Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
NOVEL POLYBENZOFULVENE DERIVATIVES, SYNTHESIS AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2008/037604
Kind Code:
A1
Abstract:
The present invention relates to polymers of formula poly-3 (I), their synthesis, intermediates and uses thereof.

Inventors:
CAPPELLI, Andrea (Via Roma 24, Civitella Marittima, I-58045, IT)
GALEAZZI, Simone (Strada Monteroni-Radi 1489b, Monteroni D'arbia, I-53014, IT)
ANZINI, Maurizio (Via del Bosco 19, Pianella, I-53010, IT)
VOMERO, Salvatore (Via Benvoglienti 6, Siena, I-53100, IT)
Application Number:
EP2007/059698
Publication Date:
April 03, 2008
Filing Date:
September 14, 2007
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
UNIVERSITÀ DEGLI STUDI DI SIENA (Via Banchi di Sotto 55, Siena, I-53100, IT)
CAPPELLI, Andrea (Via Roma 24, Civitella Marittima, I-58045, IT)
GALEAZZI, Simone (Strada Monteroni-Radi 1489b, Monteroni D'arbia, I-53014, IT)
ANZINI, Maurizio (Via del Bosco 19, Pianella, I-53010, IT)
VOMERO, Salvatore (Via Benvoglienti 6, Siena, I-53100, IT)
International Classes:
A61K47/32; C07C17/093; C07C17/35; C07C23/18; C07C35/32; C07C35/52; C07C45/67; C07C69/753; C07C69/757; C07C255/57; C07D213/16; C07D213/30; C07D213/50; C08F32/08
Domestic Patent References:
WO2005100297A12005-10-27
Other References:
CAPELLI, A.; ANZINI, M.;VOMERO, S.; DONATI, A.; ZETTA, L.; MENDICHI, R.; CASOLARO, M.; LUPETTI, P.; SALVATICI, P.; GIORGI, G.: "New Pi-Stacked Benzofulvene Polymer Showing Thermoreversible Polymerization: Studies in Macromolecular and Aggregate Structures and Polymerization Mechanism", JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY, vol. 43, no. 15, 1 August 2005 (2005-08-01), HOBOKEN, NJ, US, pages 3289 - 3304, XP002462153
CAPELLI, A.; PERICOT MOHR, G.; ANZINI, M.; VOMERO, S.; DONATI, A.; CASOLARO, M.; MENDICHI, R.; GIORGI, G..; MAKOVEC, F.: "Synthesis and Characterization of a New Benzofulvene Polymer Showing a Thermoreversible Polymerization Behaviour", JOURNAL OF ORGANIC CHEMISTRY, vol. 68, no. 24, 31 October 2003 (2003-10-31), EASTON, US, pages 9473 - 9476, XP002462155
AHN, JIN HEE ET AL.: "Indenone Derivatives: A Novel Template for Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) Agonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 49, no. 15, 29 June 2006 (2006-06-29), WASHINGTON, US, pages 4781 - 4784, XP002462156
RAYABARAPU, D.K.; YANG, C.-H.; CHENG, C.-H.: "Regioselective Synthesis of Indenols via Nickel-Catalyzed Carbocyclization Reaction", JOURNAL OR ORGANIC CHEMISTRY, vol. 68, no. 17, 31 July 2003 (2003-07-31), EASTON, USA, pages 6726 - 6731, XP002462157
CHANG, K.-J.; RAYABARAPU, D. K.; CHENG, C.-H.: "Cobalt-Catalyzed Regioselective Carbocyclization Reaction of o-Iodophenyl Ketones and Aldehydes with Alkynes, Acrylates, and Acrylonitrile: A Facile Route to Indenols and Indenes", JOURNAL OF ORGANIC CHEMISTRY, vol. 69, no. 14, 16 June 2004 (2004-06-16), Easton, USA, pages 4781 - 4787, XP002462158
CAPELLI, A.; GALEAZZI, S.; GUILIANI, G.; ANZINI, M.; DONATI, A.; ZETTA, L.; MEDICHI, R.; AGGRAVI, M.; GIORGI, G. ET AL.: "Structural Manipulation of Benzofulvene Derivatives Showing Spontaneous Thermoreversible Polymerization. Role of the Substituents in the Modulation of Polymer Properties", MACROMOLECULES, vol. 40, no. 9, 30 March 2007 (2007-03-30), WASHINGTON, DC, US, pages 3005 - 3014, XP002462154
Attorney, Agent or Firm:
CAPASSO, Olga et al. (De Simone & Partners S.p.A, Via Vincenzo Bellini 20, Rome, I-00198, IT)
Download PDF:
Claims:

Claims

1. A polymer of formula poly-3:

poly-3 wherein Ri is H, CH 3 , CN, a halogen, COOR wherein R = H, a Ci-C 5 alkyl group, or -(CH 2 -CH 2 O) m -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; n is a number comprised between 1 and 10.000. 2. The polymer according to claim 1 wherein the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15.

3. The polymer according to claim 1 being the Poly(l-Methylene-3-phenyl-lH-indene).

4. The polymer according to claim 1 being the Poly(2-Chloro-l-methylene-3-phenyl-lH- indene).

5. The polymer according to claim 1 being the Poly(2-Bromo-l-methylene-3-phenyl-lH- indene) .

6. The polymer according to claim 1 being the Poly(2-Methyl- 1 -methylene-3 -phenyl- IH- indene). 7. The polymer according to claim 1 being the Poly(l-Methylene-3-phenyl-lH-indene-2- carbonitrile).

8. The polymer according to claim 1 being the Poly-[l-Methylene-3-(4-methylphenyl)-lH- indene-2-carbonitrile] .

9. The polymer according to claim 1 being the Poly(6-Methyl-l-methylene-3-phenyl-lH- indene-2-carbonitrile) .

10. The polymer according to claim 1 being the Poly(Ethyl l-Methylene-3-phenyl-lH- indene-2-carboxylate) .

11. The polymer according to claim 1 being the PoIy[I -Methylene-3-phenyl-2[2-(2- pyridyl)- 1 -ethynyl]- lH-indene] .

12. The polymer according to claim 1 being the Poly(2-Fluoro-l-methylene-3-phenyl-lH- indene) . 13. The polymer according to claim 1 being the Poly[2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Methylene-3-(4-methylphenyl)-lH-indene-2-carboxylate].

14. The polymer according to claim 1 being the Poly[2,5,8, 11,14,17,20,23,26- Nonaoxaoctacosan-28-yl 1 -Methylene-3-(4-methylphenyl)- lH-indene-2-carboxylate] .

15. The polymer according to claim 1 being the Poly(Ethyl l-Methylene-6-methoxy-3- phenyl- IH- indene-2-carboxylate) .

16. Use of the polymer according to any of previous claims for the preparation of a drug controlled release pharmaceutical formulation.

17. A pharmaceutical formulation comprising the polymer according to claims 1 to 15 as drug controlled release pharmaceutical formulation. 18. An intermediate compound of formula 3 :

wherein

Ri is η, CH 3 , CN, a halogen, COOR wherein R = H, a Ci-C 5 alkyl group, or -(CH 2 -CH 2

O) m -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group.

19. The intermediate according to claim 18 wherein the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15. 20. The intermediate according to claim 18 being the l-Methylene-3 -phenyl- lH-indene.

21. The intermediate according to claim 18 being the 2-Chloro-l-methylene-3-phenyl-lH- indene.

22. The intermediate according to claim 18 being the 2-Bromo-l-methylene-3-phenyl-lH- indene.

23. The intermediate according to claim 18 being the 2-Methyl-l-methylene-3-phenyl-lH- indene. 24. The intermediate according to claim 18 being the l-Methylene-3-phenyl-lH-indene-2- carbonitrile.

25. The intermediate according to claim 18 being the l-Methylene-3-(4-methylphenyl)- lH-indene-2-carbonitrile.

26. The intermediate according to claim 18 being the 6-Methyl-l-methylene-3-phenyl-lH- indene-2-carbonitrile.

27. The intermediate according to claim 18 being the Ethyl l-Methylene-3 -phenyl- IH- indene-2-carboxylate.

28. The intermediate according to claim 18 being the 2-Fluoro-l-methylene-3-phenyl-lη- indene. 29. The intermediate according to claim 18 being the l-Methylene-3 -phenyl-2[2-(2- pyridyl)- 1 -ethynyl]- lH-indene.

30. The intermediate according to claim 18 being the 2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Methylene-3-(4-methylphenyl)-lH-indene-2-carboxylate.

31. The intermediate according to claim 18 being the 2,5,8,11,14,17,20,23,26- Nonaoxaoctacosan-28-yl 1 -Methylene-3-(4-methylphenyl)- lH-indene-2-carboxylate.

32. The intermediate according to claim 18 being the Ethyl l-Methylene-6-methoxy-3- phenyl- lH-indene-2-carboxylate.

33. An intermediate compound of formula 2:

2 wherein

Ri is H, CH 3 , CN, a halogen, COOR wherein R = a Ci-C 5 alkyl group or -(CH 2 -CH 2 O) m - CH3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group. 34. The intermediate according to claim 33 wherein the hydroxyl group of R 2 and R3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) H1 -CH 3 wherein m is a number comprised between 3 and 15. 35. The intermediate according to claim 33 being the l-Methyl-3 -phenyl- 1 H- 1-indenol.

36. The intermediate according to claim 33 being the l-Methyl-3-phenyl-2- (trimethylsilyl)- IH-I -indeno 1.

37. The intermediate according to claim 33 being the 2-Chloro- l-methyl-3 -phenyl- 1 H-I- indeno 1. 38. The intermediate according to claim 33 being the 2-Bromo- l-methyl-3 -phenyl- 1 H-I- indeno 1.

