Title of Invention	A PROCESS FOR THE PREPARATION OF CYCLOPENTADIENYL DERIVATIVES
Abstract	(57) Abstract: This invention relates to a process for preparing cyclopentadienyl derivatives of the Formula 1a (1ai) A ketone is condensed witli an ester of succinic acid R3OOC-CHR2-CHR1-COOP3, subjecting the resulting compound to intramolecular condensation followed by hydrolysis decarboxylation and reduction of the condensation product. PRICE: THIRTY RUPEES

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The present invention re1ates to a process for the preparation of cyclopentadienyi deR1vatives. It is known that the more useful soluble catalysts for the homo- and co-polymeR1sation of a-olefins consist of zirconium or titanium complexes beaR1ng ligands of bis-indenyl, bis-fluorenyl type, or mixed fluorenyl cyclopentadienyl type (P.C. MohR1ng, N.J. Ccville, J. Orgacmet. Chem. 479, 1, 1994). It is also known that the ccrrespcnding tetrahydroindene deR1vatives, beside having a high activity, are more effective in the incorporation of CO- and ter-monomers and are, therefore, among the preferred catalysts. The indene or fluorene deR1vatives are easily avai1able, but the corresponding tertrahydroindenyl deR1vatives are obtained by direct hydrogenotion of the zirconium ccmplex, as it is difficult to chemcselectively hydrogenate the starting ligands. The hydrogenation process of the complex shows, notwithstanding, some incoveniences. In fact, as is reported by some experts (see E. Samuel, Bull. Soc Chim. Fr., 3548, 1966 and S. Collins et a1. in Organometallic Chem., 342, 21, 1988), in effecting said hydrogenation difficulties are found due to low yields and/or drastic conditions. New cyclopentadienyl deR1vatives have, now, been found, which overcome the above-mentioned disadvantages, because of their structure, they do not need the above-mentioned hydrogenation step of the complex with the zirconium. In accordance with this, the present invention re1ates to cyclopentadienyl deR1vatives having general formu1a (I) wherein: R, R1, R2, R4 equivalent to or different from one another, are selected from: - H, - alkyl radicals having a number of carbon atoms from 1 to 5, cycloalkyl radicals having a number of carbon atoms from 5 to 8, - aryl and alky1aryl radicals having a number of carbon atoms from 6 to 8, - aralkyl radicals having a number of carbon atoms from 7 to 9; n is an integer from 2 to 18; with the proviso that the number of R different from H does not exceed 2; with the exclusion of the compound having n=3, R=R1=R2=R4=H. Typical examples of alkyl radicals from C1 to C5 are methyl, ethyl, n-propyl1 iso-propyl1 n-butyl1 iso-buty1, ter-buty1, n-penty1, iso-penty1 neo-penty1, Typical examples of cycloalkyl radicals having a number of carbon atoms from 5 to 8 are cyclopentyl, cyclohexyl, methyl cyclopentyl, methyl cyclohexyl. Typical examples of aryl and alky1aryl radicals having a number of carbon atoms from 6 to 8 are phenyl, methyl phenyl, ethyl phenyl, dimethyl pheny1. Typical examples of aralkyl radicals having a number of carbon atoms from 7 to 9 are benzyl, methyl benzyl, ethyl benzyl, propyl benzyl. In a preferred form of embodiment, R, R1, R2, and R4 are selected from H and alkyl radicals from CI to C3, In an even more preferred form of embodiment, n is selected from 3, 5, 6, 10, R=R2=R1=H, R4 is selected from H and alkyl radicals from C1 to C3. Typical examples of compounds having general formu1a (I) are: - 2, 4, 5, 6, 7, 8-hexahydroazulene (compound 1a in scheme 1, where R=R1=R2=H, n=5) ; 4, 5, 6, 7, 8, 9-hexahydro-2H-cyclopentacyclooctene (compound ia in scheme 1, where R=R1=R2= H, n=6) ; - 4, 5, 6, 7, 8, 9, 10, 11, 12, 13-decahydro-2H- cyclopentacyclododecene (compound ia in scheme 1, where R=R1=R2=H, n=10) ; - 1-methyl-4, 5, 6, 7, 8, 9, 10, 11, 12, 13- decahydro-2H-cyclopentacyclododecene (compound ib in scheme 1, where R=R1=R2=H, R4=CH3, n=10) . The compounds' having