ES2237309B1 - POLYMERS WITH STANNYL GROUPS DERIVED FROM THE VINYL POLYMERIZATION OF STANNED NORBORNENS, PROCEDURE FOR THEIR OBTAINING AND APPLICATIONS. - Google Patents

Abstract

Polymers with stannyl groups derived from the vinyl polymerization of stagnant norbornenes, process for obtaining them and applications. These are new polymers obtained from the vinyl polymerization of norbornene derivatives with Sn (R) 2R '' groups or the copolymerization of those derivatives with norbornene, where R is an alkyl group and R '' can be a group, alkyl, aryl, vinyl or a halide. These polymers are useful in synthesis reactions of organic compounds that use tin derivatives as reagents (for example in the Stille reaction or in other stoichiometric reactions of C-C bond formation), since they give rise to easily recoverable and recyclable by-products. Its saturated, stable and very little reactive aliphatic skeleton makes them interesting in the rest of applications where additives containing tin are used.

Description

Polymers with stannyl groups derived from vinyl polymerization of stagnant norbornenes, process for obtaining and applications.

Technical sector

The present invention falls within the field of polymers that contain tin and provide polymers with a fully aliphatic and saturated skeleton containing groups stannyl, which makes them applicable as recyclable reagents in the synthesis of organic products on a large scale and in the rest of uses where tin derivatives are used as additives.

State of the art

Tin organometallic derivatives (R 3 SnR ', R = alkyl group, R' = hydrocarbon group such as aryl or alkenyl, etc.) constitute common reagents and very useful in organic synthesis for the formation of new CC bonds. They are more stable derivatives than other organometallic representative elements (Li, Mg, Al, etc.), therefore more manageable, and are compatible with the presence of a wide variety of functional groups. This has turned reactions such as the coupling of organic electrophiles with tin derivatives catalyzed by palladium complexes (Stille reaction) into one of the most versatile and used in fine chemistry (see Farina, V .; Krishnamurthy, V .; Scott, WJ The Stille Reaction , Wiley, New York, 1998).

A problem that appears in this process is the effective separation of tin halide or sulphonate (R 3 SnX, X = halide, organic sulphonate) that is produced as a byproduct of the reaction mixture. Some method has been developed that allows remove it, primarily by converting in the corresponding insoluble trialkyltin fluoride by addition of an alkaline fluoride. The insoluble fluoride however is not can effectively convert into a tetraorganostannan that could be used again in the reaction, so in the C-C coupling process is generated inevitably an undesirable residue, potentially toxic, that It contains a heavy metal (Sn) and is therefore difficult to store and remove. This is a very important difficulty if the reaction of Stille or other C-C coupling reactions with tin reagents are to be carried out to scale industrial.

The present invention consists in the development of a polymeric material containing -SnR 2 R 'groups (R = alkyl group, R' = hydrocarbon group such as aryl, alkenyl, alkyl, acyl, etc.). When this polymer is used as a reagent in the Stille reaction, the reaction byproduct, a polymer with -SnR2 X groups (X = halide, sulfonate), can be easily separated without the need to transform it into the corresponding fluroride. Finally, the regeneration of the reagent (of the SnR2R 'groups) allows the recycling of the tin derivative. There are some precedents for the use of polymers containing Sn-H groups as reagents in radical organic reactions (Gerigk, U .; Gerlach, M .; Neumann, WP; Vieler, R .; Weintritt, V. Synthesis , 1990, 448-452 ; Bolkemann, C .; Neumann, WP; Peterseim, M. J. Chem. Soc. Perkin Trans. I , 1992, 3165-3166; see also the recent review by Kirschning, A .; Monenschein, H .; Wittenberg, R Angew. Chem. Int. Ed . 2001, 40, 650-679) and also an example in Stille's reaction (Kuhn, H .; Neumann, WP Synlett , 1994, 123-124). In the latter case, a functionalized polystyrene different from the totally aliphatic skeleton of the polymers of the present invention was used.

