Title of Invention

"METHOD FOR ACYLATION USING ZIRCONIUM (IV) COMPOUND AS CATALYSTS"

Abstract A process for acylation of substituted or unsubstituted alkyl, aryl, alkyl aryl or heteroaryl compounds using substituted or unsubstituted carboxylic acid anhydride or carboxylic acid in presence of zirconium (IV) compound as catalysts in the presence or absence of a solvent at a room temperature in the range of 0 to 110°C to obtain the required acylated product.
Full Text Field of invention
The present invention relates to a process for the acylation of various substrates using in zirconium (IV) compound as a catalyst. The present invention particularly relates to the use of zirconium (IV) compounds as catalyst for acylation of substituted or unsubstituted alkyl, aryl, alkyl aryl or heteroaryl compounds using substituted or unsubstituted carboxylic acid anhydride or carboxylic acid as an acylating reagent. It is also applicable to electron deficient, sterically hindered and chiral substrates.
Acylation process plays an important role in synthesizing chemicals and pharmaceuticals. The work relates to the acylation of aromatics, phenols, alcohols, amines and thiols, with a carboxylic anhydride or carboxylic acid using novel catalysts. The invention also relates to the use of various acid anhydrides for acylation of different substrates to study the influence of "electronic" and "steric" factor. Further, the work also relates to the achievement of economics in esterification by using acetic acid instead of acid anhydride in acylation of alcohols as an acylating reagent.
Background Art
Chemical processes utilizing environmentally benign conditions are in increasing demand in organic synthesis. Acylated phenols, thiols, alcohols, amines and aromatics are key intermediates for drugs and pharmaceuticals eg. diltiazem (Yoshioka, M. et al, EP Pat. 488210, 1992), pravastatin (J. Org. Chem., 1992, 57, 7133-7139), cephalosporins (Guna, R. et al, WO Pat. 99/23098,1999), taxol (Gibson, F. S. et al, US Pat. 6020507, 2002), vitamin D analogs (Daniewski, A. R. et al, US Pat.6353123, 2002), arbutin (Lee, Y. S. et al, US Pat. 6388103, 2002).
Steglich et al. (Angew. Chem. Int. Ed. Engl. 1969, 8, 981) describes investigation involving the use of 4-dimethylamino pyridine (DMAP) as promotor for the acylation of alcohols with anhydrides. The process requiring halogenated solvents. Need to use stoichiometric quantities of a base e.g. pyridine or trimethylamine limit the use of DMAP for base sensitive substrates? The high toxicity of DMAP does not make it appealing for large-scale operation.

Iqbal, J et al. (J. Org. Chem. 1992, 57, 2001-2007) describes investigation involving the use of cobalt (II) chloride as catalyst for acylation of alcohols with acetic anhydride. The process however was not effective for tertiary alcohols.
Vedejs E. et al. (J. Am. Chem. Soc. 1993, 115, 3358-3359) describes investigation involving the use of tributylphosphine as catalyst for acylation reaction, which is flammable and air sensitive.
Kawada, A. et al. (J. Chem. Soc, Chem. Commun. 1993, 1157-1158; Chem. Commun. 1996, 183-184) describes investigation involving the use of 5-100 mol % of lanthanide trifluoromethanesulfonates [Ln(OTf)3] as reusable catalyst for substituted benzenes. The reactions were carried out at 50°C for 3-48 hours. The same group has also described investigation involving the use of Ln(OTf)3 (20 mol %) in combination with lithium perchlorate (20 to 400 mol %) for acylation of aromatics using acetic anhydrides.
Ishihara, K et al. (J. Am. Chem. Soc. 1995, 117, 4413-4414) describes investigation involving the use of scandium triflate as a active acylation catalyst. High cost and susceptibility to moisture does not make the catalyst suitable for industrial application. Further the strong lewis acid character of the catalyst causes side reaction for acid sensitive substrates.
Wang; Q. L. et al. (J. Chem. Soc. Chem. Commun. 1995, 2307-2308) describes investigation involving the use of HZSM-5 catalyst for acylation of anisole using carboxylic acid. The temperature of the reaction 120-150°C and the 1000-g of catalyst HZSM-5 zeolite used per mole of the reactant.
Kobayashi, S. et al. (Tetrahedron Lett. 1995, 36, 409-412; Tetrahedron Lett. 1998, 39, 4697-4700) describes investigation involving the use of hafnium triflate (10-20 mol %) as catalyst along with lithium perchlorate in nitromethane. The excess use of lithium perchlorate and the need to prepare hafnium triflate makes this process not for commercial importance. The same group has reported an investigation describing the use of hafnium triflate (10-20 mol %) in combination with trifluoromethanesulfonic acid (10-30 mol %) for acylation of aromatic compound. The use of costly triflate along with the strong acid triflic acid makes this process uneconomical.
Ishihara, K et al. (Synlett 1996, 265-266) describes investigation involving the use of complex formed from scandium acetate and trifluoromefhanesulfonimide as acylation catalyst for phenols and alcohols using acid anhydrides and aryl carboxylic acids. Apart from the tedious procedure for its preparation like high temperature and pressure, the process also requires the presence of 4-nitrobenzoic anhydride for benzoylation of alcohols with benzoic anhydride, using 0.5 to 2-mol % of the catalyst.
Vedejs E. et al. (J. Am. Chem. Soc. 1996, 118, 1809-1810) describes investigation involving the use of chiral dimethylaminopyridine derivative as catalyst for acylation reaction which otherwise is toxic in nature.
Vedejs E. et al. (J. Org. Chem. 1996, 61, 5702-5703) describes investigation involving the use of magnesium bromide in combination with triethylamine as a dual activation catalyst for esterification of alcohols with anhydrides. The process utilizes 2 equivalent of magnesium bromide and 3 equivalent of triethylamine. It also requires 2 equivalent of acylating agent.
Li, A-X et al. {J. Chem. Soc. Chem. Commun. 1997, 1389-1390) describes investigation involving the use of montmorillonite K-10 and KSF as catalyst for acetylation but has limited application and the acylation of phenols and alcohols are usually carried out at higher temperature with 2 equivalents of acetic anhydride in halogenated solvents.
Kodomari, M. et al. {Chem. Commun. 1997, 1567-1568) describes investigation involving the use of graphite as catalyst for Friedel-Crafts acylation of anisole and activated aromatics using 1.5 equivalent of acid chloride under refluxing with dichloroethane. The yields obtained were moderate.
Procopiou, P. A et al. {J. Org. Chem. 1998, 63, 2342-2347) describes investigation involving the use of trimethylsilyl triflate for the acylation of alcohols with acid anhydrides which otherwise is highly moisture sensitive catalyst and not suitable for acid sensitive substrates.
Ballini, R et al. {Tetrahedron Lett. 1998, 39, 6049- 6052) describes investigation involving the use of zeolite HSZ-360 as a reusable catalyst for acetylation
of alcohols and phenols but has limited application. The process utilizes drastic reaction conditions (reactions carried out at 60°C) for longer durations (1-8 hrs).
Chandrasekhar, S et al. (Tetrahedron Lett. 1998, 39, 3263-3266) describes investigation involving the use of tantalum (V) chloride as a catalyst for the acylation of alcohols and has limited application.
Damen, E et al. (Tetrahedron Lett. 1998, 39, 6081-6082) describes investigation involving the use of lanthanide triflate as a catalyst for acylation of 10-deacetyl baccatin III selectively. The high cost and sensitivity to moisture are major drawbacks for metal triflates in general.
Singh, V. K et al. (Tetrahedron Lett. 1999, 40, 2611-2614) describes investigation involving the use of copper triflate for acylation of phenols and alcohols which otherwise is costly and not effective for acid sensitive substrates.
Chauhan, K. K et al. (Synlett. 1999, 1743-1744) describes investigation involving the use of indium triflate as an efficient catalyst for acylation of phenols and alcohols with limited examples.
Olah, G.A. et al. (Tetrahedron 2000, 56, 7199-7203) describes investigation involving the use of trifluoromethanesulfonic acid as a catalyst for the acylation of aromatics with methyl benzoate. The process though gave excellent yields in the range of 70-90%, the use of 5.0 equivalent of strong acid i.e. triflic acid makes it undesirable to industrial process due to environmental constrains.
Kawada, A. et al. (Bull. Chem. Soc. Jpn, 2000, 73, 2325-2333) describes investigation involving the use of rare earth metal trifluoromethanesulfonates like ytterbium and scandium triflate (25-50 mol %) for acylation of anisole and aromatics using acid anhydrides and acid chlorides. The process however gave yields in the range of 50%, which were enhanced by the addition of lithium perchlorate (20-400 mol %).
Orita, A et al. (Angew. Chem. Int. Ed. Engl. 2000, 39, 2877-28) describes investigation involving bismuth triflate as an acylation catalyst for phenols and alcohols. This catalyst though proven to be the most effective among all the acylation catalyst reported so far suffers from several disadvantages. Bismuth triflate is a costly
catalyst and also moisture sensitive. Acid sensitive and allylic substrates require either excess of solvent or temperature control (-20 to 0°C). It is not available commercially and involves special efforts for its preparation.
Kobayashi, S. et al. (Synlett. 2000, 3, 403-405) describes investigation involving the use of gallium nonafluorobutanesulfonate (1-10 mol %) as acylation catalyst for aromatics with acid chlorides under reflux conditions. The process however suffers from the disadvantage of preparing the catalyst by a tedious procedure.
Singh, V. K. et al. (Tetrahedron 2001, 57, 241-247) describes investigation involving the use of copper and tin triflates for acylation, sulfonylation and alkylation of aromatic compounds. The process makes use of 5-10 mol % of the catalyst and the temperature used were in a range of 50-80°C for 4-12 hours.
Chapman, C. J. et al. {Tetrahedron Lett. 2001, 42, 773-775) describes investigation involving the use of indium complexes (1 mol %) with lithium perchlorate (25-100 mol %) for acylation of aromatics using acid anhydrides.
Dubac, J. et al. (Synlett. 2002, 2, 181-200) describes investigation involving the use of bismuth chloride (10 mol %) and bismuth triflate (1-5 mol %) for Friedel-Crafts acylation using acid chlorides and acid anhydrides, with optimal reaction temperature ranges from 80-100°C with excellent yields. However due to commercial unavailability of bismuth triflate and also the high cost of these catalyst makes them unfavourable for industrial use.
Kaur, J. et al. (J. Catal. 2002, 208, 448-455) describes investigation involving the use of hetopoly acids for acylation of anisole using acetic anhydride. The process makes use of 10-20 equivalent of acetic anhydride and temperature in the range of 70-110°C. The process also requires special efforts in the preparation and characterization of the catalyst apart from the large amount (40-50%) of catalyst used in the acylation reactions.
Barrett A.G.M. et al. (Synlett. 2002, 10, 1653-1656) describes investigation involving the use of ytterbium tri[tris(nonafluorobutatanesulfonyl)methide] for acylation of anisole and other aromatic compounds. The process though makes use of 0.1-10-mol % of the catalyst but the yields are in the range of 20-70 %. However to
obtain quantitative yields higher catalyst loading along with higher temperature i.e. 150°C were required. The use of such harsh condition and the tedious method for the preparation of the catalyst makes it unsuitable for large-scale process.
A cost-effective catalyst for acylation catalyst is, therefore, needed which must be versatile, moisture resistant, non-toxic and eco-friendly. The work embodied in the present invention deals with the acylation (0-, N-, S-, and C- acylation) reactions under milder conditions; preferably at room temperature and solvent free conditions under the catalytic influence of zirconium (IV) salts catalyst such as zirconyl perchlorate [ZrO(C104)2 8H20] and zirconium tetrachloride [ZrCl4].
Acylation of phenols, alcohols, thiols, amines and aromatic compounds are of tremendous importance to the pharmaceuticals, chemical and agrobased industries. Acylation is generally carried in the presence of a catalyst. The various catalyst developed for the purpose include the nucleophilic agents such as DMAP and BU3P and the Lewis acids such as CoCl2> Sc(OTf)3, Sc(NTf)3, clays, TaCl5, zeolites, TMSOTf, La(OTf)3, Cu(OTf)2, In(OTf)3, Bi(OTf)3, Nafion-H, Yttria-Zirconia, and LiC104.
The limitations of the existing protocols realized in terms of longer reaction time, stringent conditions, use of halogenated solvents, use of hazardous materials (e.g. DMAP is highly toxic, Bu3P is flammable and air sensitive), use of costly and water sensitive catalysts (e.g. the triflates, TaCls), special efforts required to prepare the catalyst (e.g. Bi(OTf)3, Sc(NTf)3, yttria-zirconia, Nafion-H), need to use excess acylating agent, potential side reactions with acid-sensitive substrates and in most of the cases being applicable to alcohols only make the necessity to develop better acylation catalyst in high demand.
The invention is related to the use of a catalyst and reaction conditions that can be made generalized for acylation of diverse kind of phenols, alcohols, thiols, amines md aromatic compounds.
Object of the present invention
The main object of the invention is directed to an improved catalytic process for acylation of phenols, alcohols, thiols, amine and aromatic compounds in presence of various zirconium (IV) compounds.
A further object of the invention is directed to obtain a feasible reaction condition with different solvents in the presence of ZrO(C104)2.8H20 as catalyst. The solvent for reaction is selected from a group consisting of chlorinated solvents such as methylene chloride (CH2C12), aprotic polar solvents such as acetonitrile (CH3CN) and nitromethane (CH3NO2), aromatic solvents such as toluene and ethereal solvents such as diethyl ether, and THF (tetrahydrofuran).
Another object of the invention is directed to study the catalytic efficiency of ZrO(C104)2.8H20 ranging from 1 mol % to 0.005 mol % in acetylation of 2-naphthol using 1 equivalent of acetic anhydride under solvent free condition at room temperature.
A further object of the invention is directed for making ZrO(C104)2.8H20 and ZrCl4 catalysts for the reaction of 2-naphthol and 4-nitrophenol with aliphatic and aromatic anhydrides.
Yet another object of the invention is directed for isobutyrlation of alcohols and phenols using isobutyric anhydride under the catalytic influence of ZrO(C104)2.8H20.
Still another object of the invention is directed for pivalation of alcohols and phenols using pivalic anhydride under the catalytic influence of ZrO(C104)2.8H20.
Yet another object of the invention is directed for benzoylation of alcohols and phenols using benzoic anhydride under the catalytic influence of ZrO(C104)2.8H20.
Still another object of the invention is directed for the direct acetylation compounds of alcohols using acetic acid under the catalytic influence of ZrO(C104)2.8H20.
Yet another object of the invention is directed towards the acylation compounds of sterically hindered phenols with different anhydride under the catalytic influence of ZrO(C104)2.8H20.
Still another object of the invention is directed towards the acylation of aromatics using different anhydride under the catalytic influence of ZrO(C104)2.8H20.
Summary of the present invention
Accordingly, the present invention provides a process for acylation of substituted or unsubstituted alkyl, aryl, alkyl aryl or heteroaryl compounds using substituted or unsubstituted carboxylic acid anhydride or carboxylic acid as an acylating agent in the presence of zirconium (IV) compound as a catalyst at a temperature range of 0 to 120°C with or without using a solvent.
Brief description of the accompanying figures
Figure 1: represents reaction of 2-naphthol with acetic anhydride at room temperature and solvent free condition under the influence of zirconium catalyst
Figure 2: represents reaction of 2,6-Di-tert-butyl-4-methyphenol and 2,6-Di-tert-butyl-4-methoxyphenol with different anhydride in presence of ZrO(ClO4)2 as catalyst at room temperature and under solvent free condition.
Figure 3: represents reaction of anisole with different anhydrides under solvent free condition.
Detailed description of the preferred embodiment
In accordance to the objectives, the present invention deals with a process for the acylation of various substrates using in zirconium (IV) compound as a catalyst, the said process comprising steps of:
a) adding the zirconium (IV) compound to the substrate in the presence or absence of a solvent at an ambient temperature,
b) adding the acylating reagent to step (a) mixture,
c) stirring the mixture of step (b) at a temperature in the range o f 0 to 120°C for a time period of 0.1 mts to 8 hrs, and
d) isolating the acylated product from step (c) reaction mixture by conventional method.
In another embodiment of the present invention, the solvent used is selected from a group consisting of chlorinated solvent such as methylene chloride, chloroform, and 1,2-dichloroethane, aprotic polar solvent such as acetontrile (CH3CN), aromatic
solvent such as benzene toluene, xylene, and etheral solvent such as diethylether, diisopropylether or tetrahydrofuran.
In yet another embodiment of the present invention, the substrate used is selected from a group consisting of substituted or unsubstituted alkyl, alkyl aryl, aryl or heteroaryl compounds.
In still another embodiment of the present invention, the temperature of the reaction is an ambient temperature in the range of 0 to 120°C.
In yet another embodiment of the present invention, the alkyl compound used may be saturated or unsaturated.
In still another embodiment of the present invention, the compound used may be acyclic or cyclic.
In yet another embodiment of the present invention, the alkyl compounds is an aliphatic alcohol selected from allylic, propargylic or alcohols containing chiral center.
In still another embodiment of the present invention, the alkyl aryl compounds is an alcohol, may have chiral center.
In yet another embodiment of the present invention, the substitution on the alkyl compound used is selected from a group consisting of fiuoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol sulphonic or combination thereof.
In still another embodiment of the present invention, substitution on the aryl compound used is selected from a group consisting of fiuoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol, sulphonic or combination thereof.
In yet another embodiment of the present invention, the substitution on the alkyl aryl compound used is selected from a group consisting of fiuoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol, sulphonic or combination thereof.
In still another embodiment of the present invention, the substitution on the hetroaryl compound used is selected from a group consisting of fiuoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol sulphonic or combination thereof.
In yet another embodiment of the present invention, the acylating reagent used is selected from a group consisting of substituted or unsubstituted aliphatic or aromatic carboxylic acid, its anhydride or mixed anhydride.
In still another embodiment of the present invention, aliphatic carboxylic acid used is acetic acid or its derivative.
In yet another embodiment of the present invention, aliphatic carboxylic anhydride used is acetic anhydride or its derivative.
In still another embodiment of the present invention, the aromatic carboxylic acid used is benzoic acid or its derivative.
In yet another embodiment of the present invention, the aromatic carboxylic acid anhydride used is benzoic anhydride or its derivative.
In still another embodiment of the present invention, the weight ratio of the catalysts to substrate used is in the range of 1: 10 to 1:20,000.
In yet another embodiment of the present invention, the weight ratio of the catalysts to substrate used is preferably in the range of 1: 100.
In still another embodiment of the present invention, the molar ratio of acylating anhydrides reagent to substrate used is in the range of 1:1 to 1.5.
In yet another embodiment of the present invention, the molar ratio of acylating acid reagent to substrate used is in the range of 1:5 to 35.
In still another embodiment of the present invention, the molar ratio of substrate to solvent used is in the range of 1:1 to 100.
In yet another embodiment of the present invention, the molar ratio of substrate to solvent used is preferably in the range of 1:10.
The present invention is illustrated with reference to the examples, which should not be construed to limit the scope of the present invention.
In example 1, various zirconium-derived catalyst were used for acetylation of 2-naphthol using 1 equivalent of acetic anhydride at room temperature and solvent free condition.
In example 2, the acetylation of 2-naphthol and 2,4-dinitrophenols was carried out using acetic anhydride using catalytic amount of ZrO(C104)2.8H20 in presence and absence of solvent.
In example 3, the catalytic efficiency of ZrO(C104)2-8H20 was ascertained as low as 0.005 mol % for the acetylation of 2-naphthol with acetic anhydride at room temperature and under solvent free condition.
In example 4, structurally diverse phenols containing electron withdrawing, electron donating and sterically hindered groups, thiols and substituted amines were acetylated at room temperature in presence of 1 mol % of ZrO(C104)2-8H20 and ZrCU under solvent free conditions.
In example 5, different aliphatic and aromatic anhydrides were used for acylation of 2-naphthol and 4-nitrophenol in presence of ZrO(C104)2-8H20 and ZrCU catalyst at room temperature.
In example 6, different alcohols containing chiral center, allylic and propargyllic groups were used for acetylation with acetic anhydride at room temperature using catalytic amount of ZrO(C104)2.8H20 and ZrCU.
In example 7, 1 mol % of ZrO(C104)2.8H20 was used for isobutyrlation of different alcohols and phenols under mild conditions.
In example 8, 1 mol % of ZrO(C104)2.8H20 was used for pivalation of different alcohols and phenols under mild conditions.
In example 9, 1 mol % of ZrO(C104)2.8H20 was used for benzoylation of different alcohols and phenols under mild conditions.
In example 10, acetylation of different alcohols was carried out directly with acetic acid in presence of ZrO(C104)2.8H20 as a catalyst.
In example 11, sterically hindered substrates were acylated using different acid anhydrides and the effect of R group was seen as indicated with the increase in reaction time with increase in the size of R.
In example 12, acylation of anisole was carried out in presence of 1 mol % of ZrO(C104)2.8H20 using different anhydrides under solvent free conditions.
Example 1:
Acetylation of 2-naphthol (1 equivalent) with acetic anhydride (1 equivalent) catalyzed by various zirconium (IV) salts was carried out at room temperature and under solvent free conditions for the stated period and the results are summarized as below. (Refer to Figure 1 of accompanying drawings).

(Table Removed)
Example 1 (Entry 1-11) IR (KBr) 1755 cm"1; *H NMR (CDCI3) 5 2.36 (s, 3H), 7.24 (d, J = 8.85 Hz, 1H), 7.47 (m, 2H), 7.56 (s, 1H), 7.78 (m, 3H); EIMS (m/z) 186 (M+), 144(100).
Example 2:
To find out the feasibility of acylation reactions in different solvents the reactions were carried for acetylation of 2-naphthol (1) and 2,4-dinitrophenol (2) with 1 equivalent of acetic anhydride in presence of 1 mol% of ZrO(C104)2-8H20. The results of which are summarized in table below.
Example 2 (Entry 1-6) IR (KBr) 1755 cm"1; 'H NMR (CDCI3) 5 2.36 (s, 3H), 7.24 (d, J = 8.85 Hz, IH), 7.47 (m, 2H), 7.56 (s, IH), 7.78 (m, 3H); EMS (m/z) 186 (M+), 144 (100).
Example 2 (Entry 7-12) IR (Neat) 1785 cm"1; 'H NMR (CDC13) 5 2.43 (s, 3H), 7.50 (d, J= 8.90 Hz, IH), 8.54 (d, J= 8.90 Hz, IH), 8.96 (s, IH); EIMS (m/z) 226 (M+), 43 (100).
Example 3:
To evaluate the catalytic efficiency of ZrO(C104)2.8H20 the reactions were carried out using 1 equivalent of 2-naphthol (1) and 1 equivalent of acetic anhydride with varying
^ amount of the catalyst under solvent free conditions at room temperature. The reactions were carried out at a maximum of 250-mmole scale and the amount of catalyst used was as low as 0.005 mol% wherein acetylation proceeded quantitatively in 10 minutes (entry 5).

(Table Removed)
Example 3 (Entry 1-5) IR (KBr) 1755 cm"1; 'H NMR (CDC13) 5 2.36 (s, 3H), 7.24 (d, J= 8.85 Hz, IH), 7.47 (m, 2H), 7.56 (s, IH), 7.78 (m, 3H); EMS (m/z) 186 (M+), 144 (100).
Example 4:
The catalytic efficiency of ZrO(C104)2.8H20 and ZrCUcatalyst were further tested by carrying out the acetylation of various phenols, thiols and amines. The reactions were carried out using 1 equivalent of substrate and 1 or 1.5 equivalent of acetic anhydride with 0.1 mol % to 1 mol % of the catalyst under solvent free conditions at room temperature. Excellent results were obtained in most of the cases. The results are summarized in table below.

(Table Removed)
a Substrate : Acetic anhydride
Example 4 (Entry 1) ER (KBr) 1765 cm"1; !H NMR (CDC13) 6 2.45 (s, 3H), 7.23-7.25 (d, J = 6.59 Hz, IH), 7.43-7.55 (m, 3H), 1.12-1.15 (d, J= 8.29 Hz, IH), 7.84-7.88 (m, 2H); EIMS (m/z) 186 (M+), 144 (100).
Example 4 (Entry 2) IR (KBr) 1755 cm"1; 'H NMR (CDCI3) 5 2.36 (s, 3H), 7.24 (d, J = 8.85 Hz, IH), 7.47 (m, 2H), 7.56 (s, IH), 7.78 (m, 3H); EIMS (m/z) 186 (M+), 144 (100).
Example 4 (Entry 3) IR (KBr) 1761 cm"1; !H NMR (CDC13) 5 2.27 (s, 3H), 3.79 (s, 3H), 6.88 (d,J= 8.8 Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H); EIMS (m/z) 166 (M+), 124 (100).
Example 4 (Entry 4) IR (neat) 1760 cm'1; 'H NMR (CDC13) 5 2.29 (s, 3H), 6.97 (d, J = 8.7 Hz, 2H), 7.48 (d, 7= 8.1 Hz, 2H); EIMS (m/z) 216(M+), 172(100).
Example 4 (Entry 5) IR (KBr) 1764, 1684 cm"1; 1H NMR (CDC13) 5 2.33 (s, 3H), 2.60 (s, 3H), 7.20 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.6 Hz, 2H); EIMS (m/z) 178 (M+), 121(100).
Example 4 (Entry 6) IR (KBr) 1756, 1716 cm"1; lH NMR (CDCI3) 5 2.32 (s, 3H), 3.92 (s, 3H), 7.18 (d, J= 9 Hz, 2H), 8.08 (d, J= 9 Hz, 2H); EIMS (m/z) 194 (M+), 121(100).
Example 4 (Entry 7) IR (neat) 2229, 1768 cm"1; 1H NMR (CDCI3) 5 2.33 (s, 3H), 7.25 (d, J= 8.5 Hz, 2H), 7.70 (d, J= 8.5 Hz, 2H); EIMS (m/z) 161 (M+), 43 (100).
Example 4 (Entry 8) IR (neat) 1777 cm"1; *H NMR (CDC13) 8 2.35 (s, 3H), 7.23 (d, J = 8.10 Hz, 1H), 7.37 (t, /= 7.75 Hz, 1H), 7.64 (t, J= 7.75 Hz, 1H), 8.06 (d, J = 8.10 Hz, 1H,); EMS (m/z) 181 (M+), 139 (100).
Example 4 (Entry 9) IR (KBr) 1762 cm"1; *H NMR (CDCI3) 5 2.36 (s, 3H), 7.29 (d, J = 8.8 Hz, 2H), 8.28 (d, J= 9.2 Hz, 2H); EIMS (m/z) 181 (M+), 43 (100).
Example 4 (Entry 10) IR (KBr) 1763 cm"1; 'H NMR (CDCI3) 5 1.33 (s, 18H), 2.31 (s, 3H), 2.33 (s, 3H), 7.11 (s, 2H); EMS (m/z) 262 (M+), 43 (100).
Example 4 (Entry 11) IR (KBr) 1762 cm"1; 1H NMR (CDCI3) 5 1.33 (s, 18H), 2.33 (s, 3H), 3.79 (s, 3H), 6.86 (s, 2H); EMS (m/z) 278 (M+), 43 (100).
Example 4 (Entry 12) IR (neat) 1759 cm"1; !H NMR (CDCI3) 5 2.10 (s, 6H), 2.25 (s, 3H), 2.31 (s, 3H), 6.86 (s, 2H); EIMS (m/z) 178 (M+), 43 (100).
Example 4 (Entry 13) acetate IR (KBr) 1761 cm"1; 'H NMR (CDC13) 5 2.04 (s, 3H), 2.16 (s, 3H), 2.23 (s, 3H), 2.31 (s, 3H), 6.93 (s, 2H); EMS (m/z) 178 (M+), 135 (100).
Example 4 (Entry 14) IR (KBr) 1762 cm"1; ]H NMR (CDC13) 5 2.29 (s, 6H), 7.10 (s, 4H); EIMS (m/z) 194 (M+), 110 (100).
Example 4 (Entry 15) IR (neat) 1772 cm"1; 1H NMR (CDCI3) 5 2.25 (s, 6H), 7.19 (m, 4H); EIMS (m/z) 194 (M+), 43(100).
Example 4 (Entry 16) IR (neat) 1768, 1601 cm-1; 'HNMR (CDC13) 5 2.28 (s, 6H), 6.92 (s, 1H), 6.98 (d, J= 6.28 Hz, 2H), 7.37 (t, 7= 8.16 Hz, 1H); EIMS (m/z) 194 (M+), 43 (100).
Example 4 (Entry 17) IR (KBr) 1772 cm"1; 'H NMR (CDCI3) 5 1.31 (s, 9H), 2.28 (s, 3H), 2.29 (s, 3H), 7.08 (s, 1H), 7.13 (d, /= 8.5 Hz, 1H), 7.26 (d, J= 8.35 Hz, 1H); EIMS (m/z) 250 (M+), 43 (100).
Example 4 (Entry 18) IR (KBr) 1765, 1608 cm"1; 'H NMR (CDC13) 6 2.27 (s, 9H), 7.11 (d, J= 8.03 Hz, 2H), 7.25 (t, J= 7.50 Hz, 1H); EMS (m/z) 252 (M+), 43(100).
Example 4 (Entry 19) IR (KBr) 1742, 1646, 1522 cm"1; !H NMR (CDCI3) 5 1.24 (t, J = 7.11 Hz, 3H), 2.00 (s, 3H), 2.29 (s, 3H), 3.12 (d, J = 5.67 Hz, 2H), 4.16 (q, J= 7.03 Hz, 2H), 4.86 (m, 1H), 5.96 (d, J= 7.10 Hz, 1H), 7.01 (d, J= 8.45 Hz, 2H), 7.12 (d, J= 8.42 Hz, 2H); CMS (m/z) 294 (MH+), 61(100); APCMS (m/z) 294.1 (MH+).
Example 4 (Entry 20) IR (KBr) 1748, 1641, 1526 cm"1; 'H NMR (CDCI3) 6 1-27 (t, J = 7.13 Hz, 3H), 2.28 (s, 3H), 3.26 (m, 2H), 4.21 (q, J= 7.11 Hz, 2H), 5.06 (m, 1H), 6.63 (d, J= 7.10 Hz, 1H), 7.01 (d, J= 8.34 Hz, 2H), 7.16 (d, J= 8.42 Hz, 2H), 7.47 (m, 3H), 7.74 (d, J= 7.09 Hz, 2H); APCMS (m/z) 356 (MH+).
Example 4 (Entry 21) IR (neat) 1707 cm"1; !H NMR (CDC13) 8 2.40 (s, 3H), 7.40 (m, 5H); EIMS (m/z) 152 (M+), 43 (100).
Example 4 (Entry 22) IR (neat) 1708 cm-1; 1H NMR (CDC13) 5 2.35 (s, 3H), 2.38 (s, 3H), 7.20 (d, J = 8.0 Hz, 2H, ), 7.28 (d, J = 8.1 Hz, 2H); EMS (m/z) 166 (M+), 43(100).
Example 4 (Entry 23) IR (neat) 1705 cm-1; 1H NMR (CDC13) 5 2.38 (s, 3H), 3.84 (s, 3H), 6.93 (d, J= 8.57 Hz, 1H), 7.31 (d, J = 8.57 Hz, 1H); EIMS (m/z) 182 (M+), 43 (100).
Example 4 (Entry 24) IR (neat) 1691 cm-1; 'H NMR (CDC13) 6 2.33 (s, 3H), 4.11 (s, 2H), 7.26 (m, 5H); EIMS (m/z) 166 (M+), 43 (100).
Example 4 (Entry 25) IR (KBr) 1701 cm-1; 'H NMR (CDC13) 5 2.30 (s, 3H), 7.18 (t, J = 7.86 Hz, 3H), 7.65 (t,J= 7.86 Hz, 1H), 8.22 (d, 7- 8.50 Hz, 1H), 8.77 (d, J= 8.50 Hz, 1H), 10.33 (s, 1H); EIMS (m/z) 180 (M+), 43(100).
Example 4 (Entry 26) IR (KBr) 1745 cm-1; 1H NMR (CDC13) 5 2.38 (s, 3H), 8.48 (d, J = 9.40 Hz, 2H), 9.09-9.15 (several peaks, 3H), 10.65 (s, 1H); EIMS (m/z) 225 (M+), 43(100).
Example 5:
Acylation of 2-naphthol (1) and 4-nitrophenol (3), 1 equivalent each with 1 equivalent of various anhydrides like acetic, propionic, wo-butyric, pivalic and benzoic anhydrides was carried out at room temperature in absence of solvent (except for entry 5 and 10 where an organic solvent was used) under the catalytic influence of ZrO(C104)2.8H20 and ZrCU. The results are summarized in table below.

(Table Removed)
Example 5 (Entry 1) IR (KBr) 1755 cm"1; 'H NMR (CDC13) 8 2.36 (s, 3H), 7.24 (d, J = 8.85 Hz, 1H), 7.47 (m, 2H), 7.56 (s, 1H), 7.78 (m, 3H); EIMS (m/z) 186 (M+), 144 (100).
Example 5 (Entry 2) IR (KBr) 1758 cm"1; 'H NMR (CDC13) 5 1.31 (t, 7 = 7.49 Hz, 3H ), 2.65 (q, J= 7.53 Hz, 2H), 7.23 (d, J = 8.89 Hz, 1H), 7.47 (m, 2H), 7.55 (s, 1H), 7.80 (d, J= 9.04 Hz, 1H), 7.85 (m, 2H); EIMS (m/z) 200 (M+), 144 (100).
Example 5 (Entry 3) IR (KBr) 1748 cm"1; 'H NMR (CDC13) 8 1.36 (d, J= 7.00 Hz, 6H), 2.86 (q, J= 7.00 Hz, 1H), 7.21 (d, J= 8.90 Hz, 1H), 7.47 (m, 2H,), 7.54 (s, 1H), 7.80 (d,7= 8.90 Hz, 1H), 7.85 (d, J- 8.90 Hz, 2H); EIMS (m/z) 214 (M+), 144 (100).
Example 5 (Entry 4) IR (KBr) 1748 cm-1; 1H NMR (CDCI3) 8 1.41 (s, 9H), 7.20 (d, J = 8.71 Hz, 1H), 7.46 (m, 2H), 7.53 (s, 1H), 7.79 (d, J= 8.71 Hz, 1H), 7.85 (d, J= 9.64 Hz, 2H); EMS (m/z) 228 (M+), (100).
Example 5 (Entry 5) IR (KBr) 1733 cm"1; 'H NMR (CDCI3) 8 7.36 (d, J= 8.86 Hz, 1H), 7.48 (m, 2H), 7.54 (s, 1H), 7.63 (m, 3H), 7.83 (m, 3H), 8.13 (d, J = 8.86 Hz, 1H), 8.27 (d, J= 8.86 Hz, 1H); EIMS (m/z) 248 (M+), 105(100).
Example 5 (Entry 6) IR (KBr) 1762 cm"1; !H NMR (CDCI3) 8 2.36 (s, 3H), 7.29 (d, J = 8.8 Hz, 2H), 8.28 (d, J= 9.2 Hz, 2H); EIMS (m/z) 181 (M+), 43 (100).
Example 5 (Entry 7) IR (KBr) 1754 cm"1; ]H NMR (CDCI3) 8 1.28 (t, J = 7.50 Hz, 3H), 2.65 (q, J= 7.50 Hz, 2H), 7.28 (d, J= 9.30 Hz, 2H), 8.28 (d, J = 9 Hz, 2H); EIMS (m/z) 195 (M+), 57(100).
Example 5 (Entry 8) IR (neat) 1764 cm"1; 'H NMR (CDCI3) 8 1.34 (d, J = 6.96 Hz, 6H), 2.85 (m, p, J= 6.98 Hz, 1H), 7.28 (d, J= 9 Hz, 2H), 8.28 (d, J= 9 Hz, 2H,); EIMS (m/z) 209 (M+), 43 (100).
Example 5 (Entry 9) ER (KBr) 1757 cm"1; ]H NMR (CDCI3) 8 1.38 (s, 9H), 7.26 (d, J = 9 Hz, 2H), 8.28 (d, J= 9 Hz, 2H); EIMS (m/z) 223 (M+), 57 (100).
Example 5 (Entry 10) IR (KBr) 1740 cm"1; !H NMR (CDCI3) 8 7.43 (d, J=9 Hz, 2H), 7.56 (t, /= 7.65 Hz, 2H), 7.70 (t, J= 7.35 Hz, 2H), 8.21 (d, J = 7 Hz, 2H), 8.34 (d, J = 9 Hz, 2H); EIMS (m/z) 243 (M+), 105 (100).
Example 6:
Acetylation of various structurally diverse alcohols with 1 equivalent of acetic anhydride was carried out mild conditions with catalytic amount of ZrO(C104)2-8H20 and ZrCU and were found to be effective for secondary and tertiary alcohols, allylic and propargylic substrates and optically active compounds. The reactions were carried out at room temperature in absence of solvent (except for entry 3, 6, 12-15 and 17 where a organic solvent was used), the results of which are summarized in table below.

(Table Removed)
Example 6 (Entry 1) IR (neat) 1740 cm-1; 1H NMR (CDC13) 5 2.10 (s, 3H), 5.10 (s, 2H), 7.35 (m, 5H); EIMS (m/z) 150 (M+), 43(100).
Example 6 (Entry 2) IR (neat) 1740 cm"1; !H NMR (CDC13) 5 2.02 (s, 3H), 2.92 (t, J = 7.09 Hz, 2H), 4.27 (t, J = 7.09 Hz, 2H), 7.29 (m, 5H); EIMS (m/z) 104 (M-60+), 43(100).
Example 6 (Entry 3) IR (neat) 1744 cm"1; 1H NMR (CDCI3) 5 1.53 (d, J= 6.6 Hz, 3H), 2.06 (s, 3H), 5.88 (q, J= 6.6 Hz, 1H), 7.30 (m, 5H); EIMS (m/z) 104 (M-60+), 43(100).
Example 6 (Entry 4) IR (neat) 1739, 1696 cm-1; 'H NMR (CDC13) 5 2.21 (s, 3H), 6.86 (s, 1H), 7.34-7.54 (several peaks, 8H), 7.94 (d, J= 8.69 Hz, 2H); EIMS (m/z) 254 (M+), 105(100).
Example 6 (Entry 5) IR (neat) 1737 cm-1; 'H NMR (CDCI3) 5 0.87 (t, J= 7.38 Hz, 3H), 1.73-1.99 (several peaks, 2H), 2.06 (s, 3H), 5.66 (t, J= 6.86 Hz, 1H), 7.28 (m, 5H); EIMS (m/z) 178 (M+), 43(100).
Example 6 (Entry 6) IR (neat) 1732 cm"1; !H NMR (CDC13) 5 1.42 (m, 10H), 1.99 (s, 3H), 2.12 (d,/= 11.39 Hz, 3H); EIMS (m/z) 125 (M-31+), 43(100).
Example 6 (Entry 7) IR (Neat) 1742 cm"1; :H NMR (CDCI3) 6 0.91 (d, 3H), 1.18 (m, 1H), 1.48 (m, 4H), 5.09 (t, J= 7.0 Hz, 1H); EIMS (m/z) 199 (M+l+), 43 (100).
Example 6 (Entry 8) IR (neat) 1735 cm"1; ]H NMR (CDCI3) 5 0.76 (d, J= 6.58 Hz, 3H), 0.90 (d, J= 6.32 Hz, 6H), 1.01 (m, 4H), 1.36 (m, 1H), 1.50 (m, 1H), 1.67 (m, 2H), 1.88 (m, 1H), 2.04 (s, 3H), 4.66 (m, 1H); EIMS (m/z) 138(M-60+), 43(100).
Example 6 (Entry 9) IR (neat) 1708, cm"1; !H NMR (CDCI3) 5 0.84 - 0.86 (d, J= 6.64 Hz, 3 H), 0.92 - 0.95 (d, J= 5.33 Hz, 6 H), 1.26-1.31 (m, 2 H), 1.45 - 1.60 (m, 2 H), 1.73 - 1.75 (m, 1 H), 1.88 - 1.889 (m, 1 H), 2.03 (s, 3 H), 4.99 - 5.05 (m, 1 H); EIMS (m/z) 138 (M+-60), 43 (100).
Example 6 (Entry 10) IR (Neat) 1723 cm"1; 'H NMR (CDCI3) 5 0.83 (s, 3H), 0.87 (s, 3H), 0.90 (s, 3H), 1.25 (m, 4H), 1.71 (m, 2H), 1.93 (m, 1H), 2.06 (s, 3H), 2.35 (m, 1H), 4.88 (d, J= 9.79 Hz, 1H); EIMS (m/z) 196 (M+), 43(100).

Example 6 (Entry 11) IR (KBr) 1733 cm"1; 'H NMR (CDCl3) 5 1.66 (m, 6H), 1.96 (s, 3H), 2.11 (m, 9H); EIMS (m/z) 194 (M+), 134 (100).
Example 6 (Entry 12) IR (Neat) 1741 cm"1; 'H NMR (CDCI3) 5 1.60 (s, 3H), 1.68 (s, 3H), 1.70 (s, 3H), 2.05 (s, 3H), 2.09 (m, 4H), 4.59 (d, J= 7.1 Hz, 2H), 5.08 (m, 1H), 5.34 (t,/= 7.1 Hz, 1H);EIMS (m/z) 136 (M-60+), 693 (100).
Example 6 (Entry 13) IR (neat) 1730 cm"1; 'H NMR (CDC13) 5 1.48 (m, 9), 1.96-2.06 (several peaks, 4H), 2.05 (s, 3H), 5.13 (m, 3H), 5.93 (m, 1H).
Example 6 (Entry 14) IR (neat) 1737 cm"1; 'H NMR (CDC13) 5 1.71 (s, 3H), 1.76 (s, 3 H), 2.05 (s, 3H), 4.57 (d, J= 8.20 Hz, 2H), 5.35 (m, 1H).
Example 6 (Entry 15) IR (neat) 1735 cm-1; 1H NMR (CDCI3) 5 1.71 (s, 3H), 1.76 (s, 3H), 2.05 (s, 3H), 4.57 (d, /= 8.20 Hz, 2H), 5.35 (m, 1H).
Example 6 (Entry 16) IR (neat) 1740 cm"1;1H NMR (CDC13) 5 2.11 (s, 3H), 2.51 (t, J = 2.40 Hz, 1H), 4.68 (d, J= 2.38 Hz, 2H).
Example 6 (Entry 17) IR (neat) 1712 cm"1; 'H NMR (CDCI3) 5 1.67 (s, 6H), 2.03 (s, 3H), 2.55 (s, 1H).
Example 6 (Entry 18) IR (neat) 1742 cm"1; 'H NMR (CDCI3) 6 1.03 (t, J = 7.42 Hz, 3H), 1.66 (s, 3H), 1.90 (several peaks, 2H), 2.03 (s, 3H), 2.56 (s, 1H).
Example 6 (Entry 19) IR (neat) 1744 cm"1; 'H NMR (CDC13) 5 1.63 (several peaks, 6H), 1.81-1.89 (m, 2H), 2.05 (s, 3H), 2.12 (m, 2H), 2.60 (1H, s); EIMS (m/z) 123 (M-43+), 43(100).
Example 7:
To further extend the scope of this catalyst isobutyrlation of various alcohols and phenols with 1 equivalent of isobutyric anhydride was carried out in presence of 1 mol % ZrO(C104)2-8H20 at room temperature. The results are summarized in table below.
Entry Substrate Time (min) Yield (%)

(Table Removed)
Example 7 (Entry 1) IR (KBr) 1748 cm-1; 'H NMR (CDC13) 5 1.36 (d, J = 7.00 Hz, 6H), 2.86 (q, J = 7.00 Hz, IH), 7.21 (d,/= 8.90 Hz, IH), 7.47 (m, 2H,), 7.54 (s, IH), 7.80 (d,J= 8.90 Hz, IH), 7.85 (d, J= 8.90 Hz, 2H); EIMS (m/z) 214 (M+), 144 (100).
Example 7 (Entry 2) IR (neat) 1755 cm"1; 1H NMR (CDCI3) 8 1.30 (d, J = 7.00 Hz, 6H), 2.765 (m, p, J = 7.00 Hz, IH), 6.86 (d, J= 9 Hz, 2H), 6.97 (d, J = 9 Hz, 2H,); EIMS (m/z) 194 (M+), 57 (100).
Example 7 (Entry 3) IR (neat) 1764 cm"1; 1H NMR (CDCI3) 5 1.34 (d, J= 6.96 Hz, 6H), 2.85 (m, p, /= 6.98 Hz, IH), 7.28 (d, J= 9 Hz, 2H), 8.28 (d, J= 9 Hz, 2H,); EMS (m/z) 209 (M+), 43(100).
Example 7 (Entry 4) IR (neat) 1754 cm"1;1'H NMR (CDC13) 5 1.34 (d, J= 7.00 Hz, 6H), 2.08 (s, 6H), 2.24 (s, 3H), 2.84 (m, J= 7.00 Hz, IH), 6.84 (s, 2H); EIMS (m/z) 206 (M+), 43 (100).
Example 7 (Entry 5) IR (KBr) 1755 cm"1; 'H NMR (CDC13) 5 1.34 (s, 18H), 1.39 (d, J= 7.00 Hz, 6H), 2.33 (s, 3H), 2.87 (m, J = 7.00 Hz, IH), 7.13 (s, 2H); EIMS (m/z) 220 (M-70), 43(100).
Example 7 (Entry 6) IR (Neat) 1751 cm-1; 1H NMR (CDC13) 5 1.34 (s, 18H), 1.39 (d, J = 7.00 Hz, 6H), 2.86 (m, J= 7.00 Hz, IH), 3.81 (s, 3H), 6.87 (s, 2H); EIMS (m/z) 306 (M+), 43(100).
Example 7 (Entry 7) IR (neat) 1736 cm-1; 1H NMR (CDCI3) 5 1.18 (d, J= 7.00 Hz, 6H), 1.22 (m, J= 7.00 Hz, IH), 5.11 (s, 2H), 7.34 (m, 5H); EIMS (m/z) 178 (M)+, 91 (100).
Example 7 (Entry 8) IR (neat) 1734 cm"1; lH NMR (CDC13) 5 1.10 (d, J= 7.00 Hz, 6H), 2.47 (m, J= 7.00 Hz, IH), 2.88 (t, J = 6.97 Hz, 2H), 4.25 (t, J= 6.97 Hz, 2H), 7.22 (m, 5H); EIMS (m/z) 104 (M-88), (100).
Example 7 (Entry 9) IR (neat) 1731 cm"1; !H NMR (CDC13) 8 0.76 (d, J= 6.94 Hz, 3H), 0.91 (d, J= 6.11 Hz, 6H), 1.01 (m, 3H), 1.15 (d, /= 6.90 Hz, 6H), 1.39 (m, 2H), 1.67 (m, 2H), 1.92 (m, 2H), 2.51 (m, J= 6.97 Hz, IH), 4.67 (m, IH); EIMS (m/z) 138 (M-88), 43 (100).
Example 7 (Entry 10) IR (neat) 1734 cm-1; 1H NMR (CDCI3) 5 0.83 (s, 3H), 0.91 (d, J = 10.30 Hz, 6H), 1.17 (d, J = 6.95 Hz, 6H), 1.24 (s, 3H), 1.71 (m, 2H), 1.95 (m, IH), 2.34 (m, IH), 2.56 (m, J = 6.98 Hz, IH), 4.88 (d, J = 9.79 Hz, IH); EIMS (m/z) 154 (M-85), 57 (100).
Example 7 (Entry 11) IR (neat) 1741 cm"1; !H NMR (CDCI3) 8 1.17 (d, J= 6.97 Hz, 6H), 1.39 (m, IH), 1.51 (m, IH), 1.62 (m, 4H), 1.92 (m, 2H), 2.08 (m, 2H), 2.52 (m, J = 6.97 Hz, IH), 2.57 (s, IH); EMS (m/z) 124 (M-70), 43(100).
Example 7 (Entry 12) IR (neat) 1742 cm"1; *H NMR (CDCI3) 8 1.15 (d, J = 6.97 Hz, 6H), 1.67 (s, 6H), 2.50 (m, 2H).
Example 7 (Entry 13) IR (neat) 1742 cm"1; 1H NMR (CDCI3) 8 1.03 (t, J= 7.4 Hz, 3H), 1.15 (d, J = 6.95 Hz, 6H), 1.65 (s, 3H), 1.92 (m, J = 7.4 Hz, 2H), 2.50 (m, J = 6.95 Hz, IH), 2.55 (s, IH).
Example 7 (Entry 14) IR (neat) 1728 cm"1; 'H NMR (CDC13) 6 1.11 (d, 7= 6.96 Hz, 6H), 1.66 (m, 6H), 2.09 (m, 6H), 2.15 (bs, 3H), 2.41 (m,J= 6.96 Hz, 1H).
Example 8:
To further extend the scope of this catalyst pivalation of various alcohols and phenols with 1 equivalent of pivalic anhydride was carried out in presence of 1 mol % ZrO(C104)2-8H20 at room temperature. The results are summarized in table below.
Entry Substrate Time (min) Yield (%)

(Table Removed)
Example 8 (Entry 1) IR (KBr) 1748 cm'1; !H NMR (CDC13) 5 1.41 (s, 9H), 7.20 (d, J = 8.71 Hz, 1H), 7.46 (m, 2H), 7.53 (s, 1H), 7.79 (d, 7 = 8.71 Hz, 1H), 7.85 (d, 7 = 9.64 Hz, 2H); EMS (m/z) 228 (M+), (100).
Example 8 (Entry 2) IR (KBr) 1757 cm-1; !H NMR (CDC13) 5 1.38 (s, 9H), 7.26 (d, 7 = 9 Hz, 2H), 8.28 (d, 7 = 9 Hz, 2H); EIMS (m/z) 223 (M+), 57 (100).
Example 8 (Entry 3) IR (neat) 1749 cm"1; 1H NMR (CDC13) 5 1.39 (s, 9H), 2.08 (s, 6H), 2.25 (s, 3H), 6.84 (s, 2H); EIMS (m/z) 220 (M+), 57 (100).
Example 8 (Entry 4) IR (neat) 1732 cm"1; 'H NMR (CDCI3) 5 1.22 (s, 9H), 5.10 (s, 2H), 7.31 (m, 5H); EIMS (m/z) 105 (M-87), 57 (100).
Example 8 (Entry 5) IR (neat) 1728 cm"1; 1H NMR (CDCI3) 5 1.53 (s, 9H), 2.92 (t, 7 = 6.9 Hz, 2H), 4.27 (t, 7 = 6.9 Hz, 2H), 7.22 (m, 5H); EIMS (m/z) 104 (M-202), (100).
Example 8 (Entry 6) IR (neat) 1725 cm"1; 'H NMR (CDC13) 8 0.75 (d, y = 6.9 Hz, 3H), 0.90 (d, y = 6.9 Hz, 6H), 1.03 (m, 1H), 1.19 (s, 9H), 1.45 (m, 2H), 1.68 (m, 2H), 1.96 (m, 2H), 4.62 (m, 1H); EIMS (m/z) 139 (M-101), 83 (100).
Example 8 (Entry 7) IR (neat) 1728 cm-1; 1H NMR (CDCI3) 5 0.83 (s, 3H), 0.88 (s, 3H), 0.91 (s, 3H), 1.21 (s, 9H), 1.28 (m, 2H), 1.71 (m, 3H), 1.97 (m, 1H), 2.34 (m, 1H), 4.85 (d, y= 9.58 Hz, 1H); EIMS (m/z) 154 (M-85), 57 (100).
Example 8 (Entry 8) IR (neat) 1724 cm"1; 1H NMR (CDCI3) 5 1.14 (s, 9H), 1.64 (m, 9H), 2.12 (m, 6H); EIMS (m/z) 136 (M-101), 135 (100).
Example 9:
To further extend the scope of this catalyst, benzoylation of various alcohols and phenols with 1-1.5 equivalent of benzoic anhydride per hydroxyl group was carried out in presence of 1 mol % ZrO(C104)2.8H20. The results are summarized in table below.
Entry Substrate Amt of BA, Temp, Solvent Time Yield
(min) (%)

(Table Removed)
Example 9 (Entry 1) IR (KBr) 1730 cm-1; 'H NMR (CDC13) 8 7.29 (s, 4H), 7.53 (t, J = 7.57 Hz, 4H), 7.65 (t, J= 7.35 Hz, 2H), 8.21 (d, J= 7.26 Hz, 4H); EIMS (m/z) 318 (M+), 105 (100).
Example 9 (Entry 2) IR (KBr) 1736 cm-1; 1H NMR (CDCI3) 5 7.17 (m, 3H), 7.50 (t, J = 7.86 Hz, 5H), 7.64 (t, J= 7.37 Hz, 2H), 8.20 (d, J = 7.28 Hz, 4H); EIMS (m/z) 318 (M+), 105 (100).
Example 9 (Entry 3) IR (KBr) 1738 cm"1; 'H NMR (CDCI3) 5 7.38 (m, 8H), 7.53 (t, J = 7.35 Hz, 2H), 8.06 (d, /= 7.57 Hz, 2H); EIMS (m/z) 318 (M+), 105 (100).
Example 9 (Entry 4,5) IR (neat) 1730 cm"1; 1H NMR (CDC13) 8 2.15 (s, 6H), 2.29 (s, 3H), 6.91 (s, 2H), 7.51 (t, J= 7.61 Hz, 2H), 7.63 (t, J= 7.39 Hz, IH), 8.24 (d, J= 7.23 Hz, 2H); EMS (m/z) 240 (M+), 105 (100).
Example 9 (Entry 6,7) IR (neat) 1734 cm"1; 1H NMR (CDCI3) 8 2.08 (s, 3H), 2.15 (s, 3H), 2.27 (s, 3H), 6.99 (s, 2H), 7.50 (t, J= 7.5 Hz, 2H), 7.63 (t, J= 7.4 Hz, IH), 8.25 (d, J= 7.2 Hz, 2H); EIMS (m/z) 240 (M+), 105 (100).
Example 9 (Entry 8,9) IR (KBr) 1733 cm-1; 1H NMR (CDCI3) 8 7.36 (d, J= 8.86 Hz, IH), 7.48 (m, 2H), 7.54 (s, IH), 7.63 (m, 3H), 7.83 (m, 3H), 8.13 (d, J = 8.86 Hz, IH), 8.27 (d, J = 8.86 Hz, IH); EIMS (m/z) 248 (M+), 105(100).
Example 9 (Entry 10,11) IR (neat) 1739 cm"1; lH NMR (CDC13) 5 7.36 (d, J= 7.25 Hz, IH), 7.49 (m, 5H), 7.54 (s, IH), 7.64 (t, 7 = 7.39 Hz, IH), 7.76 (d, J= 8.19 Hz, IH), 7.88 (m, 2H), 8.32 (d, 7 = 7.23 Hz); EMS (m/z) 248 (M+), 105(100).
Example 9 (Entry 12,13) IR (KBr) 1740 cm-1; 1H NMR (CDCI3) 5 7.43 (d, 7=9 Hz,
2H), 7.56 (t, 7 = 7.65 Hz, 2H), 7.70 (t, 7 = 7.35 Hz, 2H), 8.21 (d, 7 = 7 Hz, 2H), 8.34 (d, 7 = 9 Hz, 2H); EIMS (m/z) 243 (M+), 105 (100).
Example 9 (Entry 14,15) !H NMR (CDCI3) 5 3.82 (s, 3H), 6.94 (d, 7 = 6.8 Hz, 2H),
7.12 (d, 7 = 6.8 Hz, 2H), 7.50 (t, 7 = 7.55 Hz, 2H), 7.62 (t, 7 = 6.2 Hz, IH), 8.19 (d, 7 =
7.1 Hz, 2H); EIMS (m/z) 228 (M+), 105 (100).
Example 9 (Entry 16,17) IR (neat) 1747 cm"1; 1H NMR (CDCI3) 5 7.38 (m, 2H), 7.51 (t, 7 = 7.40 Hz, 2H), 7.65 (m, 2H), 8.11 (dd, 7= 8.2, 1.45 Hz, IH), 8.20 (d, 7= 7.21 Hz, 2H); EIMS (m/z) 105 [(M+), (100)].
Example 9 (Entry 18,19) IR (neat) 1719 cm"1; 'H NMR (CDCI3) 5 5.41 (s, 2H), 7.48 (m, 8H), 8.14 (d, 7= 7.27 Hz, 2H); EMS (m/z) 212(M+), 105 (100).
Example 9 (Entry 20) IR (neat) 1719 cm"1; !H NMR (CDC13) 5 3.05 (t, 7 = 7.0 Hz, 2H), 4.51 (t, 7= 7.0 Hz, 2H), 7.27 (m, 5H), 7.38 (t, 7= 7.69 Hz, 2H), 7.50 (t, 7= 7.05 Hz, IH), 8.00 (d, 7= 7.81 Hz, 2H); EMS (m/z) 105 (M-121), 104 (100).
Example 9 (Entry 21,22) IR (neat) 1712, 1694 cm"1; *H NMR (CDCI3) 8 7.10 (s, IH), 7.48 (m, 11H), 8.01 (d, 7= 7.2 Hz, 2H), 8.12 (d, 7= 7.2 Hz, 2H); EIMS (m/z) 211(M-105), 105 (100).
Example 9 (Entry 23,24) IR (neat) 1714 cm"1; *H NMR (CDC13) 5 0.80 (d, 7= 7.0 Hz, 3H), 0.93 (dd,7= 7.0 Hz, 6H), 1.10 (m, 2H), 1.55 (m, 2H), 1.74 (m, 3H), 1.98 (m, IH),
2.13 (m, IH), 4.94 (m, IH), 7.44 (t, 7= 7.45 Hz, 2H), 7.55 (t, 7= 7.35 Hz, IH), 8.05 (d,
J= 7.15 Hz, 2H); EIMS (m/z) 139 (M-131), 105 (100).
Example 9 (Entry 25) IR (neat) 1719 cm"1; 'H NMR (CDCI3) 5 0.90 (s, 3H), 0.91 (s, 3H), 0.96 (s, 3H), 1.12 (m, IH), 1.35 (m, 2H), 1.77 (m, 2H), 2.13 (m, IH), 2.47 (m, IH), 5.14 (d, 7= 9.82 Hz, IH), 7.42 (t, 7= 7.47 Hz, 2H), 7.52 (t, 7= 7.31 Hz, IH), 8.06 (d, 7= 7.29 Hz, 2H); EIMS (m/z) 258 (M+), 105 (100).
Example 10:
Acylation of various alcohols using acetic acid directly under milder conditions were carried out in presence of 1 mol % of ZrO(C104)2.8H20 catalyst. Acetylation of alcohols can thus be achieved through a direct reaction with acetic acid in excellent yields. The results are summarized in table below.
Entry Substrate Amt (equiv.), Temp. Time
Yield

(Table Removed)
The spectral data of the above compounds are given below Example 6.

Example 11
Acylation of sterically hindered phenol such as 2,6-di-tert-butyl-4-methylphenol (4) and 2,6-di-tert-butyl-4-methylphenol (5) with equivalent quantities of different anhydrides like acetic, propionic, and i'so-butyric anhydrides was carried out at room temperature in absence of solvent under the catalytic influence of ZrO(C104)2-8H20. The rate of acylation with (RCO)2O decrease as R becomes larger in size and can be seen with the increasing reaction time as the R group increases from CH3 to C2H5 to (CH)3)2CH. The results are summarized in table below (See Figure 2).
(Table Removed)
Example 11 (Entry 1) IR (KBr) 1763 cm-1; 'H NMR (CDCI3) 5 1.33 (s, 18H), 2.31 (s, 3H), 2.33 (s, 3H), 7.11 (s, 2H); EIMS (m/z) 262 (M+), 43 (100).
Example 11 (Entry 2) IR (KBr) 1761 cm"1; !H NMR (CDC13) 5 1.32 (t, J= 7.60 Hz, 3H), 1.36 (s, 18H), 2.35 (s, 3H), 2.68 (q, J= 7.60 Hz, 2H), 7.14 (s, 2H); EIMS (m/z) 276 (M+), 57 (100).
Example 11 (Entry 3) IR (KBr) 1755 cm"1; 'H NMR (CDCI3) 8 1.34 (s, 18H), 1.39 (d, J= 7.00 Hz, 6H), 2.33 (s, 3H), 2.87 (m, J= 7.00 Hz, 1H), 7.13 (s, 2H); EIMS (m/z) 220 (M-70), 43(100).
Example 11 (Entry 4) IR (KBr) 1762 cm"1; ]H NMR (CDCI3) 5 1.33 (s, 18H), 2.33 (s, 3H), 3.79 (s, 3H), 6.86 (s, 2H); EIMS (m/z) 278 (M+), 43 (100).
Example 11 (Entry 5) IR (Neat) 1758 cm"1; 1'H NMR (CDC13) 5 1.29 (t, J= 7.60 Hz, 3H), 1.34 (s, 18H), 2.65 (q, J= 7.60 Hz, 2H), 3.80 (s, 3H), 6.87 (s, 2H); EIMS (m/z) 292 (M+), 57(100).
Example 11 (Entry 6) IR (Neat) 1751 cm"'; 1H NMR (CDCI3) 5 1.34 (s, 18H), 1.39 (d, J- 7.00 Hz, 6H), 2.86 (m, J= 7.00 Hz, IH), 3.81 (s, 3H), 6.87 (s, 2H); EIMS (m/z) 306 (M+), 43(100).
Example 12:
Acylation of anisole with equivalent quantities of different anhydrides like acetic, propionic, /so-butyric, pivalic and benzoic anhydrides was carried out at 100°C for 3-6 hours in absence of solvent under the catalytic influence of ZrO(C104)2-8H20. The results of which are summarized in table below (See Figure 3).
(Table Removed)
Example 12 (Entry 1) IR (Neat) 1676 cm"1; 1H NMR (CDCI3) 5 2.56 (s, 3H), 3.87 (s, 3H), 6.93 (d, J = 8.11 Hz, 2H), 7.94 (d, J= 7.97 Hz, 2H); EIMS (m/z) 150 (M+), 135 (100).
Example 12 (Entry 2) IR (Neat) 1679 cm-1; 1H NMR (CDCI3) 5 1.21 (t, J= 7.30 Hz, 3H), 2.94 (q, J= 7.30 Hz, 2H), 3.85 (s, 3H), 6.93 (d, J= 6.9 Hz, 2H), 7.95 (d, J= 6.9 Hz, 2H); EIMS (m/z) 164 (M+), 135 (100).
Example 12 (Entry 3) IR (Neat) 1674 cm"1; 1H NMR (CDC13) 5 1.20 (d, J = 7.80 Hz, 6H), 3.52 (m, J= 6.80 Hz, IH), 3.85 (s, 3H), 6.93 (d, J= 8.7 Hz, 2H), 7.95 (d, J= 8.7 Hz, 2H); EIMS (m/z) 178 (M+), 135 (100).
Example 12 (Entry 4) IR (Neat) 1666 cm-1; 1H NMR (CDC13) 5 1.36 (s, 9H), 3.82 (s, 3H), 6.89 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H); EIMS (m/z) 192 (M+), 135 (100).
Example 12 (Entry 5) IR (KBr) 1692 cm-1; 1H NMR (CDCI3) 5 1.20 (d, J= 7.80 Hz, 6H), 3.52 (m, J = 6.80 Hz, IH), 3.85 (s, 3H), 6.93 (d, J = 8.7 Hz, 2H), 7.95 (d, J = 8.7 Hz, 2H); EMS (m/z) 212 (M+), 135 (100).






We Claim:
1. A process for the acylation of various substrates using in zirconium (IV)
compound as a catalyst, the said process comprising steps of:
a) adding the zirconium (IV) compound to the substrate in the presence or absence of a solvent such as herein described at an ambient temperature,
b) adding the acylating reagent such as herein described to step (a) mixture,
c) stirring the mixture of step (b) at a temperature in the range of 0 to 120°C for a time period of 5 mts to 8 hrs, and
d) isolating the acylated product from step (c) reaction mixture by conventional method.

2. The process as claimed in claim 1, wherein in step (a) the Zirconium (IV) compound used as a catalyst is selected from ZrO(ClO4)2.8H2O, ZrCl3, ZrCl4, ZrCl4 on SiO2, ZrOCl2 8H2O, Sulphonated Zirconia, ZrF4, Zr(ipro)4, ZrSiO4, MgZrO3, Zr(ac.ac)2 and Bi(ZrO3)2.
3. The process as claimed in claim 2 wherein, the Zirconium (IV) compounds used as a catalyst is Zirconyl perchlorate [ZrO(ClO4)2 8H2O].
4. The process as claimed in claim 1, wherein step (a) the solvent used is selected from a group consisting of chlorinated solvent such as methylene chloride, chloroform, and 1,2-dichloroethane, aprotic polar solvent such as acetontrile (CH3CN), aromatic solvent such as benzene, toluene, xylene, and etheral solvent such as diethylether, diisopropylether or tetrahydrofuran.
5. The process as claimed in claim 1, wherein in step (a) the substrate used is selected from a group consisting of substituted or unsubstituted alkyl, alkyl aryl, aryl or heteroaryl compounds.
6. The process as claimed in claim 1, wherein in step (c) the temperature of the reaction is in the range of 0 to 110°C.
7. The process as claimed in claim 5, wherein the alkyl compound used may be saturated or unsaturated.
8. The process as claimed in claim 7, wherein the compound used may be acyclic or cyclic.
9. The process as claimed in claim 7, wherein the alkyl compound used is an aliphatic alcohol selected from allylic, propargylic or alcohols containing chiral center.
10. The process as claimed in claim 9, wherein the alkyl aryl alcohol used may have chiral center.
11. The process as claimed in claim 5, wherein the substitution on the alkyl compound used is selected from a group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol sulphonic or combination thereof.
12. The process as claimed in claim 5, wherein the substitution on the aryl compound used is selected from a group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol, sulphonic or combination thereof.
13. The process as claimed in claim 5, wherein the substitution on the alkyl aryl compound used is selected from a group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol, sulphonic or combination thereof.
14. The process as claimed in claim 5, wherein the substitution on the hetroaryl compound used is selected from a group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, amino, alkoxy, alkyl, hydroxyl, thiol sulphonic or combination thereof.
15. The process as claimed in claim 1, wherein step (b) the acylating reagent used is selected from a group consisting of substituted or unsubstituted carboxylic acid, its anhydride or mixed anhydride.
16. The process as claimed in claim 15, wherein aliphatic carboxylic acid used is acetic acid or its derivative.
17. The process as claimed in claim 15, wherein aliphatic carboxylic anhydride used is acetic anhydride or its derivative.
18. The process as claimed in claim 1, wherein the weight ratio of the catalysts to substrate used is in the range of 1: 10 to 1:20,000.
19. The process as claimed in claim 1, wherein the weight ratio of the catalysts to substrate used is preferably in the range of 1: 100.
20. The process as claimed in claim 1, wherein the molar ratio of acylating reagent to substrate used is in the range of 1:5 to 35.
21. The process as claimed in claim 1, wherein the molar ratio of substrate to solvent used is in the range of 1:1 to 100.
22. The process as claimed in claim 1, wherein the molar ratio of substrate to solvent used is preferably in the range of 1:10.
23. A process for the preparation of acylated compound using Zirconium (IV) compound catalyst and an acylating reagent substantially as herein described with reference to the accompanying example.



Documents:

336-DEL-2003-Abstract-(21-05-2010).pdf

336-del-2003-abstract.pdf

336-del-2003-claims (23-06-2011).pdf

336-del-2003-Claims-(15-03-2011).pdf

336-del-2003-claims.pdf

336-del-2003-Correspondence Others-(15-03-2011).pdf

336-DEL-2003-Correspondence-Others-(18-02-2011).pdf

336-DEL-2003-Correspondence-others-(21-05-2010).pdf

336-del-2003-correspondence-others.pdf

336-del-2003-correspondence-po.pdf

336-del-2003-Description (Complete)-(15-03-2011).pdf

336-del-2003-description (complete).pdf

336-DEL-2003-Drawings-(21-05-2010).pdf

336-del-2003-drawings.pdf

336-del-2003-form-1.pdf

336-del-2003-form-18.pdf

336-del-2003-form-2.pdf

336-del-2003-form-26.pdf

336-del-2003-form-3.pdf

336-del-2003-form-5.pdf


Patent Number 248501
Indian Patent Application Number 336/DEL/2003
PG Journal Number 29/2011
Publication Date 22-Jul-2011
Grant Date 20-Jul-2011
Date of Filing 21-Mar-2003
Name of Patentee NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH (NIPER)
Applicant Address 1860, HAVING ITS OFFICE AT SECTOR 67, PHASE X, S.A.S. NAGAR, MOHALI, DISTRICT ROPAR, PUNJAB 160062, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 ASIT K. CHAKRABORTI PHARMACEUTICAL EDUCATION AND RESEARCH, SECTOR 67, S.A.S. NAGAR-160 062, PUNJAB, INDIA.
2 RAJESH GULHANE NATIONAL INSTITUTE PHARMACEUTICAL EDUCATION AND RESEARCH, SECTOR 67, S.A.S. NAGAR-160 062, PUNJAB, INDIA.
PCT International Classification Number A61K 7/34
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA