O or N-CH3 and Ar as stated above.. The compounds of this invention are all novel and possess specific hot, pungent and spicy taste when subjected to direct pungency evaluation. The compounds of the present invention does not give any nuturitional value. These compounds may be useful as food additives and anti-oxidants. The synthesised compounds can possess useful pharmacological properties which is expected to find application in new test models for the development of anti-inflammatory drugs, bioavailability enhancers and for the study of hepatic drug metabolising mechanism. Aroma, flavour and taste are considered to be the three important parameters for determining the quality of spices or condiments. The aroma and flavour of a spice depends upon the presence of volatile components , which are perceived through the olfactory epithelium present in the nose. The olfactory substances are primarily mono-, sesqui- or diterpenes, low molecular weight hydrocarbons, heteroacyclic or heterocyclic compounds. The taste is perceived by the taste buds present on the surface of the tongue. The interactions between the pungent molecules and receptors present on the surface of the tongue are the main cause of generation of hot sensation or thermogenecity which is associated with pungency. More pungent the substance, more is the duration of the feeling of hotness. This feeling of hotness may also be perceived on other tender parts of the skin. Most of the known natural pungent substances are aromatic in nature. Some of the most commonly known natural pungent substances include piperamides such as pipeline from black pepper (Piper nigrum), capsaicinoids such as capsaicin and dihydro-capsaicin from red chillies (Capsicum annum) and gingeroids like gingerol from ginger ( Zingiber officianalis) etc. The chemistry and properties of pungent compounds from natural sources has recently been reviewed ( Nakatani, Nobugi; Koryo, 1995, 185. p 59-64, Chem. Abs. 123, 5520 n). These pungent principles which possess anti-oxidant properties are also associated with many physiological actions viz piperamides, capsaicinoids as well as gingeroids are reported to possess anti- inflammatory properties (Lewis,D. A. in And- inflammatory drugs from plant and marine sources; Birkhauser Verlag, Berlin, 1989, p 216-220; Janusz, J.M., J. Med. Chem. 1993,36, p 2595). Both pipeline and dihydrocapsaicin were found to interact irreversibly with hepatic drug metabolizing enzymes thereby inhibiting their activity as indicated by prolongation of pentobarbital sleeping time in rats (SushYoung- Joon, A, et al., Life sciences, 1995, 56(16), p 305-31 1; Atal, C. K. et al., J. Pharmacol. Exp. Therp. 1985, 232. p 258-262). Only few reports have appeared in the literature related to the evaluation of structure with respect to pungency. Direct subjective method of analysis of capsaicin and related extracts for their pungency evaluation was developed by Wilbur Scoville in 1912. In this method potency of pepper was measured as heat units by diluting the extracts until pungency was just detected after placing a drop on the tongue. Pure capsaicin was thus assigned 107 units and jalapeno 103 units ( Scoville, W. J. , Am. Pharm. Assoc, 1912, i, p 453-454). Indirect evaluation of pungency through the measurement of physiological effects have also been employed. For example Watnabe et al. reported the assessment of pungency related thermogenecity to structure of capsaicin analogues by correlating it with adrenal catecholamine secretion in rats ( Watnabe, Tatsno et al. Life. Sci. , 1994, 54(5), p 369- 374; Chem. Abs. , 120: 94792f). Astringent and pungent substances were studied using a multichannel taste sensor by observing the changes in electric potential in lipid membranes. However pungent substances were found to have no effect on the membrane potentials (liyama, Satoru et al., Chem. Senses, 1994, 19(1), p 87-96; Chem. Abs. 120: 295156). Known natural or synthetic pungent substances are invariably oxygenated aromatic compounds with an alkyl side chain and a hetero atom comprising preferably an amide linkage in the side chain. Some of these compounds were found to possess hot pungent characteristics on preliminary evaluation. On the basis of above observation several new series of aryl alkenoic acid amides were synthesised and their structure and pungency relationship has also been established. Another important aspect of the development of these compounds is the possibility of their utilisation as new test models for the study and management of the phenomenon of pain and inflammation. These observations are based on the recent work carried out by the David Julius et al. who have identified the capsaicin receptor by isolating the complimentary DNA encoding the binding protein (Julius, D. et al. Nature, 1997, 389, p 816-824 ). Isolation and identification of the receptor protein is an important development for the study of new pharmacological targets which will help in understanding the phenomenon of chronic pain caused by arthritis, spinal cord injury or diabetic neuropathy. It is expected that vanilloid receptor and the receptor for the synthesised compounds of formula 1 may turn out to be the same. Therefore, the development of these novel compounds may provide a diverse and effective alternate to capsaicin and related vanilloids. The main object of the present invention is to provide the novel substituted aryl alkenoic acid heterocyclic amides. Another object of the present invention is to provide novel synthetic compounds useful as thermogenic, pungent and spicy agents. Yet another object of the present invention is to provide novel compounds which can find application as new test models for the development of anti- inflammatory drugs, bioavailability enhancers and for the study of hepatic drug metabolising mechanism. The novel aryl alkenoic acid heterocyclic amides of formula 1 shown in the drawing accompanying the specification may be useful as hot, pungent and spicy agents, and also as food additives, anti-oxidants, bioavailability enhancers and for the study of hepatic drug metabolising mechanism including UDP- glucose dehydrogenase and glucuronidation activities. Accordingly the present invention provides novel aryl alkenoic acid heterocyclic amide of formula 1, where n=l or 2, x=O or N-CH3 and Ar represents:- 4-substituted phenyl moiety where R= C 1.5 alkyl group, Ar also represents heterobicyclic 3,4-disubstituted phenyl group such as 3',4'- dihydro-2',2' dimethyl benzopyran-6'-yl, 3',4'- methylenedioxy or 3',4'-ethylenedioxyphenyl. Accordingly the present invention provides a process for the preparation of aryl alkenoic acid heterocyclic amides of formula 1 where n is 1 or 2, x=O or N-CH3 and Ar represents as stated above in claim 1 which comprises reacting aldehyde of formula 5 with methyl magnesium halide preferably methyl magnesium iodide with constant stirring at ambient temperature in an anhydrous ether solvent to produce corresponding phenyl ethanol of formula 4, the compound of formula 4 is treated with dimethyl formamide and phosphorus oxychloride mixture at 0-10°C for 20-40 hours, to produce substituted phenyl-2E-propenaldehyde of formula 3, wherein—n is4 and Ar as stated above which on reaction with Wittig reagent prepared by triphenyl phosphine and bromoethyl acetate in presence of a base at temperature in the range of 15-80°C for a period in the range of 1-80 hrs., isolating the corresponding