The introduction of tin derivatives in carbon polymeric materials has an industrial interest because tin is a fundamental element in the manufacture of highly resistant rubbers, as well as in the preparation of paints that prevent the proliferation of living organisms on surfaces, and which are used in the outer covering of boats. Tin compounds are generally introduced afterwards, onto the already formed polymeric material (Hsu, W. -L .; Halasa, AF US patent, Appl. No. 364200, 1999; Takeichi, H .; Graves, DF; Sarkar, SB; Lawson, D. US patent, Appl. No. 229025, 1999; Mercier, FAG; Biesemans, M .; Altman, R. Willem, R .; Pintelon, R .; Schoukens, J .; Delmon, B .; Dumartin, G. Organometallics , 2001, 20 , 958-962). There are, however, fewer processes that allow the polymerization or copolymerization of monomers that already contain the group -SnR 3. The polymerization of some norbornene derivatives with stannyl groups has been described by a ROMP (Ring Opening Metathesis Polymerization or ring breaking metathesis) process that leads to polymers in which the norbornene unit has been broken and whose chain contains unsaturations ( double bonds) and therefore centers that can potentially lead to undesirable side reactions (Lequan, M .; Lequan, RM; Villemin, D. Chem. & Ind . 1984, 379; Cummins, CC; Beachy, MD; Schrock, RR ; Vale, MG; Sankaran, V .; Cohen, RE Chem. Mat . 1991, 3 , 1153-1163). The polymers collected here maintain the norbornene bicycles and have a totally aliphatic and saturated skeleton, therefore very little reactive, which makes them good candidates for use in all those applications in which derivatives with tin are useful and require stable support. .

Description of the invention

The present invention collects the synthesis of new polymers resulting from the vinyl polymerization of monomers derived from the norbornene skeleton with groups SnR 2 R ', where R is an alkyl group and R' can be a group hydrocarbon or halide.

The polymers described are valuable in the preparation of organic compounds in the field of industry Fine chemistry by Stille reaction. The ease of Reagent of tin reagent and total product separation objective makes them applicable in the manufacture of products Pharmaceuticals

Also useful are said tin polymers as stable additives in the manufacture of rubbers and paints.

Detailed description of the invention

A monomer derived from the norbornene skeleton with a double bond and a substituent SnR 2 R 'in a non-vinyl position where R is an alkyl group and R' can be a hydrocarbon group is polymerized. It is also possible to polymerize a mixture of monomers such as exo -5-SnR2R'-bicyclo [2.2.1] hept-2-eno (hereinafter exo -5-SnR2R'NBN), endo -5-SnR 2 R'-bicyclo [2.2.1] hept-2-eno (hereinafter endo -5-SnR 2 R'NBN), 7-SnR 2 R'-bicyclo [2.2. 1] hept-2-eno (hereinafter 7-SnR_ {2} R'NBN) and 3-SnR_ {2} R'-nortricylan (hereinafter 3-SnR_ {2} R'NTC). Said mixture of monomers (SnR 2 R'NBN) is obtained in two steps, by radical addition of SnR 2 HCl to norbornadiene (or a norbornadiene derivative in the case of other mixtures of similar monomers) to obtain a mixture of exo -5-SnR 2 ClNBN, endo -5-SnR 2 ClNBN, 7-SnR 2 ClNBN and 3-SnR 2 ClNTC, and subsequent treatment with the corresponding Grignard derivative XMgR '. The polymerization of SnR 2 R'NBN is carried out by means of a procedure consisting in the use as catalysts of nickel complexes of the [Ni (Rx) 2 L 2] type where Rx = haloaryl group, aryl 2 , 6-substituted; L = labile ligand, and leads to polymers soluble in organic solvents such as dichloromethane or tetrahydrofuran but poorly soluble in methanol, with molecular weights around 15,000 dalton (Mw) and polydispersities between 1.5 and 3 depending on the specific polymer. The polymerization yields are acceptable (about 70% of the total vinyl monomers in the mixture).

