Title of Invention	PREPARATION OF NEW CLASS OF "ANTHRANILATE BASED" POTENTIAL SUNSCREENS BY SELECTIVE TRANSESTERIFICATION
Abstract	The invention relates to the synthesis of new class of anthranillates which can be used as potential sunscreens .The said compounds were prepared by the selective transesterification of Methyl-(2-amino and /2-methylamino) benzoate with 2, 4-dihydroxy-2-methylpentane. Determination of Sun protection factor (SPF) and Photostability of the said compounds signify their use as potential UV sunscreen agents.

Title of Invention

PREPARATION OF NEW CLASS OF "ANTHRANILATE BASED" POTENTIAL SUNSCREENS BY SELECTIVE TRANSESTERIFICATION

Abstract

The invention relates to the synthesis of new class of anthranillates which can be used as potential sunscreens .The said compounds were prepared by the selective transesterification of Methyl-(2-amino and /2-methylamino) benzoate with 2, 4-dihydroxy-2-methylpentane. Determination of Sun protection factor (SPF) and Photostability of the said compounds signify their use as potential UV sunscreen agents.

Full Text	FORM 2 THE PATENT ACT 1970 (30 of 1970) & The Patents Rules, 2003 PROVISIONAL/COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION Preparation of New class of Anthramilate based potential Sunscreen by selective Transestrification 2 . APPLICANT (S) (a) NAME: Thatte chittaranjan sharad (b) NATIONALITY: Indian (c)ADDRESS: yashodey CHS D wing 203 kolshat Rd, kolshat Thane-400607,Maharashtra India. 3. PREAMBLE TO THE DESCRIPTION COMPLETE The following specification particularly describes Ihe invention and the manner in which it is to be performed. 4. DESCRIPTION (Description shall start from next page.) see page 3. As Attached 5. CLAIMS (not applicable for provisional specification, Claims should start with the preamble — "I/we Claim" on separate page) See page 11 As Attached 6. DATE AND SIGNATURE (to be given at the end of last page of specification) 7. ABSTRACT OF THE INVENTION (to be given along with complete specification on separate page) AS Attached Note.- Repeat boxes in case of more than one entry. To be signed by the applicant(s) or by authorized registered patent agent .Name of the applicant should be given in full, family name in the beginning . ' Complete address of the applicant should be given stating the postal index no./code, state and country. *Strike out the column which ls/are not applicable Title: Preparation of New class of "Anthranilate Based" Potential Sunscreens by Selective Transesterification. Preparation of 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methyl pentan-2yl (2-methylamino) benzoate and their use as potential sunscreen agents. References Cited: 1. Rai.R, Sriniwas CR Photoprotection. Indian J.Dermatol Venereol Leprol, 2007;73:73-9 2. Sunscreen Drug Products for over-the-Counter Human Use; Final Monograph, Federal Register 64 27666, U.S. Food and Drug Administration, Rockville, MD, 2000, http://www.cfsan.fda.gov/ lrd/fr990521.html 3. W. Johncock, Cosmet. Toiletries, 1999,114, 75-80. 4. Hess etal, U.S.Patent, 4135050 5. Mansur J S, Breder MNR, Mansur MCA, Azulay RD. Determinacao Do Fator De Protecao Solar Por Espectrofotometria. An Bras Dermatol Rio De Janeiro 1986; 61:121-. 6. Santos EP, Freitas ZM, Souza KR, Garcia S, Vergnanini A. in vitro and in vivo determinations of sun protection factors of sunscreen lotions with octylmethoxycinnamate. Int J Cosmet Sci 1999;21:1-5 7. Ashawat MS, Saraf S, Saraf S. Photo protective properties of Boerhavia diffusa, Biosciences. Biotech Res 2006; 3:257-60. 8. Helena Gonzalez, Nils Tarras-wahlberg, Birgitta Stromdahll, BMC Dermatology 2007, 7:1 FIELD OF INVENTION: The invention concerns Synthesis of new class of anthranilates by selective transesterification of the Methyl-(2-amino and /2-methylamino) benzoate with 2, 4-dihydroxy-2-methylpentane and the determination of photestability and sun protection factor of the said compounds BACKGROUND OF INVENTION Prior Art The anthranilate derivatives such as Methyl anthranilate and p-amino benzoic acid derivative like Padimate 0 are currently available sunscreens. They are mainly UVB absorbers. Padimate 0 is the most potent UV-B absorber. The decline in its use, along with the demand for higher SPF products has led to the incorporation of multiple active ingredients into a single product to achieve the desired SPF, replacing