KADYROV RENAT (DE)
B. NOSSE; A. SCHALL; W. B. JEONG; 0. REISER, ADV. SYNTH. CATAL., vol. 347, 2005, pages 1869, XP002691098
B. NOSSE; A. SCHALL; W. B. JEONG; 0. REISER, ADV. SYNTH. CATAL., vol. 347, 2005, pages 1869
S. R SIECK; M. D. MCREYNOLDS; C. E. SCHROEDER; P. R. HANSON, J. ORGANOMET. CHEM., vol. 691, 2006, pages 5311
LANDOLT-BORNSTEIN: "Zahlenwerte und Funktionen aus Physik, Chemie und Astronomie, Geophysik und Technik", vol. IV, 1976, SPRINGER VERLAG
K. J. IVIN: "Olefin Metathesis", 1983, ACADEMIC PRESS
R. R. SCHROCK, TETRAHEDRON, vol. 55, 1999, pages 8141
G. C. VOUGIOUKALAKIS; R. H. GRUBBS, CHEM. REV., vol. 110, 2010, pages 1746
| Method for producing metathesis products comprising contacting metathesis starting materials under metathesis conditions with a metathesis catalyst, wherein the metathesis catalyst is employed in an amount of from 0.0001 mol-% to 1 mol-% based on half of the sum of the reactive double bonds of the metathesis starting materials and wherein the ethylene or propylene generated in the course of the reaction is removed from the reaction mixture . Method according to claim 1, wherein the metathesis catalyst is selected from the group consisting of WCl6/SnBu4, WOCl4/EtAlCl2, Mo03/Si02, Re207/Al203, and catalysts of general formulas 1, 2, and 3. Method according to claim 2, wherein the metathesis catalyst is a ruthenium catalyst of general formula 3. Method according to claim 3, wherein the metathesis catalyst is selected from formulas A, B, C and D. Method according to claims 1 to 4, wherein ethylene or propylene are removed from the reaction mixture by volatilization . Method according to claim 5, wherein the reaction mixture is sparged with inert gas to remove ethylene or propylene. Method according to claim 6, wherein the reaction mixture is continuously sparged with inert gas to remove ethylene or propylene. Method according to claims 1 to 7, wherein the metathesis starting materials are olefinic compounds having at least one reactive double bond in the form of an -olefin and/or β-olefin, with the proviso that not more than one β-olefin is present in the same molecule. Method according to claims 1 to 7, wherein the metathesis starting material is an olefinic compound having two reactive double bonds in the form of two -olefins or one a-olefin and one β-olefin. Method according to claim 1, wherein the metathesis starting materials are olefinic compounds having at least one reactive double bond in the form of an a-olefin and/or β-olefin, with the proviso that not more than one β-olefin is present in the same molecule, and the concentration of the starting materials is in a range of from 0.2 mM to 400 mM, wherein further ethylene or propylene is removed by continuously sparging the reaction mixture with inert gas, and wherein the reaction temperature is in a range of from 20°C to 150°C Method according to claim 10, wherein the metathesis starting material is an olefinic compound having two reactive double bonds in the form of two α-olefins or one a-olefin and one β-olefin. Method according to claim 10 or 11, wherein the metathesis catalyst is selected from the group consisting of WCl6/SnBu4, WOCl4/EtAlCl2, Mo03/Si02, Re207/Al203, and catalysts of general formulas 1, 2, and 3. Method according to claim 12, wherein the metathesis catalyst is a ruthenium catalyst of general formula 3. 14. Method according to claim 13, wherein the metathesis catalyst is selected from formulas A, B, C and D. 15. Method according to claims 1 to 14, wherein the metathesis reaction is a ring-closing metathesis reaction or cross- metathesis reaction. |
The field of the invention belongs to the formation of olefins via metathesis reactions.
The present invention relates to a method for producing metathesis products comprising contacting metathesis starting materials under metathesis conditions with a metathesis catalyst, wherein the metathesis catalyst is employed in an amount lower than usual and wherein the ethylene or propylene generated in the course of the reaction is removed from the reaction mixture.
Metathesis reactions have emerged as a valuable tool in modern organic chemistry. During the last three decades so-called "well defined" catalysts have attracted much attention due to their high activity. Despite these advances, olefin metathesis is still plagued by catalyst deactivation, consequently requiring high catalyst loading. Therefore, major research efforts have been focused on increasing catalytic activity and catalyst lifetime through optimization of the ligand sphere around the metal center. The evaluation of efficiency of metathesis catalysts is typically performed under standard conditions. Several techniques were explored to perform RCM more efficiently including substrate encapsulation, microwave irradiation and use of a continuous stirred-tank reactor.
Major improvements were achieved by tuning of the metathesis catalysts. Nevertheless, it is still common that catalyst loadings in a range of from 1 mol-% to 50 mol% are used in metathesis reactions. Reducing of the loading of commercially available catalysts is desired to promote this technology in industrial practice, especially where Ru catalysts are
applied. A high catalyst loading is not only expensive in terms of costs but also a source of undesirable side
reactions. At higher catalyst loading the metal hydride species formed from the decomposition of the metathesis catalysts promote undesirable isomerisation to a significant extent. This side reaction in olefin metathesis considerably alters the product distribution and decreases the yield of the desired product. Additionally, the side products resulting from unwanted isomerization are frequently difficult to remove using standard purification techniques.
Furthermore, high concentrations of ethylene or propylene, which are byproducts in olefin metathesis reactions, favor a high rate of nonproductive metathesis, providing additional opportunities for catalyst decomposition. Two groups
previously reported a beneficial effect on metathesis
performance by sparging the reaction mixture with an inert gas, but they also used catalyst loadings in a range of from 5 mol% to 22.5 mol-% for the production of tetrasubstituted double bonds (B. Nosse, A. Schall, W. B. Jeong, 0. Reiser, Adv. Synth. Catal. 2005, 347, 1869) and 1 mol-% to 10 mol-% for the production of cyclophosphamides respectively (S. R Sieck, M. D. McReynolds, C. E. Schroeder, P. R. Hanson, J. Organomet. Chem. 2006, 691, 5311) .
It is therefore the task of the present invention to overcome the above-mentioned disadvantages and to significantly reduce the catalyst loading in metathesis reactions.
In one aspect the present invention relates to a method for producing metathesis products comprising contacting metathesis starting materials under metathesis conditions with a
metathesis catalyst, wherein the metathesis catalyst is employed in an amount of from 0.0001 mol-% to 1 mol-% based on half of the sum of the metathesis starting materials and wherein the ethylene or propylene generated in the course of the reaction is removed from the reaction mixture. According to the present invention the reaction temperature can be varied in a range of from 20°C to 150°C. An increase in temperature significantly enhances the reaction rates without loss of productivity (TON) . Furthermore, a higher reaction temperature leads to a decrease in solubility of ethylene and propylene (Landolt-Bornstein, Zahlenwerte und Funktionen aus Physik, Chemie und Astronomie, Geophysik und Technik, IV.
Band: Technik, 4. Teil: Warmetechnik, Bandteil c:
Gleichgewicht der Absorption von Gasen in Flussigkeiten mit niedrigem Dampfdruck, H. Borcbers, H. Hausen, K.-H. Hellwege und K. Schafer, bearbeitet von A. Kruis, Springer Verlag, Berlin, 1976) . According to the present invention the
preferred reaction temperature is in a range of from 50°C to 150°C, wherein a range of from 60°C to 110°C is more preferred and a temperature of 80°C is particularly preferred.