Copolymerization of the monomer mixture anterior with norbornene (NBN) using the same type of catalysts leads to copolymers poly-SnR 2 R'NBN-NBN where R is an alkyl group and R 'can be a hydrocarbon group such as alkyl, aryl, vinyl or also X (and X = Cl, Br, I). These copolymers have higher molecular weights than the previous ones (Mw, 30,000-60,000 dalton). The incorporation of NBN in the copolymer it can be controlled by varying the monomer ratio initial and thus the NBN / SnR2 R'NBN molar ratio in the polymer goes from 1.13 to 2.7 when an initial molar ratio is used NBN / SnR 2 R'NBN of 0.5 and 2. There is also an increase in molecular weight by increasing the incorporation of NBN. However yes the NBN molar ratio: SnR 2 R'NBN reaches 3: 1 part of the NBN no it is incorporated into the copolymer and polymerized independently obtaining a mixture of polymers. Starting from the same proportion of monomers there are variations in the percentage of incorporation NBN that also depends on other factors such as concentration of the solutions containing the monomer mixture. As in the In the case of homopolymers, the copolymers obtained are soluble in dichloromethane or tetrahydrofuran but poorly soluble in methanol; the solubility in other organic solvents varies according to the nature of R 'which is advantageous for some of the applications described below. The returns of the polymerization are good (between 70% and 100% with respect to the total of vinyl monomers in the mixture and depending on the ratio of initial monomers).

Both polymers poly-SnR 2 R'NBN as the poly-SnR 2 R'NBN-NBN present a saturated aliphatic carbon skeleton as corresponds to a polymerization of vinyl type and as the spectra of proton nuclear magnetic resonance. Said aliphatic skeleton It is little reactive and chemically stable for many applications. The reactivity on tin, without altering the carbon skeleton, It can be modulated and designed at will by modifying the nature of R '. If R '= alkyl the resulting polymers are derived Very chemically stable tetraalkyltin.

\hbox{R' =}

grupo hidrocarbonado) en presencia de un catalizador de paladio de los habitualmente usados en la reacción de Stille, conduce a los productos orgánicos de acoplamiento R'-R'' y a un nuevo polímero estannilado poli-SnR_{2}XNBN o poli-SnR_{2}XNBN-NBN. Este polímero, generalmente menos soluble que el de partida, puede recuperarse de la mezcla de reacción por simple enfriamiento o por adición de un disolvente como metanol y posterior filtración.The nature of these polymers allows their use as reagents in the Stille reaction, where they behave as transfer agents of a group R '. The heating of an organic electrophile (R '' X) with the poly-SnR2 R'NBN or poly-SnR2R'NBN-NBN polymers described above (where

 \ hbox {R '=} 

hydrocarbon group) in the presence of a palladium catalyst of those commonly used in the Stille reaction, leads to organic coupling products R'-R '' and a new standard poly-SnR2 XNBN or poly-SnR_ { 2} XNBN-NBN. This polymer, generally less soluble than the starting one, can be recovered from the reaction mixture by simple cooling or by adding a solvent such as methanol and subsequent filtration.

The poly-SnR2 XNBN polymer or poly-SnR2 XNBN-NBN recovered can be transformed back into poly-SnR2R'NBN or poly-SnR 2 R'NBN-NBN by treatment with the corresponding organo-derivative of lithium (LiR ') or of magnesium (XMgR ') and reused in the Stille reaction. He process can be repeated several times without loss of activity reagent.

Embodiment

The present invention is illustrated by following examples that should not be considered as limiting the same.

Example 1 Homopolymerization of SnR 2 R'NBN with R = R '= n-butyl

The synthesis of the SnBu 3 NBN monomer was carried out by radical addition of HSnBu 3 over norbornadiene using AIBN as an initiator. The product is a mixture of exo -5-SnBu 3 NBN, endo -5-SnBu 3 NBN, 7-Sn Bu 3 NBN and 3-Sn Bu 3 NTC in molar proportions (%), 25: 37: 10: 28. These isomers were identified by multinuclear magnetic resonance in the mixture and the proportions between them by integration of the 1 H NMR signals.

About 0.5615 g (1.47 mmol) of the mixture of SnBu 3 NBN monomers deposited in a schlenk under nitrogen are add 3 mL of dry dichloromethane and 0.0322 g (0.029 mmol) of nickel catalyst [Ni (C 6 F 5) 2 (SbPh 3) 2]. An orange solution is obtained which is kept under stirring at room temperature for one day. Yellow solution resulting it is poured on methanol under stirring obtaining a white solid that is filtered and dried. (0.2479 g, yield: 45%). He polymer has a molecular weight Mw = 15163 and Mw / Mn = 3.19, determined by size exclusion chromatography.