sunscreens with single PABA esters1. Several commercially available class of compounds either have absorbance in the UVA region (320-400nm) or UVB region (290-320nm).Due to unavailability of any single anthranilate derivative as sunscreen with UVA and UVB absorbance, sunscreen lotion contains mixtures of two different compounds. This not only increases the cost of sunscreen lotion but also increase the potential risk in mixing the two different sunscreens. The combination of commercial octylmethoxycinamate and butylmethoxydibenzoylmethane (Parsol 1789; also known as avobenzone) is not recommended2 because of its photo instability, photo adducts are formed between OMC and photo generated fragments3. Thus there is a need of sunscreen compounds that can cover both UVA and UVB range. SUMMARY OF THE INVENTION The present invention relates to synthesis of new class of chemical compounds, which are 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methylpentan-2-yl 2-(methylamino)benzoate, which can be potential UV sunscreens, Their method of preparation and in vitro testing as UV sunscreen agents by the way of determining Sun protection factor (SPF) is reported in the present invention. Anthranillates are generally synthesized by means of esterification of anthranilic acid with alcohol or by transesterification of ester of anthranilic acid and alcohol using either acid or base as a catalyst4 .Later route was adopted for the preparation of Novel anthranilates. No references been reported in published literature for proposed UV sunscreen agents and their method of preparation. Pertaining to the high ultraviolet absorbance entirely in UVA and UVB region (see Fig.2. & Fig3), proposed invented compound can be used as UV Sunscreen agent. The compounds also exhibit good photostability. The said compounds are in liquid form and have wide UV range of about 300-380nm than the previously reported anthranillates such as methyl anthranilate. The free hydroxyl group in the invented moiety is helpful to enhance the bathochromic shift in the UV A region, thus making these compounds more effective in treating the sunburns. Invented compounds can offer good solubility in polar solvents such as alcohols, and ketones. Objects of Invention The one object of the invention comprises the use of synthetic strategy such as transesterification for the synthesis of the novel anthranilates mentioned as compounds in example 1 and example2 Another object of invention relates to the use of metal doped catalysts for the synthesis of such novel anthranilates. Yet another object of invention is the use of said compounds as UV sunscreen agents, either individually or in combination. BRIEF DESCRIPTION OF THE INVENTION The present invention, relates to new class of sun screen agents based on anthranilate derivatives such as 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methylpentan-2-yl 2-(methylamino)benzoate (Scheme 1) their method of preparation, their photo stability study and sun protection factor (SPF) determination. The process for the preparation of said anthranilate derivatives comprises a selective transesterification reaction i.e. reacting an excess moles of 2,4-dihydroxy-2-methylpentane with Methyl 2-amino benzoate (Example 1) and Methyl 2-(methyl amino)benzoate (Example 2) using catalyst like calcium oxide and sodium doped calcium oxide. Reaction illustrated in Fig. 1. Figurel. Preparation of anthranilate derivative. The catalysts required for the present invention were prepared as follows: Preparation of alkali metal doped catalysts: The calcium hydroxide about 90% pure from Qualigens with particle size l50 mμ was used for the preparation of catalyst. The alkali metal Na or K doped CaO was prepared by wet impregnation of the corresponding carbonates on calcium hydroxide with a theoretical metal content varied to get 1.25% and 2.5% metal loading on calcium oxide. The catalyst is prepared by following process. 