According to the present invention the reaction is allowed to proceed for any suitable period of time. In some cases the reaction is allowed to proceed for 1 min, 5 min, 10 min, 20 min, 30 min, 60 min, 90 min, 2h, 3h, or 6h.
According to the present invention aliquots of the reaction mixture may be removed and analyzed by GC at an intermediate time to determine the progress of the reaction. The reaction is completed once the conversion reaches a plateau, if conversion is plotted versus time.
According to the present invention the solvent is not
critical, any solvent suitable for metathesis reactions can be applied. In some cases the metathesis reaction may also be performed in the absence of any solvent. According to the present invention solvents can be selected from the group of diethyl ether, glycol, pentane, heptane, hexane, cyclohexane, petroleum ether, dichloromethane, dichlorethane, chloroform, carbon tetrachloride, dioxane, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, ethyl acetate, benzene,
chlorobenzene, p-cresol, xylene, mesitylene, toluene or perfluorobenzene . Preferred solvents are heptane,
dichloromethane, dichloroethane, benzene or toluene.
The reaction mixture may be agitated during metathesis
reaction, which may be accomplished by stirring, shaking or any other method known to the person skilled in the art.
During the course of metathesis reactions according to the present invention considerable amounts of ethylene or
propylene are generated. According to the present invention any method to remove this ethylene or propylene can be
applied. Preferably, volatilization of ethylene or propylene is applied, which can be accomplished for example by vigorous stirring, by applying vacuum, i.e. by reducing the pressure of the gaseous phase above the reaction mixture, or by sparging techniques. Sparging the reaction mixture with an inert gas, wherein a gas stream is introduced into the reaction mixture, is particularly suitable to remove ethylene or propylene.
Furthermore, it is preferred to continuously sparge the reaction mixture with an inert gas. Suitable inert gases are for example nitrogen or argon. Furthermore, vigorous stirring can positively influence the vacuum or sparging techniques to volatilize ethylene or propylene.
The method according to the present invention for producing metathesis products can be applied in all metathesis reactions known to those skilled in the art. Therefore, the formation of a broad variety of olefins can be accomplished by the method according to the present invention.
Depending on the type of metathesis reaction, e.g. ring- closing metathesis reaction (RCM) , homo-metathesis or cross- metathesis reaction (CM) , different metathesis starting materials are employed according to the present invention and different metathesis products are thus obtainable. RCM is a variation of olefin metathesis reactions that allows the formation of cyclic olefins. RCM is an intramolecular olefin metathesis, yielding the cyclic olefin and a volatile alkene, mainly ethylene or propylene.
CM is the interchange reaction of alkylidene groups between two acyclic olefins resulting in the formation of olefins having internal double bonds. Statistically, the reaction can lead to three possible pairs of geometric isomers, i.e. E/Z pairs for two homocouplings and the cross-coupling - resulting in a total of 6 possible products.
Homometathesis is a variation of cross metathesis reactions, wherein only one olefin species is involved in the reaction.
According to the present invention irrespective of the type of metathesis reaction the term metathesis starting materials refers to any species having at least one reactive double bond in the form of an -olefin or β-olefin, with the proviso that not more than one β-olefin is present in the same molecule, such as linear and branched-chain aliphatic olefins,
cycloaliphatic olefins, aryl substituted olefins and the like, which may optionally be substituted. The total number of carbon atoms of the metathesis starting materials according to the present invention can be from 2 to 50, preferably from 4 to 25.
An -olefin in the sense of the present invention is a 1- olefin or terminal olefin, wherein the double bond is located between first and second carbon atom of the acyclic olefin, e.g. in 1-butene or but-l-ene: CH 2 =CH-CH 2 -CH 3 .
A β-olefin in the sense of the present invention is a 2-olefin or internal olefin, wherein the double bond is located between second and third carbon atom of the acyclic olefin, e.g. in 2- butene or but-2-ene: CH 3 -CH=CH-CH 3 . According to the present invention the metathesis starting materials generally comprise molecules of general formulas I- IV H 2 C=CH-R 1 -HC=CH 2 (I),
H 3 C-CH=CH-R 1 -HC=CH 2 (II),
H 2 C=CHR 2 (III),
H 3 C-CH=CH-CH 2 -R 2 (IV), wherein R 1 is selected from (d-C 24 ) -alkylidene, ( Ci - C 24 ) - heteroalkylidene, (C5-C14) -arylidene, (C5-C14) -heteroarylyidene, (C3-C 24 ) -cycloalkylidene, and (C3-C 24 ) -heterocylcoalkylidene, which may each be substituted with ( Ci - C 24 ) -alkyl, ( Ci - C 24 ) - heteroalkyl, (C5-C14) -aryl, (C5-C14) -heteroaryl, (C 3 -C 24 ) - cycloalkyl, (C 3 -C 24 ) -heterocycloalkyl , F, CI, Br, N0 2 , OR', COOR', OCOOR', NHCOOR', CONH 2 , CONHR', CONR' 2 , S0 2 R' , NHS0 2 R' , P(O) (OR') 2, and NHP (0) (OR') 2, wherein R' is selected from ( Ci - C 24 ) -alkyl, ( Ci-C 24 ) -heteroalkyl, (C5-C14) -aryl, (C5-C14) - heteroaryl, (C 3 -C 24 ) -cycloalkyl, and (C 3 -C 24 ) -heterocylcoalkyl, preferably R' is selected from Me, Et, n-Pr, i-Pr, n-Bu, Bn, Ph and p-MeC 6 H 5 ; and R 2 is selected from H, ( Ci-C 24 ) -alkyl, ( Ci-C 24 ) -heteroalkyl, (C5-C 14 ) -aryl, (C5-C 14 ) -heteroaryl, (C 3 -C 24 ) -cycloalkyl, and (C 3 - C 24 ) -heterocylcoalkyl, which may each be substituted with Ci - C 24 ) -alkyl, ( Ci - C 24 ) -heteroalkyl, (C5-C14) -aryl, (C5-C14) - heteroaryl, (C 3 -C 24 ) -cycloalkyl, (C 3 -C 24 ) -heterocycloalkyl, F, CI, BR, N0 2 , OR', COOR', OCOOR', NHCOOR', CONH 2 , CONHR',
CONR' 2 , S0 2 R' , NHS0 2 R' , P(0) (OR') 2 , and NHP (0) (OR' ) 2 , wherein R' is selected from ( Ci-C 24 ) -alkyl, ( Ci-C 24 ) -heteroalkyl, (C5-C 14 ) - aryl, (C5-C14) -heteroaryl, (C3-C24) -cycloalkyl, and (C3-C24) - heterocylcoalkyl, preferably R' is selected from Me, Et, n-Pr, i-Pr, n-Bu, Bn, Ph and p-MeC 6 H 5 . According to the present invention a (C1-C24) -alkyl group or (C1-C24) -alkylidene bridge is a linear or branched-chain alkyl group, which may be substituted as described before, wherein the sum of the carbon atoms is 1-24. Branched-chain alkyl groups may exhibit the branch at any carbon atom. Preferred are linear (C1-C22) -alkyl groups, e.g. methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, nonyl, n-decyl, n-undecyl, n-dodecyl, n-tetradecyl , n-pentadecyl , n-hexydecyl, n-heptadecyl , n-octadecyl, n-nonadecyl, n-icosyl, which may each be substituted as described before. Even more preferred are linear (C3-C18) -alkyl groups, which may each be substituted as described before.