ester by conventional method followed by base hydrolysis to acid of formula 2 wherein n is 2, converting acid of formula 2 where n is lor 2 to corresponding acid chloride using thionyl chloride and reacting the acid chloride with heterocyclic amine in an inert organic solvent at temperature in the range of 0-50°C , isolating the compound of formula 1 by conventional method, wherein n is lor 2 and Ar represents as stated above. In a preferred embodiment of the present invention aryl alkenoic acid heterocyclic amide of formula 1 where n=2, x=O or N-CH3 and Ar represents as stated above i.e. substituted phenyl 2E, 4E-pentadienoic acid heterocyclic amide of the formula I are synthesised from the corresponding aromatic aldehyde of formula 5. The substituted aromatic aldehyde of formula 5 is first reacted with methyl magnesium halide preferably methyl magnesium iodide with constant stirring at ambient temperature in an anhydrous ether solvent such as diethyl ether, tetrahydrofuran and the like to produce corresponding phenyl ethanol of formula 4. The compound of formula 4 is treated with dimethyl formamide and phosphorus oxychloride mixture at 0-10°C for 20-40 hrs, contents neutralised with dilute alkali solution to produce substituted phenyl-2E-propenaldehyde of formula 3_. The aldehyde of formula 3 is thereafter condensed with a ylide prepared from triphenyl phosphine and ethyl bromoacetate equimolar mixture in presence of a strong base such as sodium hydride, sodium methoxide and the like at temperature 15-80°C for 1 to 24 hrs in an ethereal medium such as diethyl ether, dimethoxy ethane and the like to yield corresponding ethyl substituted phenyl- 2E,4E-pentadienoate which is hydrolysed without purification with a strong alkali solution using sodium hydroxide, potassium hydroxide and the like followed by acidification to furnish substituted phenyl-2E.4E -pentadienoic acid of formula 2. The solution of aryl alkenoic acid of formula 2 where n=2 and Ar as stated above in an inert organic solvent such as benzene, dichloromethane is treated with thionyl chloride and solvent removed. The acyl chloride intermediate thus obtained is condensed with heterocyclic amine in inert organic solvent such as dichloromethane, benzene, diethylether, and the like in the temp, range of 0 to 50°C, after the purification by crystallisation or column chromatography to produce aryl alkenoic acid heterocyclic amide of formula 1. Substituted aryl 2E-propenoic acid of formula 2 (n=l) which is known in the art of synthesis (Miroslav, K. etal: collect.Czech Chem. Commun., 1981, 46 (5), p 1173 - 87; Theopil, E. et al, Synthesis, 1996, 6, p 755 - 62) is converted to acyl chloride by treatment with thionyl chloride in an inert organic solvent such as dichloromethane, benzene, diethylether and the like, followed by condensation with heterocyclic amine in an inert solvent, purification by column chromatography or crystallisation to yield substituted aryl -2E-propenoic acid heterocyclic amide of formula 1 where (n=l) and Ar as stated above. The compounds of above invention were assessed in terms of the heat units for ascertaining their potency, by a panel of five untrained volunteers through a subjective or direct analysis using modified W. Scoville method. A stock solution of the compound (1%) in alcohol: water (1:1) was diluted until the sensation of pungency/ hotness just detected by placing 5uJ of the solution on the tip of the tongue of the volunteers. In all the cases the pungency measurement was made in the reverse order i.e. from less dilute to more dilute solutions till pungency detection was just possible. Mouth and tongue were thoroughly washed with water after each evaluation, sufficient time gap was given before the next evaluation was initiated. In most of the compounds a clear solution was obtained in stock solutions. In some cases where solubility was poor, a uniform suspension was prepared through magnetic stirring or sonication. Although individual perception of pungency varied from person to person, on an average fair consistency was achieved. The invention is described further with reference to examples given below. These examples should not be construed as to restrict the scope of the reaction. Example-1 Preparation of 5-(4-isopropyloxv phenyl)- 2E,4E-pentadienoic acid morpholine amide of formula 1 where n=2, x=O and Ar = 4-isopropyloxv phenvl Preparation of l-(4-isopropvloxy phenyl) ethanol of formula 4, where R = (Formula Removed) A solution of 4-isopropyloxy benzaldehyde of formula 5 (5g,30 mmol) prepared in dry diethyl ether is slowly added to an ethereal solution of Grignard reagent prepared from magnesium metal (0.84g, 35 mmol) and iodomethane (2.6 ml, 40 mmol) and the contents stirred for 1hour at room temperature. After the completion of the reaction, the mixture is worked up by adding saturated aqueous solution of ammonium chloride (10 ml) followed by dilution with water (100 ml), separating the organic layer and extracting the aqueous layer with solvent ether (2x100 ml). The combined organic layer washed with water (2x20 ml) dried over anhydrous sodium sulphate and concentrated in vacuo to yield l-(4 -isopropyloxy phenyl) ethanol, a semisolid of formula 4 in 92.5% yield. (ii) Preparation of 3-(4-isopropyloxv phenvl)- 2E - propenal of formula 3, where R = C3H7(Formula Removed) A solution of 1-(4-isopropyloxy phenyl) ethanol of formula 4 (4.8g, 27 mmol) in dimethyl formamide (10 ml) is slowly added to phosphorus oxychloride (8 ml) in DMF (12 ml) with stirring while maintaining the temperature at 0°C . The reaction mixture is stirred for 2 hour then allowed to attain room temperature followed by heating on an oil bath for 36 hour at 40°C . After the completion of the reaction as monitored by TLC, contents of the reaction mixture are poured into ice cold water (500 ml), neutralised with dilute alkali solution and saturated by adding sodium chloride. The aqueous portion is extracted with ethyl acetate (3x100 ml), organic layer washed with water, dried over anhydrous sodium sulphate and stripped off the solvent under vacuo to furnish crude product (4.8g). It was purified by column chromatography over silica gel to yield a semi-solid 3 -(4-isopropyloxy phenyl) - 2E - propenal of formula 3_( 80%). Preparation of 5-(4- isopropyloxy phenvl)-2E. 4E-pentadienoic acid of formula2. where n=2 and R = C3H7 (Formula Removed) A mixture of triphenyl phosphine (4.7g, 18 mmol) and ethyl bromoacetate (20 ml, 18 mmol) in anhydrous dimethoxy ethane is refluxed for 2 hour and to the intermediate thus formed is added 3-(4-isopropyloxy phenyl)- 2E- propenal of formula 3 (2.5g, 13mmol), sodium hydride (0.5g) in small proportions. The reaction mixture is continously stirred for 72 hour at 60° C. The reaction mixture is then worked up by pouring into ice cold water and extraction with dichloromethane (3x100 ml). The organic layer washed with water, dried over anhydrous calcium chloride and concentrated into vacuo. The crude 5-(4-isopropyloxy phenyl ) -2E,4E-pentadienoate obtained above is hydrolysed directly without purification in 10% methanolic potassium hydroxide solution on a water bath for 6 hour. On cooling, the contents diluted with water (200 ml) and extracted with dichloromethane ( 2x40 ml), the extracted aqueous portion is acidified with 2N hydrochloric acid solution. The resulting precipitate is filtered, washed with water and air dried to furnish crude acid ( 2.40g, 