35g of calcium hydroxide (90%) was impregnated with 1.46g of Sodium carbonate. The aqueous suspension was heated under stirring for 2hrs, then evaporated to dryness and the resulting powder was subsequently calcined at 750°C for 6hrs. The theoretical metal content was about 2.5% sodium on CaO DETAILED DESCRIPTION OF THE INVENTION It is well known that ultraviolet radiation (light) having a wavelength from about 280nm or 290nm to about 320nm (UV-B) is harmful to human skin, causing burns that are detrimental to the development of good sun tan. The UV-A radiation (about 320nm to about 400nm), produces tanning of skin, also it can cause damage, particularly to very light colored or sensitive skin, leading to reduction of skin elasticity and wrinkles. Therefore sunscreen compounds for use on human skin preferably include both a UV-A & UV-B filter to prevent most of the sunlight within the full range of about 280nm to 400nm from damaging the human skin. The New compounds in the class of anthranilates have broad absorbance in the UVA and UVB region. Transesterification is very selective towards the hydroxyl group attached to the secondary carbon atom; therefore the free hydroxyl group attached to the tertiary carbon is protected by the selective transesterification strategy. This is confirmed on the basis of spectral data of compounds. Forward path of the reaction is achieved by continuous removal of liberated methanol using dean and stark collector. Anthranilate derivatives are prepared by transesterification reaction catalyzed by alkali metal doped Calcium oxide, following examples are sited to illustrate theme of the invention. (A) EXAMPLE 1 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate (Figure 1, R, R'= CH3, R"=CH3, R'"=H, R""=H) Added 151 g (lmole) of Methyl-2-aminobenzoate, 472.72 g (4 moles) of 2,4- dihydroxy-2-methylpentane, and 12.5 g of 2.5% Sodium doped CaO into 21itre glass reactor assembled with overhead stirrer, with thermometer pocket, dean & stark apparatus and condenser. The resulting mixture was heated at 185-190 °C. During reaction liberated methanol is collected in dean and stark. After completion of reaction, reaction mixture was filtered to remove the catalyst, and then it was distilled under reduced pressure to furnish 4-hydroxy-4-methylpentan- 2-yl 2-aminobenzoate. (Yield - 150g, 63.29%) Purity: 95%, by G.C. Empirical formula: C13 H19 N O3 Boiling point: 155° C at 15mm Hg Elemental Analysis: Found C, 65.85, H, 8.05, N, 5.94 C13 H19 N O3 requires C, 65.82, H, 8.01, N, 5.90). IR (KBr, vmax, cm'1) 1683 (lactonic keto), 3375 (OH), 1255-1235 (ether C-O- Ar) 1589.4 (Aromatic ring stretch) 1H NMR (DMSO-d6) ppm :1.075 (3H, s, CH3 ), 1.111(3H, s, CH3 ), ), 1.249- 1.265(3H, d, CH3 ), 1.6-1.7 (1H, d, C-H), 1.8-2.0 (1H, q, C-H), 4.3 (1H, s, C-H), 6.4-7.8 (4H, m, aromatic), 6.6 (1H, s, OH), On D2O exchange the peak at 6.6 disappears which confirms the presence of free OH group m/z(EI)237,(M+,C13H19NO3 requires 237), 137(100%), 119.1(77.76),59.1 (15.02), 43(15.49), (A) EXAMPLE 2 4-hydroxy-4-methylpentan-2-yl2-(methylamino)benzoate (Figure 1, R, R'= CH3, R"=CH3, R'"=H,R""=CH3) Added 165 g (lmole) of Methyl-2-methylaminobenzoate, 472.72 g (4 moles) of 2,4-dihydroxy-2-methylpentane, and 12.75 g of 2.5% Sodium on CaO into 21itre glass reactor assembled with overhead stirrer, thermometer pocket, dean & stark apparatus and condenser. The resulting mixture was heated at 185-190 °C. During reaction liberated methanol is collected in dean and stark. After completion of reaction, reaction mixture was filtered to remove the catalyst, and then it was distilled under reduced pressure to furnish 4-hydroxy-4-methylpentan-2-yl 2-(methylamino) benzoate. (Yield - 160g, 67.51%) Purity: 95 %, Determined by G.C. Empirical formula: C14 H21N O3 Boiling point: 180° C at 5mm Hg Elemental Analysis: Found C, 66.96, H, 8.32, N, 5.52 C14 H21N O3 requires C, 66.93, H,8.36,N, 5.57). The IR (KBr, vmax, cm-1) 1730 (lactonic keto), 3227 (OH), 1255-1235 (ether C- O-Ar) 1593 (Aromatic ring strech) 1HNMR (DMSO-d6) ppm 1.075 (3H, s, CH3 ), 1.111(3H, s, CH3 ), ), 1.249- 1.265(3H, d, CH3 ), 1.6-1.7 (1H, d, C-H), 1.8-2.0 (1H, q, C-H), 2.8(3H, s, Ar- NH-CH3)5.0-5.117 (2H, bs, OH merged with C-H), 5.212-5.247 (lH,q,NH), 6.4-7.8 (4H, m, aromatic), On D2O exchange the peak at 5.0 disappears which confirms the presence of free OH group. m/z (EI) 251 (M+, C14 H21 N O3 requires 251), 151.05 (100 %), 134.1(47.59),105.05 (83.33),77(29.09), 65(2.57). B) UV ABSORBANCE OF THE ANTHRANILATE DERIVATIVES The compounds, (Examplel and Example2) were scanned in UV range using about 150 ppm solutions in Ethanol, and the spectrum is recorded. (See Fig.2 and Fig.3) Based on their absorbance and concentration, the Molar extinction coefficient is determined. Values