39. The intermediate according to claim 33 being the l,2-Dimethyl-3 -phenyl- 1 H-I- indeno 1.

40. The intermediate according to claim 33 being the 1 -Hydroxy- l-methyl-3 -phenyl- IH- indene-2-carbonitrile.

41. The intermediate according to claim 33 being being the 1 -Hydroxy- l-methyl-3 -(4- methylphenyl)- 1 H-indene-2-carbonitrile.

42. The intermediate according to claim 33 being the l,6-Dimethyl-l-hydroxy-3-phenyl- lH-indene-2-carbonitrile. 43. The intermediate according to claim 33 being the Ethyl 1 -Hydroxy- l-methyl-3 - phenyl- 1 H-indene-2-carboxylate.

44. The intermediate according to claim 33 being the l-Methyl-3-phenyl-2-[2-(2-pyridyl)- l-ethynyl]-lH-l-indenol.

45. The intermediate according to claim 33 being the 2-Fluoro- l-methyl-3 -phenyl- 1 H-I- indeno 1.

46. The intermediate according to claim 33 being the 2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Hydroxy-l-methyl-3-(4-methylphenyl)-lH-indene-2-carboxylate.

47. The intermediate according to claim 33 being the 2,5,8,11,14,17,20,23 ,26- Nonaoxaoctacosan-28-yl 1 -Hydroxy- l-memyl-3-(4-methylphenyl)-lH-indene-2- carboxylate.

48. The intermediate according to claim 33 being the Ethyl 1 -Hydroxy- 1 -methyl-6- methoxy-3-phenyl-lH-indene-2-carboxylate.

49. A substituted indenone derivative of formula 1

wherein R 1 = H, CH 3 , CN, COOR wherein R = -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group.

50. The substituted indenone derivative according to claim 49 wherein the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) m -CH 3 wherein m is a number comprised between 3 and 15.

51. The derivative according to claim 49 being the 3 -Phenyl-2-[2-(2-pyridyl)-l -ethynyl] - IH-I -indenone.

52. The derivative according to claim 49 being the 2-[2-(2-Methoxyethoxy)ethoxy]ethyl 3- (4-Methylphenyl)- 1 -oxo- lH-indene-2-carboxylate.

53. The compound according to claim 49 being the 2,5,8,11,14,17,20,23,26- Nonaoxaoctacosan-28-yl 3-(4-Methylphenyl)-l-oxo-lH-indene-2-carboxylate.

54. A method for the preparation of a substituted indenone derivative of formula 1

wherein R 1 = η, CH 3 , CN, COOR wherein R = -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group; R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15; comprising the step of transforming a 2-bromoindenone derivative (e. g. Id) by means of a transition metal catalyst.

55. The method according to claim 54 wherein the metal catalyst is Pd(PPh 3 ) 2 Cl 2 .

56. A method for the preparation of the polymer according to claim 1 comprising the steps of:

a) transforming an indenone of formula la-j,l-n into an indenol derivative of formula 2a- j,l-n as indicated in Scheme 2 with a suitable methylating agent and an appropriate solvent; b) transforming an indenol derivative of formula 2a-n into a trans-dime of formula 3 by means of a suitable dehydrating agent and an appropriate solvent; c) polymerization of diene derivatives of formula 3 in the presence of usual initiators or by spontaneous polymerization by solvent removal.

57. The method of claim 56 wherein the suitable methylating agent is A1(CH 3 ) 3 .

58. The method of claim 56 wherein the appropriate solvent of step a) is CH 2 Cl 2 . 59. The method of claim 56 wherein the suitable dehydrating agents are PTSA or formic acid. 60. The method of claim 56 wherein the appropriate solvent of step b) is CHCI3.

Description:

Novel polybenzofulvene derivatives, synthesis and uses thereof

Field of the Invention

The present invention is directed to new polymers based on functionalized indene monomeric units showing favourable properties such as a stable regulated π-stacked structure, thermoreversible polymerization/depolymerization behaviour, high solubility in the most common organic solvents, susceptibility to molecular manipulation, and liability of giving nanostructured macromolecular aggregates. The invention also refers to a method for synthesizing the compounds.

Background of the Invention

In the chemistry of the advanced materials, the synthesis of vinyl polymers possessing stable, regulated π-stacked conformations represents an important objective and, in this context, the properties of polydibenzofulvene derivatives (e. g. poly-DBF) are being largely investigated. 1"7 Very interestingly, poly-DBF is a new synthetic "π-way" molecule showing a hole drift mobility only slightly lower than that of Se, 8 an inorganic semiconductor, but it has been reported to show poor solubility and miscibility with other polymers. 1 ' 2 ' 6 Although thermoreversible polymerization processes are capable of potentially providing materials possessing varied and unique utility (e. g. recyclable materials), there have been very few reported examples exploring the formation and the properties of thermally reversible polymers. 9

A survey of the literature (a substructure search in CAS database) revealed that several dibenzofulvene polymers have been reported, while a single polymer based on the 3- phenylbenzofulvene structure has been so far described (poly-BF2). 10

The authors recently reported that benzofulvene derivative BFl [ethyl l-methylene-3-(4- methylphenyl)-lH-indene-2-carboxylate, Scheme 1] undergo spontaneous polymerization to give poly-BFl, a polymer showing outstanding properties such as thermoreversible polymerization/depolymerization behavior, high solubility in the most common organic solvents, susceptibility to molecular manipulation and characterized by both a vinyl structure stabilized by aromatic stacking interactions and a very high molar mass. 11 ' 12

Scheme 1

poly-BFl

Moreover, transmission electron microscopy (TEM) revealed that this interesting polymer is liable to give nanostructured macro molecular aggregates.

However, the synthesis of poly-BFl involved the reaction of the appropriate indenone derivative with methylmagnesium bromide to give the corresponding indenol derivative in low yield (31%), π and the general applicability of the synthetic method to the preparation of novel polymers has not been investigated.

The whole research shows that there is a great interest to find novel polymeric materials possessing favourable properties such as a stable regulated π-stacked structure, thermoreversible polymerization/depolymerization behaviour, high solubility in the most common organic solvents, susceptibility to molecular manipulation, and liability of giving nanostructured macromolecular aggregates.

In accordance with this need, the object of the present invention is to provide a viable general method applicable to the synthesis of novel polybenzofulvene derivatives properly functionalized in the key positions of the monomeric unit.

Detailed Description of the Invention

It is an object of the invention a polymer of formula poly-3:

poly-3 wherein

Ri is H, CH 3 , CN, a halogen, COOR wherein R = H, a Ci-C 5 alkyl group, or -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; n is a number comprised between 1 and 10.000. Preferably, the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 - CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15.

Preferred polymers are the poly(l-Methylene-3-phenyl-lH-indene), the poly(2-Chloro-l- methylene-3-phenyl-lH-indene), the poly(2-Bromo-l-methylene-3-phenyl-lH-indene), the poly(2-Methyl-l-methylene-3-phenyl-lH-indene), the poly(l-Methylene-3-phenyl-lH- indene-2-carbonitrile), the poly-[l-Methylene-3-(4-methylphenyl)-lH-indene-2- carbonitrile], the poly(6-Methyl-l-methylene-3-phenyl-lH-indene-2-carbonitrile) , the poly(Ethyl l-Methylene-3 -phenyl- IH- indene-2-carboxylate), the poly[l-Methylene-3- phenyl-2 [2-(2-pyridyl)- 1 -ethynyl] - 1 η-indene] , the poly(2-Fluoro- 1 -methylene-3 -phenyl- lη-indene), the poly[2-[2-(2-Methoxyethoxy)ethoxy] ethyl l-Methylene-3 -(4- methylphenyl)-lH-indene-2-carboxylate], the poly[2,5,8,l 1,14,17,20,23,26- Nonaoxaoctacosan-28-yl l-Methylene-3-(4-methylphenyl)- IH- indene-2-carboxylate] and the poly(Ethyl l-Methylene-6-methoxy-3-phenyl- IH- indene-2-carboxylate) . It is a further object of the invention the use of the polymer of the invention for the preparation of a drug controlled release pharmaceutical formulation. It is another object of the invention a pharmaceutical formulation comprising the polymer of the invention as drug controlled release pharmaceutical formulation.

It is another object of the invention an intermediate compound of formula 3:

wherein

Ri is H, CH 3 , CN, a halogen, COOR wherein R = H, a Ci-C 5 alkyl group, or -(CH 2 -CH 2 O) m -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group. Preferably, the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 - CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15. Preferred intermediates of formula 3 are: l-Methylene-3 -phenyl- lH-indene, 2-Chloro-l- methylene-3-phenyl-lH-indene, 2-Bromo-l-methylene-3-phenyl-lH-indene, 2-Methyl- 1 - methylene-3 -phenyl- 1 H-indene, 1 -Methylene-3 -phenyl- lH-indene-2-carbonitrile, 1 - Methylene-3-(4-methylphenyl)- lH-indene-2-carbonitrile, 6-Methyl- 1 -methylene-3 -phenyl- lH-indene-2-carbonitrile, Ethyl l-Methylene-3-phenyl-lH-indene-2-carboxylate, 2- Fluoro- 1 -methylene-3 -phenyl- 1 η-indene, 1 -Methylene-3 -phenyl-2 [2-(2-pyridyl)- 1 - ethynyl]- IH- indene, 2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Methylene-3 -(4- methylphenyl)-lH-indene-2-carboxylate, 2,5,8,11, 14, 17,20,23, 26-Nonaoxaoctacosan-28-yl l-Methylene-3-(4-methylphenyl)-lH-indene-2-carboxylate or Ethyl 1 -Methylene-6- methoxy-3-phenyl-lH-indene-2-carboxylate. It is another object of the invention an intermediate compound of formula 2:

Wherein

Ri is H, CH 3 , CN, a halogen, COOR wherein R = a Ci-C 5 alkyl group or -(CH 2 -CH 2 O) m - CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group. Preferably the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 - CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15.