general formu1a (I) are useful as ligands in the preparation of the complexes with transition metals, Zirconium in particu1ar, typical catalyst components in the (co)polymeR1sation of a-olefins. A process for the preparation of chemical compounds having general formu1a (I) constitutes a further object of the present invention. This process, schematically represented in scheme 1, where the compounds having general formu1a (I) are subdivided into (ia) and (ib) compounds, whether R4 is equivalent to or different from H, foresees some common steps and a different final step as a function of R4. The process of the present invention, simple and oR1ginal, is schematized in Scheme 1. In accordance with this, the present invention re1ates to a process for the preparation of the compounds having general formu1a (ia), where n is an integer from 2 to 18, preferably n is selected from 3, 5, 6, 10, and R, R1 and R2 have the above-mentioned meaning, preferably R=R1=R2=H, which compR1ses the following steps: a) Stobbe type condensation between a ketone having general formu1a (II) (-CHR-)n+1 C=0 with an ester of the succinic acid having general formu1a (III) R3OOC-CHR2-CHR1-COOR3, where the groups R3, equivalent or different from one another, are selected from monofunctional alkyl radicals C1-C5, preferably R3 is selected from CH3 and C2H5 to give the a-(a'-cyclo-alkenyl)-p-hydroxycarbonyl-alkyl propionate having general formu1a (IV); b) intramolecu1ar condensation of the compound (IV) obtained in step (a) to give the condensed R1ngs compound having general formu1a (V); c) hydrolysis and decarboxy1ation of the compound (V) obtained in step (b) to give the α-β unsaturated condensed R1ngs ketone having general formu1a (VI); d) reduction of the α-β unsaturated condensed R1ngs ketone (VI) obtained in step (c) to give the condensed R1ngs conjugated diene having general formu1a (ia), steps (b) and (c) also being able to be carR1ed out in inverted order as compared to the above-mentioned one, or in a single step, preferably in the sequence (a), (b), (c), (d) . Step (a) of the present invention is a typical condensation between ketones and esters of the succinic acid, known as Stobbe reaction. This reaction (see H. House, Modern Synthetic Reactions, pages 663-666, Organic Reactions, Volume VI, pages 2-58) consists in the condensation of a carbonyl deR1vative with a diester of the succinic acid. In case the carbonyl deR1vative is a cycloalkanone, as in the above-mentoned case, the hemiester of the cyclo alkenyl substituted succinic acid, having general formu1a (IV) is formed. Step (a) is carR1ed out in the presence of strong bases, such as sodium methoxide, sodium hydR1de, tertiary alcohol alcoho1ates, preferably potassium terbuty1ate, a typical non-nucleophile strong base. As far as the other expeR1mental details of the Stobbe reaction are concerned, please refer to the above-mentioned references. Typical cyclic ketones having general formu1a (II) are cyclobutanone, cyciopentanone, cycionexanone, cycloheptanone, cyclooctanone, cyclododecanone, 2-, 3-, 4- methyl cyclohexanone, phenyl cyclohexanone, benzyl cyclohexanone. One of the advantages of the process of the present invention consists in the fact that many ketones having general formu1a (II) are commercially avai1able products. The condensation of step (a) occurs with a diester of the succinic acid having general formu1a (III), preferably with a diethyl or dimethl succinate, eventually monosubstituted or disubstituted. Step (b) of the process of the present invention consists in an intramolecu1ar condensation, with the elimination of water, of the product having general formu1a (IV) obtained in step (a) to give the condensed R1ngs compound having general formu1a (V) . This step is carR1ed out in the presence of usual condensation agents, for instance, strong acids such as sulphuR1c acid, hydrofluoR1c acid, phosphoR1c acid, polyphosphoR1c acid, preferably in the presence of polyphosphoR1c acid. The above-mentioned acid can be used as commercially avai1able or prepared in situ by mixing phosphoR1c acid and P205. If polyphosphoR1c acid is used, it is preferable , to carry out step (b) at temperatures between 70 and 110°C. Alternatively, step (b) can be carR1ed out in the presence of ZnCl2 in acetic acid - acetic anhydR1de, as is descR1bed in the above-mentioned quotation from Organic Reactions. Step (c) consists in the hydrolysis of the ester group and in the subsequent decarboxy1ation of the compound having general formu1a (V) to give the α-β unsaturated condensed R1ngs ketone having general formu1a (VI). The reaction is preferably carR1ed out in an acid environment and at such temperatures as to facilitate the elimination and the removal of CO2, preferably in a mixture of acetic acid/hydrochloR1c acid at reflux temperature. The α-β unsaturated ketone (VI) formed in step (c) is then reduced (step d) to a cyclopentadienyl deR1vative having general formu1a (1a) in the presence of reducing agents such as sodium or lithium boron hydR1de, sodium hydR1de, lithium hydR1de, lithium aluminium hydR1de, preferably with LiAlH4, According to another form of embodiment of the process of the present invention, step (c) , i. e. the hydrolysis to carboxylic acid and the subsequent decarboxy1ation, can be carR1ed out before the step of intramolecu1ar condensation (b) , or the two steps can be carR1ed out in a single step by selecting the most appropR1ate reaction conditions. The process of the present invention does not necessaR1ly require the iso1ation of the single reaction products at the end of the single steps. Beside the advantage to start from easily avai1able cycloalkanones, the process foresees rather simple chemical steps and has a satisfactory global yield. The present invention also re1ates to a process for the preparation of the compounds having general formu1a (ib), where n is an integer from 2 to 18, preferably selected from 3, 5, 6, 10, R, R1, R2, R4 have the above-mentioned meaning but with the proviso that R4 is different from H, preferably R=R1=R2=H, which compR1ses the following steps: a) Stobbe type condensation between a ketone having general formu1a (II) (-CHR-)n+1 C=0 with an ester of the succinic acid having general formu1a (III) R3OOC-CHR2-CHR1-COOR3, where the groups R3, equivalent or different from one another, are selected from monofunctional alkyl radicals C1-C5, preferably R3 is selected from CH3 and C2H5, to give the a-(a'-cyclo-alkenyl)-β-hydroxycarbonyl-alkyl propionate having general formu1a (IV); b) intramolecu1ar condensation of the compound (IV) obtained in step (a) to give the condensed R1ngs compound having general formu1a (V) / c) hydrolysis and decarboxy1ation of the compound (V) obtained in step (b) to give the a-p unsaturated condensed R1ngs ketone having general formu1a (VI); d) reaction of the α-β unsaturated condensed R1ngs ketone (VI) obtained in step (c) with an alkyl, aralkyl, alky1aryl, cycloalkyl deR1vative of an alkali metal and subsequent hydrolysation to give the condensed R1ngs conjugated diene having general formu1a (ib), steps (b) and (c) being also able to be carR1ed out in inverted order as compared to the above-mentioned one, or in a single step, preferably in the sequence (a), (b), (c), (d) . As far as steps (a) to (c) are concerned, they are carR1ed out under the same conditions as the above-mentioned ones for the synthesis of (1a) compounds. Step (d) is carR1ed out by reacting the α-β unsaturated condensed R1ngs ketone (VI) obtained in step (c) with an alkyl, aralkyl, alky1aryl, cycloalkyl deR1vative of an alkali metal, preferably lithium. The hydrocarbon deR1vative of lithium is a function of the type of R4 that one is willing to introduce in the compound having general formu1a (1b). So, for instance, in case one is willing to prepare an (1b) compound where R4 is equivalent to -CH3, one will use methyl lithium; in case one is willing to prepare an (1b) compound where R4 is equivalent to -C2H5, one will use ethyl lithium. Step (d) then foresees a subsequent hydrolysis step, preferably carR1ed out in the presence of acid catalysiS; and then a dehydration step, preferably carR1ed out in the presence of acid catalysis, too. The product (1b) thus obtained can be iso1ated according to usual techniques. (d) reduction in a known manner of the a,β-unsaturated condensed R1ngs ketone (VI) obtained in step (c) to give the conjugated condensed R1ng diene having tbnnu1a (1a) steps (b) and (c) also being able to be carR1ed out in the inverted order as compared to the above-mentioned one, or in a single step and recovery of the compound of formu1a (1a) in a known manner. The following examples are reported for a better illustration of the present invention. EXAMPLE 1 - Synthesis of 2. 4. 5, 6. 7, 8-hexaliydroazulene (compound of scheme 1 where R=R1=R2=H, n=5). To a solution of cycloheptanone, compound (II) where n=5, (56 grams corresponding to 0.5 moles) and of diethyl succinate, compound (III) vvhere both R3S are equal to -C2Hs, HO giams (0.63 moles ) in 500 ml N,N dimetliyl formamide (UMF), pota.ssium terbuty1ate (75 grams, 0.67 moles) is slowly added (in about 1 hour), maintaining the temperature between 20 and 30°C. At the end a yellow suspension is obtained which, after about one hour is dissolved again to give, then, a complete solidification of the reaction product. It is all poured in about 2 liters water, thus obtaining a limpid solution. The solution is extracted for some times with ethyl ether and the aqueous solution is then acidified to a pH of 2-3, by using dilute HCl. The aqueous solution thus acidized is then extracted with ether and the organic extract, after washing with water to neutrality and after drying, is evaporated. 118 grams (99% yield) a-(a'-cycloheptenyl)-β-hydroxycarbonyl-ethyl propionate (compound IV) are obtained pure at the NMR analysis. The emiester (IV) is then added to a mixture consisting of 400 grams H3PO4 85% and 650 grams P2O5, maintaining the temperature between 90 and 92°C. Once the addition has ended, the temperature is maintained for further 4 hours, duR1ng which there is an abundant development of foam. The mixture is then hydrolized with water and extracted with diethyl ether. The ethereal extract is neutralized and dR1ed. After the evaporation of the solvent, 35 grams of raw residue (64% yield of product V)are obtained, which are poured into 100 ml AcOH, 100 ml water and 10 ml concentrated HCl and then maintained at reflux temperature for one night. The reaction mass is diluted with water and extracted with petroleum ether. After the neutralization, drying and evaporation of the solvent, 16 grams 3, 4, 5, 6, 7, 8-hexahydro-2H-azulen-1-one (64% yield of product VI) are obtained. 16 grams of product (VI) dissolved in 200 ml diethyl ether are added to a solution of 3,0 grams of LiAlH4 in 300 ml diethyl ether, maintaining the temperature between 5 and 10°C. The reaction mixture is then hydrolized, the ethereal 1ayer separated and the aqueous step extracted, again with 200 ml diethyl ether. The ethereal extracts, (800 ml) after neutralisation and anhydR1fication are treated with ) 1,0 grams p-toluenesulphonic acid for 1.5 hours at room temperature. The organic phase is then neutralized with NaHCOs and evaporated. The residue obtained is puR1fied by chromatography on a silica gel column by eluting it with petroleum ether. 5 14 grams of 2, 4, 5, 6, 7, 8-hexahydroazulene, (compound 1a with n=5) are obtained with a yield of 98% from the product (VI) and of 40% from the starting cycloheptanone, which has the following NMR spectrum: s1H-NMR (CDCI3, 5 ppm rel. TMS) : 5.96 (s, br, 2H) ; 2.84 (t, 2H, J=2Hz); 2.47 (m, 4H); 1.61 (m, 6H) . EXAMPLE 2 - Synthesis of 4, 5, 6, 7, 8, 9-hexahydro-2H-cyclopentacyclooctene (compound 1a of scheme 1 where R=R1=R2=H, n=6) . ) A solution of 63 grams (0.5 moles) of cyclooctanone (II) and 110 grams (0.63) moles diethyl succinate is prepared. 75 grams (0.67 moles) Potassium terbuty1ate are added to this solution in small portions. i After the addition, the mixture is left under stirR1ng for 4 hours. The orange mass is hydrolized with water and ice, one acidizes and one extracts with diethyl ether. 140 grams of a raw semi-solid containing two products in a ratio 84:16 are obtained upon evaporation, 70 grams of the raw ester thus prepared are added to the polyphosphoR1c acid (consisting of 300 grams 85% H3PO4 and 450 grams P2O5) ■ Exothermic reaction takes p1ace and at 70°C the ester goes into a solution, the mass browns and the temperature goes up to 92°C, The reaction mass is stirred for about hour. The temperature goes down to 80°C, The reaction mixture is pored into ice, is extractd with diethyl ether, neutralized with an aqueous solution of NaHCOa, anhydR1fied and the solvent evaporated. 35 grams brown oil are obtained. A mixture is prepared containing the 35 grams of the above-mentoned raw oil, 100 ml AcOH, 100 ml water and 10 ml concentrated HCl. This mixture is maintained at reflux temperature for 6 hours, at the end of which is hydrolized and extractd with diethyl ether. Many pitches separate. The mixture is washed with NaOH (pitches dissolve) and water, anhydR1fied and the solvent evaporated. 12 grams yellow oil are obtained. These 12 grams yellow oil (corresponding to product VI), dissolved in 100 ml diethy ether, are added to a solution of 3.0 grams LiAlH4 in 200 ml diethyl ether, maintaining the temperature between 5 and 10°C. The reaction mixture is then hydrolized, the ethereal 1ayer separated and the aqueous step extracted, still with 100 ml diethyl ether. The ether extracts (400 ml), after neutralisation and anhydR1fication, are treated with 1.0 grams p-toluenesulphonic acid for 1.5 hours at room temperature. The organic phase is then neutralized with NaHCOa and evaporated. The residue obtained is puR1fied by chromatography on a silica gel column by eluting with petroleum ether. 7 grams of (1a) product, pure at the NMR and GC analysis, are obtained. The yield, as compared to the starting 1 cyclooctanone (II), is of 20%. The NMR spectrum of the 4, 5, 6, 7, 8, 9-hexahydro-2H-cyclopentacyclooctene thus obtained is the following: 1H-NMR (CDCl3, 6 ppm rel. TMS): 6.02 (t, 2H) ; 2.88 (bs, 2H); 2.50 (t, 4H); 1.70-1.40 (m, 8H). EXAMPLE 3 - Synthesis of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13-decahydro-2H-cyclopentacyclododecene (compound 1a of scheme 1 where R=R1=R2=H, n=10). To a solution of 100 grams (0.549 moles) cyclododecanone (compound II, n=10) in 700 ml THE, 70 grams Potassium terbuty1ate are slowly added ,; about 1 hour) . At the end, a yellow suspension is obtained which is agitated for 1 hour. The whole is poured in about 2 liters water, thus obtaining a limpid solution. The aqueosus solution is washed for some times with diethyl ether and then acidicified to a pH of 2-3, by using diluted HCl. The aqueous solution is then extracted with ether and the organic extract, after washing with water to neutrality and after drying, is evaporated. 160 grams (94% yield) of a product having a low melting point (product IV in scheme 1 where n=10, R=R1=R2=H, R3=Et) are obtained. The ester thus obtained (120 grams, 0.387 moles) is poured in one hour into a f1ask, maintained at about 93-95°C, containing 2.5 Kg polyphosphoR1c acid having a P2O5 content of 84%. Once the addition has ended, the temperature is raised to 96-97°C and the mixture left under stirR1ng for 4 hours The mixture is then hydrolized with water and extracted with diethyl ether. The ether extract is neutralized and dR1ed. After the evaporation of the solvent, 90 grams of a raw residue, pure at the GC analysis (product V in scheme 1, where n=10, R=R1=R2=H, R3=Et) are obtained. The solid is put into a solution consisting in 125 ml AcOH, 125 ml water and 10 ml concentrated HCl, and maintained under reflux temperature for 20 hours. The reaction mass is diluted with water and extracted with petroleum ether. After the neutralization, drying and evaporation of the solvent, the residue is distilled under vacuum and the fraction which passes at 125-130°C/0.2 mmHg is collected. 43 grams (51% yield) of product VI in scheme 1 having n=10, R=R1=R2=H, are obtained. 24 grams (0.11 moles) of the product thus obtained are dissolved in 200 ml diethyl ether and then added to a solution of 3.0 grams LiAlH4 in 300 ml diethyl ether, maintaining the temperature between 5 and 10°C. The reaction mixture is then hydrolized with some diluted HCl, the ethereal 1ayer separated and the aqueous phase extracted still with 200 ml diethyl ether. The ethereal extracts, (800 ml) after neutralisation and anhydR1fication are treated with 2.7 grams p-toluenesulphonic acid for 1.5 hours at room temperature, then at 30-35°0 for 5-6 hours until the alcohol (TLC) has disappeared. The organic phase is then neutralized with NaHCOs and evaporated. The residue obtained is puR1fied by chromatography on a silica gel column by eluting with petroleum ether. 21 grams (99% yield) of a mixture consisting m two products in a ratio of 81:19, of which the main product is 4, 5, 6, 7, 8, 9, 10, 11, 12, 13-decahydro-2H-cyclopentacyclododecene (compound 1a in scheme 1, n=10, R=R1=R2=H) are obtained. EXAMPLE 4 - Synthesis of 1-methyl- 4, 5, 6, 7, 8, 9, 10, 11, 12, 13-decahydro-2H-cyclopentacyclododecene (compound lb in scheme 1, where R=R1=R2=H, R4=CH3, n=10). To a solution, in 100 ml diethyl ether, of 10 grams (0.045 moles) of the carbonylic deR1vative prepared in example 3 (product VI in scheme 1, n=10, R=R1=R2=H) , maintained at -70°C, 30 ml of a solution 1.6 M of MeLi in diethyl ether are added. The mixture is left under stirR1ng for one night, then hydrolyzed. The ethereal phase is separated, 1 gram p-toluenesulphonic acid is added and the mixture is left under stirR1ng for 2 hours. The mixture is neutralized with a saturated solution of sodium bicarbonate, dR1ed on Na2S04 and the solvent is evaporated. The product is eluted on a silica gel column by using petroleum ether and by collecting the first fraction. 7 grams of a product consisting in two isomers in a ratio of 3:1 from the gaschromatographic analysis are obtained. The main product of the above-mentioned mixture is consisting in 1-methyl- 4, 5, 6, 7, 8, 9, 10, 11, 12, 13-decahydro-2H-cyclopentacyclododecene. (d) reduction in a known manner of the α-β-unsaturated condensed R1ngs ketone (VI) obtained in step (c) to give the conjugated condensed R1ng diene having fomu1a (1a) steps (b) and (c) also being able to be carR1ed out in the inverted order as compared to the above-mentioned one, or in a single step and recovery of the compound of formu1a (1a) in a known manner. 2. The process according to c1aim 1, wherein R3 is selected from-CH3 and - C2H3. 3. The process according to c1aim 1, wherein R=R1=R2=H. 4. The process according to c1aim 1. wherein n is selected from 3, 5, 6, 10. 5. The process according to c1aim 1, wherein step (a) is carR1ed out in the presence of Pota.ssium terbuty1ate. 6. The process according to c1aim 1, wherein step (b) is earned out in the presence of polyphosphoR1c acid as such or prepared in situ. 7. The- process according to c1aim 1, wherein step (c) is carR1ed out at acid pHs. 8. The process according to c1aim 1. wherein step (d) is carR1ed out in the presence of LiAlH4. 9. The process according to c1aim 1, wherein the process is earned out in the following step sequence: step (a), step (b), step (c), step (d). 10. A process for the preparation of cyclopentadienyl deR1vatives having formu1a 1a substantially as herein descR1bed.

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