of respective compounds are given below Molar Extinction coefficient, G = 3258 Molar Extinction coefficient, G = 3750 C) DETERMINATION OF (in vitro) SUN PROTECTION FACTOR The sun protection factor was determined according to the method of Mansur5,6,7 0.1% solution of the compounds from Examplel and Example2 were prepared in pure ethyl alcohol. The absorbences were recorded at different wavelengths & the SPF was determined using the following formula. The SPF (in vitro) for compounds in Example 1 and Example2 are given in Table-1. Wavelength EE(A) employed Abs(λ) for (Example 1) Abs(λ) for (Example 2) EE(λ,) x I (λ) x A(λ) (Example 1) EE(λ) x I (λ) x A (λ) (Example 2) 290 0.015 0.385 0.614 0.006 0.009 295 0.082 0.615 1.030 0.050 0.084 300 0.287 0.974 1.646 0.280 0.473 305 0.328 1.502 3.000 0.492 0.983 310 0.186 2.212 3.000 0.412 0.559 315 0.084 2.750 3.000 0.230 0.251 320 0.018 2.950 2.950 0.053 0.053 SPF for compound in Example 1 = 15.24 SPF for compound in Example2 = 24.13 D) PHOTOSTABILITY: Compound A and B were tested for their photostability as per literature method8. Solutions of two compound with concentration about 25mg/lit were prepared and their AUC (Area under the curve) before exposure to UVA and UVB wavelength were recorded. These compounds were then kept at the same wavelength for 90min to study the photostability and their absorbances were recorded. The compounds are said to be photostable if the AUCI i.e. Area under the curve index (ratio of AUC before / AUC after) is more than 0.8. From the Table given below it was found that the AUCI was found to be equal to or 1, hence the compounds are photostable. Table-2 UVB UVA AUC before at 300nm AUC after at 300nm AUC before at 360nm AUC after at 360nm Compound A (25ppm) 0.201 0.228 0.376 0.403 Compound B (25ppm) 0.2 0.199 0.513 0.552 AUCI = AUC after/AUC before (Compound A) AUCI = AUC after/AUC before (Compound B) 1.134 0.995 1.072 1.076 Claims I claim: 1. A synthetic strategy such as transesterification of the Methyl-(2-amino/2-methylamino) benzoate with 2-methyl-2,4-dihydroxypentane to furnish 4-hydroxy-4-methylpentan-2-yl 2-(amino / methylamino)benzoate of the formula in Fig. 1 of Example 1 and Example 2. 2. A pharmaceutical composition, suitable for use in UV sunscreen lotions for the protection of UV rays in the sunlight to prevent damage of the skin, comprising a compound of claim 1, in an amount effective for said purpose i.e. 1 to 10% by weight, in association with any other compound of sunscreen property or used without any additives. 3. The Diols claimed are as shown in Fig.l. Where R= CH3, C2H5, and R' = CH3, C2H5, Hexylene glycol, Ethylene glycol, propylene glycol, 1,2-propanediol, 1,3-propanediol etc. 4. The acids claimed are anthranilic acid, Cinamic acid, salicylic acid, palmitic acid, 4-hydroxy benzoic acid,N-benzoyl anthranilic acid, Dimethyl anthranilic acid, 5-chloro methyl anthranilic acid, Essential amino acids like Glycine, Alanine, Leucine, Isoleucine, Lysine, Methonine, Valine, Threonine, Phenyl alanine, The esters claimed are methyl anthranilate, Dimethyl anthranilate, 5-chloro methyl anthranilate, Ethyl anthranillate, Methyl ethyl anthranilate methyl cinamate, ethyl cinamate, methyl methoxy cinamate, methyl salicylate, ethyl salicylate .4-hydroxy methyl anthranilate, 4-hydroxy ethyl anthranilate, Methyl N,N-dimethyl anthranilates, Butyl anthranilate, Ethyl N-methyl anthranilate, Ethyl N-Ethyl anthranilates, Isobutyl N-methyl anthranilate, Methyl N-formyl anthranilate, Methyl N-acetyl anthranilate, Ethyl-4-amino-3-methylbenzoate. 5. Compound of claim 1, wherein the compound is 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate 6. Compound of claiml, wherein the compound is 4-hydroxy-4- methylpentan-2-yl2-(methylamino)benzoate 7. Synthetic strategy such as Transesterification and esterification according to claiml using sodium or potassium metal doped calcium oxide catalyst, calcium oxide, potassium carbonate, sodium carbonate, magnesium oxide, sodium methoxide, potassium butoxide, barium hydroxide, trisodium phosphate, berilium hydroxide, and any such modified or supported catalytic systems. 8. Temperature used for the synthesis is in the range of 100-250°C, preferably 140-220°C and more preferably 180-190°C. 9. The purity of the compounds of claim 1 in the range of 90-95%, preferably 95-97 and more preferably 99-100%

Full Text

FORM 2
THE PATENT ACT 1970
(30 of 1970)
&
The Patents Rules, 2003
PROVISIONAL/COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
Preparation of New class of Anthramilate based potential Sunscreen by selective Transestrification
2 . APPLICANT (S)
(a) NAME: Thatte chittaranjan sharad
(b) NATIONALITY: Indian
(c)ADDRESS: yashodey CHS D wing 203 kolshat Rd,
kolshat Thane-400607,Maharashtra India.
3. PREAMBLE TO THE DESCRIPTION

COMPLETE
The following specification particularly describes Ihe invention and the manner in which it is to be performed.
4. DESCRIPTION (Description shall start from next page.)
see page 3.
As Attached
5. CLAIMS (not applicable for provisional specification, Claims should start with the preamble —
"I/we Claim" on separate page)
See page 11 As Attached
6. DATE AND SIGNATURE (to be given at the end of last page of specification)
7. ABSTRACT OF THE INVENTION (to be given along with complete specification on separate
page)

AS Attached
Note.-
*Repeat boxes in case of more than one entry.
*To be signed by the applicant(s) or by authorized registered patent agent
.*Name of the applicant should be given in full, family name in the beginning . '
*Complete address of the applicant should be given stating the postal index no./code, state and country.
*Strike out the column which ls/are not applicable

Title: Preparation of New class of "Anthranilate Based" Potential Sunscreens by Selective Transesterification.
Preparation of 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methyl pentan-2yl (2-methylamino) benzoate and their use as potential sunscreen agents.
References Cited:
1. Rai.R, Sriniwas CR Photoprotection. Indian J.Dermatol Venereol Leprol, 2007;73:73-9
2. Sunscreen Drug Products for over-the-Counter Human Use; Final Monograph, Federal Register 64 27666, U.S. Food and Drug Administration, Rockville, MD, 2000, http://www.cfsan.fda.gov/ lrd/fr990521.html
3. W. Johncock, Cosmet. Toiletries, 1999,114, 75-80.
4. Hess etal, U.S.Patent, 4135050
5. Mansur J S, Breder MNR, Mansur MCA, Azulay RD. Determinacao Do Fator De Protecao Solar Por Espectrofotometria. An Bras Dermatol Rio De Janeiro 1986; 61:121-.
6. Santos EP, Freitas ZM, Souza KR, Garcia S, Vergnanini A. in vitro and in vivo determinations of sun protection factors of sunscreen lotions with octylmethoxycinnamate. Int J Cosmet Sci 1999;21:1-5
7. Ashawat MS, Saraf S, Saraf S. Photo protective properties of Boerhavia diffusa, Biosciences. Biotech Res 2006; 3:257-60.
8. Helena Gonzalez, Nils Tarras-wahlberg, Birgitta Stromdahll, BMC Dermatology 2007, 7:1
FIELD OF INVENTION:
The invention concerns Synthesis of new class of anthranilates by selective transesterification of the Methyl-(2-amino and /2-methylamino) benzoate with 2,

4-dihydroxy-2-methylpentane and the determination of photestability and sun protection factor of the said compounds
BACKGROUND OF INVENTION Prior Art
The anthranilate derivatives such as Methyl anthranilate and p-amino benzoic acid derivative like Padimate 0 are currently available sunscreens. They are mainly UVB absorbers. Padimate 0 is the most potent UV-B absorber. The decline in its use, along with the demand for higher SPF products has led to the incorporation of multiple active ingredients into a single product to achieve the desired SPF, replacing sunscreens with single PABA esters1. Several commercially available class of compounds either have absorbance in the UVA region (320-400nm) or UVB region (290-320nm).Due to unavailability of any single anthranilate derivative as sunscreen with UVA and UVB absorbance, sunscreen lotion contains mixtures of two different compounds. This not only increases the cost of sunscreen lotion but also increase the potential risk in mixing the two different sunscreens. The combination of commercial octylmethoxycinamate and butylmethoxydibenzoylmethane (Parsol 1789; also known as avobenzone) is not recommended2 because of its photo instability, photo adducts are formed between OMC and photo generated fragments3.
Thus there is a need of sunscreen compounds that can cover both UVA and UVB range.
SUMMARY OF THE INVENTION
The present invention relates to synthesis of new class of chemical compounds, which are 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methylpentan-2-yl 2-(methylamino)benzoate, which can be potential UV sunscreens, Their method of preparation and in vitro testing as UV sunscreen agents by the way of determining Sun protection factor (SPF) is reported in the present invention.