Example 2 Copolymerization of SnR 2 R'NBN with R = n-butyl and R '= 4-methoxyphenyl (in forward SnBu_ {An} BN) with norbornene (NBN)

Prior to the description of the reaction of copolymerization details the preparation of the monomers used.

Synthesis of SnBu_ {2} ClNBN . In a low nitrogen schlenk, AIBN (0.041 g, 0.2133 mmol), norborne Canadian (2.2631 g, 24.6 mmol) are weighed in excess, and SnBu 2 Cl 2 (1.2459 g, 4.1 mmol). The mixture is stirred to obtain a solution that is immersed in a water bath at room temperature and over it the Bu 2 SnH 2 (0.9528 g, 4.1 mmol) is added very slowly with a syringe; prepared as described in Van der Kerk, GJM; Noltes, JG; Luijten, JGA J. Appl. Chem . 1957, 366-374). After the addition, the reaction mixture is kept under stirring and in the bath for about twelve hours, being observed that it loses its yellowish coloration. Finally, the excess of Norbornadiene is evaporated from the mixture, obtaining a colorless liquid (2.4439 g, yield: 82.4%). The product is a mixture of the exo -5-SnR 2 ClNBN, endo -5-SnR 2 ClNBN, 7-SnR 2 ClNBN and 3-SnR 2 ClNTC isomers in molar proportions (%) 48: 41:
8: 3. The products were identified by multinuclear magnetic resonance in the mixture and the proportions between them by integration of the 1 H NMR signals.

Synthesis of SnBu_ {2} AnNBN . A solution of the magnesium derivative MgBr ( p -OMe-C 6 H 4) in dry THF (20 mL) is prepared. On the above solution, at 10 ° C, SnBu 2 ClNBN (2.8000 g, 7.7 mmol) is added leaving the mixture under stirring at room temperature for twelve hours. After that time, the mixture is taken to a separatory funnel and extracted twice with Et2O / H2O (10 mL / 10 mL) and the organic phase is washed with a saturated NH_ solution. 4} Cl (15 mL) and then twice with a NaCl solution (15 mL). Dry over anhydrous magnesium sulfate, filter and evaporate the solvent to dryness. A somewhat viscous yellow-orange liquid is obtained (2.9461g, yield: 87%). The product is a mixture of the isomers exo-5-SnR 2 ClNBN, endo -5-SnR 2 ClNBN, 7-SnR 2 ClNBN and 3-SnR 2 ClNTC in molar proportions (%) 39: 36: 9: 16. The products were identified by multinuclear magnetic resonance in the mixture and the proportions between them by integration of the 1 H NMR signals.

Copolymerization of SnBu2 AnNBN with NBN . In a schlenk under nitrogen 1.09 mL of a 0.838 M solution of NBN in dichloromethane (0.913 mmol), the mixture of SnBu2 AnNBN monomers (0.3 mL, 0.913 mmol) 2.5 mL of dichloromethane are added and finally 0.0207 g (0.018 mmol ) of [Ni (C 6 Cl 2 F 3) 2 (SbPh 3) 2]. The yellow mixture is kept under stirring for one day at room temperature. After this time, it is poured onto methanol under stirring to obtain a white solid that is filtered, washed with methanol and dried (0.3224 g, yield: 67%). The polymer has a molecular weight Mw = 38200 and Mw / Mn = 1.87, determined by size exclusion chromatography. It was also characterized by multinuclear magnetic resonance. The incorporation of NBN is determined by comparing the relative intensity of the signals corresponding to the 4-methoxyphenyl group and the aliphatic zone. 1 H NMR (CDCl 3, \ Box, 300 MHz): 7.4 (broad, 2H, aromatic), 6.8 (wide, 2H, aromatic), 3.7 (singlet, 3H, OMe), 0.7-2.6 ( wide signals, Bu, H 1-7 of the norbornene skeleton).