Preferred intermediate of formula 2 are: l-Methyl-3 -phenyl- 1 H- 1-indenol, l-Methyl-3- phenyl-2-(trimethylsilyl)- IH-I -indeno 1, 2-Chloro- 1 -methyl-3 -phenyl- IH-I -indenol, 2- Bromo- 1 -methyl-3 -phenyl- IH-I -indeno 1, 1 ,2-Dimethyl-3 -phenyl- IH-I -indenol, 1 - Hydroxy- 1 -methyl-3 -phenyl- 1 H-indene-2-carbonitrile, 1 -Hydroxy- 1 -methyl-3 -(4- methylphenyl)- 1 H-indene-2-carbonitrile, 1 ,6-Dimethyl- 1 -hydroxy-3 -phenyl- 1 H-indene-2- carbonitrile, Ethyl 1 -Hydroxy- 1 -methyl-3 -phenyl- lH-indene-2-carboxylate, 1 -Methyl-3 - phenyl-2- [2-(2-pyridyl)- 1 -ethynyl] - 1 H- 1 -indeno 1, 2-Fluoro- 1 -methyl-3 -phenyl- 1 H- 1 - indenol, 2-[2-(2-Methoxyethoxy)ethoxy]ethyl 1 -Hydroxy- l-methyl-3-(4-methylphenyl)- lH-indene-2-carboxylate, 2,5,8,11,14,17,20,23 ,26-Nonaoxaoctacosan-28-yl 1-ηydroxy-l- methyl-3-(4-methylphenyl)-lH-indene-2-carboxylate and Ethyl 1 -Hydroxy- 1 -methyl-6- methoxy-3-phenyl-lH-indene-2-carboxylate.

It is a further object of the invention a substituted indenone derivative of formula 1

wherein Rj = η, CH 3 , CN, COOR wherein R = -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group.

Preferably the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -

CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15. Preferred substituted indenone derivative of formula 1 are: 3 -Phenyl-2- [2-(2-pyridyl)-l- ethynyl]-lH-l-indenone, 2-[2-(2-Methoxyethoxy)ethoxy]ethyl 3-(4-Methylphenyl)-l-oxo- lH-indene-2-carboxylate and 2,5,8,11,14,17,20,23, 26-Nonaoxaoctacosan-28-yl 3-(4-

Methylphenyl)- 1 -oxo- lH-indene-2-carboxylate.

It is an object of the invention a method for the preparation of a substituted indenone derivative of formula 1

wherein R 1 = H, CH 3 , CN, COOR wherein R = -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15, a substituted ethynyl group, or an alkyl group;

R 2 and R 3 represent a hydrogen atom, a halogen atom, an alkyl group or a hydroxyl group; the hydroxyl group of R 2 and R 3 is substituted to OR' wherein R' is -(CH 2 -CH 2 O) 1n -CH 3 wherein m is a number comprised between 3 and 15; comprising the step of transforming a 2-bromoindenone derivative (e. g. Id) by means of a transition metal catalyst.

Preferably the metal catalyst is Pd(PPh 3 ) 2 Cl 2 .

It is a further object of the invention a method for the preparation of the polymer of the invention comprising the steps of: a) transforming an indenone of formula la-j,l-n into an indenol derivative of formula 2a- j,l-n as indicated in Scheme 2 with a suitable methylating agent and an appropriate solvent; b) transforming an indenol derivative of formula 2a-n into a trans-dicnc of formula 3 by means of a suitable dehydrating agent and an appropriate solvent; c) polymerization of diene derivatives of formula 3 in the presence of usual initiators or by spontaneous polymerization by solvent removal.

Preferably the suitable methylating agent is A1(CH 3 ) 3 . More preferably, the appropriate solvent of step a) is CH 2 Cl 2 . Still preferably the suitable dehydrating agents are PTSA or formic acid. Yet preferably the appropriate solvent of step b) is CHCl 3 . On the basis of the interesting properties (e. g. the thermoreversible polymerization/depolymerization behavior, the high solubility in the most common organic solvents, the susceptibility to molecular manipulation, and the liability of giving nanostructured macro molecular aggregates) the new polymers can be used in drug controlled release as well as in synthesis, in the development of photoconducting and luminescent materials, in solid phase synthesis, and in catalysis.

In particular, the compounds of the invention can be used in the preparation of pharmaceutical forms such as tablets, capsules, suspensions, solutions, suppositories or patches, which may be administered orally, parenterally, rectally or transdermally, or other forms suitable for achieving the therapeutic effect such as, for example, solid preparations for oral use with protracted actions which permit controlled release of the active substance over time.

The invention will now be described by means of non-limiting examples in particular referring to the following figures:

Figure 1. Thermo-induced depolymerization of poly-3i followed by 1 H-NMR (in nitrobenzene-ds, 200 MHz).

Figure 2. A) SEM micrograph of freshly prepared poly-3a, B) SEM micrograph of freshly prepared poly-BFl.

Figure 3. Crystallographic structure of compound Ie.

Figure 4. Crystallographic structure of compound 5g. Figure 5. Crystallographic structure of compound Ih

Figure 6. Crystallographic structure of compound 2e

Figure 7. MALDI-TOF spectrum of poly-3a.

The methods for preparing the polybenzofulvene derivatives of the present invention consist of series of reactions which are reported below as non-limiting examples (Schemes 2-6).

Scheme 2. Synthesis of novel polybenzofulvene derivatives Poly-3a,c-n.

poly-3a,c-n

Reagents: (i) A1(CH 3 ) 3 , CH 2 Cl 2 ; (ii) PTSA, CHCl 3 (or HCOOH for 2j); (iii) solvent elimination.

Table 1. Compounds Shown in Scheme 1.

Ri R 2 R 3 Indenone Preparation Indenol Monomer/Polymer

H H H Ia ref l3 2a 3a

Si(CH 3 ) 3 H H Ib ref l3 2b 3a a

Cl H H Ic Scheme 3 2c 3c

Br H H Id ref l3 2d 3d

CH 3 H H Ie Scheme 4 2e 3e

CN H H If ref 14 2f 3f

CN CH 3 H Ig Scheme 5 2g 3g

CN H CH 3 Ih Scheme 5 2h 3h

COOC 2 H 5 H H Ii ref 15 2i 3i

C≡C-2-Pyr H H Ij Scheme 4 2j 3j

F H H 2k b 3k

COO(CH 2 CH 2 O) 3 CH 3 CH 3 H 11 Scheme 7 21 31

COO(CH 2 CH 2 O) 9 CH 3 CH 3 H Im Scheme 7 2m 3m

COOC 2 H 5 H OCH 3 In ref 16 2n 3n a Poly-3a was obtained instead of poly-3b because indenol derivative 2b desilylated ssppoonnttaanneeoouussll)y in the dehydration conditions. Indenol 2k was prepared from 2d as shown in Scheme 6.

The synthesis of polybenzofulvene derivatives poly-3a,c-n was accomplished starting from suitable indenones la-j,l-n (see Table 1) as reported in Scheme 2. The reaction of la-j,l-n with trimethylaluminium gave the expected indenol derivatives 2a-n; the structure of 1,2- addition product 2e was solved by X-ray diffraction.

The C-methylation of indenone derivatives 1 with trimethylaluminium represents an outstanding improvement in the synthesis of indenol derivatives 2 because the yields are higher (typically 80-90%) with respect to those obtained by means of other standard methods and, in most cases, the indenol derivative could be used in the following step of the synthesis without any further purification. This result is extremely important for the industrial application of these new polymers.

Dehydration of 2a-i,k-n with/?-toluenesulfonic acid (PTSA) in chloroform (or with formic acid in the case of 2j) gave compounds of difficult isolation because the solvent removal

led to the isolation of polymeric materials containing only trace amounts of the expected trans-diene derivatives 3. When the dehydration was performed in CDCI 3 , allowing the 1 H- NMR analysis to be performed without the solvent elimination, clear 1 H-NMR spectra compatible with the structures of 3a,c-n were obtained. Thus, dehydration of 2a,c-n gave 3a,c-n which were stable in solution and polymerized upon solvent removal to give poly- 3a,c-n. On the other hand, dehydration of 2b led to 3a because 2b desilylated spontaneously in the dehydration conditions.

Chloroindenone derivative Ic was prepared by reaction of Ib with solforylchloride (Scheme 3). Scheme 3. Synthesis of indenone Ic.

Reagents: (i) SO 2 Cl 2 , CH 3 COOH.

The procedure for the preparation of indenones le,j is shown in Scheme 3. Bromoindenone derivative Id (see ref 12) was reacted with tetramethyltin in the presence of Pd(PPh 3 ) 2 Cl 2 (as an example of Stille coupling) 17 to obtain Ie, or with 2-ethynylpyridine in the presence of the same catalyst (as an example of Sonogashira coupling) 18 to synthesize Ij. The reactivity of bromoindenone derivative Id in different cross-coupling reactions catalyzed by transition metal catalysts demonstrate that the synthetic procedure described in the present patent can be used for the preparation of a wide variety of indenone derivatives 1, indenol derivatives 2, and finally polybenzofulvene derivatives 3.

Scheme 4. Synthesis of indenones le,j

Reagents: (i) Sn(CH 3 ) 4 , LiCl, Pd(PPh 3 ) 2 Cl 2 , DMF; (ii) 2-ethynylpyridine, Pd(PPlIs) 2 Cl 2 , CuI, TEA.

The procedure for the preparation of indenones lg,h is shown in Scheme 5. 4- Methylbenzophenone (4) was reacted with ethyl cyanoacetate to afford the mixture of the geometric isomers 5g,h (ratio ca. 2:1) from which major isomer 5g was isolated by recrystallization from n-hexane to obtain X-ray quality crystals. Basic hydrolysis of the 5g,h mixture gave the corresponding carboxylic acid derivatives 6g,h. The mixture of the acids was promptly cyclized with concentrated sulfuric acid to obtain the mixture of indenone derivatives lg,h, which were separated by fractioned recrystallization from ethyl acetate. The structure of compound Ih was confirmed by X-ray diffraction studies.

Scheme 5. Synthesis of indenones lg,h

Reagents: (i) CNCH 2 COOC 2 H 5 , C 6 H 6 , CH 3 COOH, CH 3 COONH 4 ; (ii) KOH, H 2 O, C 2 H 5 OH; (iii) H 2 SO 4 .

The introduction of a fluorine atom was performed at the stage of the indenol as depicted in Scheme 6. The indenol 2d underwent lithium-halogen exchange and subsequent fluorination with N-fluorobenzenesulfonimide (NFSI) 19 to afford fluoroindenol derivative 2k.

Scheme 6. Synthesis of fluoroindenol derivative 2k.

Reagents: (i) a) Z-BuLi, THF; b) N-fluorobenzenesulfonimide, THF.

Finally, indenones ll,m (Scheme 7) were synthesized by reaction of acid 10 (obtained by acid cleavage of £-butyl ester 9 20 ) with the appropriate monomethyl PEG chains 71,m in the presence of EDC and DMAP. While 71 is a commercially available intermediate,

compound 7m was synthesized starting from 71 and hexaethylene glycol as outlined in scheme 7.

Scheme 7. Synthesis of indenone derivatives ll,m

Reagents: (i) PBr 3 , CHCl 3 ; (ii) HO(CH 2 CH 2 O) 6 H, NaH, toluene; (iii) PTSA, CHCl 3 ; (iv) EDC, DMAP, CH 2 Cl 2 .

The characterization of polymers poly-3a,c-k,n by a multi-angle laser light scattering online to a size exclusion chromatography (SEC-MALS) system gave molar mass values ranging from 4.0 to about 1,600 kg/mol and variable dispersity indexes (see Table 2). Interestingly, the molar mass appears to be roughly related to the steric hindrance in position 2 of indenone nucleus rather than to the volume of substituent R 1 .

Table 2. Macromolecular features of the synthesized polymers.

Polymer Ri R 2 R 3 M w D h

(kg/mol) a (nm) c

3a H H H 4.0 1.3

3k F H H 25.6 4.5

3c Cl H H 47.6 2.1

3d Br H H 109.1 3.1

3e CH 3 H H 530.8 4.7 43.0

3j C≡C-2-Pyr H H 289.2 2.5

3f CN H H 391.5 6.3 32.5

3g CN CH 3 H 500.2 4.4 26.8

3h CN H CH 3 475.9 4.3 24.3

3n COOC 2 H 5 H OCH 3 439.0 3 .3

3i COOC 2 H 5 H H 1,593 3 .7 44.6 a M w : weight-average molar mass; b D: the dispersity index D = M w /M n where M n denotes the numeric-average molar mass; c R g : the radius of gyration i.e. the dimension of the macromo lecules .

Matrix-assisted laser desorption/ionization time-of-fly (MALDI-TOF) mass spectrometry of the poly-3a,c-n confirmed the structure of these polymeric materials. The MALDI spectra obtained with dithranol as the matrix (see the examples) showed the presence of a series of peaks differing by the molecular weight of the corresponding monomer up to a mass-to-charge ratio of about 4,000-10,000, whereas heavier polymeric species were undetectable under MALDI-TOF conditions.

The heating to reflux the solutions of the polymers in solvents showing different boiling points led to both the depolymerization of poly-3c-n and the regeneration of the corresponding benzofulvene monomers. On the basis on these findings, the depolymerization process was characterized by NMR spectroscopy at high temperature (experiments at different times in nitrobenzene or DMSO at 150 0 C). For example, Figure 1 shows that the broad lines typical of poly-3i progressively disappeared as a consequence of the exposure to high temperature to be replaced by the sharp signals of the benzofulvene monomer 3i. Therefore, the restoring of the solvated conditions led the polymers to release the monomer at a temperature-dependent rate. Finally, scanning electron microscopy (SEM) studies showed that the polymers are liable to give nanostructured aggregates. For example, poly-3a is particularly susceptible to give nanospheres characterized by favorable dimensions and morphology (Figure 2A). The superior aggregation properties of poly-3a become evident when Figure 2A is compared with the SEM micrograph obtained with the previously published poly-BFl (Figure 2B).

Examples Example 1 3-Phenyl-lH-l-indenone (Ia).

Procedure A: The title compound was prepared according to literature 13 to obtain indenone Ia as yellow oil. 1 H-NMR (200 MHz, CDCl 3 ): 5.99 (s, IH), 7.24-7.53 (m, 7H), 7.60-7.67 (m, 2H). MS(EI): m/z 206 (M + , 100).

Procedure B: A mixture of indenone Ib (0.60 g, 2.2 mmol) and p-toluensulfonic acid (PTSA) (0.083 g, 0.44 mmol) in CHCl 3 , was refluxed for 1 hour. The reaction mixture was washed with a saturated solution of NaHCO 3 , the organic layer was dried over sodium sulfate and evaporated under reduced pressure to give pure indenone Ia as a yellow oil (0.43 g, yield 95%). Example 2 3-Phenyl-2-(trimethylsilyl)-lH-l-indenone (Ib).

This compound was obtained according to the literature 13 with modifications. A mixture of 2-bromobenzaldheyde (7.4 g, 40 mmol) in DMA (200 mL) containing l-phenyl-2- (trimethylsilyl)acetylene (13.9 g, 80 mmol), (/7-Bu) 4 NBr (12.9 g, 40 mmol), Pd(CH 3 COO) 2 (0.090 g, 0.4 mmol), Na 2 CO 3 (4.2 g, 40 mmol) was heated at 100 0 C under stirring for 17 h. The reaction mixture was then cooled, diluted with a saturated solution of NH 4 CI (150 mL) and extracted with petroleum ether (100 mL x 6). The combined organic extracts were washed with water, dried over sodium sulfate and concentrated under reduced pressure. Purification of the residue by flash chromatography with petroleum ether-CH 2 Cl 2 (8:2) as the eluent gave indenone Ib as a yellow solid (6.9 g, yield 62 %, mp 54-56 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 0.05 (s, 9H), 6.88 (m, IH), 7.20-7.51 (m, 8H). MS(EI): m/z 278 (M + , 50), 263 (M- 15). Example 3

2-Chloro-3-phenyl-lH-l-indenone (Ic). To a mixture of indenone Ib (1.2 g, 4.3 mmol) in acetic acid (20 mL), a IM solution of SO 2 Cl 2 in CH 2 Cl 2 (6.5 mL, 6.5 mmol) was added. The resulting mixture was stirred under N 2 for 30 minutes and the resulting reaction mixture was evaporated under reduced pressure. The residue was chromatographed using «-hexane/ CH 2 Cl 2 (1 : 1) as eluent, to yield chloroindenone Ic as an orange solid (0.72 g, 70 %, mp 97-98 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 7.08-7.33 (m, 3H), 7.47 (m, 4H), 7.59 (m, 2H). MS(EI): m/z 240 (M + , 100). Example 4

2-Bromo-3-phenyl-lH-l-indenone (Id).

This compound was synthesized according to literature with modifications. 13 A mixture of indenone Ib (0.18 g, 0.65 mmol) and NBS (0.23 g, 1.3 mmol) in CH 2 Cl 2 (10 mL) was

refluxed for 1 h. The solvent was removed under reduced pressure and the residue was washed with petroleum ether until it became white. The organic solvent was evaporated and the solid residue was recrystallized from n-hexane to yield Id as orange crystals (0.18 g, yield 97%, mp 108-109 0 C, literature 13 112-113 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 7.12- 7.16 (m, IH), 7.22-7.39 (m, 2H), 7.52-7.57 (m, 4H), 7.63-7.68 (m, 2H). MS(EI): m/z 284 (M + , 100). Example 5

2-Methyl-3-phenyl-lH-l-indenone (le). A mixture of indenone Id (4.0 g, 14 mmol), LiCl (3.3 g, 78 mmol), and (CH 3 ) 4 Sn (9.4 mL, 68 mmol) in dry DMF (30 mL) was vigorously stirred under an argon stream for 10 min. Pd(PPh 3 )Cl 2 (1.1 g, 1.6 mmol) was added and the reaction mixture was heated at 140 0 C for 40 min, then poured in ice-water and extracted with dichloromethane. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed using n-hexane-ethyl acetate (9: 1) as eluent. Indenone Ie (Figure 3) was recrystallized from rø-hexane to obtain the pure compound as yellow-orange crystalline solid (2.0 g, yield 65 %, mp 90-92 0 C, literature 21 86-87 0 C). 1 H- NMR (200 MHz, CDCl 3 ): 1.92 (s, 3H), 7.04 (d, J = 7.1, IH), 7.14-7.33 (m, 2H), 7.48 (m, 6H). MS(ESI): m/z 221 (M + H + ). Example 6 l-Oxo-S-phenyl-lH^-indenecarbonitrile (If).

The title compound was synthesised according to the literature. 14 The reaction mixture was chromatographed using n-hexane/ethyl acetate (8:2) as the eluent to yield ketone If as a red solid. An analytical sample was recrystallized from «-hexane-CH 2 Cl 2 to give red crystals (mp 171-171.5 0 C, literature 14 172-173.5 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 7.50- 7.84 (m, 9H). MS(EI): m/z 231 (M + , 100). Example 7

Ethyl (E)-2-Cyano-3-(4-methylphenyl)-3-phenyl-2-propenoate (5g) + Ethyl (Z)-2- cyano-3-(4-methylphenyl)-3-phenyl-2-propenoate (5h). The mixture of the geometrical isomers 5g,h was prepared according to a procedure described in literature 14 starting from 4-methylbenzophenone 4 (49 g, 0.25 mol) and ethyl cyanoacetate (26.6 mL, 0.25 mol). The reaction mixture was purified by washing with n- hexane to give a white solid. GC-MS analysis showed that the resulting solid was a mixture (2: 1) of E and Z isomers 5g and 5h (35 g, yield 48%). 1 H-NMR (200 MHz,

CDCI3), for the sake of simplification the integral values have not been given: 1.09-1.22 (m), 2.39 (s), 4.07-4.19 (m), 7.04 (m), 7.13-7.44 (m). MS(EI): m/z 29\ (M + , 100). Example 8

Ethyl (E)-2-Cyano-3-(4-methylphenyl)-3-phenyl-2-propenoate (5g). The mixture (2: 1) of two geometrical isomers 5g and 5h was recrystallized from n-hexane to give pure 5g (Figure 4) as colourless crystals (mp 89-93 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.13 (t, J = 7.4, 3H), 2.39 (s, 3H), 4.13 (q, J = 7.1, 2H), 7.12-7.48 (m, 9H). MS(EI): m/z 291 (M + , 100). Example 9 (E)-2-Cyano-3-(4-methylphenyl)-3-phenyl-2-propenoic Acid (6g) + (Z)-2-Cyano-3-(4- methy]phenyl)-3-phenyl-2-propenoic Acid (6h).

The mixture (2:1) of two geometrical isomers 5g and 5h (9.9 g, 34 mmol) in ethanol (10 mL) and water (10 mL) with KOH (5.0 g, 89 mmol) was stirred at room temperature for 20 minutes. The resulting reaction mixture was diluted with water (180 mL) and filtered; the filtrate was acidified with concentrated HCl. The precipitated was collected by filtration, washed with water, and dried under reduced pressure to give the mixture (2: 1) of two geometrical isomers 6g and 6h as a light yellow solid (5.8 g, yield 65%). 1 H-NMR (200 MHz, CDCl 3 ) 2.40 (s, 3H), 7.02-7.50 (m, 9H), 9.73 (br s, IH). MS(ESI, negative ions): m/z 262 (M - H + ). Example 10

3-(4-Methylphenyl)-l-oxo-lH-2-indenecarbonitrile (Ig) + 6-Methyl-l-oxo-3-phenyl- lH-2-indenecarbonitrile (Ih).

This mixture was prepared from a mixture (2: 1) of E and Z isomers 6g and 6h (5.8 g, 22 mmol) in H 2 SO 4 (41 mL) according to a procedure described in the literature. 14 The reaction mixture was chromatographed using «-hexane/ethyl acetate (65:35) as the eluent to give the mixture of Ig and Ih as an orange solid (4.6 g, yield 85%). The 1 H NMR analysis showed that this solid is a mixture (2:1) of compounds Ig and Ih. The separation of two isomers occurred by recrystallization from ethyl acetate by slow evaporation. Compound Ih (Figure 5) gave red prisms (mp 178.5-179.5 0 C); 1 H-NMR (CDCl 3 ): 2.41 (s, 3H), 7.27-7.37 (m, 2H), 7.44 (s, IH), 7.53-7.62 (m, 3H), 7.71-7.81 (m, 2H). MS(EI): m/z 245 (M+, 100). On the other hand compound Ig gave an orange spongy solid that was mechanically separated from the crystals of Ih and recrystallized other three times to yield

an orange solid (mp 175-175.5 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 2.47 (s, 3H), 7.41 (m,

2H), 7.51 (m, 3H), 7.65 (m, IH), 7.74 (m, 2H). MS(EI): m/z 245 (M + , 100).

Example 11

Ethyl l-Oxo-S-phenyl-lH-l-indenecarboxylate (Ii). A mixture of 2-benzoylbenzoic acid (3.88 g, 16.7 mmol) in CH 2 Cl 2 (15 mL), SOCl 2 (6.0 mL, 82 mmol), DMF (0.13 mL, 1.7 mmol) was stirred under N 2 atmosphere for 4 hours. The thionyl chloride excess was removed by azeotropic distillation with toluene under reduced pressure to yield the correspondent acyl chloride as brown oil. To a mixture of magnesium turnings (0.40 g, 16.7 mmol) in absolute ethanol (0.50 mL), and CCU (0.10 mL) was added freshly distilled diethyl ether (10 mL). After stirring at room temperature for 10 min, a solution of diethyl malonate (2.5 mL, 16.5 mmol) in freshly distilled diethyl ether (10 mL) and absolute ethanol (2 mL) was added dropwise. The resulting mixture was refluxed under for 3 h and, after this time, a solution of the acyl chloride in diethyl ether (15 mL) was added. The reaction mixture was refluxed for 30 min, cooled to 0-5 0 C, and acidified with 10% H 2 SO 4 . The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to yield a brown oil. A mixture of this residue in ethanol (80 mL) and water (30 mL) with Na 2 CO 3 (4.0 g, 38 mmol) was refluxed for 20 minutes, then concentrated under reduced pressure, diluted with water, acidified with IN HCl, and extracted with CH 2 Cl 2 . The organic layer was washed with a diluted solution of NaHCO 3 , dried over sodium sulfate, and evaporated under reduced pressure. The residue was purified by crystallization from diethyl ether at - 18 0 C to give indenone Ii as yellow crystalline solid (2.9 g, yield 62 %, mp 85-87 0 C, literature 15 88-89 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.16 (t, J = 7.1, 3H), 4.20 (q, J = 7.2, 2H), 7.20 (m, IH), 7.38-7.53 (m, 7H), 7.59 (m, IH). Example 12

3-Phenyl-2-[2-(2-pyridyl)-l-ethynyl]-lH-l-indenone (lj).

A mixture of compound Id (1.1 g, 3.86 mmol) in triethylamine (TEA, 80 mL), 2- ethynylpyridine (0.52 g, 5.06 mmol) and CuI (0.037 g, 0.19 mmol) was degassed under stirring in an ice bath for 10 min. Pd(PPh 3 )Cl 2 (0.137 g, 0.19 mmol) was then added and the reaction mixture was stirred at 0 0 C for 1 h and refluxed for 3 h. The resulting mixture was diluted with diethyl ether, washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed using petroleum ether-ethyl acetate (65:35) as the eluent to give Ij as a red solid (0.72 g, yield 61 %, mp

160.5-161 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 7.19 (m, IH), 7.30-7.67 (m, 9H), 7.86-7.91 (m, 2H), 8.58 (d, J= 4.8, IH). MS(ESI): m/z 308 (M + H + ). Example 13

2-[2-(2-Methoxyethoxy)ethoxy]ethyl 3-(4-Methylphenyl)-l-oxo-lH-indene-2- carboxylate (11).

A mixture of acid 10 (2.0 g, 7.6 mmol) in dry CH 2 Cl 2 (20 mL) with triethylene glycol monomethyl ether (71) (1.2 mL, 7.6 mmol), EDC hydrochloride (1.7 g, 8.9 mmol), and DMAP (0.092 g, 0.76 mmol) was stirred overnight at room temperature. The reaction mixture was then concentrated under reduced pressure and the residue was purified by flash chromatography with dimethoxyethane-petroleum ether (3:7) as the eluent to yield indenone 11, as a yellow oil (2.1 g, yield 67 %). 1 H-NMR (200 MHz, CDCl 3 ): 2.38 (s, 3H), 3.29 (s, 3H), 3.52 (m, 10H), 4.26 (t, J = 4.9, 2H), 7.18 (m, IH), 7.21-7.42 (m, 6H), 7.51 (m, IH). MS(ESI): m/z 433 (M+Na + ). Example 14 2,5,8,1 l,14,17,20,23,26-Nonaoxaoctacosan-28-yl 3-(4-Methylphenyl)-l-oxo-lH-indene- 2-carboxylate (Im).

A mixture of acid 10 (2.0 g, 7.6 mmol) in dry CH 2 Cl 2 (20 mL) with nonaethylene glycol monomethyl ether (7m) (3.2 g, 7.5 mmol), EDC hydrochloride (1.7 g, 8.9 mmol), and DMAP (0.092 g, 0.76 mmol) was stirred overnight at room temperature. The reaction mixture was then concentrated under reduced pressure and the residue was purified by flash chromatography with dimethoxyethane-petroleum ether (6:4) as the eluent to yield indenone Im, as a yellow oil (3.5 g, yield 68 %). 1 H-NMR (200 MHz, CDCl 3 ): 2.40 (s, 3H), 3.33 (s, 3H), 3.48-3.69 (m, 34H), 4.27 (t, J = 4.9, 2H), 7.19 (m, IH), 7.27 (m, 2H), 7.35-7.44 (m, 4H), 7.55 (m, IH). MS(ESI): m/z 697 (M+Na + ). Example 15 l-Bromo-2-(2-(2-methoxyethoxy)ethoxy)ethane (8).

A mixture of triethylene glycol monomethyl ether (71) (9.7 mL, 57.6 mmol) in CHCl 3 (20 mL) with PBr 3 (10.8 mL, 115.2 mmol) was stirred at room temperature for 4 h. The mixture was poured into ice, and neutralized with Na 2 CO 3 . The organic layer was washed with water, dried over Na 2 SC> 4 , and concentrated under reduced pressure. Purification of the residue by flash chromatography with petroleum ether-ethyl acetate (65:35) as the eluent gave bromide 8 as a colourless oil (3.3 g, yield 25 %). 1 H-NMR (200 MHz, CDCl 3 ):

3.34 (s, 3H), 3.42 (t, J = 6.4, 2H), 3.49-3.53 (m, 2H), 3.59-3.66 (m, 6H), 3.77 (t, J = 6.4,

2H). MS (ESI): rø/z 249 (M+Na + ).

Example 16

2,5,8,1 l,14,17,20,23,26-Nonaoxaoctacosan-28-ol (7m). NaH (0.39 g, 16 mmol) was added to a solution of hexaethylene glycol (5.5 mL, 22 mmol) in dry toluene (20 mL) and the resulting mixture was stirred at room temperature for 2 hours. Then bromide 8 (2.5 g, 11 mmol) was added and the reaction mixture was stirred at room temperature for one additional hour. The reaction mixture was then filtered, concentrated under reduced pressure and the residue was purified by flash chromatography with dimethoxyethane-n-exane (7:3) as the eluent to give 7m as a colourless oil (2.4 g, yield 51 %). 1 H-NMR (200 MHz, CDCl 3 ): 2.85 (br s, IH), 3.23 (s, 3H), 3.31-3.50 (m, 36H). MS (ESI): m/z 451 (M+Na + ).

General Procedure for the Synthesis of Indenol Derivatives 2a-j,l-n. To a solution of the appropriate indenone (la-j) in CH 2 CI 2 (10 mL/1 mmol of indenone) was added a solution (2M in THF) of Al(CH 3 )S, (2.5 equivalents) and the resulting mixture was stirred under nitrogen for 30 minutes. The A1(CH 3 ) 3 excess was cautiously decomposed with a 30% NaOH solution until the gas evolution ceased. The mixture was filtered and the filtrate was dried over sodium sulfate and evaporated under reduced pressure. Purification of the residue by flash chromatography with the appropriate eluent (typically «-hexane-ethyl acetate 8:2 or 65:35) gave the corresponding indenol (2a-j). Example 17 l-Methyl-3-phenyl-lH-l-indenol (2a). This compound was obtained from indenone Ia (0.10 g, 0.485 mmol) as a white crystalline solid (0.094 g, yield 87%, mp 100.5-101.5 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.68 (s, 3H), 1.93 (s, IH), 6.34 (s, IH), 7.23-7.30 (m, 2H), 7.38-7.59 (m, 7H). MS(EI): m/z 222 (M + , 100).

Example 18 l-Methyl-3-phenyl-2-(trimethylsilyl)-lH-l-indenol (2b). This compound was obtained from indenone Ib (0.75 g, 2.7 mmol) as a white crystalline solid (0.66 g, yield 83%, mp 112-112.5 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 0.24 (s, 9H), 1.79 (s, 3H), 2.75 (s, IH), 6.98 (m, IH), 7.26-7.56 (m, 8H). MS(EI): m/z 294 (M + , 44). Example 19

2-Chloro-l-methyl-3-phenyl-lH-l-indenol (2c).

This compound was obtained from indenone Ic (0.30 g, 1.25 mmol) as a colourless oil

(0.27 g, yield 84%). 1 H-NMR (200 MHz, CDCl 3 ): 1.66 (s, 3H), 7.21-7.30 (m, 3H), 7.43-

7.61 (m, 6H). MS(EI): m/z 256 (M + , 40), 221(M - 35). Example 20

2-Bronio-l-methyl-3-phenyl-lH-l-indenol (2d).

This compound was obtained from indenone Id (0.080 g, 0.28 mmol) as a colourless oil, which crystallized on standing (0.078 g, yield 92%, mp 70-71 0 C). 1 H-NMR (200 MHz,

CDCl 3 ): 1.64 (s, 3H), 1.93 (br s, IH), 7.16-7.28 (m, 3H), 7.39-7.52 (m, 6H). MS(EI): m/z 300 (M + , 12), 221 (M - 79).

Example 21 l,2-Dimethyl-3-phenyl-lH-l-indenol (2e).

This compound (Figure 6) was obtained from indenone Ie (2.8 g, 12.7 mmol) as a white crystalline solid (2.0 g, yield 67%, pf 109-110 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.57 (s, 3H), 1.98 (s, 3H), 7.10-7.26 (m, 3H), 7.35-7.50 (m, 6H).

Example 22 l-Hydroxy-l-methyl-3-phenyl-lH-indene-2-carbonitrile (2f).

This compound was obtained from indenone If (1.0 g, 4.3 mmol) as a white crystalline solid (1.0 g, yield 94%, mp 127-128 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.78 (s, 3H), 7.33- 7.70 (m, 9H). MS(EI): m/z 247 (M + , 39), 232 (M - 15).

Example 23 l-Hydroxy-l-methyl-3-(4-methylphenyl)-lH-indene-2-carbonitri le (2g).

This compound was obtained from indenone Ig (0.50 g, 2.04 mmol) as a white crystalline solid (0.45 g, yield 84%, mp 135.4-136 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.77 (s, 3H), 2.44 (s, 3H), 7.32-7.60 (m, 8H). MS(EI): m/z 261 (M + , 41).

Example 24 l,6-Dimethyl-l-hydroxy-3-phenyl-lH-indene-2-carbonitrile (2h).

This compound was obtained from indenone Ih (0.50 g, 2.04 mmol) as a white crystalline solid (0.46 g, yield 86%, mp 147.8-148.5 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.76 (s, 3H), 2.43 (s, 3H), 7.17 (d, J= 7.6, IH), 7.32-7.53 (m, 5H), 7.66 (m, 2H). MS(EI): m/z 261 (M + ,

40).

Example 25

Ethyl l-Hydroxy-l-methyl-3-phenyl-lH-indene-2-carboxylate (2i).

This compound was obtained from indenone Ii (1.1 g, 3.95 mmol) as a white crystalline solid (0.73 g, yield 63%, mp 55-57 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.04 (t, J= 6.7, 3H), 1.78 (s, 3H), 3.66 (s, IH), 4.01-4.24 (m, 2H), 7.15 (d, J= 7.2, IH), 7.29-7.42 (m, 7H), 7.58 (d, J= 7.2, IH). MS(EI): m/z 294 (M + , 100). Example 26 l-Methyl-S-phenyl^-P-^-pyridylH-ethynyll-lH-l-indenol Cj). This compound was obtained from indenone Ij (0.40 g, 1.3 mmol) as a white crystalline solid (0.33 g, yield 79 %). An analytical sample was recrystallized from dichloromethane- diethyl ether by slow evaporation to obtain X-ray quality crystals (mp 164-164.5 0 C). 1 H- NMR (200 MHz, CDCl 3 ): 1.83 (s, 3H), 4.74 (br s, IH), 7.00 (m, IH), 7.26-7.54 (m, 8H), 7.61 (d, J = 6.9, IH), 7.79 (d, J = 7.2, 2H), 8.12 (d, J = 4.5, IH). MS(ESI): m/z 324 (M + H + ).

Example 27 2-Fluoro-l-methyl-3-phenyl-lH-l-indenol (2k). To a solution of indenol 2d (0.19 g, 0.63 mmol) in dry THF (10 mL) cooled at -78 0 C was added a solution of £-BuLi (1.7 M in pentane, 0.74 mL, 1.26 mmol). After stirring the mixture at the same temperature for 10 min, N-fluorobenzenesulfonimide (0.20 g, 0.63 mmol) was added and the reaction mixture was stirred at -78 0 C for other 30 min. Then, a saturated solution of νH4CI and diethyl ether were added and the mixture was allowed to warm to room temperature. The organic layer was separated, dried over sodium sulfate and evaporated under reduced pressure. Purification of the residue by flash chromatography with 9:1 petroleum ether-ethyl acetate as eluent gave indenol 2k as a colourless oil (55 mg, yield 36 %). 1 H-NMR (200 MHz, CDCl 3 ): 1.69 (s, 3H), 2.22 (br s, IH), 7.19-7.28 (m, 2H), 7.31-7.53 (m, 5H), 7.60 (m, 2H). MS(EI): m/z 240 (M + , 62). Example 28

2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Hydroxy-l-niethyl-3-(4-methylphenyl)-lH- indene-2-carboxylate (21).

This compound was obtained from indenone 11 (0.84 g, 2.05 mmol) and purified by flash chromatography with dimethoxyethane-petroleum ether (3 :7) as the eluent to give a colourless oil (0.72 g, yield 82 %). 1 H-NMR (CDCl 3 ): 1.76 (s, 3H), 2.38 (s, 3H), 3.29 (s, 3H), 3.50 (m, 10H), 3.76 (br s, IH), 4.22 (t, J = 4.8, 2H), 7.12-7.37 (m, 7H), 7.52 (m, IH). MS(ESI): m/z 449 (M+Na + ). Example 29

2,5,8,ll,14,17,20,23,26-Nonaoxaoctacosan-28-yl l-Hydroxy-l-methyl-3-(4- methy]phenyl)-lH-indene-2-carboxylate (2m).

This compound was obtained from indenone Im (3.5 g, 5.2 mmol) and purified by flash chromatography with dimethoxyethane-petroleum ether (6:4) as the eluent to give a colourless oil (2.6 g, yield 72 %). 1 H-NMR (CDCl 3 ): 1.73 (s, 3H), 2.36 (s, 3H), 3.31 (s, 3H), 3.41-3.59 (m, 34H), 4.21 (t, J = 4.6, 2H), 7.11 (m, IH), 7.18-7.37 (m, 6H), 7.51 (m, IH). MS(ESI): m/z 713 (M+Na + ). Example 30 Ethyl l-Hydroxy-l-methyl-ό-methoxy-S-phenyl-lH-indene^-carboxylat e (2n). This compound was obtained from indenone In (1.2 g, 3.9 mmol) and purified by recrystallization from n-hexane to obtain colourless prisms (0.84 g, yield 66%, mp 88.5-89 0 C). 1 H-NMR (200 MHz, CDCl 3 ): 1.04 (t, J = 7.0, 3H), 1.76 (s, 3H), 3.69 (br s, IH), 3.86 (s, 3H), 4.10 (m, 2H), 6.79 (dd, J = 8.3, 2.3, IH), 7.05 (d, J = 8.6, IH), 7. 14 (d, J = 2.0, IH), 7.37 (m, 5H). MS(ESI): m/z 347 (M+Na + ).

General Procedure for the Preparation of Solutions of Benzofulvene Monomers 3a,c- i,k-n in Chloroform or CDCl 3 .

A mixture of the appropriate indenol derivative (2a-i,k-n, typically 1.6 mmol) in chloroform or CDCl 3 (16 mL) with a catalytic amount of p-toluenesulfonic acid monohydrate (PTSA) (64 mg, 0.33 mmol) was heated under reflux for the appropriate time (typically from 30 min to 4 h) and cooled to room temperature. The reaction mixture was washed with a saturated solution of NaHCO 3 and dried over sodium sulfate to afford a stock (about 0.1 M) solution of the corresponding monomer (3a,c-i,k-n), which was stored under an argon atmosphere. Example 31 l-Methylene-3-phenyl-lH-indene (3a).

This monomer was obtained from indenol derivatives 2a or 2b following the above described general procedure. 1 H-NMR (200 MHz, CDCl 3 ): 5.78 (s, IH), 6.11 (s, IH), 6.62 (s, IH), 7.16-7.55 (m, 6H), 7.68 (m, 3H). MS(EI): m/z 204 (M + , 100). Example 32

2-Chloro-l-methylene-3-phenyl-lH-indene (3c).

This monomer was prepared from indenol 2c. 1 H-NMR (200 MHz, CDCl 3 ): 6.02 (s, IH),

6.16 (s, IH), 7.24 (m, 3H), 7.36-7.63 (m, 6H). MS(EI): m/z 238 (M + , 100).

Example 33 2-Bromo-l-methylene-3-phenyl-lH-indene (3d).

This monomer was prepared from indenol 2d. 1 H-NMR (200 MHz, CDCl 3 ): 6.01 (s, IH),

6.19 (s, IH), 7.26 (m, 2H), 7.42-7.62 (m, 7H). MS(EI): m/z 282 (M + , 100). Example 34

2-Methyl-l-methylene-3-phenyl-lH-indene (3e).

This monomer was prepared from indenol 2e. 1 H-NMR (200 MHz, CDCl 3 ): 2.18 (s, 3H),

5.78 (s, IH), 6.09 (s, IH), 6.99-7.62 (m, 9H). MS(EI): m/z 218 (M + , 100).

Example 35 l-Methylene-3-phenyl-lH-indene-2-carbonitrile (3f).

This monomer was prepared from indenol 2f. 1 H-NMR (200 MHz, CDCl 3 ): 6.17 (s, IH),

6.37 (s, IH), 7.40-7.76 (m, 9H). MS(EI): m/z 229 (M + , 100).

Example 36 l-Methylene-3-(4-methylphenyl)-lH-indene-2-carbonitrile (3g). This monomer was prepared from indenol 2g. 1 H-NMR (200 MHz, CDCl 3 ): 2.45 (s, 3H),

6.14 (s, IH), 6.34 (s, IH), 7.34-7.77 (m, 8H). MS(EI): m/z 243 (M + , 100).

Example 37

6-Methyl-l-methylene-3-phenyl-lH-indene-2-carbonitrile (3h).

This monomer was prepared from indenol 2h. 1 H-NMR (200 MHz, CDCl 3 ): 2.47 (s, 3H), 6.12 (s, IH), 6.33 (s, IH), 7.22 (d, J = 7.9, IH), 7.39-7.64 (m, 5H), 7.68-7.82 (m, 2H).

MS(EI): m/z 243 (M + , 100).

Example 38

Ethyl l-Methylene-3-phenyl-lH-indene-2-carboxylate (3i).

This monomer was prepared from indenol 2i. 1 H-NMR (200 MHz, CDCl 3 ): 1.06 (t, J= 7.1, 3H), 4.14 (q, J = 7.1, 2H), 6.39 (s, IH), 6.60 (s, IH), 7.21-7.49 (m, 8H), 7.72 (m, IH).

MS(EI): m/z 276 (M + , 100).

Example 39

2-Fluoro-l-methylene-3-phenyl-lH-indene (3k).

This monomer was prepared from indenol 2k. 1 H-NMR (200 MHz, CDCl 3 ): 5.89 (s, IH), 6.05 (s, IH), 7.13-7.27 (m, 2H), 7.31-7.52 (m, 5H), 7.63 (m, 2H). MS(EI): m/z 222 (M + ,

100).

Example 40 l-Methylene-3-phenyl-2[2-(2-pyridyl)-l-ethynyl]-lH-indene (3j).

A mixture of indenol 2j (0.25 g, 0.77 mmol) in formic acid (20 mL) was stirred at 50 0 C for 30 min. The reaction mixture was then concentrated under reduced pressure (without the complete elimination of the solvent), diluted with CDCI3 (20 mL), washed with water and dried over sodium sulfate. 1 H-NMR (200 MHz, CDCl 3 ): 6.24 (s, IH), 6.26 (s, IH), 7.15 (m, IH), 7.25-7.69 (m, 9H), 7.82 (d, J = 7.6, 2H), 8.57 (d, J = 4.5, IH). MS(ESI): m/z 306 (M + H + ). Example 41

2-[2-(2-Methoxyethoxy)ethoxy]ethyl l-Methylene-3-(4-methylphenyl)-lH-indene-2- carboxylate (31). This monomer was prepared from indenol 21 (0.60 g, 1.4 mmol). 1 H-NMR (200 MHz, CDCl 3 ): 2.41 (s, 3H), 3.34 (s, 3H), 3.51 (m, 10H), 4.26 (t, J = 4.9, 2H), 6.36 (s, IH), 6.60 (s, IH), 7.23-7.39 (m, 7H), 7.70 (m, IH). MS(ESI): m/z 43 \ (M+Na + ). Example 42 2,5,8,ll,14,17,20,23,26-Nonaoxaoctacosan-28-yl l-Methylene-3-(4-methylphenyl)-lH- indene-2-carboxylate (3m).

This monomer was prepared from indenol 2m (2.6 g, 3.76 mmol). 1 H-NMR (400 MHz, CDCl 3 ): 2.38 (s, 3H), 3.32 (s, 3H), 3.44 (t, J = 4.7, 2H), 3.48-3.60 (m, 32H), 4.23 (t, J = 4.9, 2H), 6.33 (s, IH), 6.56 (s, IH), 7.21-7.31 (m, 7H), 7.67 (ά, J= 7.4, IH). MS(ESI): m/z 695 (M+Na + ). Example 43

Ethyl l-Methylene-6-methoxy-3-phenyl-lH-indene-2-carboxylate (3n). This monomer was prepared from indenol 2n. 1 H-NMR (200 MHz, CDCl 3 ): 1.03 (t, J = 7.3, 3H), 3. 86 (s, 3H), 4.10 (q, J = 7.0, 2H), 6.32 (s, IH), 6.60 (s, IH), 6.81 (dd, J = 8.3, 2.3, IH), 7.10 (d, J = 8.2, IH), 7.25 (d, J = 2.5, IH), 7.40 (m, 5H). MS(ESI): m/z 329 (M+Na + ).

General Procedure for the Preparation of Poly-Benzofulvene Derivatives Poly-3a,c-n: Spontaneous Polymerization.

The solution of the appropriate benzofulvene monomer 3a,c-n in CHCl 3 was concentrated under reduced pressure to give a viscous oil, which was dissolved in ethyl acetate or CHCI3 (10 mL/ 1 mmol of monomer) and newly evaporated (this procedure of dissolution/evaporation was repeated four times). The final residue was dissolved in the same solvent (5 mL/mmol of monomer) and precipitated with ethanol (15 mL/mmol of

monomer) The precipitate was collected by filtration and dried under reduced pressure to give the expected polymer (poly-3a,c-k,n ). On the other hand, poly-31,m, were purified by washing with the appropriate solvents.

Example 44 Poly(l-Methylene-3-phenyl-lH-indene) (Poly-3a).

This polymer was obtained from monomer 3a as an off-white amorphous solid (yield

72%). 1 H-NMR (200 MHz, CDCl 3 ): 0.6-3.5 (br s, 2H), 5.9-8.3 (br m, 10H). MALDI-TOF spectrum: see Figure 7.

Example 45 Poly(2-Chloro-l-methylene-3-phenyl-lH-indene) (Poly-3c).

This polymer was obtained from monomer 3c as a white amorphous solid (yield 77%). 1 H-

NMR (200 MHz, CDCl 3 ): 1.3-3.3 (br m, 2H), 5.5-7.6 (br m, 9H).

Example 46

Poly(2-Bromo-l-methylene-3-phenyl-lH-indene) (Poly-3d). This polymer was obtained from monomer 3d as a white amorphous solid (yield 58%). 1 H-

NMR (200 MHz, CDCl 3 ): 1.4-3.6 (br m, 2H), 5.2-7.7 (br m, 9H).

Example 47

Poly(2-Methyl-l-methylene-3-phenyl-lH-indene) (Poly-3e).

This polymer was obtained from monomer 3e as a white amorphous solid (yield 60%). 1 H- NMR (200 MHz, CDCl 3 ): 1.2 (br s, 3H), 2.2-3.3 (br s, 2H), 5.5-7.5 (br m, 9H).

Example 48

Poly(l-Methylene-3-phenyl-lH-indene-2-carbonitrile) (Poly-3f).

This polymer was obtained from monomer 3f as a white amorphous solid (yield 82%). 1 H-

NMR (200 MHz, CDCl 3 ): 2.2-3.6 (br s, 2H), 6.1-7.9 (br m, 9H). Example 49

Poly-[l-Methylene-3-(4-methylphenyl)-lH-indene-2-carbonit rile] (Poly-3g).

This polymer was obtained from monomer 3g as a white amorphous solid (yield 90%). 1 H-

NMR (200 MHz, CDCl 3 ): 2.2 (br s, 3H), 2.9 (br s, 2H), 5.9-7.9 (br m, 8H).

Example 50 Poly(6-Methyl-l-methylene-3-phenyl-lH-indene-2-carbonitrile) (Poly-3h).

This polymer was obtained from monomer 3h as a white amorphous solid (yield 87%). 1 H-

NMR (200 MHz, CDCl 3 ): 1.8 (br s, 3H), 2.8 (br s, 2H), 6.0-7.7 (br m, 8H).

Example 51

Poly(Ethyl l-Methylene-3-phenyl-lH-indene-2-carboxylate) (Poly-3i).

This polymer was obtained from monomer 3i as a white amorphous solid (yield 73%). 1 H-

NMR (200 MHz, CDCl 3 ): 0.8 (br s, 3H), 2.7-4.3 (br m, 4H), 5.8-7.4 (br m, 9H). 13 C-NMR

(150 MHz, CDCl 3 ): 13.7, 48.4, 50.8, 57.8, 59.3, 122.9, 126.3, 130.0, 135.1, 142.7, 148.9, 151.7, 163.7, 163.9.

Example 52

Poly[l-Methylene-3-phenyl-2[2-(2-pyridyl)-l-ethyny]]-lH-inde ne] (Poly-3j). This polymer was obtained from monomer 3j as a light brown amorphous solid (yield 55%). 1 H-

NMR (200 MHz, CDCl 3 ): 1.8-3.8 (br s, 2H), 5.7-7.7 (br m, 12H), 8.0-8.7 (br s, IH). Example 53

Poly(2-Fluoro-l-methylene-3-phenyl-lH-indene) (Poly-3k).

This polymer was obtained from monomer 3k as a white amorphous solid (yield 82%). 1 H-

NMR (200 MHz, CDCl 3 ): 1.5-3.2 (br m, 2H), 5.9-7.9 (br m, 9H).

Example 54 Poly[2-[2-(2-Methoxyethoxy)ethoxy] ethyl l-Methylene-3-(4-methylphenyl)-lH- indene-2-carboxylate] (Poly-31).

This polymer was obtained from monomer 31 and purified by washing with petroleum ether giving a glassy colourless solid (yield 75%). 1 H-NMR (200 MHz, CDCl 3 ): 2.2 (br s,

3H), 2.8-3.7 (br m, 17H), 5.3-7.2 (br m, 8H). 13 C-NMR (100 MHz, CDCl 3 ): 21.1, 48.3, 57.6, 59.0, 62.2, 68.2, 70.1, 70.5, 71.9, 122.7, 126.3, 129.5, 131.5, 133.5, 135.7, 142.3,

148.4, 150.8, 163.4.

Example 55

Poly(2,5,8,ll,14,17,20,23,26-Nonaoxaoctacosan-28-yl l-Methylene-3-(4- methylphenyl)-lH-indene-2-carboxylate) (Poly-3m). This polymer was obtained from monomer 3m and purified by washing with diethyl ether giving a colourless gummy solid (yield 92%). 1 H-NMR (200 MHz, DMSO-d 6 ): 2.3 (br s,

3H), 2.7-4.0 (br m, 41H), 5.4-7.9 (br m, 8H).

Example 56

Poly(Ethyl l-Methylene-6-methoxy-3-phenyl-lH-indene-2-carboxylate) (Poly-3n). This polymer was obtained from monomer 3n as a white amorphous solid (yield 71%). 1 H-

NMR (200 MHz, CDCl 3 ): 0.3-1.2 (br m, 3H), 2.5-4.4 (br m, 7H), 5.8-7.5 (br m, 8H). 13 C-

NMR (100 MHz, CDCl 3 ): 13.4, 48.5, 54.7, 57.1, 58.6, 111.2, 113.3, 122.8, 126.0, 130.1,

132.8, 135.2, 150.1, 150.9, 158.6, 163.8.

Methods

Size Exclusion Chromatography (SEQ

The molecular characterization of polybenzofulvene derivatives was performed by a multi- angle light scattering (MALS) photometer on-line to a SEC chromatographic system. The SEC-MALS system consisted of an Alliance chromatographic system from Waters (Milford, MA, USA), a MALS Dawn DSP-F photometer from Wyatt (Santa Barbara, CA, USA), and a differential refractometer (Waters model 410) used as concentration detector. The multi-detector SEC-MALS system has been described in detail elsewhere 22 ' 23 . The column set was composed of two mixed Styragel SEC columns (HR5E and HR4E) from Waters. The experimental conditions consisted of tetrahydrofuran (THF) as mobile phase, a temperature of 35 0 C and 0.8 mL/min of flow rate. The calibration constant of the MALS photometer was calculated using toluene as standard assuming a Rayleigh Factor of 1.406 10 "5 cm 1 . The MALS angular normalization was performed by measuring the scattering intensity of a very narrow low molar mass polystyrene standard (M = 10.9 Kg/mo 1, D < 1.03) in the mobile phase which was assumed to act as an isotropic scatterer. The refractive index increment, dn/dc, of the polymer with respect to the mobile phase at 25 0 C was measured by a KMX- 16 differential refractometer from LDC Milton Roy (Rochester, NY, USA). Mass spectrometry

Mass spectra have been obtained by using an ion trap mass spectrometer. The atmospheric pressure chemical ionization technique was used with the following source parameters: positive ion mode, discharge current 8 mA, vaporizer temperature 450 0 C, capillary temperature 200 0 C, capillary voltage 1 IV. The mass spectrometry characterization of polybenzofulvene derivatives has been carried out by a MALDI-TOF/TOF instrument. 10 mL of a CHCI 3 solution of the polymer (lOmg/mL) were mixed with 1,8,9-trihydroxyanthracene (Dithranol, Fluka) as a matrix and submitted to the N 2 (337 nm) laser desorption. Scanning Electron Microscopy (SEM) Studies The material was mounted on aluminum holders by carbon conductive glue and coated with 20nm gold in a Balzer's MED 010 sputtering device. The samples were finally observed with a Philips XL20 scanning electron microscope operating at an accelerating voltage of 2O kV.

X-ray Crystallography

Single crystals of le,h, 2e, and 5g were submitted to X-ray data collection on a four-circle diffractometer with graphite monochromated Mo-Ka radiation (λ = 0.71069A). The ω/2θ scan technique was used. The structures were solved by direct methods and the refinements were carried out by full-matrix anisotropic least-squares of F2 against all reflections. The hydrogen atoms were located on Fourier difference maps, or placed in calculated positions and included in the structure-factor calculations with isotropic temperature factor. Atomic scattering factors including f ' and f " were taken from ref. 24. Structure solution was carried out by SHELXS-97. 25 Structure refinement and molecular graphics were performed by SHELX-97 24 and the WinGX package, 26 respectively.

Bibliography

[I] T. Nakano, K. Takewaki, T. Yade, Y. Okamoto, J. Am. Chem. Soc. 2001, 123, 9182-9183.

[2] T. Nakano, T. Yade, J. Am. Chem. Soc. 2003, 125, 15474-15484.

[3] T. Nakano, T. Yade, Y. Fukuda, T. Yamaguchi, S. Okumura, Macromolecules .

2005, 38, 8140-8148.

[4] T. Nakano, O. Nakagawa, M. Tsuji, M. Tanikawa,T. Yade, Y. Okamoto. Chem. Comm. 2004, 144-145.

[5] T. Nakano. Heat-Decomposable Polymer. WO03095523

[6] T. Nakano. Polymer Having Unique Optical Property and Polymerizable Monomer thereof. US2004132963

[7] T. Nakano. Optically Active High-Molecular Compounds. US2005234267 [8] T. Nakano, T. Yade, M. Yokoyama, N. Nagayama, Chem. Lett. 2004, 296-297

[9] F. Ilhan, V. M. Rotello, J. Org. Chem., 1999, 64, 1455-1458.

[10] T. M. Londergan, C. J. Teng, W. P. Weber, Macromolecules, 1999, 32, 1111-1114

[I I] A. Cappelli, G. Pericot Mohr, M. Anzini, S. Vomero, A. Donati, M. Casolaro, R. Mendichi, G. Giorgi, F. Makovec, J. Org. Chem. 2003, 68, 9473-9476. [12] A. Cappelli, M. Anzini, S. Vomero, A. Donati, L. Zetta, R. Mendichi, M. Casolaro, P. Lupetti, P. Salvatici, G. Giorgi, J. Polym. ScL Part A. 2005, 43, 3289-3304. [13] R. C. Larock, M. J. Doty, S. Cacchi. J. Org. Chem. 1993, 58, 4579-4583. [14] A. Marsili, Ann. Chim. 1961, 51, 237-251. [15] C. F. Koelsch, J. Org. Chem. 1960, 25, 2088-2091.

[16] J. H. Ahn, M. S. Shin, S. H. Jung, S. K. Kang, K. R. Kim, S. D. Rhee, W. H. Jung,

S. D. Yang, S. J. Kim, J. R. Woo, J. H. Lee, H. G. Cheon, S. S. Kim, J. Med. Chem. 2006,

49, 4781-4784.

[17] A. M. Echavarren, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 5478-5486. [18] K. Sonogashira, Y. Tohda, N. Hagihara. Tetrahedron Lett. 1975, 50, 4467-4470.

[19] C. Thibault, A. Lηeureux, R. S. Bhide, R. Ruel. Org. Lett. 2003, 5, 5023-5025.

[20] A. Cappelli, et al, J. Med. Chem. 2006, 49, 6451-6464.

[21] R. De Fazi. Gazz. Chim. Ital. 1916, 46, 256-261.

[22] R. Mendichi, A. Giacometti Schieroni, in Current Trends in Polymer Science, Vol. 6, (Ed.: S. G. Pandalai), Trans-World Research Network, Trivandrum (India), 2001, pp.

17-32.

[23] P. J. Wyatt, Anal. Chim. Acta 1993, 272, 1-40.

[24] G. Sheldrick SHELXL-97, A Program for Crystal Structure Refinement, University of Gottingen, Gottingen (Germany), Release 97-2, 1997. [25] G. Sheldrick SHELXS-97, A Program for Automatic Solution of Crystal Structures,

University of Gottingen, Gottingen (Germany), Release 97-2, 1997.

[26] L. J. Farrugia, J. Appl. Cryst. 1999, 32, 837.