Anthranillates are generally synthesized by means of esterification of anthranilic acid with alcohol or by transesterification of ester of anthranilic acid and alcohol using either acid or base as a catalyst4 .Later route was adopted for the preparation of Novel anthranilates. No references been reported in published literature for proposed UV sunscreen agents and their method of preparation.
Pertaining to the high ultraviolet absorbance entirely in UVA and UVB region (see Fig.2. & Fig3), proposed invented compound can be used as UV Sunscreen agent. The compounds also exhibit good photostability. The said compounds are in liquid form and have wide UV range of about 300-380nm than the previously reported anthranillates such as methyl anthranilate. The free hydroxyl group in the invented moiety is helpful to enhance the bathochromic shift in the UV A region, thus making these compounds more effective in treating the sunburns. Invented compounds can offer good solubility in polar solvents such as alcohols, and ketones.
Objects of Invention
The one object of the invention comprises the use of synthetic strategy such
as transesterification for the synthesis of the novel anthranilates mentioned as compounds in example 1 and example2
Another object of invention relates to the use of metal doped catalysts for the synthesis of such novel anthranilates.
Yet another object of invention is the use of said compounds as UV sunscreen agents, either individually or in combination.
BRIEF DESCRIPTION OF THE INVENTION
The present invention, relates to new class of sun screen agents based on anthranilate derivatives such as 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate and 4-hydroxy-4-methylpentan-2-yl 2-(methylamino)benzoate (Scheme 1) their method of preparation, their photo stability study and sun protection factor (SPF) determination.
The process for the preparation of said anthranilate derivatives comprises a

selective transesterification reaction i.e. reacting an excess moles of 2,4-dihydroxy-2-methylpentane with Methyl 2-amino benzoate (Example 1) and Methyl 2-(methyl amino)benzoate (Example 2) using catalyst like calcium oxide and sodium doped calcium oxide. Reaction illustrated in Fig. 1.

Figurel. Preparation of anthranilate derivative.
The catalysts required for the present invention were prepared as follows:
Preparation of alkali metal doped catalysts:
The calcium hydroxide about 90% pure from Qualigens with particle size l50 mμ
was used for the preparation of catalyst.
The alkali metal Na or K doped CaO was prepared by wet impregnation of the corresponding carbonates on calcium hydroxide with a theoretical metal content varied to get 1.25% and 2.5% metal loading on calcium oxide. The catalyst is prepared by following process.
35g of calcium hydroxide (90%) was impregnated with 1.46g of Sodium carbonate. The aqueous suspension was heated under stirring for 2hrs, then evaporated to dryness and the resulting powder was subsequently calcined at 750°C for 6hrs. The theoretical metal content was about 2.5% sodium on CaO

DETAILED DESCRIPTION OF THE INVENTION
It is well known that ultraviolet radiation (light) having a wavelength from about 280nm or 290nm to about 320nm (UV-B) is harmful to human skin, causing burns that are detrimental to the development of good sun tan. The UV-A radiation (about 320nm to about 400nm), produces tanning of skin, also it can cause damage, particularly to very light colored or sensitive skin, leading to reduction of skin elasticity and wrinkles. Therefore sunscreen compounds for use on human skin preferably include both a UV-A & UV-B filter to prevent most of the sunlight within the full range of about 280nm to 400nm from damaging the human skin.
The New compounds in the class of anthranilates have broad absorbance in the UVA and UVB region.
Transesterification is very selective towards the hydroxyl group attached to the secondary carbon atom; therefore the free hydroxyl group attached to the tertiary carbon is protected by the selective transesterification strategy. This is confirmed on the basis of spectral data of compounds. Forward path of the reaction is achieved by continuous removal of liberated methanol using dean and stark collector.
Anthranilate derivatives are prepared by transesterification reaction catalyzed by alkali metal doped Calcium oxide, following examples are sited to illustrate theme of the invention. (A) EXAMPLE 1 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate
(Figure 1, R, R'= CH3, R"=CH3, R'"=H, R""=H)
Added 151 g (lmole) of Methyl-2-aminobenzoate, 472.72 g (4 moles) of 2,4- dihydroxy-2-methylpentane, and 12.5 g of 2.5% Sodium doped CaO into 21itre glass reactor assembled with overhead stirrer, with thermometer pocket, dean & stark apparatus and condenser. The resulting mixture was heated at 185-190 °C. During reaction liberated methanol is collected in dean and stark. After completion of reaction, reaction mixture was filtered to remove the catalyst, and