80%). Crystallisation of the crude acid from ethyl acetate: benzene (19:1) furnished pure 5-(4-isopropyloxy phenyl)-2E,4E- pentadienoic acid of formula 2, m.p. 180° C. (iv) Preparation of 5 - (4 - isopropyloxy phenvl) • 2E, 4E-pentadienoic acid morpholine amide of formula 1 where n=2, x=O and R = C3H7 (Formula Removed) Freshly distilled thionyl chloride (0.5 ml) is added to a solution of 5-(4 isopropyloxy-phenyl)-2E,4E-pentadienoic acid ( 1.4g , 6mmol) of formula 2 in dry dichloromethane and mixture is refluxed on a water bath for 1 hour. Solvent is removed from the acid chloride in vacuo alongwith excess of thionyl chloride. A solution of morpholine (0.6 ml, 7mmol) in dichloromethane is added to the acid chloride prepared above and mixture stirred for 1 hour. After completion of the reaction, the organic layer is made free of excess of morpholine using dilute hydrochloric acid solution. The organic layer is washed with water, dried and concentrated under vacuum to furnish crude product (1.7g, 94%), purified by crystallisation from ethyl acetate: hexane (9:1) to yield 5-(4 - isopropyloxy phenyl)-2E, 4E-pentadienoic acid morpholine amide of formula 1 Reference to example 1 (iv) Pale yellow crystals m.p. 134° C, analysed for C18H23NO3 1H NMR (200 M Hz) CDC13 : δ 1.35 (6H, d, J=6Hz, -(CH3)2 -CH), 3.65 (8H, bs, N-(CH2)2-(CH2)2O-) 4.60 (lH,h, J=6Hz , -OCH(CH3)2), 6.40 ( 1H, d, J=14.0Hz, COCH=CH-), 6.65 -7.05 and 7.20- 7.85 (7H, 2x bs, Ar-H and olefinic H). MS (E 1): M+ - 1 at m/z 300 (35.6), 258 (11.1), 215 (18.5), 173 (100), 145 (18.2), 114 (24.0), 86 (22.6) and 70 (25.3). Example-2 Preparation of 5-(4-isopropyIoxy phenyl)-2E,4E-pentadienoic acid N-methyl piperazine amide of formula 1 where n=2, x=N-CH3and R= C3 H7 To a solution of 5-(-4-isopropyloxy phenyl)-2E, 4E-pentadienoic acid (0.93g, 4mmol) of formula 2 prepared by the method as described in example 1 (i-iii) in dry dichloromethane (40 ml) is added freshly distilled thionyl chloride (0.3ml) and the mixture is refluxed on a water bath for 1 hr. thereafter the contents concentrated in vacuo and redissolved in dichloromethane (10ml). A solution of N-methyl piperazine (0.4 ml, 4mmol, in dichloromethane is added to acid chloride solution and the mixture is stirred for 2 hr at room temp. After the completion of the reaction, the contents are taken up in water (50ml) , the organic layer separated and the aqueous layer extracted with dichloromethane (2xl5ml). The combined organic layer is concentrated and the crude product purified by column chromatography on alumina (neutral) using chloroform: methanol (9:1) as eluent to give product, a semi solid (l.lg, yield 93%), analysed for C19H26N2O2 Reference to example 2 1HNMR(200MHz) CDC13 δ 1.31 (6H, d, J=6.05 Hz, (CH3)2-C) 2.31 (3H, S, -N-CH3), 2.50 (4H, t, J=5.06, -N-(CH2)2), 3.71 (4H, m,- N-(CH2)2), 4.57 (IH, h, J= 6.0Hz, OCH-CH3)2), 6.67 (IH, d, J= 15.3 Hz: CH=CH-CO), 6.85 (2H, d J= 8.7Hz, 2xAr-H), 6.79-6.88 (1H, m, olefmic -H), 7.23-7.38 (1H, m olefmic-H), 7.44 (2H, d, J=8.7Hz, 2xAr-H) and 7.76 (1H, d, J=15.3Hz, CH=CH-CO). MS (El): M+-l at m/z 313(16.9), 214(10.8), 170(12.6),144(31.8), 118(21.9), 70(74.3) and 57(100). Example-3 Preparation of 3-(4-isopropyIoxv phenvl) -2E-propenoic acid morpholine amide of formula 1 where n=l. x=O and R = C3H7 (Formula Removed) 3-(4-isopropyloxy phenyl)-2E-propenoic acid of formula 2 where n=l and R = CjH?, (2.06, lOmmol) a known compound in the art of synthesis is reacted with freshly distilled thionyl chloride (1.0ml) in dry dichloromethane (15ml) on a water bath for 1 hr. Solvent is removed in vacuo from the intermediate acid chloride along with the excess of thionyl chloride. A solution of morpholine (0.90ml) in dry dichloromethane is added to the acid