Example 3 Use of polySnBu2 AnNBN-NBN in a reaction Stille and copolymer recovery

In a glass reactor, the copolymer polySnBu2 AnNBN-NBN (3 g, 5.15 mmol), iodopentafluorobenzene (0.55 mL, 4.12 mmol) and the palladium compound [Pd2 (\ mu-Br) 2
(C 6 F 5) 2 (AsPh 3) 2] (0.136 g, 0.1 mmol) as a catalyst in 75 mL of dry dioxane. The reactor is sealed and the solution is heated at 90 ° C for 3 days.

After this time the conversion, measured by NMR of 19_ {F}, reaches 76%. You can get conversions higher by increasing the reaction time (7 days, 91%) although in the tests performed to verify the applicability of these Polymers this standard reaction time was employed. After the three days the mixture cools appearing a blackish solid corresponding to polySnBu_ {2} INBN-NBN (impurified with metallic palladium responsible for the blackish color). The polymer is filtered, washed with dioxane and dried by passage of air (2.34 g). The filtrate is evaporated to dryness and on the residue methanol (30 mL) is added, a yellowish white solid appearing (0.91 g) containing the polySnBu 2 AnNBN-NBN unreacted together with the reaction product 4-methoxyphenylpentafluorobenzene, (which may subsequently separated by washing with more methanol). Reducing the volume of the solution in methanol a white solid appears crystalline: 4-methoxyphenylpentafluorobenzene pure.

The recovered polymer polySnBu_ {2} INBN-NBN can be converted again in polySnBu2 AnNBN-NBN by reaction with the organometallic derivative Li (4-OMe-C 6 H 4) in THF at room temperature for 2 days. The new polySnBu2 AnNBN-NBN thus obtained as a solid white can be reused again in the Stille reaction without loss of efficiency

Claims (6)

1. Polymer derived from the vinyl polymerization of a substituted norbornene characterized in that it contains: An aliphatic skeleton derived from norbornene, SnR2 R 'groups attached to the polymer chain, where R is an alkyl group and R' is a group hydrocarbon 2. Copolymer derived from the joint vinyl polymerization of norbornene and a substituted norbornene, characterized in that it contains: An aliphatic skeleton derived from norbornene, SnR2R 'groups attached to the polymer chain, where R is an alkyl group and R 'can be a hydrocarbon group or X (where X = Cl, Br, I). 3. Process for obtaining tin-containing polymers, according to claim 1, characterized in that it comprises the homopolymerization of norbornene derivatives with SnR2R 'groups through the use of a nickel complex. The norbornenes may be substituted by stanyl groups in position 5 (exo or endo) or in position 7. In the groups SnR2 R ', R is an alkyl group and R' is a hydrocarbon group. The nickel complexes conform to the formula [Ni (Rx) 2 L 2] where Rx = haloaryl group, 2,6-substituted aryl and L is a labile ligand. 4. Process for obtaining tin-containing copolymers, according to claim 2, characterized in that it comprises the copolymerization of norbornene derivatives with SnR2R 'and norbornene groups by using a nickel complex. The norbornenes contain stanyl groups in position 5 (exo or endo) or in position 7. In the groups SnR 2 R ', R is an alkyl group and R' can be a hydrocarbon or halide group. The nickel complexes conform to the formula [Ni (Rx) 2 L 2] where Rx = haloaryl group, 2,6-substituted aryl and L is a labile ligand. 5. Polymers with stannyl groups derived from vinyl polymerization of stagnant norbornenes, according to claims 1 and 2, useful as reagents in reactions of C-C coupling. Polymers containing Sn are they can react with organic electrophiles to produce as a byproduct a polymer analogous to those of the claims 1 and 2, with groups SnR 2 R 'where R is an alkyl group and R' is Cl, Br, I or sulfonate group. 6. Procedure to reuse polymers used as reagents in claim 5 comprising the treatment of polymers recovered from the reaction with groups SnR 2 R 'where R is an alkyl group and R' is group Cl, Br, I and treat them with organometallic derivatives of Mg or Li to obtain polymers with SnR2 R 'groups where R is an alkyl group and R' It is hydrocarbon group.