According to the present invention a (C5-C14) -aryl group or (C5- C14) -aryl bridge is a cyclic aromatic system with 5-14 carbon atoms, wherein mono-, and bi-cyclic aromatic systems are included, which may each be substituted as described before. Preferred are (Cs-Cs) -monocyclic aryl groups, e.g. phenyl, and (C10-C14) -bicyclic aryl groups, e.g. napththyl, which may each be substituted as described before.
According to the present invention a (C3-C24) -cycloalkyl group or (C3-C24) -cycloalkyl bridge is a cyclic alkyl group with 3-24 carbon atoms, wherein mono-, bi- and tri-cyclic alkyl groups are included, which may each be substituted as described before. Preferred are (C3-C10) -cycloalkyl groups, e.g.
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl, which may each be substituted as described before.
According to the present invention a (C1-C24) -heteroalkyl group or (C1-C24) -heteroalkyl bridge is a (C1-C24) -alkyl group as described before, wherein the sum of the atoms is 1-24 and at least one carbon atom is exchanged by a heteroatom selected from 0, N, and S, and/or a functional group selected from -NH- , -NTs-, -NBoc-, -C(=0)-, -C(=0)0-, -C(=0)NH-, -C(=0)NTs-, - C(=0)NBoc-, -S(O)-, -S (=0)NH-,-P(=0) -, -P(=0)0- and -P(=0)NH-. According to the present invention a (C5-C14) -heteroaryl group is a (C5-C14) -aryl group as described before, wherein the sum of the atoms is 5-14 and at least one carbon atom is exchanged by a heteroatom selected from 0, N, and S, and/or a functional group selected from -NH-, -NTs- , -NBoc-, -C(=0)-, -C(=0)0-, - C(=0)NH-, -C(=0)NTs-, -C(=0)NBoc-, -S(O)-, -S (=0) NH- , -P (=0) - , -P(=0)0- and -P(=0)NH-. Preferred are furan, thiophene, pyrrole, pyridine, indole.
According to the present invention a (C3-C 24 ) -heterocycloalkyl group or (C3-C24) -heterocycloalkyl bridge is a (C3-C24) - cycloalkyl group as described before, wherein the sum of the atoms is 3-24 and at least one carbon atom is exchanged by a heteroatom selected from 0, N, and S, and/or a functional group selected from -NH-, -NTs- , -NBoc-, -C(=0)-, -C(=0)0-, - C(=0)NH-, -C(=0)NTs-, -C(=0)NBoc-, -S(0)-, -S (=0) NH- , -P (=0) - , -P(=0)0- and -P(=0)NH-. Preferred are (C 3 -C 8 ) -heterocycloalkyl groups, like pyrrolidyl, piperidyl, tetrahydrofuryl .
According to the present invention preferred metathesis starting materials are those of general formulas I and II, having two reactive double bonds in the form of two -olefins or one -olefin and one β-olefin. Even more preferred
metathesis starting materials according to the present
invention are those of general formulas I and II having a linear (C1-C24) -alkylidene chain or a linear (C1-C24) - heteroalkylidene chain, wherein (C 1 -C 24 ) -alkylidene and (Ci- C 24 ) -heteroalkylidene are defined as described before.
Particularly preferred metathesis starting materials according to the present invention are those of general formulas I and II having a linear (C3-C18) -alkylidene chain or a linear (C3- C18) -heteroalkylidene chain with 1-5 heteroatoms, wherein (C3- C18) -alkylidene and (C3-C18) -heteroalkylidene are defined as described before, and wherein further the heteroatoms are independently selected from 0 and N and wherein the heteroatoms are part of a functional group selected from -NH-, -NTs-, -NBoc-, -C(=0)-, -C(=0)0-, -C(=0)NH-, -C(=0)NTs-, - C (=0)NBoc-. According to the present invention preferred metathesis products are cyclic olefins. These cyclic olefins exhibit a 4- to 50-membered ring system, more preferably the olefins exhibit a 5- to 20-membered ring system. The cyclic olefin can be either homocyclic or heterocyclic, wherein homocyclic describes a ring system of carbon atoms, and heterocyclic describes a ring system of carbon atoms together with at least one heteroatom selected from 0, N, and S and/or a functional group selected from -NH-, -NTs- , -NBoc-, -C(=0)-, -C(=0)0-, - C(=0)NH-, -C(=0)NTs-, -C(=0)NBoc-, -S(O)-, -S (=0) NH-, -P (=0) -, -P(=0)0- and -P(=0)NH-. Preferably, a heterocyclic olefin according to the present invention exhibits a 5- to 20- membered ring system with 1 to 5 heteroatoms, wherein the heteroatoms are independently selected from 0 and N and wherein the heteroatoms are part of a functional group
selected from -NH-, -NTs-, -NBoc-, -C(=0)-, -C(=0)0-, - C(=0)NH-, -C(=0)NTs-, -C(=0)NBoc-.
Examples of metathesis starting materials which are suitable for metathesis reactions according to the present invention are olefins, like 1-olefins and 2-olefins, and dienes of 1- olefins or a combination of 1-olefin and 2-olefin, wherein dienes with terminal double bonds (1-olefins) are preferred. According to the present invention metathesis starting
materials leading to cyclic olefins are acyclic olefins having two reactive double bonds in the form of two -olefins, or one -olefin and one β-olefin. Particularly preferred are
metathesis starting materials having a chain of 4 to 25 atoms, which is optionally substituted, and having two reactive double bonds in the form of two -olefins, or one a-olefin and one β-olefin. According to the present invention the metathesis starting material concentration is in a range of from 0.2 mM to 400 mM, preferably from 5 mM to 40 mM, more preferably from 8 mM to 40 mM, particularly preferred is a range of from 8 mM to 20 mM. According to the present invention the stoichiometry of starting materials is the same as for other olefin metathesis reactions: for cross-metathesis reactions equimolar amounts or a slight excess of one starting material is applied.
The method of the present invention is not limited to specific metathesis catalysts. According to the present invention any catalyst suitable for metathesis reactions can be applied. Particularly suitable are catalysts which are selected from group 1, which consists of catalysts of general formulas 1, 2, 3 and so called "ill defined" metathesis catalysts, e.g.
WCl 6 /SnBu 4 , WOCl 4 /EtAlCl 2 ) , Mo0 3 /Si0 2 , P^Ov/AlsOs) (K. J. Ivin, Olefin Metathesis, Academic Press, London, 1983) . The
molybdenum and tungsten alkylidenes of the general formulas 1 and 2 are active in metathesis transformations (R. R. Schrock, Tetrahedron 1999, 55, 8141) . Ruthenium catalysts of general formula 3 are particularly preferred due to their ability to tolerate polar functional groups (G. C. Vougioukalakis , R. H. Grubbs, Chem. Rev. 2010, 110, 1746) .
1 (M = Mo, W) 2 3
Figure 1: Metathesis catalysts. In general formulas 1-3 of figure 1,
each R,R' is selected from (C5-C14) -aryl and ( C 1 -C 24 ) -alkyl, each Ar is selected from (C5-C14) -aryl,
X-N is selected from (C3-C8) -heterocycloalkyl , like pyrrolidyl or piperidyl,
Li , L2 are each independently selected fom neutral electron donor ligands, like phosphines and N-heterocyclic carbenes (NHC) ,
wherein (C5-C14) -aryl, ( C 1 -C24) -alkyl and (C 3 -Cs) - heterocycloalkyl is defined as described before.