chloride prepared above and mixture stirred for 1 hr at room temp. After the completion of the reaction the organic layer is made free of excess of morpholine using dilute hydrochloric acid solution. The organic layer is washed with water, dried and concentrated under vaccum to furnish crude product which on crystallisation from ethyl acetate: hexane, furnished 3-(4-isopropyloxy phenyl)-2E-propenoic acid morpholine amide of formula 2 where n=l, (m.p 98° C, 2.66g, yield 97%). Reference to example 3 Creamish crystals m.p. 98°C, analysed for C16H21N03 1H NMR (200MHz) CDC13: δ 1.30 (6H, d, J= 6Hz, -( CH3)2 -C), 3.70 ( 8H, s, O(CH2)2-(CH2)2-N-), 4.55 (1H, h, J= 6Hz, OCH-(CH3)2), 6.65 (1H, d, J= 15.3Hz, COCH=CH-), 6.85 (2H, d, J= 8.5Hz, 2xAr-H), 7.40 (2H, d, J=8.5Hz, 2xAr-H) and 7.65 (1 H, d, J= 15.3Hz, CO-CH=CH). MS (El): M+ at m/z 275 (28.8), 233 (12.7), 189 (34.6), 164 (14.1), 147 (100), 119 (30.7) and 91 (24.9). Example-4 Preparation of 3-(4-butvloxv phenvl ) -2E-propenoic acid morpholine amide of formula 1 where n=l, x=O and R = C4H9 (Formula Removed) To a solution of 3-(4-butyloxyphenyl) -2E-propenoic acid (2.2g, 10 mmol) in dichloromethane (40ml) is added thionyl chloride (0.8ml) and the resulting acid chloride made to react with morpholine (0.9ml) as per procedure described in example 3 to give a solid (2.7g, 90%) which is purified by crystallisation from ethyl acetate: n-hexane (9:1), mpl 17°C , analysed for C17H23NO3 Reference to example 4 1H NMR (200MHz) CDC13: δ1.0 (3H, t, J=6.5Hz - CH2-CH3), 1.7 (2H, m, -CH2-CH2-CH3) 1.8 (2H, m, -OCH2-CH2-CH2), 3.76 (8H, bs, 2x -N(CH2)2-(CH2)2-O-), 4.03 (2H, t, J = 6.5 Hz, -OCH^-CHz-), 6.75, (1H, d, J =15Hz, -CH=CH-CO), 6.96 (2H, d, J=8Hz, 2xAr-H), 7.53 (2H, d, J = 8 Hz, 2xAr-H) & 7.78 (1H, d, J = 15Hz, - CH=CH-CO). MS(E1):M+-1 at m/z 288(28.5), 203 (91), 146(100), 118(52), 101(13) & 86(9.7). Example-5 Preparation of 3-(3,4-methylenedioxv phenyl) -2E-propenoic acid N-methyl piperazine amide of formula 1 where n=l. x=N-CH3 and Ar = 3',4'- methylenedioxy phenyl. (Formula Removed) The N-methyl piperazine amide of 3-(3,4-methylenedioxy phenyl ) -2E-propenoic acid is prepared from 3-(3,4-methylenedioxy phenyl ) -2E-propenoic acid (1.92g, lOmmol), thionyl chloride (0.8ml) and N-methyl piperazine (1.0ml,lOmmol) by the method described for example 2 to give solid (2.55g, 91%), purified by crystallisation from chloroform: methanol (9:1), m.p 84°C, analysed for C15H18N2O3 Reference to example 5 1HNMR(200 Hz) CDC13;δ 2.33 (3H, s, -N-CH3), 2.45 (4H, t, J= 5.05Hz, -N-(CH2)2), 3.72 (4H, t, J= 5.05 Hz, N-(CH2)2), 6.03 (2H, s, -OCH2O-), 6.72 (1H, d, J= 15.0Hz, CH=CH-CO), 6.82 (1H, d, J= 8.5Hz, Ar-H), 6.95-7.23 (2H, m, 2xAr-H) and 7.65 (1H, d, J= 15.0Hz, CH=CH-CO). MS(E1):\T at m/z 274(22.2) 174(17.7), 143(13.8), 115(13.2), 70(100) and 57(83.3). The main advantages of the present invention are: 1 The present invention provides novel substituted aryl alkenoic acid heterocyclic amides of formula I 2. Novel compounds with hot, pungent and spicy properties and synthetic substitutes for natural compounds and their process of preparation. 3. The compounds in the present invention provides the pungency index in the range of 103 to 107 units as compared to the known pungent substances which are in the range of 103 to 106 units. 4. Novel compounds which may also be useful in the study of bioavailability enhancers and hepatic drug metabolism. 5. Novel compounds which may be useful as new test models in the development of anti- inflammatory and antiarthritic drugs. We Claim: (1) A novel substituted aryl alkenoic acid heterocyclic amide of formula 1 where n is 1 or 2, x= O or N-CH3 and Ar represents 4-substituted phenyl group where R= C1-5 alkyl, Ar also represents heterobicyclic 3, 4 -disubstituted phenyl group such as 3', 4'-dihydro-2', 2'- dimethyl benzopyran -6'-yl, 3',4'-methylenedioxy or 3', 4'- ethylenedioxyphenyl as shown in drawings accompanying this specification. (2) A process for the preparation of aryl alkenoic acid heterocyclic amides of formula 1 where n is 1 or 2, x=O or N-CH3 and Ar represents as stated above in claim 1 which comprises reacting aldehyde of formula 5 with methyl magnesium halide preferably methyl magnesium iodide with constant stirring at ambient temperature in an anhydrous ether solvent to produce corresponding phenyl ethanol of formula 4, the compound of formula 4 is treated with dimethyl formamide and phosphorus oxychloride mixture at 0-10°C for 20-40 hours, to produce substituted phenyl-2E-propenaldehyde of formula 3, wherein n is 1 and Ar as stated above which on reaction with Wittig reagent prepared by triphenyl phosphine and bromoethyl acetate in presence of a base at temperature in the range of 15-80°C for a period in the range of 1-80 hrs., isolating the corresponding ester by conventional method followed by base hydrolysis to acid of formula 2 wherein n is 2, converting acid of formula 2 where n is lor 2 to corresponding acid chloride using thionyl chloride and reacting the acid chloride with heterocyclic amine in an inert organic solvent at temperature in the range of 0-50°C , isolating the compound of formula 1 by conventional method, wherein n is lor 2 and Ar represents as stated above. (3) A process as claimed in claim 2 wherein the compounds of formula 2 where n=l or 2 and Ar as stated above are converted to the compounds of formula 1 by reacting first with thionyl chloride in anhydrous inert solvents such as benzene, dichloromethane and the like and followed by condensation with heterocyclic amines in an anhydrous inert solvents such as benzene, dichloromethane. (4) A process as claimed in claim 2-3 above wherein the reactions of the compounds of formula 2 with thionyl chloride are effected in an inert solvents such as hydrocarbon solvents dichloro-methane, benzene and toluene to react with heterocyclic amines to produce compound of formula I. (5) A process as claimed in claims 2-4 above wherein the hydrolysis reaction of the ester intermediates to produce compounds of formula 2 are effected with a strong alkali such as sodium hydroxide, potassium hydroxide. (6) A process as claimed in claims 2-5 above where the reactions of compounds of formula 3 for conversion to compounds of formula 2 are effected in ethereal solvents such as diethyl ether, dimethoxyethane, tetrahydrofuran or their mixtures. (7) A process as claimed in claims 2- 6 above where in the compounds of formula 3 are reacted with a ylide prepared from equimolar mixture of triphenyl phosphine and ethylbromoacetate in presence of a strong base such as sodium hydride, sodium methoxide sodium ethoxide. (8) A process as claimed in claims 2-7 above wherein the reaction products of formula 3 from the reaction of compounds of formula 4 are obtained at a pH in the range of 6-8 and filtration of the precipitate obtained or extraction with the solvents such as ethyl acetate, chloroform diethyl ether dichloroethane. (9). A process as claimed in claims 2- 8 wherein 1-phenyl ethanols of formula 4 are reacted with a reagent prepared from dimethyl formamide and phosphorous oxychloride at a temperature in the range of 0-10°C. (10). A novel aryl alkenoic acid heterocyclic amide and their process for the preparation of novel aryl alkenoic acid heterocyclic amides of formula I shown in the drawings accompanying this specification substantially as herein described with reference to examples. .

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