then it was distilled under reduced pressure to furnish 4-hydroxy-4-methylpentan-
2-yl 2-aminobenzoate. (Yield - 150g, 63.29%)
Purity: 95%, by G.C.
Empirical formula: C13 H19 N O3
Boiling point: 155° C at 15mm Hg
Elemental Analysis: Found C, 65.85, H, 8.05, N, 5.94 C13 H19 N O3 requires C, 65.82, H, 8.01, N, 5.90).
IR (KBr, vmax, cm'1) 1683 (lactonic keto), 3375 (OH), 1255-1235 (ether C-O- Ar) 1589.4 (Aromatic ring stretch)
1H NMR (DMSO-d6) ppm :1.075 (3H, s, CH3 ), 1.111(3H, s, CH3 ), ), 1.249- 1.265(3H, d, CH3 ), 1.6-1.7 (1H, d, C-H), 1.8-2.0 (1H, q, C-H), 4.3 (1H, s, C-H),
6.4-7.8 (4H, m, aromatic), 6.6 (1H, s, OH),
On D2O exchange the peak at 6.6 disappears which confirms the presence of free
OH group
m/z(EI)237,(M+,C13H19NO3 requires 237), 137(100%), 119.1(77.76),59.1 (15.02), 43(15.49),
(A) EXAMPLE 2
4-hydroxy-4-methylpentan-2-yl2-(methylamino)benzoate (Figure 1, R, R'= CH3, R"=CH3, R'"=H,R""=CH3)
Added 165 g (lmole) of Methyl-2-methylaminobenzoate, 472.72 g (4 moles) of 2,4-dihydroxy-2-methylpentane, and 12.75 g of 2.5% Sodium on CaO into 21itre glass reactor assembled with overhead stirrer, thermometer pocket, dean & stark apparatus and condenser. The resulting mixture was heated at 185-190 °C. During reaction liberated methanol is collected in dean and stark. After completion of reaction, reaction mixture was filtered to remove the catalyst, and then it was distilled under reduced pressure to furnish 4-hydroxy-4-methylpentan-2-yl 2-(methylamino) benzoate. (Yield - 160g, 67.51%) Purity: 95 %, Determined by G.C. Empirical formula: C14 H21N O3 Boiling point: 180° C at 5mm Hg

Elemental Analysis: Found C, 66.96, H, 8.32, N, 5.52 C14 H21N O3 requires C,
66.93, H,8.36,N, 5.57).
The IR (KBr, vmax, cm-1) 1730 (lactonic keto), 3227 (OH), 1255-1235 (ether C-
O-Ar) 1593 (Aromatic ring strech)
1HNMR (DMSO-d6) ppm 1.075 (3H, s, CH3 ), 1.111(3H, s, CH3 ), ), 1.249-
1.265(3H, d, CH3 ), 1.6-1.7 (1H, d, C-H), 1.8-2.0 (1H, q, C-H), 2.8(3H, s, Ar-
NH-CH3)5.0-5.117 (2H, bs, OH merged with C-H), 5.212-5.247 (lH,q,NH),
6.4-7.8 (4H, m, aromatic),
On D2O exchange the peak at 5.0 disappears which confirms the presence of free
OH group.
m/z (EI) 251 (M+, C14 H21 N O3 requires 251), 151.05 (100 %),
134.1(47.59),105.05 (83.33),77(29.09), 65(2.57).
B) UV ABSORBANCE OF THE ANTHRANILATE
DERIVATIVES
The compounds, (Examplel and Example2) were scanned in UV range using about 150 ppm solutions in Ethanol, and the spectrum is recorded. (See Fig.2 and Fig.3) Based on their absorbance and concentration, the Molar extinction coefficient is determined. Values of respective compounds are given below Molar Extinction coefficient, G = 3258 Molar Extinction coefficient, G = 3750
C) DETERMINATION OF (in vitro) SUN PROTECTION FACTOR
The sun protection factor was determined according to the method of Mansur5,6,7 0.1% solution of the compounds from Examplel and Example2 were prepared in pure ethyl alcohol. The absorbences were recorded at different wavelengths & the SPF was determined using the following formula.

The SPF (in vitro) for compounds in Example 1 and Example2 are given in Table-1.