In general formula 1 of figure 1 R is preferably selected from t-Bu, CMe(CF 3 ) 2 , SiMe 3 and 2 , 6-diisopropylphenyl , R' is
preferably selected from t-Bu, CMe2 Ph and neopentyl, and Ar is preferably selected from 2 , 6-dimethylphenyl and 2,6- diisopropylphenyl .
In general formula 2 of figure 1 R is preferably selected from t-Bu, CMe(CF 3 ) 2 , SiMe 3 and 2 , 6-di (2 ' , 4 ' , 6' - triisopropylphenyl ) phenyl , R' is preferably selected from t- Bu, CMe2 Ph and neopentyl, Ar is selected from 2,6- dimethylphenyl and 2 , 6-diisopropylphenyl , and X-N is
preferably selected from pyrrol and 2 , 5-dimethylpyrrol .
In general formula 3 of figure 1 R is preferably selected from phenyl, 2 , 2 ' -dimethylvinyl and thienyl, Li is selected from PPh 3 and PCy 3 , and L 2 is selected from PCy 3 , 1, 3-bis (2, 4, 6- trimethylphenyl) imidazol-2-ylidene, 1, 3-bis (2, 4, 6- trimethylphenyl ) -4, 5-dimethylimidazol-2-ylidene, 1, 3-bis (2, 6- diisopropylphenyl ) imidazol-2-ylidene, 1, 3-bis (2,4,6- trimethylphenyl) -4, 5-dihydroimidazol-2-ylidene and 1,3- bis (2, 6-diisopropylphenyl) -4, 5-dihydroimidazol-2-ylidene .
Remarkably results have been achieved by applying commercially available Ru-catalysts of formulas A-D (see Figure 2,
experimental section) , which are special embodiments of catalysts according to general formula 3. According to the present invention irrespective of the constitution of the metathesis catalyst, the metathesis catalyst is employed in the metathesis reaction in an amount of from 1 ppm to 1 mol-% based on half of the sum of the reactive double bonds of the metathesis starting materials. The unit ppm has to be understood as follows 1 ppm = 0.0001 mol-%. According to the present invention preferably, the catalyst is employed in an amount of from 50 ppm - 2000 ppm, more preferably, the catalyst is employed in an amount of from 50 ppm to 500 ppm.
Table 1 lists reaction conditions that can be employed in embodiments of the method of the present invention.
Table 1
type of amount concentration method to metathesis catalyst of of metathesis remove conditions :
catalyst starting ethylene solvent = [ppm] materials or toluol ;
[itiM] propylene stirring
800 rpm
Catalysts of 1-10000 0.2-4000 Vacuum 20-150°C Group 1
Ru catalysts 1-10000 0.2-4000 Vacuum 20-150°C of formula 3
Catalysts of 1-10000 0.2-4000 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 20-150°C Group 1 inert gas
Ru catalysts 1-10000 0.2-4000 Sparging 20-150°C of formula 3 inert gas Catalysts of 1-10000 0.2-4000 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 20-150°C Group 1 argon
Ru catalysts 1-10000 0.2-4000 Sparging 20-150°C of formula 3 argon
Catalysts of 1-10000 0.2-4000 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 0.2-4000 Vacuum 20-150°C Group 1
Ru catalysts 50-2000 0.2-4000 Vacuum 20-150°C of formula 3
Catalysts of 50-2000 0.2-4000 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-2000 0.2-4000 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-2000 0.2-4000 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 20-150°C Group 1 argon
Ru catalysts 50-2000 0.2-4000 Sparging 20-150°C of formula 3 argon
Catalysts of 50-2000 0.2-4000 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-500 0.2-4000 Vacuum 20-150°C Group 1 Ru catalysts 50-500 0.2-4000 Vacuum 20-150°C of formula 3
Catalysts of 50-500 0.2-4000 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-500 0.2-4000 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-500 0.2-4000 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 20-150°C Group 1 argon
Ru catalysts 50-500 0.2-4000 Sparging 20-150°C of formula 3 argon
Catalysts of 50-500 0.2-4000 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 5-40 Vacuum 20-150°C Group 1
Ru catalysts 1-10000 5-40 Vacuum 20-150°C of formula 3
Catalysts of 1-10000 5-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 1-10000 5-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 1-10000 5-40 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 20-150°C Group 1 argon
Ru catalysts 1-10000 5-40 Sparging 20-150°C of formula 3 argon
Catalysts of 1-10000 5-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 5-40 Vacuum 20-150°C Group 1
Ru catalysts 50-2000 5-40 Vacuum 20-150°C of formula 3
Catalysts of 50-2000 5-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-2000 5-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-2000 5-40 Sparging 20-150°C formulas inert gas
A, B, C, D Catalysts of 50-2000 5-40 Sparging 20-150°C Group 1 argon
Ru catalysts 50-2000 5-40 Sparging 20-150°C of formula 3 argon
Catalysts of 50-2000 5-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-500 5-40 Vacuum 20-150°C Group 1
Ru catalysts 50-500 5-40 Vacuum 20-150°C of formula 3
Catalysts of 50-500 5-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-500 5-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-500 5-40 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 20-150°C Group 1 argon
Ru catalysts 50-500 5-40 Sparging 20-150°C of formula 3 argon
Catalysts of 50-500 5-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-40 Vacuum 20-150°C Group 1
Ru catalysts 1-10000 8-40 Vacuum 20-150°C of formula 3 Catalysts of 1-10000 8-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 1-10000 8-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 1-10000 8-40 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 20-150°C Group 1 argon
Ru catalysts 1-10000 8-40 Sparging 20-150°C of formula 3 argon
Catalysts of 1-10000 8-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-40 Vacuum 20-150°C Group 1
Ru catalysts 50-2000 8-40 Vacuum 20-150°C of formula 3
Catalysts of 50-2000 8-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-2000 8-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-2000 8-40 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 20-150°C Group 1 argon Ru catalysts 50-2000 8-40 Sparging 20-150°C of formula 3 argon
Catalysts of 50-2000 8-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-500 8-40 Vacuum 20-150°C Group 1
Ru catalysts 50-500 8-40 Vacuum 20-150°C of formula 3
Catalysts of 50-500 8-40 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-500 8-40 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-500 8-40 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 20-150°C Group 1 argon
Ru catalysts 50-500 8-40 Sparging 20-150°C of formula 3 argon
Catalysts of 50-500 8-40 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-20 Vacuum 20-150°C Group 1
Ru catalysts 1-10000 8-20 Vacuum 20-150°C of formula 3
Catalysts of 1-10000 8-20 Vacuum 20-150°C formulas
A, B, C, D Catalysts of 1-10000 8-20 Sparging 20-150°C Group 1 inert gas
Ru catalysts 1-10000 8-20 Sparging 20-150°C of formula 3 inert gas
Catalysts of 1-10000 8-20 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 20-150°C Group 1 argon
Ru catalysts 1-10000 8-20 Sparging 20-150°C of formula 3 argon
Catalysts of 1-10000 8-20 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-20 Vacuum 20-150°C Group 1
Ru catalysts 50-2000 8-20 Vacuum 20-150°C of formula 3
Catalysts of 50-2000 8-20 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-2000 8-20 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-2000 8-20 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 20-150°C Group 1 argon
Ru catalysts 50-2000 8-20 Sparging 20-150°C of formula 3 argon Catalysts of 50-2000 8-20 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 50-500 8-20 Vacuum 20-150°C Group 1
Ru catalysts 50-500 8-20 Vacuum 20-150°C of formula 3
Catalysts of 50-500 8-20 Vacuum 20-150°C formulas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 20-150°C Group 1 inert gas
Ru catalysts 50-500 8-20 Sparging 20-150°C of formula 3 inert gas
Catalysts of 50-500 8-20 Sparging 20-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 20-150°C Group 1 argon
Ru catalysts 50-500 8-20 Sparging 20-150°C of formula 3 argon
Catalysts of 50-500 8-20 Sparging 20-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 0.2-4000 Vacuum 50-150°C Group 1
Ru catalysts 1-10000 0.2-4000 Vacuum 50-150°C of formula 3
Catalysts of 1-10000 0.2-4000 Vacuum 50-150°C formulas
A, B, C, D Catalysts of 1-10000 0.2-4000 Sparging 50-150°C Group 1 inert gas
Ru catalysts 1-10000 0.2-4000 Sparging 50-150°C of formula 3 inert gas
Catalysts of 1-10000 0.2-4000 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 50-150°C Group 1 argon
Ru catalysts 1-10000 0.2-4000 Sparging 50-150°C of formula 3 argon
Catalysts of 1-10000 0.2-4000 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 0.2-4000 Vacuum 50-150°C Group 1
Ru catalysts 50-2000 0.2-4000 Vacuum 50-150°C of formula 3
Catalysts of 50-2000 0.2-4000 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-2000 0.2-4000 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-2000 0.2-4000 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 50-150°C Group 1 argon
Ru catalysts 50-2000 0.2-4000 Sparging 50-150°C of formula 3 argon Catalysts of 50-2000 0.2-4000 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-500 0.2-4000 Vacuum 50-150°C Group 1
Ru catalysts 50-500 0.2-4000 Vacuum 50-150°C of formula 3
Catalysts of 50-500 0.2-4000 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-500 0.2-4000 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-500 0.2-4000 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 50-150°C Group 1 argon
Ru catalysts 50-500 0.2-4000 Sparging 50-150°C of formula 3 argon
Catalysts of 50-500 0.2-4000 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 5-40 Vacuum 50-150°C Group 1
Ru catalysts 1-10000 5-40 Vacuum 50-150°C of formula 3
Catalysts of 1-10000 5-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 50-150°C Group 1 inert gas Ru catalysts 1-10000 5-40 Sparging 50-150°C of formula 3 inert gas
Catalysts of 1-10000 5-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 50-150°C Group 1 argon
Ru catalysts 1-10000 5-40 Sparging 50-150°C of formula 3 argon
Catalysts of 1-10000 5-40 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 5-40 Vacuum 50-150°C Group 1
Ru catalysts 50-2000 5-40 Vacuum 50-150°C of formula 3
Catalysts of 50-2000 5-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-2000 5-40 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-2000 5-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 50-150°C Group 1 argon
Ru catalysts 50-2000 5-40 Sparging 50-150°C of formula 3 argon
Catalysts of 50-2000 5-40 Sparging 50-150°C formulas argon
A, B, C, D Catalysts of 50-500 5-40 Vacuum 50-150°C Group 1
Ru catalysts 50-500 5-40 Vacuum 50-150°C of formula 3
Catalysts of 50-500 5-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-500 5-40 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-500 5-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 50-150°C Group 1 argon
Ru catalysts 50-500 5-40 Sparging 50-150°C of formula 3 argon
Catalysts of 50-500 5-40 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-40 Vacuum 50-150°C Group 1
Ru catalysts 1-10000 8-40 Vacuum 50-150°C of formula 3
Catalysts of 1-10000 8-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 50-150°C Group 1 inert gas
Ru catalysts 1-10000 8-40 Sparging 50-150°C of formula 3 inert gas Catalysts of 1-10000 8-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 50-150°C Group 1 argon
Ru catalysts 1-10000 8-40 Sparging 50-150°C of formula 3 argon
Catalysts of 1-10000 8-40 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-40 Vacuum 50-150°C Group 1
Ru catalysts 50-2000 8-40 Vacuum 50-150°C of formula 3
Catalysts of 50-2000 8-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-2000 8-40 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-2000 8-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 50-150°C Group 1 argon
Ru catalysts 50-2000 8-40 Sparging 50-150°C of formula 3 argon
Catalysts of 50-2000 8-40 Sparging 50-150°C formulas argon
A, B, C, D Catalysts of 50-500 8-40 Vacuum 50-150°C Group 1
Ru catalysts 50-500 8-40 Vacuum 50-150°C of formula 3
Catalysts of 50-500 8-40 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-500 8-40 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-500 8-40 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 50-150°C Group 1 argon
Ru catalysts 50-500 8-40 Sparging 50-150°C of formula 3 argon
Catalysts of 50-500 8-40 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-20 Vacuum 50-150°C Group 1
Ru catalysts 1-10000 8-20 Vacuum 50-150°C of formula 3
Catalysts of 1-10000 8-20 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 50-150°C Group 1 inert gas
Ru catalysts 1-10000 8-20 Sparging 50-150°C of formula 3 inert gas Catalysts of 1-10000 8-20 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 50-150°C Group 1 argon
Ru catalysts 1-10000 8-20 Sparging 50-150°C of formula 3 argon
Catalysts of 1-10000 8-20 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-20 Vacuum 50-150°C Group 1
Ru catalysts 50-2000 8-20 Vacuum 50-150°C of formula 3
Catalysts of 50-2000 8-20 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-2000 8-20 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-2000 8-20 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 50-150°C Group 1 argon
Ru catalysts 50-2000 8-20 Sparging 50-150°C of formula 3 argon
Catalysts of 50-2000 8-20 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 50-500 8-20 Vacuum 50-150°C Group 1 Ru catalysts 50-500 8-20 Vacuum 50-150°C of formula 3
Catalysts of 50-500 8-20 Vacuum 50-150°C formulas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 50-150°C Group 1 inert gas
Ru catalysts 50-500 8-20 Sparging 50-150°C of formula 3 inert gas
Catalysts of 50-500 8-20 Sparging 50-150°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 50-150°C Group 1 argon
Ru catalysts 50-500 8-20 Sparging 50-150°C of formula 3 argon
Catalysts of 50-500 8-20 Sparging 50-150°C formulas argon
A, B, C, D
Catalysts of 1-10000 0.2-4000 Vacuum 60-110°C Group 1
Ru catalysts 1-10000 0.2-4000 Vacuum 60-110°C of formula 3
Catalysts of 1-10000 0.2-4000 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 60-110°C Group 1 inert gas
Ru catalysts 1-10000 0.2-4000 Sparging 60-110°C of formula 3 inert gas
Catalysts of 1-10000 0.2-4000 Sparging 60-110°C formulas inert gas
A, B, C, D Catalysts of 1-10000 0.2-4000 Sparging 60-110°C Group 1 argon
Ru catalysts 1-10000 0.2-4000 Sparging 60-110°C of formula 3 argon
Catalysts of 1-10000 0.2-4000 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-2000 0.2-4000 Vacuum 60-110°C Group 1
Ru catalysts 50-2000 0.2-4000 Vacuum 60-110°C of formula 3
Catalysts of 50-2000 0.2-4000 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-2000 0.2-4000 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-2000 0.2-4000 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 60-110°C Group 1 argon
Ru catalysts 50-2000 0.2-4000 Sparging 60-110°C of formula 3 argon
Catalysts of 50-2000 0.2-4000 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-500 0.2-4000 Vacuum 60-110°C Group 1
Ru catalysts 50-500 0.2-4000 Vacuum 60-110°C of formula 3 Catalysts of 50-500 0.2-4000 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-500 0.2-4000 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-500 0.2-4000 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 60-110°C Group 1 argon
Ru catalysts 50-500 0.2-4000 Sparging 60-110°C of formula 3 argon
Catalysts of 50-500 0.2-4000 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 1-10000 5-40 Vacuum 60-110°C Group 1
Ru catalysts 1-10000 5-40 Vacuum 60-110°C of formula 3
Catalysts of 1-10000 5-40 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 1-10000 5-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 1-10000 5-40 Sparging 60-110°C formulas inert gas
A, B, C, D Catalysts of 1-10000 5-40 Sparging 60-110°C Group 1 argon
Ru catalysts 1-10000 5-40 Sparging 60-110°C of formula 3 argon
Catalysts of 1-10000 5-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-2000 5-40 Vacuum 60-110°C Group 1
Ru catalysts 50-2000 5-40 Vacuum 60-110°C of formula 3
Catalysts of 50-2000 5-40 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-2000 5-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-2000 5-40 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 60-110°C Group 1 argon
Ru catalysts 50-2000 5-40 Sparging 60-110°C of formula 3 argon
Catalysts of 50-2000 5-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-500 5-40 Vacuum 60-110°C Group 1
Ru catalysts 50-500 5-40 Vacuum 60-110°C of formula 3 Catalysts of 50-500 5-40 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-500 5-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-500 5-40 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 60-110°C Group 1 argon
Ru catalysts 50-500 5-40 Sparging 60-110°C of formula 3 argon
Catalysts of 50-500 5-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-40 Vacuum 60-110°C Group 1
Ru catalysts 1-10000 8-40 Vacuum 60-110°C of formula 3
Catalysts of 1-10000 8-40 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 1-10000 8-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 1-10000 8-40 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 60-110°C Group 1 argon Ru catalysts 1-10000 8-40 Sparging 60-110°C of formula 3 argon
Catalysts of 1-10000 8-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-40 Vacuum 60-110°C Group 1
Ru catalysts 50-2000 8-40 Vacuum 60-110°C of formula 3
Catalysts of 50-2000 8-40 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-2000 8-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-2000 8-40 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 60-110°C Group 1 argon
Ru catalysts 50-2000 8-40 Sparging 60-110°C of formula 3 argon
Catalysts of 50-2000 8-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-500 8-40 Vacuum 60-110°C Group 1
Ru catalysts 50-500 8-40 Vacuum 60-110°C of formula 3
Catalysts of 50-500 8-40 Vacuum 60-110°C formulas
A, B, C, D Catalysts of 50-500 8-40 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-500 8-40 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-500 8-40 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 60-110°C Group 1 argon
Ru catalysts 50-500 8-40 Sparging 60-110°C of formula 3 argon
Catalysts of 50-500 8-40 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-20 Vacuum 60-110°C Group 1
Ru catalysts 1-10000 8-20 Vacuum 60-110°C of formula 3
Catalysts of 1-10000 8-20 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 60-110°C Group 1 inert gas
Ru catalysts 1-10000 8-20 Sparging 60-110°C of formula 3 inert gas
Catalysts of 1-10000 8-20 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 60-110°C Group 1 argon
Ru catalysts 1-10000 8-20 Sparging 60-110°C of formula 3 argon Catalysts of 1-10000 8-20 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-20 Vacuum 60-110°C Group 1
Ru catalysts 50-2000 8-20 Vacuum 60-110°C of formula 3
Catalysts of 50-2000 8-20 Vacuum 60-110°C formulas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-2000 8-20 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-2000 8-20 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 60-110°C Group 1 argon
Ru catalysts 50-2000 8-20 Sparging 60-110°C of formula 3 argon
Catalysts of 50-2000 8-20 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 50-500 8-20 Vacuum 60-110°C Group 1
Ru catalysts 50-500 8-20 Vacuum 60-110°C of formula 3
Catalysts of 50-500 8-20 Vacuum 60-110°C formulas
A, B, C, D Catalysts of 50-500 8-20 Sparging 60-110°C Group 1 inert gas
Ru catalysts 50-500 8-20 Sparging 60-110°C of formula 3 inert gas
Catalysts of 50-500 8-20 Sparging 60-110°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 60-110°C Group 1 argon
Ru catalysts 50-500 8-20 Sparging 60-110°C of formula 3 argon
Catalysts of 50-500 8-20 Sparging 60-110°C formulas argon
A, B, C, D
Catalysts of 1-10000 0.2-4000 Vacuum 80°C Group 1
Ru catalysts 1-10000 0.2-4000 Vacuum 80°C of formula 3
Catalysts of 1-10000 0.2-4000 Vacuum 80°C formulas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 80°C Group 1 inert gas
Ru catalysts 1-10000 0.2-4000 Sparging 80°C of formula 3 inert gas
Catalysts of 1-10000 0.2-4000 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 0.2-4000 Sparging 80°C Group 1 argon
Ru catalysts 1-10000 0.2-4000 Sparging 80°C of formula 3 argon Catalysts of 1-10000 0.2-4000 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-2000 0.2-4000 Vacuum 80°C Group 1
Ru catalysts 50-2000 0.2-4000 Vacuum 80°C of formula 3
Catalysts of 50-2000 0.2-4000 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 80°C Group 1 inert gas
Ru catalysts 50-2000 0.2-4000 Sparging 80°C of formula 3 inert gas
Catalysts of 50-2000 0.2-4000 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 0.2-4000 Sparging 80°C Group 1 argon
Ru catalysts 50-2000 0.2-4000 Sparging 80°C of formula 3 argon
Catalysts of 50-2000 0.2-4000 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-500 0.2-4000 Vacuum 80°C Group 1
Ru catalysts 50-500 0.2-4000 Vacuum 80°C of formula 3
Catalysts of 50-500 0.2-4000 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 80°C Group 1 inert gas Ru catalysts 50-500 0.2-4000 Sparging 80°C of formula 3 inert gas
Catalysts of 50-500 0.2-4000 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-500 0.2-4000 Sparging 80°C Group 1 argon
Ru catalysts 50-500 0.2-4000 Sparging 80°C of formula 3 argon
Catalysts of 50-500 0.2-4000 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 1-10000 5-40 Vacuum 80°C Group 1
Ru catalysts 1-10000 5-40 Vacuum 80°C of formula 3
Catalysts of 1-10000 5-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 80°C Group 1 inert gas
Ru catalysts 1-10000 5-40 Sparging 80°C of formula 3 inert gas
Catalysts of 1-10000 5-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 5-40 Sparging 80°C Group 1 argon
Ru catalysts 1-10000 5-40 Sparging 80°C of formula 3 argon
Catalysts of 1-10000 5-40 Sparging 80°C formulas argon
A, B, C, D Catalysts of 50-2000 5-40 Vacuum 80°C Group 1
Ru catalysts 50-2000 5-40 Vacuum 80°C of formula 3
Catalysts of 50-2000 5-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 80°C Group 1 inert gas
Ru catalysts 50-2000 5-40 Sparging 80°C of formula 3 inert gas
Catalysts of 50-2000 5-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 5-40 Sparging 80°C Group 1 argon
Ru catalysts 50-2000 5-40 Sparging 80°C of formula 3 argon
Catalysts of 50-2000 5-40 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-500 5-40 Vacuum 80°C Group 1
Ru catalysts 50-500 5-40 Vacuum 80°C of formula 3
Catalysts of 50-500 5-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 80°C Group 1 inert gas
Ru catalysts 50-500 5-40 Sparging 80°C of formula 3 inert gas Catalysts of 50-500 5-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-500 5-40 Sparging 80°C Group 1 argon
Ru catalysts 50-500 5-40 Sparging 80°C of formula 3 argon
Catalysts of 50-500 5-40 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-40 Vacuum 80°C Group 1
Ru catalysts 1-10000 8-40 Vacuum 80°C of formula 3
Catalysts of 1-10000 8-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 80°C Group 1 inert gas
Ru catalysts 1-10000 8-40 Sparging 80°C of formula 3 inert gas
Catalysts of 1-10000 8-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-40 Sparging 80°C Group 1 argon
Ru catalysts 1-10000 8-40 Sparging 80°C of formula 3 argon
Catalysts of 1-10000 8-40 Sparging 80°C formulas argon
A, B, C, D Catalysts of 50-2000 8-40 Vacuum 80°C Group 1
Ru catalysts 50-2000 8-40 Vacuum 80°C of formula 3
Catalysts of 50-2000 8-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 80°C Group 1 inert gas
Ru catalysts 50-2000 8-40 Sparging 80°C of formula 3 inert gas
Catalysts of 50-2000 8-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-40 Sparging 80°C Group 1 argon
Ru catalysts 50-2000 8-40 Sparging 80°C of formula 3 argon
Catalysts of 50-2000 8-40 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-500 8-40 Vacuum 80°C Group 1
Ru catalysts 50-500 8-40 Vacuum 80°C of formula 3
Catalysts of 50-500 8-40 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 80°C Group 1 inert gas
Ru catalysts 50-500 8-40 Sparging 80°C of formula 3 inert gas Catalysts of 50-500 8-40 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-500 8-40 Sparging 80°C Group 1 argon
Ru catalysts 50-500 8-40 Sparging 80°C of formula 3 argon
Catalysts of 50-500 8-40 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 1-10000 8-20 Vacuum 80°C Group 1
Ru catalysts 1-10000 8-20 Vacuum 80°C of formula 3
Catalysts of 1-10000 8-20 Vacuum 80°C formulas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 80°C Group 1 inert gas
Ru catalysts 1-10000 8-20 Sparging 80°C of formula 3 inert gas
Catalysts of 1-10000 8-20 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 1-10000 8-20 Sparging 80°C Group 1 argon
Ru catalysts 1-10000 8-20 Sparging 80°C of formula 3 argon
Catalysts of 1-10000 8-20 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-2000 8-20 Vacuum 80°C Group 1 Ru catalysts 50-2000 8-20 Vacuum 80°C of formula 3
Catalysts of 50-2000 8-20 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 80°C Group 1 inert gas
Ru catalysts 50-2000 8-20 Sparging 80°C of formula 3 inert gas
Catalysts of 50-2000 8-20 Sparging 80°C formulas inert gas
A, B, C, D
Catalysts of 50-2000 8-20 Sparging 80°C Group 1 argon
Ru catalysts 50-2000 8-20 Sparging 80°C of formula 3 argon
Catalysts of 50-2000 8-20 Sparging 80°C formulas argon
A, B, C, D
Catalysts of 50-500 8-20 Vacuum 80°C Group 1
Ru catalysts 50-500 8-20 Vacuum 80°C of formula 3
Catalysts of 50-500 8-20 Vacuum 80°C formulas
A, B, C, D
Catalysts of 50-500 8-20 Sparging 80°C Group 1 inert gas
Ru catalysts 50-500 8-20 Sparging 80°C of formula 3 inert gas
Catalysts of 50-500 8-20 Sparging 80°C formulas inert gas
A, B, C, D Catalysts of 50-500 8-20 Sparging 80°C
Group 1 argon
Ru catalysts 50-500 8-20 Sparging 80°C of formula 3 argon
Catalysts of 50-500 8-20 Sparging 80°C formulas argon
A, B, C, D
Experimental Section Practically, the reactions were carried out in round bottomed flasks fitted with an effective reflux condenser and placed in an oil bath. Inert gas sparging was provided by a vigorous argon stream through a long thin needle introduced through a rubber septum. Stirring at high rate gives rise to better dispersion of the gas bubbles and therefore increases the speed of the gas transfer.
The results of the catalytic runs can be rather sensitive to impurities present in the substrates when working with
ultralow catalyst loadings. Therefore, all starting dienes were prepared by careful purification using repeated vacuum distillation or recrystallization .
Toluene was purified using recommended methods, then dried over 3A molecular sieves, thereby lowering moisture content to 1-2 ppm, and degassed by ultrasonication .
In order to evaluate the catalytic performance in toluene solutions, RCM reactions were performed at 80°C and
concentrations from 8 to 40 mM in the presence of alkanes (dodecane, tetradecane and octadecane) as internal standards. The course of the reaction was monitored by GC analysis taking aliquots with syringes and quenching in ethyl vinyl ether solution . As metathesis catalysts ruthenium catalysts of formulas A-D have been applied.
B
Figure 2: Ru-catalysts .
Examples of Metathesis Reactions
Table 2: Identified products in metathesis of olefins.
Olefin Products
9 10
16
Table 3: Metathesis of olefins 1, 3, 5, 7, 9, 11 and 13 in toluene at 80°C according to procedure B.
Olefin mM [a] Catalyst ppm [b] TOF [c] Conv. [d]
1 40 B 50 2063 95
1 40 C 50 4173 95
1 40 D 50 2984 92
3 20 A 100 122 77
3 20 B 100 372 52
3 20 C 100 826 79
5 20 A 50 199 78
5 20 B 50 810 69
5 20 C 50 1762 78
7 20 A 50 85 65
7 20 B 50 572 57
7 20 C 50 1281 85
9 40 A 50 56 54
9 40 B 50 1285 76
9 40 C 50 1711 80
11 20 A 100 394 98 11 20 B 100 1048 81
11 20 C 100 1380 90
13 20 A 500 36 94
13 20 B 500 40 92
13 20 C 500 87 96
[a] starting concentration of olefin; [b] catalyst loading 1 ppm = 0.0001 mol%; [c] turn-over frequency [min -1 ] ; [d] conversion of starting olefin measured after complete
standstill of the reaction [%] .
Table 4: Isolated products in metathesis of protected amines.
34
Table 5: Metathesis of protected amines in toluene at 80°C according to procedure B.
Olefin mM [a] Catalyst ppm [b] TOF [c] Conv. [d]
17 20 A 50 277 59
17 20 B 50 1010 60
17 20 C 50 1820 54
17 200 C 100 1700 88
19 20 A 50 764 99
19 20 B 50 1043 68
19 20 B 100 900 96
19 20 C 50 1152 62
19 20 C +50 541 92
21 20 A 200 55 74
21 20 B 200 129 72
21 20 C 200 150 74
23 20 A 100 188 82
23 20 B 100 433 66
23 20 C 100 586 81
23 20 C +100 113 97
26 8 A 250 52 60
26 8 B 500 109 79
26 8 C 250 179 65
28 20 A 500 67 95
28 20 B 500 127 83
28 20 C 500 152 92 33 8 A 200 79 100
33 8 B 150 478 90
33 8 C 200 357 99
[a] starting concentration of olefin; . [b] catalyst loading 1 ppm = 0.0001 mol%, + denotes additional amounts of catalyst added after stopping of the reaction; [c] turn-over frequency
[min -1 ] ; [d] conversion of starting olefin measured after complete standstill of the reaction [%] .
Table 6: Metathesis of 2-allylphenol esters.
Olefin Products
Table 7: Metathesis of 2-allylphenol esters in toluene at 80°C according to procedure B.
Olefin mM [a] Catalyst ppm [b] TOF [c] Conv. [d]
35 20 A 100 267 82
35 20 B 100 761 68
35 20 C 100 1100 89
38 20 B 50 1026 64
38 8 C 200 474 99
41 8 B 100 656 76
41 8 C 100 1381 72
44 8 B 150 471 98
44 20 B 100 753 96 44 8 C 150 1047 98
47 8 A 100 36 88
47 8 B 150 446 91
47 8 C 100 1026 70
47 8 C +100 365 100
51 8 A 500 35 93
51 8 B 500 76 80
51 8 C 500 107 84
[a] starting concentration of olefin; . [b] catalyst loading 1 ppm = 0.0001 mol%, + denotes additional amounts of catalyst added after stopping of the reaction; [c] turn-over frequency
[min -1 ] ; [d] conversion of starting olefin measured after complete standstill of the reaction [%] .
Table 8: Metathesis of Ι,ω-dienyl esters.
61 62
70 71
Table 9: Metathesis of Ι,ω-dienyl esters in toluene at 80°C according to procedure B.
Olefin mM [a] Catalyst ppm [b] TOF [c] Conv. [d]
61 40 A 50 278 100
61 10 B 50 739 100
61 40 B 50 1022 95
61 20 C 50 1049 86
61 40 C 50 1495 88
61 400 C 50 2422 89
64 10 A 75 105 84
64 10 B 75 321 92
64 10 C 75 430 98
67 8 B 100 118 40
67 8 C 100 280 58
67 20 C 250 356 100
70 8 A 75 542 100 70 40 A 50 115 99
70 8 B 50 1014 92
70 8 C 75 2265 100
[a] starting concentration of olefin; . [b] catalyst loading 1 ppm = 0.0001 mol%; [c] turn-over frequency [min -1 ] ; [d] conversion of starting olefin measured after complete standstill of the reaction [%] .
Table 11: Metathesis of prolines in toluene at 80°C according to procedure B.
Olefin mM [a] Catalyst ppm [b] TOF [c] Conv. [d]
76 8 A 1000 67 85
76 8 B 2000 30 70
76 8 C 1000 66 75
79 8 A 1000 14 80
79 8 B 1000 32 50
79 8 B +500 31 74
79 8 C 1000 43 58
79 8 C +500 32 79
82 8 A 200 126 91
82 8 B 200 261 80
82 8 B +100 102 94
82 8 C 200 375 91 85 8 A 1000 26 95
85 8 B 1000 52 80
85 8 B +500 15 92
85 8 C 1000 61 74
85 8 C +500 21 88
87 8 A 200 119 90
87 8 B 200 259 80
87 8 B +200 63 99
87 8 C 200 344 82
87 8 C +200 56 98
[a] starting concentration of olefin; . [b] catalyst loading 1 ppm = 0.0001 mol%, + denotes additional amounts of catalyst added after stopping of the reaction; [c] turn-over frequency [min -1 ] ; [d] conversion of starting olefin measured after complete standstill of the reaction [%] .
Experimental Procedures
Procedure for metathesis of neat dienes (A)
A 250 ml round bottomed flask equipped with reflux condenser closed with oil bubbler, 3 cm magnetic stir bar and two rubber septa was flame-dried under vacuum, charged with substrate (0.2 mol) , then filled with argon and the flask was placed in an oil bath heated to 80°C. Stirring (800 rpm) was started and argon was passed through a needle inserted through the septum and connected to a gas supply. After 30 min temperature equilibration a solution of catalyst in 0.8 ml of degassed toluene were added using a syringe. Samples were taken at regular intervals via syringe through the septum, quenched with 100 μΐ ethylvinylether in 1 ml toluene and analyzed using GC. Procedure for metathesis in diluted solution (B)
Toluene was degassed 10 min in an ultrasonic bath under argon prior to use. A 500 ml round bottomed flask equipped with intensive reflux condenser (50 cm) closed with oil bubbler, 3 cm magnetic stir bar and two rubber septa was flame-dried under vacuum, charged with substrate and internal standard (dodecane, tetradecane or octadecane was added as internal standard) then filled with argon and 250 ml of degassed toluene were added through steel capillary under argon. The flask was placed in an oil bath heated to 80°C, stirring (800 rpm) was started and argon was passed through a needle
inserted through the septum and connected to a gas supply (100-300 ml/min) . After 30 min temperature equilibration a solution of catalyst in 0.8 ml of degassed toluene were added using a syringe. Samples were taken at regular intervals via syringe through the septum, quenched with 50 μΐ
ethylvinylether in 0.5 ml toluene and analyzed using GC . Metathesis diethyl 2 , 2-diallylmalonate (1)
Metathesis of neat diene 1 (48 g, 200 mmol) according to general procedure A using 0.01 mol% of catalyst B as a
solution in toluene afforded complete conversion and 41 g (97%) of diethyl 3-cyclopentene-l , 1-dicarboxylate (2) were isolated by distillation of reaction mixture under vacuum using a 10 cm Vigreux column; bp = 82°C/2mbar.
Metathesis of 4-benzyloxy-hepta-l , 6-diene (3)
Metathesis of neat diene 3 (40.46 g, 200 mmol) according to general procedure A using 0.02 mol% catalyst C as a solution in toluene afforded complete conversion and 33.4 g (96%) of 3- benzyloxy-cyclopentene-1 (4) were isolated by distillation of reaction mixture under vacuum using a 10 cm Vigreux column; bp 74°C/0.8 mbar. Metathesis 4-benzyloxy-4-methyl-1 , 6-heptadiene (5)
Metathesis of neat diene 5 (43.26 g, 0.2 mol) according to general procedure A using 0.01 mol% catalyst C as a solution in toluene afforded complete conversion and 36.5 g (97%) of 3- benzyloxy-3-methyl-cyclopentene-l (6) were isolated by
distillation under vacuum using a 5 cm Vigreux column; bp 66- 68°C/0.7mbar . Metathesis of 4-benzyloxy-l , 7-octadiene (7)
Metathesis of neat diene 7 (43.26 g, 0.2 mol) according to general procedure A using 0.01 mol% catalyst C as a solution in toluene afforded complete conversion and 35.8 g (95%) of 4- benzyloxy-l-cyclohexene (8) were isolated by distillation of reaction mixture under vacuum using a 10 cm Vigreux column; bp = 71-73°C/0.6 mbar.
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