Wavelength EE(A)
employed Abs(λ) for (Example 1) Abs(λ) for (Example 2) EE(λ,) x I (λ) x
A(λ) (Example 1) EE(λ) x I (λ) x A (λ) (Example 2)
290 0.015 0.385 0.614 0.006 0.009
295 0.082 0.615 1.030 0.050 0.084
300 0.287 0.974 1.646 0.280 0.473
305 0.328 1.502 3.000 0.492 0.983
310 0.186 2.212 3.000 0.412 0.559
315 0.084 2.750 3.000 0.230 0.251
320 0.018 2.950 2.950 0.053 0.053
SPF for compound in Example 1 = 15.24 SPF for compound in Example2 = 24.13
D) PHOTOSTABILITY:
Compound A and B were tested for their photostability as per literature method8.
Solutions of two compound with concentration about 25mg/lit were prepared and their AUC (Area under the curve) before exposure to UVA and UVB wavelength were recorded. These compounds were then kept at the same wavelength for 90min to study the photostability and their absorbances were recorded. The compounds are said to be photostable if the AUCI i.e. Area under the curve index (ratio of AUC before / AUC after) is more than 0.8. From the Table given below it was found that the AUCI was found to be equal to or 1, hence the compounds are photostable. Table-2

UVB UVA
AUC before at 300nm AUC after at 300nm AUC before at 360nm AUC after at 360nm
Compound A (25ppm) 0.201 0.228 0.376 0.403
Compound B (25ppm) 0.2 0.199 0.513 0.552
AUCI = AUC after/AUC before (Compound A) AUCI = AUC after/AUC before (Compound B) 1.134
0.995 1.072 1.076

Claims
I claim:
1. A synthetic strategy such as transesterification of the Methyl-(2-amino/2-methylamino) benzoate with 2-methyl-2,4-dihydroxypentane to furnish 4-hydroxy-4-methylpentan-2-yl 2-(amino / methylamino)benzoate of the formula in Fig. 1 of Example 1 and Example 2.
2. A pharmaceutical composition, suitable for use in UV sunscreen lotions for the protection of UV rays in the sunlight to prevent damage of the skin, comprising a compound of claim 1, in an amount effective for said purpose i.e. 1 to 10% by weight, in association with any other compound of sunscreen property or used without any additives.
3. The Diols claimed are as shown in Fig.l. Where R= CH3, C2H5, and R' = CH3, C2H5, Hexylene glycol, Ethylene glycol, propylene glycol, 1,2-propanediol, 1,3-propanediol etc.
4. The acids claimed are anthranilic acid, Cinamic acid, salicylic acid, palmitic acid, 4-hydroxy benzoic acid,N-benzoyl anthranilic acid, Dimethyl anthranilic acid, 5-chloro methyl anthranilic acid, Essential amino acids like Glycine, Alanine, Leucine, Isoleucine, Lysine, Methonine, Valine, Threonine, Phenyl alanine, The esters claimed are methyl anthranilate, Dimethyl anthranilate, 5-chloro methyl anthranilate, Ethyl anthranillate, Methyl ethyl anthranilate methyl cinamate, ethyl cinamate, methyl methoxy cinamate, methyl salicylate, ethyl salicylate .4-hydroxy methyl anthranilate, 4-hydroxy ethyl anthranilate, Methyl N,N-dimethyl anthranilates, Butyl anthranilate, Ethyl N-methyl anthranilate, Ethyl N-Ethyl anthranilates, Isobutyl N-methyl anthranilate, Methyl N-formyl anthranilate, Methyl N-acetyl anthranilate, Ethyl-4-amino-3-methylbenzoate.
5. Compound of claim 1, wherein the compound is 4-hydroxy-4-methylpentan-2-yl 2-aminobenzoate

6. Compound of claiml, wherein the compound is 4-hydroxy-4-
methylpentan-2-yl2-(methylamino)benzoate
7. Synthetic strategy such as Transesterification and esterification according
to claiml using sodium or potassium metal doped calcium oxide catalyst,
calcium oxide, potassium carbonate, sodium carbonate, magnesium oxide,
sodium methoxide, potassium butoxide, barium hydroxide, trisodium
phosphate, berilium hydroxide, and any such modified or supported
catalytic systems.
8. Temperature used for the synthesis is in the range of 100-250°C, preferably 140-220°C and more preferably 180-190°C.
9. The purity of the compounds of claim 1 in the range of 90-95%, preferably 95-97 and more preferably 99-100%

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Patent Number

270569

Indian Patent Application Number

1672/MUM/2011

PG Journal Number

01/2016

Publication Date

01-Jan-2016

Grant Date

31-Dec-2015

Date of Filing

07-Jun-2011

Name of Patentee

THATTE CHITTARANJAN SHARAD

Applicant Address

YASHODEEP CHS, KOLSHET, THANE, MAHARASHTRA, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	THATTE CHITTARANJAN SHARAD	YASHODEEP CHS, KOLSHET, THANE, MAHARASHTRA, INDIA

PCT International Classification Number

A61Q19/00

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA