Patent Application: US-201314426049-A

Abstract:
the present application discloses novel amino - sulfide metal catalysts for organic chemical syntheses including hydrogenation of unsaturated compounds or dehydrogenation of substrates . the range of hydrogenation substrate compounds includes esters , lactones , oils and fats , resulting in alcohols , diols , and triols as reaction products . the catalysts of current application can be used to catalyze a hydrogenation reaction under solvent free conditions . the present catalysts also allow the hydrogenation to proceed without added base , and it can be used in place of the conventional reduction methods employing hydrides of the main - group elements . furthermore , the catalysts of the present application can catalyze a dehydrogenation reaction under homogenous and / or acceptorless conditions . as such , the catalysts provided herein can be useful in substantially reducing cost and improving the environmental profile of manufacturing processes for a variety of chemicals .

Description:
unless defined otherwise , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs . as used in the specification and claims , the singular forms “ a ”, “ an ” and “ the ” include plural references unless the context clearly dictates otherwise . the term “ comprising ” as used herein will be understood to mean that the list following is non - exhaustive and may or may not include any other additional suitable items , for example one or more further feature ( s ), component ( s ) and / or ingredient ( s ) as appropriate . as used herein , “ heteroatom ” refers to non - hydrogen and non - carbon atoms , such as , for example , o , s , and n . as used herein , “ alkyl ” means a hydrocarbon moiety that consists solely of single - bonded carbon and hydrogen atoms , for example a methyl or ethyl group . as used herein , “ alkenyl ” means a hydrocarbon moiety that is linear , branched or cyclic and comprises at least one carbon to carbon double bond . “ alkynyl ” means a hydrocarbon moiety that is linear , branched or cyclic and comprises at least one carbon to carbon triple bond . “ aryl ” means a moiety including a substituted or unsubstituted aromatic ring , including heteroaryl moieties and moieties with more than one conjugated aromatic ring ; optionally it may also include one or more non - aromatic ring . “ c 5 to c 8 aryl ” means a moiety including a substituted or unsubstituted aromatic ring having from 5 to 8 carbon atoms in one or more conjugated aromatic rings . examples of aryl moieties include phenyl . “ heteroaryl ” means a moiety including a substituted or unsubstituted aromatic ring having from 4 to 8 carbon atoms and at least one heteroatom in one or more conjugated aromatic rings . as used herein , “ heteroatom ” refers to non - carbon and non - hydrogen atoms , such as , for example , 0 , s , and n . examples of heteroaryl moieties include pyridyl , furanyl and thienyl . “ alkylene ” means a divalent alkyl radical , e . g ., — c f h 2f — wherein f is an integer . “ alkenylene ” means a divalent alkenyl radical , e . g ., — chch —.] “ substituted ” means having one or more substituent moieties whose presence does not interfere with the desired reaction . examples of substituents include alkyl , alkenyl , alkynyl , aryl , aryl - halide , heteroaryl , cycloalkyl ( non - aromatic ring ), si ( alkyl ) 3 , si ( alkoxy ) 3 , halo , alkoxyl , amino , alkylamino , alkenylamino , amide , amidine , hydroxyl , thioether , alkylcarbonyl , alkylcarbonyloxy , arylcarbonyloxy , alkoxycarbonyloxy , aryloxycarbonyloxy , carbonate , alkoxycarbonyl , aminocarbonyl , alkylthiocarbonyl , phosphate , phosphate ester , phosphonato , phosphinato , cyano , acylamino , imino , sulfhydryl , alkylthio , arylthio , thiocarboxylate , dithiocarboxylate , sulfate , sulfato , sulfonate , sulfamoyl , sulfonamide , nitro , nitrile , azido , heterocyclyl , ether , ester , silicon - containing moieties , thioester , or a combination thereof . the substituents may themselves be substituted . for instance , an amino substituent may itself be mono or independently disubstitued by further substituents defined above , such as alkyl , alkenyl , alkynyl , aryl , aryl - halide and heteroarylcycloalkyl ( non - aromatic ring ). the present application provides catalysts that are useful in catalytic hydrogenation ( reduction ) processes . the hydrogenation process is useful in hydrogenation of , for example , c 2 - c n ( n = 3 - 200 ) substrates possessing one or more ester or lactone groups to afford the corresponding alcohol , diol , or triol products . thus , the present application further provides a practical reduction method that can be used in place of the main - group hydride reduction to obtain alcohols , diols , or triols in a simple , efficient , and “ green ” fashion . the catalyst of the present application is also useful in catalytic dehydrogenation process , which can be , for example , a homogeneous dehydrogenation process . the processes described herein are carried out in the presence of a catalyst or a pre - catalyst in the form of a transition metal complex of tridentate sns or bidentate sn amino - sulfide ligands . the transition metal is preferably a metal from groups 7 ( manganese group ), 8 ( iron group ), and 9 ( cobalt group ), in which ru and os are particularly preferable . the coordinating groups of the tridentate sns ligand consist of two thioether groups and one nitrogen ( amino ) group . the coordinating groups of a bidentate sn ligand consist of one thioether and one nitrogen ( amino ) group . the general structure of the sn ligand is represented by formula ia and the structure of the sns ligand is represented by formula ib . sr 1 is a thioether group , which is coordinated to the metal center of the catalyst or pre - catalyst ; r 1 , r 2 , r 5 , and r 6 are each independently h , a substituted or unsubstituted linear or branched c 1 - c 20 alkyl ( such as a c 1 - c 8 alkyl ), a substituted or unsubstituted cyclic c 3 - c 8 alkyl , or a substituted or unsubstituted alkenyl , a substituted or unsubstituted c 5 - c 20 aryl ( such as a c 5 - c 14 or c 5 - c 8 aryl ), or or nr 2 ; or when taken together , r 1 and r 2 groups or r 5 and r 6 groups can form a saturated or partially saturated cycle ; r 3 and r 4 are each independently h , a substituted or unsubstituted linear , branched or cyclic c 1 - c 8 alkyl or alkenyl , a substituted or unsubstituted c 5 - c 8 aromatic group , ester group ; or , when taken together , r 3 and r 4 can form an optionally substituted saturated or partially saturated hetero - aromatic ring ; r 5 when taken together with r 4 can form an optionally substituted saturated or partially saturated aromatic ring ; r 7 is h , a substituted or unsubstituted linear or branched c 1 - c 8 alkyl ( such as a c 1 - c 8 alkyl ), a substituted or unsubstituted cyclic c 3 - c 8 alkyl , a substituted or unsubstituted alkenyl , or a substituted or unsubstituted c 5 - c 20 aryl ( such as a c 5 - c 14 or c 5 - c 8 aryl ); and n , m , and q are simultaneously or independently 0 , 1 , or 2 . the sn and sns ligands can be synthesized using standard procedures which are well known in the art and by the person skilled in the art . for example , sn ( ia ) and sns ( ib ) ligands can be obtained by alkylation of a mercaptane by 2 - chloro - ethylamine hydrochloride or bis -( 2 - chloroethyl ) amine hydrochloride , respectively , under basic conditions . according to one embodiment of the invention , the catalyst or pre - catalyst is a metal complex of the general formulae ii - iii : wherein sn is the bidentate ligand of formula ia ; a is 1 , 2 or 3 ; p is 1 or 2 ; sns is the tridentate ligand of formula ib ; and each z represents simultaneously or independently a hydrogen or halogen atom , a c 1 - c 6 alkyl radical , a carbene group , a hydroxyl group , or a c 1 - c 7 alkoxy radical , a nitrosyl ( no ) group , co , cnr ( r = alkyl , aryl ), nitrile , phosphite , phosphinite , or phosphine such as pme 3 or pph 3 . the catalysts and pre - catalysts can exist in both neutral and cationic forms . the transition metal m is preferably a metal from groups 7 ( manganese group ), 8 ( iron group ), and 9 ( cobalt group ), in which ru and os are particularly preferable . in one embodiment , the complexes of formulae ii - iii can be prepared by reaction of the ligands of formulae ia , or ib with a metal precursor , such as those well known in the state of the art . preferably , the metal precursor is a ruthenium or osmium compound , including , for example , a compound of the following formulae : rucl 2 ( asph 3 ) 3 , ruhcl ( asph 3 ) 3 , rucl 2 ( pph 3 ) 3 , ruhcl ( pph 3 ) 3 , rucl 2 ( co )( pph 3 ) 3 , rucl 2 ( co )( asph 3 ) 3 , ruhcl ( co )( asph 3 ) 3 , oshcl ( asph 3 ) 3 , oscl 2 ( asph 3 ) 3 , oshcl ( pph 3 ) 3 , oscl 2 ( pph 3 ) 3 , [ rucl 2 ( p - cymene )] 2 , [ oscl 2 ( p - cymene )] 2 , rucl 2 ( co )( p - cymene ), oscl 2 ( co )( p - cymene ), rucl 2 ( co )( dmf )( pph 3 ) 2 , [ ircl ( cod )] 2 , [ ircl ( coe ) 2 ] 2 , irhcl 2 ( pph 3 ) 3 , irh 2 cl ( pph 3 ) 3 , irhcl 2 ( asph 3 ) 3 , or irh 2 cl ( asph 3 ) 3 . the reactions can be conducted in various organic solvents , such as , but not limited to , toluene , xylene , benzene , diglyme , dmf or dme . the present application additionally provides a catalytic hydrogenation process . the catalyst complexes of formulae ii - iii described above , have been shown to have high reactivity in reduction of the polar c ═ x ( x ═ n , o ) bonds . for examples , esters , ketones , fats , esters with multiple ester groups and imines can be mentioned . in one embodiment , there is provided a process for hydrogenation of esters using metal catalysts based on the sns ligand of formula ib . the ester substrates are compounds of the following formulae : the term “ substrate ”, as used herein , and as commonly understood by those of skill in the art , refers to the reactant that will be converted to a product during a catalytic reaction . groups g1 and g2 , simultaneously or independently , represent a linear , branched c 1 - c 40 or cyclic c 3 - c 40 alkyl , alkenyl or aromatic group , optionally substituted . also contemplated herein is a situation when g1 and g2 together form a c 4 - c 40 saturated or unsaturated radical . the substrate of the hydrogenation reaction can be any organic compound containing one , or more than one , carboalkoxy group or c ═ x ( x = 0 , n ) bond . in this respect , natural fats such as olive , canola , corn , peanut , palm and other plant oils are useful substrates that can be reduced to form a mixture of alcohols . imines can be reduced to amines and ketones to secondary alcohols . when the substrate is a monoester or a lactone , the products are alcohols or a diol , respectively . the naturally occurring triglycerides , oils and fats , can be reduced to glycerol and the corresponding fatty alcohols . substrates with multiple ester groups , like phthalates , are reduced to diols and polyols . when the substrates are imines or ketones , the products are secondary amines and alcohols , respectively . according to one embodiment , the process of catalytic reduction of imines and esters implies the usage of at least one of the metal complexes ii or iii , hydrogen pressure , and optionally a base and a solvent . the base may be necessary in those cases when the metal catalyst iii contains one or more halogen atoms bonded to the metal . the treatment with base can be done prior to the reduction or in situ by adding base to the reaction mixture during hydrogenation . the catalysts and pre - catalysts of this invention can be used in a wide range of concentrations , preferably between about 10 and about 1000 ppm , and the loadings of 500 ppm or less are particularly preferred . the preferred amount of the catalyst will depend , as it is known to the person skilled in the art , on the type of the substrate , and increasing the catalyst loading may result in faster hydrogenation . the temperature at which the hydrogenation can be carried out is between about 0 ° c . and about 150 ° c ., more preferably in the range between about 20 ° c . and about 100 ° c . and , as it is known to the person skilled in the art , the reaction rate will increase with an increase of the reaction temperature . the hydrogenation reaction requires a pressure of h 2 gas and should be performed in a suitable pressure vessel . the surface area of the reactor as well as the hydrogen pressure , as it is known to the person skilled in the art , can greatly influence the reaction rate . the greater the hydrogen pressure and / or the surface area of the reactor , the faster the hydrogenation reaction rate . in one embodiment the hydrogen pressure is in range of about 5 to about 200 bar . again , the person skilled in the art is well able to adjust the pressure as a function of the catalyst load and of the dilution of the substrate in the solvent . examples of typical pressures used in the present hydrogenation reactions are from about 5 to about 50 bar ( 5 to 50 × 10 5 pa ). it should be well understood , however , that the catalyst complexes described herein are also useful in catalyzing hydrogenation of substrates including functional groups other than esters and imines . the table below provides a non - limiting list of substrates and products that can be formed from a catalytic hydrogenation reaction using a catalyst of formula ii or iii . the present application further provides a process of catalytic dehydrogenation using the catalyst complexes of formulae ii and iii . for example , these catalysts or pre - catalysts are suitable for dehydrogenation of c n ( n = 2 - 200 ) alcohols possessing one or more — ch 2 oh groups thereby affording hydrogen gas and the corresponding esters or lactones . the substrates are compounds of the following formulae : r ═ c 1 - c n alkyl or aryl substituents ( optionally substituted ) in this embodiment , r groups , simultaneously or independently , represent a linear , branched c 1 - c 40 or cyclic c 3 - c 40 alkyl , alkenyl or aromatic group , optionally substituted . also contemplated herein is the situation when r is a c 4 - c 40 saturated or unsaturated cyclic radical . this implies that the substrate can be any organic compound containing one , or more than one , hydroxyl ( oh ) group . the reduction process of this embodiment is illustrated below . when the substrate is an alcohol or a diol , the product is an ester or a lactone , respectively . r ═ c 1 - c n alkyl or aryl substituent ( optionally functionalized ) according to one embodiment , the process of catalytic acceptorless dehydrogenation implies the usage of at least one of the metal complexes of formulae ii or iii and ( optionally ) the use of a base and a solvent . the base may be necessary in those cases when the metal catalyst of formula ii or iii contains one or more halogen or alkoxy (— or ) groups bonded to the metal . the catalyst can be treated with base prior to mixing with the substrate or in situ by adding base to the reaction mixture during dehydrogenation . the catalysts and pre - catalysts described herein can be used in a wide range of concentrations , preferably between about 10 and about 1000 ppm , and the loadings of 1000 ppm or less are particularly preferred . the preferred amount of the catalyst will depend , as it is known to the person skilled in the art , on the type of the substrate ; and increasing the catalyst loading should result in faster dehydrogenation . the temperature at which the dehydrogenation can be carried out is between about 0 ° c . and about 200 ° c ., more preferably in the range between about 50 ° c . and about 150 ° c . and , as it is known to the person skilled in the art , the reaction rate will increase with increase of the reaction temperature . the dehydrogenation process can generate a pressure of h 2 gas and , in such cases , can be performed in a suitable pressure vessel that is , if necessary , equipped with a pressure - release valve . it should be well understood , however , that the catalyst complexes described herein are also useful in catalyzing dehydrogenation of substrates including functional groups other than alcohols . the table below provides a non - limiting list of substrates and products that can be formed from a catalytic dehydrogenation reaction using a catalyst of formula ii or iii . a h 2 is also a byproduct of these reactions . it is either liberated from the reaction as h 2 or transferred to an acceptor . as noted above , a byproduct of the dehydrogenation reactions is h 2 . accordingly , the present application further provides a process for producing h 2 . the process can conveniently make use of readily available substrates in a straightforward catalytic dehydrogenation process under relatively mild conditions to generate h 2 . to gain a better understanding of the invention described herein , the following examples are set forth . it should be understood that these examples are for illustrative purposes only . therefore , they should not limit the scope of this invention in any way . unless mentioned otherwise , all manipulations have been performed under an atmosphere of argon in a glove box , or using standard schlenk techniques . nmr spectra were recorded on a varian unity inova 300 mhz spectrometer . all 31p chemical shifts are relative to 85 % h3po4 . 1h and 13c chemical shifts were measured relative to the solvent peaks but they are reported relative to tms . rucl 3 . 3h 2 o was purchased from pressure chemicals . ru - macho ( vi ), rucl 2 ( ph 2 pc 2 h 4 ml 2 ) 2 ( v ), and milstein &# 39 ; s catalyst iii were purchased from strem chemicals . all other compounds and anhydrous grade solvents were obtained from aldrich and alfa aesar . commercial anhydrous grade ethanol was further distilled over sodium metal and stored in the argon glovebox . ruhcl ( co )( asph 3 ) 3 [ d . spasyuk , s . smith , d . g . gusev , angew . chem . 2012 , 51 , 2772 - 2775 ] and rucl 2 ( pph 3 ) 3 [ s . rajagopal , s . vancheesan , j . rajaram , j . c . kuriacose , j . mol . cat . 1983 , 22 , 131 - 135 ] were prepared according to previously reported methods .. all manipulations were carried in air . in a 250 ml flask , 24 g ( 0 . 191 mol ) of naoh was dissolved in 100 ml of ch 3 oh and etsh ( 15 g , 0 . 242 mol ) was added . after 10 minutes of reaction , 28 . 07 g ( 0 . 242 mol ) of 2 - chloroethylamine hydrochloride was slowly added to the mixture and the reaction was left to stir overnight . in the following morning , methanol was removed in vacuo and the remaining semisolid was extracted with 3 × 30 ml of et 2 o . the obtained extract was filtered through a short plug ( 2 cm × 1 cm ) of al 2 o 3 and ether was removed under reduced pressure ( 15 mm hg ) to yield a pale yellow oil ( 23 . 4 g , 92 %) 1 h nmr ([ d6 ] benzene ) δ = 2 . 54 ( t , j = 6 . 2 hz , 2h , ch 2 ), 2 . 25 ( t , j = 6 . 2 hz , 2h , ch 2 ), 2 . 18 ( q , j = 7 . 4 hz , 2h , sch 2 ), 1 . 02 ( t , j = 7 . 4 hz , 3h , ch 3 ), 0 . 76 ( br , 211 , nh 2 ). 13 c { 1 h } nmr ([ d6 ] benzene ) δ = 41 . 72 ( s , 1c , nch 2 ), 36 . 22 ( s , 1c , ch 2 s ), 25 . 72 ( s , 1c , sch 2 ), 15 . 11 ( s , 1c , ch 3 ). all manipulations were carried in air . to a solution of bis ( 2 - chloroethyl ) amine hydrochloride ( 23 . 9 g , 0 . 134 mol ) in 80 ml of methanol were added naoh ( 6 . 27 g , 0 . 157 mol ) and sodium ethanethiolate ( 25 g , 0 . 298 mol ). the resulting mixture was stirred overnight at room temperature . after that time , methanol was removed in vacuo . the remaining yellow slurry was extracted with 3 × 15 ml of et 2 o and the obtained extract was filtered through a short plug ( 2 cm × 1 cm ) of al 2 o 3 . the solvent was removed in vacuo to yield a pale yellow oil ( 23 . 0 g , 89 %). alternatively , ( ets ( ch 2 ) 2 ) 2 nh was prepared by the following , slightly different method . again all manipulations were performed in air . to a solution of naoh ( 6 . 27 g , 0 . 157 mol ) and sodium ethanethiolate ( 25 g , 0 . 298 mol ) in 80 ml of methanol was slowly added bis ( 2 - chloroethyl ) amine hydrochloride ( 23 . 9 g , 0 . 134 mol ) in 65 ml of methanol . the mixture was stirred overnight at room temperature , and then the solvent was removed under reduced pressure . the resulting yellow slurry was extracted with 3 × 20 ml of hexane and the obtained extract was filtered through a short plug ( 2 × 1 cm ) of basic alumina . the solvent was evaporated to give a pale yellow oil with the same yield as above ( 23 . 0 g , 89 %). 1 h nmr ([ d6 ] benzene ) δ = 2 . 62 ( t , j = 6 . 6 hz , 4h , 2 × nch 2 ), 2 . 46 ( t , j = 6 . 5 hz , 4h , 2 × sch 2 ), 2 . 27 ( q , j = 7 . 4 hz , 4h , 2 × sch 2 ), 1 . 42 ( br , 1h , nh ), 1 . 06 ( t , j = 7 . 4 hz , 6h , 2 × ch 3 ). 13 c { 1 h } nmr ([ d6 ] benzene ) 8 = 49 . 04 ( s , 2c , 2 × nch 2 ), 32 . 50 ( s , 2c , 2 × ch 2 s ), 26 . 03 ( s , 2c , 2 × sch 2 ), 15 . 15 ( s , 2c , 2 × ch 3 ). all manipulations were performed in air . to a solution of naset ( 5 . 41 g , 64 . 4 mmol ) in 40 ml of methanol was added a solution of bis ( 2 - chloroethyl ) ether ( 4 . 6 g , 32 . 2 mmol ) in 20 ml of methanol . the mixture was stirred overnight at 40 ° c ., and then the solvent was removed under reduced pressure . the resulting slurry was extracted with 2 × 20 ml of hexanes and the obtained extract was filtered through a short plug ( 2 × 1 cm ) of basic alumina . the solvent was evaporated to give a transparent oil ( 4 . 07 g , 64 %). 1 h nmr ([ d6 ] benzene ) 8 3 . 39 ( t , j = 6 . 9 hz , 4h , och 2 ), 2 . 52 ( t , j = 6 . 9 hz , 4h , ch 2 s ), 2 . 31 ( q , j = 7 . 4 hz , 4h , sch 2 ), 1 . 05 ( t , j = 7 . 4 hz , 6h , ch 3 ). 13 c { 1h } nmr ([ d6 ] benzene ) s 71 . 38 ( s , 2c , ch 2 o ), 31 . 50 ( s , 2c , ch 2 s ), 26 . 66 ( s , 2c , sch 2 ), 15 . 13 ( s , 2c , ch 3 ). all manipulations were performed in air . a mixture of ( ets ( ch 2 ) 2 ) 2 nh ( 500 mg , 2 . 59 mmol ), formic acid ( 477 mg , 10 . 36 mmol ) and 1 ml of formaldehyde ( 40 % in water ) was refluxed for 2 h . the reaction mixture was cooled , treated with 10 ml of a 20 % aqueous solution of naoh and extracted with 3 × 10 ml of et 2 o . the combined ether solution was washed with 2 × 10 ml of water and evaporated under vacuum . the residue was further dried under vacuum at 50 ° c . the product was isolated as a transparent oil . yield : 397 mg ( 65 %). 1 h nmr ([ d ] chloroform ) δ 2 . 65 - 2 . 59 ( m , 8h , ch 2 ), 2 . 54 ( q , j = 7 . 4 hz , 4h , sch 2 ), 2 . 28 ( s , 3h , nch 3 ), 1 . 25 ( t , j = 7 . 4 hz , 6h , ch 3 ). 13 c { 1h } nmr ([ d ] chloroform ) δ 57 . 49 ( s , nch 2 ), 42 . 15 ( s , nch 3 ), 29 . 30 ( s , ch 2 s ), 26 . 29 ( s , sch 2 ), 14 . 98 ( s , ch 3 ). a 100 ml schlenk flask containing a mixture of rucl 2 ( pph 3 ) 3 ( 5 . 00 g , 5 . 22 mmol ) and ( ets ( ch 2 ) 2 ) 2 nh ( 1 . 01 g , 5 . 23 mmol ) in 40 ml of toluene was heated at 100 ° c . for 2 h to get a yellow suspension . the product was filtered in air , washed with 10 - 15 ml of et 2 o giving a cream yellow solid which was dried under vacuum for 2 h . yield : 2 . 98 g ( 91 %). the compound was isolated as a mixture of three isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . the synthesis was repeated using a mixture of rucl 2 ( pph 3 ) 3 ( 15 . 00 g , 15 . 66 mmol ) and ( ets ( ch 2 ) 2 ) 2 nh ( 3 . 03 g , 15 . 7 mmol ) in 50 ml of toluene . the yield was 8 . 64 g ( 88 %) and the product was again isolated as a mixture of the three isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h { 31 p } nmr ([ d2 ] dcm ) δ 7 . 70 - 7 . 38 ( m ), 7 . 40 - 6 . 95 ( m ), 5 . 21 ( br , nh ), 4 . 99 ( br , nh ), 4 . 61 ( br , nh ), 3 . 25 ( m ), 3 . 06 ( m ), 2 . 97 - 2 . 58 ( m ), 2 . 46 - 2 . 24 ( m ), 1 . 71 - 1 . 39 ( m ), 1 . 03 ( t , j = 7 . 0 hz , ch 3 ), 1 . 04 ( t , j = 7 . 0 hz , ch 3 ). 13 c { 1 h } nmr ([ d2 ] dcm ) δ major isomer = 137 . 42 ( d , j ( cp )= 39 . 3 hz , 3c , { par } c ipso ), 134 . 87 ( d , j ( cp )= 10 . 0 hz , 6c , { par } c ortho ), 129 . 46 ( d , j ( cp )= 6 . 7 hz , 3c , { par } c para ), 127 . 91 ( d , j ( cp )= 9 . 4 hz , 6c , { par } c meta ), 49 . 24 ( s , 2c , 2 × nch 2 ), 39 . 81 ( s , 2c , 2 × ch 2 s ), 29 . 96 ( s , 2c , 2 × sch 2 ), 13 . 23 ( s , 2c , 2 × ch 3 ). 31 p { 1 h } nmr ([ d2 ] dcm ) δ = 51 . 08 ( major isomer , s , 1p ), 49 . 51 ( minor isomer , br . s , 1p ), 48 . 02 ( minor isomer , br . s , 1p ). a 50 ml schlenk flask containing a mixture of oscl 2 ( pph 3 ) 3 ( 3 . 00 g , 3 . 07 mmol ) and ( ets ( ch 2 ) 2 ) 2 nh ( 0 . 594 g , 3 . 07 mmol ) in 25 ml of toluene was heated at 100 ° c . for 2 h to get a yellow suspension . the product was filtered in air , washed with 10 - 15 ml of et 2 o giving an orange solid which was dried under vacuum for 2 h . yield : 1 . 91 g ( 87 %). the compound was isolated as a mixture of 3 isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h { 31 p } nmr ([ d2 ] dcm ) δ sum 7 . 70 - 7 . 38 ( m ), 7 . 40 - 6 . 95 ( m ), 5 . 21 ( br , nh ), 4 . 99 ( br , nh ), 4 . 61 ( br , nh ), 3 . 25 ( m ), 3 . 06 ( m ), 2 . 97 - 2 . 58 ( m ), 2 . 46 - 2 . 24 ( m ), 1 . 71 - 1 . 39 ( m ), 1 . 04 ( t , j = 7 . 0 hz , ch 3 ),), 0 . 936 ( br , ch 3 ). 13 c { 1 h } nmr ([ d2 ] dcm ) δ major isomer = 139 . 20 ( d , j ( cp )= 46 . 3 hz , 3c ,){ arp } c ipso ), 134 . 72 ( d , j ( cp )= 9 . 9 hz , 6c ,){ arp } c ortho ), 129 . 34 ( d , j ( cp )= 7 . 9 hz , 3c , { arp } c para ), 127 . 86 ( d , j ( cp )= 9 . 3 hz , 6c , { arp } c meta ), 50 . 14 ( s , 2c , 2 × nch 2 ), 40 . 27 ( s , 2c , 2 × ch 2 s ), 30 . 81 ( s , 2c , 2 × sch 2 ), 12 . 99 ( s , 2c , 2 × ch 3 ). 31 p { 1 h } nmr ([ d2 ] dcm ) s = 2 . 00 ( major isomer , s , 1p ), − 0 . 23 ( minor isomer , br . s , 1p ), − 2 . 35 ( minor isomer , br . s , 1p ). a 100 ml schlenk flask containing a mixture of ruhcl ( pph 3 ) 3 ( 4 . 80 g , 5 . 20 mmol ) and ( etsc 2 h 4 ) 2 nh ( 1 . 01 g , 5 . 23 mmol ) in 30 ml of toluene was heated at 100 ° c . for 2 h to form a dark - green solution . diethyl ether ( 10 ml ) was added and the product was left to crystallize in a freezer . the precipitate was filtered , washed with 20 ml of ether to give a dark - green solid which was dried under vacuum for 2 h . yield : 1 . 97 g ( 64 %). the product was isolated as a mixture of 3 isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h nmr ([ d2 ] dcm ) δ 8 . 04 - 7 . 39 ( m ,){ ph } h ortho ), 7 . 47 - 6 . 93 ( m , { ph } h meta +{ ph } h para ), 4 . 79 , 4 . 63 , 4 . 21 ( br , nh ), 3 . 64 - 3 . 00 ( m , ch 2 ), 3 . 07 - 2 . 48 ( m , ch 2 ), 2 . 21 - 1 . 70 ( m , ch 2 ), 0 . 84 ( t , j ( hh )= 7 . 2 hz , 2 × ch 3 ), − 20 . 16 ( d , j ( hp )= 26 . 1 hz ruh ), − 21 . 01 ( d , j ( hp )= 25 . 4 hz , ruh ), − 21 . 55 ( d , j ( hp )= 27 . 4 hz , ruh ). 13 c { 1h } nmr ([ d2 ] dcm ) of the major isomer , δ 140 . 35 ( d , j ( cp )= 38 . 4 hz ,) { ph } c ispo ), 134 . 14 ( d , j ( cp )= 11 . 0 hz , { ph } c ortho ), 128 . 55 ( s , { ph } c ′), 127 . 44 ( d , j ( cp )= 8 . 9 hz , { ph } c meta ), 51 . 33 ( s , nhch 2 ), 37 . 35 ( s , ch 2 s ), 36 . 24 ( s , sch 2 ), 13 . 94 ( s , ch 3 ). 31 p { 1h } nmr ([ d2 ] dcm ) δ 72 . 62 ( s , 34 %), 70 . 86 ( s , 35 %), 68 . 31 ( s , 31 %). anal . calcd for c 26 h 35 clnprus 2 : c , 52 . 64 ; h , 5 . 95 ; n , 2 . 36 . found : c , 52 . 35 ; h , 5 . 86 ; n , 1 . 81 . a 100 ml schlenk flask containing a mixture of rucl2 ( asph3 ) 3 ( 2 . 24 g , 2 . 06 mmol ) and ( etsc 2 h 4 ) 2 nh ( 400 mg , 2 . 06 mmol ) in 20 ml of toluene was heated at 110 ° c . for 2 h to form a dark - grey suspension . the precipitate was filtered , washed with 15 ml of et 2 o to give a grey solid which was purified by recrystallization from thf / et 2 o in a freezer . yield : 456 mg ( 33 %). the compound was isolated as a mixture of 3 isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h nmr ([ d2 ] dcm ) δ 7 . 75 - 7 . 47 ( m ,){ ph } h ortho ), 7 . 44 - 7 . 13 ( m , { ph } h meta , { ph } h para , { toluene } h ), 4 . 92 , 4 . 69 , 4 . 48 ( br , nh ), 3 . 56 - 3 . 26 ( m , ch 2 ), 3 . 32 - 2 . 57 ( m , ch 2 ), 2 . 62 - 2 . 32 ( m , ch 2 ), 2 . 12 ( s , { toluene } ch 3 ) 1 . 93 - 1 . 43 ( m , ch 2 ), 1 . 14 - 0 . 91 ( br overlapped t , j = 7 . 3 hz , ch 3 ). 13 c { 1h } nmr ([ d2 ] dcm ) δ 137 . 46 ( s , { toluene } c ipso ), 134 . 23 ( s , { asph } c ipso ), 134 . 12 ( s , { asph } c ortho n , 129 . 17 ( s , { asph } c meta ), 129 . 08 ( s ,){ toluene } c ortho ), 128 . 14 ( s , { toluene } c meta ), 128 . 02 ( s , { asph } c para ), 125 . 32 ( s , { toluene } c para ), 49 . 66 ( s , ch 2 ), 39 . 49 ( s , ch 2 ), 30 . 39 ( s , ch 2 ), 12 . 99 ( s , ch 3 ). anal . calcd for c 26 h 34 cl 2 nruass 2 : c , 46 . 50 ; h , 5 . 10 ; n , 2 . 09 . found : c , 46 . 52 ; h , 4 . 98 ; n , 2 . 05 . a 100 ml schlenk flask containing a mixture of ruhcl ( co )( asph 3 ) 3 ( 5 . 61 g , 5 . 20 mmol ) and ( etsc 2 h 4 ) 2 nh ( 1 . 00 g , 5 . 20 mmol ) in 50 ml of toluene was refluxed for 3 h to form a dark - green suspension . the precipitate was filtered , washed with 15 ml of et 2 o to give a dark - green solid which was dried under vacuum for 2 h . yield : 1 . 60 g ( 85 %). the compound was isolated as a mixture of 3 isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h { 31 p } nmr ([ d2 ] dcm ) δ 4 . 28 ( br , nh ), 3 . 62 - 3 . 23 ( m , 4h , ch 2 ), 3 . 11 - 2 . 25 ( m , 8h , ch 2 ), 1 . 30 ( t , j = 7 . 3 hz , ch 3 ), − 16 . 84 ( s , 28 %, ruh ), − 17 . 14 ( s , 51 %, ruh ), − 17 . 48 ( s , 21 %, ruh ). 13 c { 1 h } nmr ([ d2 ] dcm ) of the mixture of isomers , s 205 . 01 ( d , j ( ch )= 4 . 5 hz , due to the residual coupling to the hydride , co ), 52 . 46 ( s , ch 2 ), 52 . 39 ( s , ch 2 ), 50 . 95 ( s , ch 2 ), 50 . 82 ( s , ch 2 ), 40 . 96 ( s , ch 2 ), 40 . 57 ( s , ch 2 ), 39 . 16 ( s , ch 2 ), 32 . 64 ( s , ch 2 ), 32 . 10 ( s , ch 2 ), 13 . 25 ( s , ch 3 ), 13 . 17 ( s , ch 3 ), 13 . 13 ( s , ch 3 ). anal . calcd for c 9 h 20 clnorus 2 : c , 30 . 12 ; h , 5 . 62 ; n , 3 . 90 . found : c , 30 . 71 ; h , 5 . 48 ; n , 3 . 63 . synthesis of ruh ( oet )( pph 3 )[( etsc 2 h 4 ) 2 nh ]. etoh ( 6 . etoh ) a mixture of complex 1 ( 1 . 7 g , 2 . 71 mmol ) and etona ( 553 mg , 8 . 13 mmol ) in 30 ml of ethanol was refluxed for 1 h to give a yellow solution ( caution : vigorous h + evolution !). the solvent was removed under reduced pressure ( without heating ) to give a highly air - sensitive yellow oil . the product was mixed with 20 ml of diethyl ether / toluene ( 3 : 1 ) and placed in a freezer for 1 h , then filtered through a glass frit , using 4 - 5 ml of hexane to wash the collected solids . the filtrate was evaporated under vacuum to dryness ( without heating ) to yield a yellow , air - sensitive solid . yield : 1 . 32 g ( 75 %). the compound was isolated as a mixture of 3 isomers differing by the relative orientation of the set groups with respect to the sns ligand plane . 1 h nmr ([ d6 ] benzene ) δ 7 . 99 ( m , { ph } h ortho ), 7 . 59 ( br , 2h , nh + oh ), 7 . 10 ( m , { ph } h meta +{ ph } h para ), 3 . 99 ( br , 4h , och 2 ), 3 . 54 - 1 . 49 ( m , 12h , ch 2 ), 1 . 44 ( br , 6h , ch 3 ), 0 . 97 - 0 . 11 ( br , 6h , ch 3 ), − 20 . 30 - 21 . 73 ( overlapped d , ruh ). 31 p { 1 h } nmr ([ d6 ] benzene ) δ minor isomers 70 . 44 - 69 . 00 ( br . s ), major isomer 69 . 00 - 67 . 49 ( br . s ). in the solid state , 5 . etoh rapidly changes color to black when exposed to air . no satisfactory elemental analysis could be obtained for 5 . etoh because of the sensitivity to air . synthesis of ruh 2 ( pph 3 )[( etsc 2 h 4 ) 2 nh ] ( 7 ) a solution of complex 6 ( 200 mg , 0 . 309 mmol , in 2 ml of benzene ) was kept in an oil bath at 60 ° c . for 30 min , then moved in a refrigerator , at + 3 ° c . the product crystallized and was isolated by filtration . it was briefly ( 25 min ) dried under vacuum thus affording an air - sensitive , yellow solid ( 74 mg , 44 %) as a single isomer . 1h nmr ([ d8 ] thf ) δ 8 . 38 ( s , 1h , nh ), 7 . 85 ( m , 6h ,){ ph } h ortho ), 7 . 25 - 6 . 97 ( m , 9h , { ph } hmeta +{ ph } hpara ), 3 . 00 - 1 . 45 ( overlapped br , 12h , ch2 ), 0 . 84 ( t , j ( hh )= 7 . 1 hz , 6h , ch3 ), − 12 . 20 ( d , j ( hp )= 27 . 9 hz , 1h , ruh ). 13c { 1h } nmr ([ d8 ] thf ) δ 144 . 96 ( d , j ( cp )= 33 . 0 hz , 3c , { ph } cipso ), 134 . 22 ( d , j ( cp )= 11 . 2 hz , 6c , { ph } cortho ), 127 . 58 ( s , 3c , { ph } cpara ), 127 . 26 ( d , 6c , j ( cp )= 8 . 5 hz , { ph } cmeta ), ch2 carbons were not observed due to line broadening , 14 . 33 ( s , ch3 ). 31p { 1h } nmr ([ d8 ] thf ) δ 82 . 00 ( s ). in the solid state , 7 rapidly changes color to black when exposed to air . no satisfactory elemental analysis could be obtained for 6 because of the sensitivity to air . synthesis of rucl 2 ( pph 3 )[( etsc 2 h 4 ) 2 o ] ( 8 ) a 100 ml schlenk flask containing a mixture of rucl 2 ( pph 3 ) 3 ( 4 . 93 g , 5 . 15 mmol ) and ( etsc 2 h 4 ) 2 o ( 1 . 00 g , 5 . 15 mmol ) in 40 ml of toluene was heated at 100 ° c . for 2 h to give a light - brown suspension . the product was filtered in air , washed with 15 ml of et 2 o affording a light - brown solid which was dried under vacuum for 2 h . yield : 2 . 16 g ( 68 %). the compound was isolated as a mixture of 2 isomers differing by the relative orientation of the set groups with respect to the sos ligand plane . 1 h nmr ([ d2 ] dcm ) δ 7 . 83 - 7 . 48 ( m , { ph } h ), 7 . 48 - 7 . 10 ( m , { ph } h ), 4 . 40 - 4 . 18 ( m , ch 2 ), 4 . 21 - 3 . 83 ( m , ch 2 ), 3 . 32 - 3 . 01 ( m , ch 2 ), 3 . 01 - 2 . 37 ( m , ch 2 ), 1 . 76 - 1 . 37 ( m , ch 2 ), 1 . 00 ( t , j = 6 . 8 hz , 2 × ch 3 ). 13 c { 1 h } nmr ([ d2 ] dcm ) 6 major isomer 136 . 81 ( d , j ( cp )= 45 . 2 hz ,){ ph } c ipso ), 134 . 84 ( d , j ( cp )= 9 . 7 hz ,){ ph } c ortho ), 129 . 70 ( s , { ph } c para ), 127 . 82 ( d , j ( cp )= 9 . 5 hz , { ph } c meta ), 69 . 80 ( s , och 2 ), 36 . 99 ( s , ch 2 s ), 27 . 59 ( s , sch 2 ), 12 . 92 ( s , ch 3 ). 31 p nmr ([ d2 ] dcm ) δ major isomer 62 . 32 ( s ), minor isomer 60 . 42 ( s ). anal . calcd for c 26 h 34 cl 2 orups 2 : c , 49 . 67 ; h , 5 . 29 ; s , 10 . 18 . found : c , 49 . 29 ; h , 5 . 18 s , 10 . 00 . synthesis of rucl 2 ( pph 3 )[( etsc 2 h 4 ) 2 nme ] ( 9 ) a 50 ml schlenk flask containing a mixture of rucl 2 ( pph 3 ) 3 ( 924 mg , 0 . 964 mmol ) and ( etsc 2 h 4 ) 2 nme ( 200 mg , 0 . 964 mmol ) in 10 ml of toluene was heated at 110 ° c . for 2 h to give a yellow suspension . the product was filtered in air , washed with 3 × 5 ml of et 2 o affording a yellow solid which was dried under vacuum for 2 h . yield : 407 mg ( 66 %). 1 h nmr ([ d2 ] dcm ) δ 7 . 97 - 7 . 62 ( m , 6h , { pph 3 } h orhto ), 7 . 51 - 7 . 12 ( m , 9h , { pph 3 } h meta + para ), 3 . 45 ( m , ch 2 ), 3 . 17 ( s , 3h , ch 3 ), 3 . 02 ( m , 1h ), 2 . 79 ( m , 3h ), 2 . 51 ( m , 2h ), 2 . 22 ( m , 3h ), 1 . 71 ( m , 1h ), 0 . 80 ( overlapped , 6h , ch 3 ), 0 . 09 ( m , 1h ). 13 c { 1 h } nmr ([ d2 ] dcm ) δ 137 . 21 ( d , j ( cp )= 41 . 4 hz , { pph 3 } c ipso ), 135 . 08 ( d , j ( cp )= 9 . 2 hz ,){ pph 3 } c ortho ), 129 . 50 ( s , { pph 3 } c meta ), 127 . 94 ( d , j ( cp )= 9 . 1 hz , { pph 3 } c para ), 60 . 55 ( s , ch 2 n ), 58 . 91 ( s , ch 2 n ), 50 . 97 ( s , nch 3 ), 36 . 40 ( s , ch 2 s ), 33 . 50 ( s , ch 2 s ), 29 . 37 ( s , sch 2 ), 27 . 64 ( s , sch 2 ), 13 . 09 ( s , ch 3 ), 12 . 90 ( s , ch 3 ). 31 p nmr ([ d2 ] dcm ) δ 44 . 94 ( s ). typical procedure for hydrogenation of esters or imines using complex 1 a solution of catalyst 1 in thf ( 3 . 2 mg / ml ) and 1 mol % of a base was mixed together with 0 . 02 mol of a substrate ( ester or imine ) in 6 g of thf ( or neat ). the mixture was then transferred into a 75 ml stainless - steel reactor ( parr 4740 ) equipped with a magnetic stir bar . the reactor was purged by two cycles of pressurization / venting with h 2 ( 150 psi , 10 bar ) and then pressurized with h 2 ( 725 psi , 50 bar ) and disconnected from the h 2 source . the reaction was conducted for a predetermined length of time at 20 - 100 ° c . at the end of the reaction time , the reactor was placed into a cold water bath ( if necessary ) and it was depressurized after cooling to the ambient temperature . 1 ml of a thf solution of complex 1 ( 3 . 2 mg / ml , 0 . 025 mol %) was added to koch 3 ( 14 mg , 0 . 2 mmol ). the obtained mixture was stirred for 1 - 2 min and then methyl benzoate ( 2 . 72 g , 20 . 0 mmol ) in 5 ml of thf was added . the subsequent manipulations were carried out following the procedure in example 13 . 1 ml of a thf solution of complex 1 ( 3 . 2 mg / ml , 0 . 0025 mol %) was added to naoet ( 136 mg , 2 . 0 mmol ). the obtained mixture was stirred for 1 - 2 min and then ethyl acetate ( 17 . 6 g , 0 . 20 mol ) was added . the subsequent manipulations were carried out following the procedure in example 5 except that a 300 ml reactor was used and the reaction was conducted under a constant pressure of h 2 ( 50 bar ). in an argon glovebox , a 50 ml schlenk tube equipped with a stirbar was charged with 0 . 02 mmol of the catalysts 1 or 2 and 136 mg ( 2 . 0 mmol ) of etona . then , 9 . 21 g ( 0 . 2 mol ) of ethanol was added . after taking the stoppered flask out of the box , it was attached to a vacuum / ar manifold . under argon , the stopper was replaced by a finger condenser connected to a circulating refrigerated bath . when the temperature in the bath reached − 10 c , the flask was placed in an oil bath preheated to 90 c . during dehydrogenation , the argon tank was kept closed and the h 2 gas produced passed through a mineral oil bubbler . the conversion to product was monitored by 1 h nmr spectroscopy . an attractive “ green ” alternative to the classical methods for reduction of carboxylic esters is the catalytic hydrogenation shown in scheme 1 , a method which has attracted much recent interest for the reduction of esters under h 2 . [ 3 - 7 ] the disclosure of milstein &# 39 ; s catalysts in 2006 ( such as complex iv ; scheme 1 )[ 3 ] was quickly followed by the development of the firmenich catalysts in 2007 ,[ 4 ] among which [ rucl 2 ( h 2 nc 2 h 4 pph 2 ) 2 ] ( ii ) is effective at 100 ° c . at a 0 . 05 mol % catalyst loading . [ 4a ] in 2011 , a new catalyst , ru - macho ( iii ), was patented by takasago chemists [ 5 ] ru - macho is useful at a 0 . 05 mol % loading for the hydrogenation of methyl lactate and methyl menthoxyacetate , giving high yields of ( r )- 1 , 2 - propanediol and 2 -( 1 - menthoxy ) ethanol , respectively . the most recent additions to this list of efficient catalysts are osmium and ruthenium complexes from the present inventors ,[ 6 ] particularly the air - stable complex [ rucl 2 —( pph 3 ){ pych 2 nhc 2 h 4 pph 2 }] ( iv ), which demonstrated unprecedented activity in the hydrogenation of esters andimines at [ ru ] loadings as low as 50 ppm at 40 ° c . it can be seen that all of the ester hydrogenation catalystsin scheme 1 possess amino - phosphine ligands . more generally , many noyori - type catalysts incorporate a combination of phosphorus and nitrogen donors . [ 8 ] despite the widespread application and tremendous success of phosphines in catalysis , they have well - known disadvantages . their preparations are often far from trivial and require handling under an inert atmosphere . as a result , the amino - phosphines are costly chemicals that can be challenging to make on a large scale . not surprisingly , catalysts i - iii ( available from strem chemicals ) are very expensive , especially i , which costs $ 680 pergram . considering that ruthenium contributes less than 1 % to this cost , it is apparent that the development of practical esterhydrogenation calls for using practical ligands , preferably ones containing no phosphorus . in the present study , the catalytic activity of ruthenium complexes with the hn ( c2h4set ) 2 ( sns ) ligand was evaluated for ester hydrogenation . the sns ligand was obtained nearly quantitatively by adding bis -( 2 - chloroethyl ) amine hydrochloride to a solution of ethanethiol and naoh in ethanol . [ 9b ] this synthesis has the practical advantages of being straightforward and scalable ; it can be conveniently performed in air , and it provides the sns ligand at a small fraction of the cost of the amino - phosphines used in catalysts i - iv . the present application provides details of the preparation of an air - stable ruthenium — sns complex that has now been found to be the most efficient catalyst for ester hydrogenation to date , outperforming the known catalytic systems i - iii by a large margin . the significance of this finding goes beyond esterhydrogenation . it is now apparent that a new class of catalysts for the noyori - type hydrogenation of compounds with c ═ x bonds can be made based on amino - sulfides that have the potential to replace the ubiquitous phosphorus - based ligands used in this area . the ruthenium complexes shown below were obtained by the conventional ligand substitution reactions of hn —( c 2 h 4 set ) 2 with [ rucl 2 ( pph 3 ) 3 ], [ ruhcl ( pph 3 ) 3 ], [ rucl 2 ( asph3 ) 3 ], and [ ruhcl ( co )( pph 3 ) 3 ], as documented in the above examples . complexes 1 and 5 have been crystallographically characterized and their molecular geometries are presented in fig1 and 3 . [ 10 ] the catalytic results of this example are organized in tables 3 and 4 . first , the effectiveness of catalysts iii - vii and present complexes 1 , 3 - 5 were compared . two typical substrates were selected for the comparative study : methylbenzoate and methyl hexanoate . the hydrogenations were performed at 40 ° c ., under h 2 ( 50 bar ), using a catalyst loading of 0 . 05 mol % in all cases . the reaction mixtures were analyzed by 1 h nmr spectroscopy after 3 h of hydrogenation . [ b ] concentration ( mol %) of benzyl alcohol in the product mixture ; data in parentheses is the concentration ( mol %) of benzyl benzoate . the balance of material present was unreacted starting material . [ c ] concentration ( mol %) of 1 - hexanol in the product mixture ; data in parentheses is the concentration ( mol %) of hexyl hexanoate . the balance of material present was unreacted starting material . in all cases , they were found to contain the product alcohols together with varied amounts of byproduct from transesterification , as well as methanol and unreacted starting material . the results in table 3 demonstrate that the milstein and takasago catalysts iv and v are the least effective in the group and produce little product under the test conditions . the firmenich catalyst v shows a moderate performance , whereas complex vii is the most effective of the known systems . the new catalysts 1 and 3 - 5 are all active for esterhydrogenation ; among these , the dichloride and hydrido - chloride complexes 1 and 3 give the best conversions to products , accompanied by formation of the smallest amounts of the symmetrical ester byproducts . to gain a broader understanding of the catalytic performance of complex 1 , it was tested in the hydrogenation of the diverse group of substrates shown below , accompanied by variation of the reaction temperature , time , and substrate - to - catalyst ( s / c ) ratios . the data in table 4 support the assessment of complex 1 as an outstanding hydrogenation catalyst possessing excellent efficiency and thermal stability and longevity in catalytic solutions . large turnover numbers were observed for methyl and ethyl benzoates e1 and e2 , respectively . for methyl hexanoate ( e6 ), a high ton of 9800 is achieved in 2 h at 100 ° c . with 1 , whereas firmenich catalyst iv is known to be 6 . 5 times slower at this temperature for a similar substrate , methyl octanoate , giving a ton of 1880 after 2 . 5 h . [ 4a ] the reduction of neat ethyl acetate ( e5 ) is particularly impressive with 1 , affording a ton of 58 400 after 21 h under very mild reaction conditions ( t = 40 ° c .). a relatively difficult substrate , methyl phthalate ( e3 ) is also rapidly reduced with 1 ( 0 . 1 mol %) at 100 ° c . catalyst 1 was successfully tested for the hydrogenation of typical imines and ketones shown above , where tons up to 40000 have been observed when running the reactions at 23 - 40 ° c . catalyst 1 also has some activity for olefin hydrogenation . styrene was reduced relatively rapidly at 40 ° c . with 1 ( 0 . 05 mol %). however , the reduction of 1 - pentene was considerably slower , and 2 - pentene was largely unchanged even after 48 h at 40 ° c . the latter observation is promising for the selective hydrogenation of esters , ketones , and imines containing internal c ═ c bonds . for example , the hydrogenation of methyl 3 - nonenoate at 40 ° c . afforded trans - 3 - nonen - 1 - ol in a 73 % yield . such selectivity is rare among catalysts that are active for ester hydrogenation . so far , only one ruthenium catalyst from firmenich [ 4 ] and an osmium catalyst from our group [ 6a ] have shown good selectivity for the reduction of esters with internal c ═ c bonds . as commented recently , [ 6b ] high catalytic efficiency in ester hydrogenation is expected to correlate with activity in the reverse reaction of acceptorless dehydrogenative coupling ( adc ) of alcohols , affording symmetrical esters . indeed , when tested in the adc reaction of ethanol under reflux , with s / c = 2000 and 10 000 , complex 1 gave 97 % and 89 % conversion to ethyl acetate in 16 and 24 h , respectively . this performance is similar to that of catalyst vii , and complexes 1 and vii are currently among the most efficient adc catalysts . [ 11 ] when studying the reactions of complex 1 upon heating in basic ethanol , a quantitative conversion of the dichloride into species 6 was observed , which was isolated and characterized as [ ruh ( oet )( pph 3 ){ hn ( c 2 h 4 set ) 2 }] and crystallized with one equivalent of hydrogen - bonded ethanol , 6 . etoh ( fig4 ). the preparation of 6 containing no ethanol was also possible by treating hydrido - chloride species 3 with etona in toluene . interestingly , whereas 6 is thermally stable in solution , 6 . etoh is readily and selectively converted into [ ruh 2 ( pph 3 ){ hn ( c 2 h 4 set ) 2 }] ( 7 ) and ethyl acetate upon mild heating in toluene , as shown in scheme 2 . [ 12 ] the molecular structure of 7 is presented in fig5 ; unlike the related mer - sns compounds 1 - 6 , the dihydride 7 adopts a fac - sns geometry . scheme 2 has mechanistic implications , as the forward reaction is part of the adc process , whereas the reverse reaction is ester hydrogenation . complex 6 . etoh rapidly hydrogenates ethyl acetate at room temperature ( 23 ° c . ), giving 77 % conversion into ethanol within 1 h , under h 2 ( 50 bar ), with [ ru ] ( 0 . 02 mol %) and naoet ( 1 mol %) and with an efficiency corresponding to tof = 3850 h − 1 . without wishing to be bound by theory , it appears that dihydride 6 is the hydrogenation catalyst involved in this process , as well as in the reactions of table 4 , where 6 is presumably produced under h 2 from 1 and base . the nh group also appears to be important for catalysis . we synthesized two analogues of catalyst 1 : [ rucl 2 ( pph 3 ){ o ( c 2 h 4 set ) 2 }]( 8 ) and [ rucl 2 ( pph 3 ){ men ( c 2 h 4 set ) 2 }] ( 9 ), and these complexes proved to be inactive in the hydrogenation of methyl benzoate at 40 - 100 ° c ., under the reaction conditions given in table 3 . the mechanism of ester hydrogenation is poorly understood . [ 7i ] according to milstein et al [ 3a ] and saudan et al ,[ 4a ] the concerted transfer of a metal hydride and a ligand proton to the c ═ o group of the substrate first takes place , affording a hemiacetal intermediate . dissociation of the hemiacetal gives rise to an aldehyde , which is hydrogenated again by the catalyst , thus completing the reduction process . in the present study , examination of the reaction mixtures by 1h nmr spectroscopy gave no evidence of the presumed hemiacetal or aldehyde intermediates of ester hydrogenation , ethanoldehydrogenation reactions , or the reaction shown in scheme 2 . it is likely that no free organic intermediate , hemiacetal or aldehyde , is released into the reaction solution during the reactions catalyzed by the sns complexes presented herein . a tentative mechanism for the base - free hydrogenation of ethyl acetate catalyzed by 6 is presented in scheme 3 . free energies for all of the intermediates shown in scheme 3 were calculated in ethyl acetate using the m06 - l functional . among the proposed key steps is the insertion of ethylacetate into a ru — h bond of 7 , to afford int 1 , which isanalogous to the hemiacetaloxide formation in the reaction of trans -[ ruh 2 {( r )- binap } {( r , r )- dpen }] with g - butyrolactone , as documented by bergens et al . [ 7g ] inspection of the dft - optimized structure of int 1 revealed an interesting feature : int 1 has a six - membered cycle formed by the h — n — ru — och ( me )- oet groups and closed by an nh — o hydrogen bond ( d o — h = 1 . 92 å ). the single c — o bond of int 1 is elongated to 1 . 493 å from the corresponding 1 . 345 å distance in ethylacetate . without wishing to be bound by theory , it is conceivable that intramolecular nucleophilic substitution in step b results in the formation of bis ( ethoxide ) int 2 , which rearranges in step c to afford the dihydrogen complex int 3 . heterolytic splitting of the η 2 - h 2 ligand instep d gives int 4 . ethanol elimination accompanied by h 2 coordination and heterolysis in steps e and f regenerate dihydride 7 . the isolated complex 6 . etoh ( a mer - sns isomer of int 4 ) is apparently a resting state of the catalyst . formation of 6 . etoh from 7 , ethyl acetate , and h 2 is favorable by δg =− 6 . 2 kcalmol − 1 , which is 6 . 7 kcalmol − 1 more stable than int 4 . base has a tremendous accelerating effect on the hydrogenation rate . without base , 6 . etoh ( 0 . 02 mol %) gave only 4 % conversion into ethyl acetate in 2 h at 40 ° c . under h 2 ( 50 bar ), which corresponds to tof = 100 − 1 vs . tof = 4100 h − 1 with naoet ( 1 mol %) in 1 h under otherwise identical conditions . according to bergens et al ,[ 13 ] base helps by labilizing the alkoxide intermediates ( such as int 2 and int 4 ) for eto − substitution , through deprotonation of the nh group . in conclusion , this example demonstrates the successful use of embodiments of the present catalysts based on the hn ( c 2 h 4 set ) 2 ligand . the air - stable complex [ rucl 2 ( pph 3 ){ hn -( c2h4set ) 2 }] ( 1 ) shows outstanding efficiency for the hydrogenation of a broad range of substrates with c ═ x bonds ( esters , ketones , imines ) as well as for the acceptorless dehydrogenative coupling of ethanol to ethyl acetate . this study has demonstrated that the phosphorus groups of noyori - type catalysts can be successfully replaced by sulfide groups , thus overcoming the many drawbacks of working with phosphines and phosphine - based catalysts , such as high synthetic costs and the need for handling under inert atmosphere . complex 1 is a practical and highly active green hydrogenation catalyst for substrates with c ═ x ( x ═ o , n ) bonds , and has a high potential to replace the use of main - group hydrides for the reduction of esters in the chemical industry and academic laboratories . a ) comprehensive organic synthesis , vol . 8 ( eds . : b . m . trost , i . fleming ), pergamon , new york , 1991 ; 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e ) t . touge , t . hakamata , h . nara , t . kobayashi , n . sayo , t . saito , y . kayaki , t . ikariya , j . am . chem . soc . 2011 , 133 , 14960 - 14963 ; f ) m . ito , t . ootsuka , r . watari , a . shiibashi , a . himizu , t . ikariya , j . am . chem . soc . 2011 , 133 , 4240 - 4242 ; g ) s . takebayashi , s . h . bergens , organometallics 2009 , 28 , 2349 - 2351 ; h ) i . carpenter , s . c . eckelmann , m . t . kuntz , j . a . fuentes , m . b . france , m . l . clarke , dalton trans . 2012 , 41 , 10136 - 10140 ; i ) m . l . clarke , catal . sci . technol . 2012 , 2 , 2418 - 2423 ; j ) w . w . n . 0 , r . h . morris , acs catal . 2013 , 3 , 32 - 40 . for recent reviews , see : a ) c . wang , x . f . wu , j . l . xiao , chem . asian j . 2008 , 3 , 1750 - 1770 ; b ) s . gladiali , e . alberico , chem . soc . rev . 2006 , 35 , 226 - 236 ; c ) j . s . m . samec , j . e . backvall , p . g . andersson , p . brandt , chem . soc . rev . 2006 , 35 , 237 - 248 ; d ) t . ikariya , k . murata , r . noyori , org . biomol . chem . 2006 , 4 , 393 - 406 ; e ) s . e . clapham , a . hadzovic , r . h . morris , coord . chem . rev . 2004 , 248 , 2201 - 2237 ; f ) r . noyori , angew . chem . 2002 , 114 , 2108 - 2123 ; angew . chem . int . ed . 2002 , 41 , 2008 - 2022 . a ) d . s . mcguinness , p . wasserscheid , d . h . morgan , j . t . dixon , organometallics 2005 , 24 , 552 - 556 ; b ) m . konrad , f . meyer , k . heinze , l . zsolnai , j . chem . soc . dalton trans . 1998 , 199 - 205 . the mer - sns complexes form isomers in solution . this is due to the different arrangements of the set groups relative to the sns ligand plane . two of the isomers have eclipsed set groups ( arranged on one side of the sns plane ), and the third isomer has staggered set groups ( occupying the opposite sides of the sns plane ). a ) j . zhang , g . leitus , y . ben - david , d . milstein , j . am . chem . soc . 2005 , 127 , 10840 - 10841 ; b ) j . zhang , m . gandelman , l . j . w . shimon , d . milstein , dalton trans . 2007 , 107 - 113 ; c ) j . zhang , e . balaraman , g . leitus , d . milstein , organometallics 2011 , 30 , 5716 - 5724 ; d ) c . gunanathan , l . j . w . shimon , d . milstein , j . am . chem . soc . 2009 , 131 , 3146 - 3147 ; e ) c . del pozo , m . iglesias , f . s_nchez , organometallics 2011 , 30 , 2180 - 2188 ; f ) s . musa , i . shaposhnikov , s . cohen , d . gelman , angew . chem . 2011 , 123 , 3595 - 3599 ; angew . chem . int . ed . 2011 , 50 , 3533 - 3537 ; g ) m . nielsen , a . kammer , d . cozzula , h . junge , s . gladiali , m . beller , angew . chem . 2011 , 123 , 9767 - 9771 ; angew . chem . int . ed . 2011 , 50 , 9593 - 9597 ; h ) m . nielsen , h . junge , a . kammer , m . beller , angew . chem . 2012 , 124 , 5809 - 5811 ; angew . chem . int . ed . 2012 , 51 , 5711 - 5713 , a related transformation of a ruthenium isopropoxide into a hydride species , facilitated by isopropanol , has been studied ; see : w . baratta , m . ballico , g . esposito , p . rigo , chem . eur . j . 2008 , 14 , 5588 - 5595 . r . j . hamilton , s . h . bergens , j . am . chem . soc . 2006 , 128 , 13700 - 13701 ; see also ref . [ 7g ]. in all cases , the catalytic reactions were studied by 1 h nmr spectroscopy using approximately 0 . 65 ml samples taken from the reactions mixtures without dilution or mixing with other solvents . the nmr spectra were collected without 2h lock , using 0 . 3 μs 1h pulses and a 10 s acquisition time to ensure accurate integration of the peaks . examples of typical dehydrogenation and hydrogenation procedures are given below . in an argon glovebox , the required amount of a 1 . 9 mg / g solution of 1 in thf was added to the desired amount of base ( tbuok , meok , or etok ). the catalyst solution was further mixed with the substrate ( 0 . 02 - 0 . 20 mol ) and transferred into a stainless - steel parr reactor ( 75 ml or 300 ml ) equipped with a magnetic stir bar . the reactor was closed , taken out of the glovebox , tightened and connected to a hydrogen tank . after purging the line , the reactor was pressurized to p ( h 2 )= 725 psi ( 50 bar ) and disconnected from the h 2 source ( with the exception of reactions conducted in the 300 ml reactor using 0 . 2 mol of substrate ). then , the reactor was placed in an oil bath preheated to the desired temperature . at the end of the reaction time , the reactor was moved into a cold water bath for 5 min and depressurized . in an argon glovebox , a 50 ml schlenk tube equipped with a stir bar was charged with the required amounts of the catalyst and etona . then , 4 . 61 g ( 0 . 1 mol ) or 9 . 21 g ( 0 . 2 mol ) of ethanol was added . after taking the stoppered flask out of the box , it was attached to a vacuum / ar manifold . under argon , the stopper was replaced by a finger condenser connected to a circulating refrigerated bath . when the temperature in the bath reached − 10 ° c ., the flask was placed in an oil bath preheated to 90 ° c . during dehydrogenation , the argon tank was kept closed and the h 2 gas produced passed through a mineral oil bubbler . single crystals of complexes 1 and 5 were grown by slow diffusion of hexanes into their saturated solutions in dichloromethane . single crystals of complexes 6 and 7 were grown by slow diffusion of hexanes into their saturated solutions in toluene . the crystallographic data for complexes 1 , 5 , 6 , and 7 were collected on a brukerapex ii quazar equipped with the iμs ™ x - ray source generator , a kappa nonius goniometer and a platinum135 detector . cell refinement and data reduction were done using saint . [ saint ( 1999 ) release 6 . 06 ; integration software for single crystal data . bruker axs inc ., madison , wis ., usa ] an empirical absorption correction , based on the multiple measurements of equivalent reflections , was applied using the program sadabs . [ sheldrick , g . m . ( 1999 ). sadabs , bruker area detector absorption corrections . bruker axs inc ., madison , wis ., usa ] the space group was confirmed by xprep routine [ xprep ( 1997 ) release 5 . 10 ; x - ray data preparation and reciprocal space exploration program . bruker axs inc ., madison , wis ., usa ] of shelxtl . [ shelxtl ( 1997 ) release 5 . 10 ; the complete software package for single crystal structure determination . bruker axs inc ., madison , wis ., usa ] the structures were solved by direct - methods and refined by full - matrix least squares and difference fourier techniques with shelx - 97 [( a ) sheldrick , g . m . ( 1997 ). shelxs97 , program for the solution of crystal structures . univ . of gottingen , germany . ( b ) sheldrick , g . m . ( 1997 ). shelxl97 , program for the refinement of crystal structures . university of gottingen , germany .] as a part of linxtl [ linxtl is a local program and it can be obtained free of charge from http :// sourceforge . net / projects / linxtl /] tool box . all non - hydrogen atoms were refined with anisotropic displacement parameters . hydrogen atoms were set in calculated positions and refined as riding atoms with a common thermal parameter , except those of the nh , oh moieties and hydrides , which were positioned from residual peaks in the difference fourier map . all publication materials ( cif files validation and ortep drawings ) were prepared using linxtl and platon [ a . l . spek , acta cryst . 2009 , d65 , 148 - 155 ] programs . table 5 . crystal data collection and refinement parameters for complexes 1 , 5 , 6 and 7 all calculations were carried out in gaussian 09 [ gaussian 09 , revision c . 01 , m . j . frisch , g . w . trucks , h . b . schlegel , g . e . scuseria , m . a . robb , j . r . cheeseman , g . scalmani , v . barone , b . mennucci , g . a . petersson , h . nakatsuji , m . caricato , x . li , h . p . hratchian , a . f . izmaylov , j . bloino , g . zheng , j . l . sonnenberg , m . hada , m . ehara , k . toyota , r . fukuda , j . hasegawa , m . ishida , t . nakajima , y . honda , o . kitao , h . nakai , t . vreven , j . a . montgomery , jr ., j . e . peralta , f . ogliaro , m . bearpark , j . j . heyd , e . brothers , k . n . kudin , v . n . staroverov , r . kobayashi , j . normand , k . raghavachari , a . rendell , j . c . burant , s . s . iyengar , j . tomasi , m . cossi , n . rega , j . m . millam , m . klene , j . e . knox , j . b . cross , v . bakken , c . adamo , j . jaramillo , r . gomperts , r . e . stratmann , o . yazyev , a . j . austin , r . cammi , c . pomelli , j . w . ochterski , r . l . martin , k . morokuma , v . g . zakrzewski , g . a . voth , p . salvador , j . j . dannenberg , s . dapprich , a . d . daniels , ö . farkas , j . b . foresman , j . v . ortiz , j . cioslowski , and d . j . fox , gaussian , inc ., wallingford conn ., 2009 .] ( revision c . 01 ) using the m06 - l functional ,[ y . zhao , d . g . truhlar , j . chem . phys . 2006 , 125 , 194101 - 194118 ] tight optimizations , and the ultrafine integration grid ( a pruned 99 , 590 grid ). the basis sets , listed by their corresponding gaussian 09 keywords , included qzvp [ this basis set is also known as deft - qzvp ; f . weigend , r . ahlrichs , phys . chem . chem . phys . 2005 , 7 , 3297 .] ( with the corresponding ecp [ the ecps are available from the emsl basis set library ( bse . pnl . gov )]) for ru , and tzvp [ a . schaefer , c . huber , r . ahlrichs , j . chem . phys . 1994 , 100 , 5829 - 5835 ; this basis set is also known as def - tzvp ( singly polarized ).] for all other atoms . the following density fitting basis sets were employed : qzvp ( ru ) and tzvpfit ( all other atoms ). the polarizable continuum model using the integral equation formalism ( iefpcm ) was used for all calculations , with the radii and non - electrostatic terms of truhlar and co - workers &# 39 ; smd solvation model ( scrf = smd ). [ a . v . marenich , c . j . cramer , d . g . truhlar , j . phys . chem . b , 2009 , 113 , 6378 - 6396 ] the optimized geometries were verified to have no negative frequencies by frequency calculations , which also provided the enthalpies and free energies reported here . the free energies were calculated at 298 . 15 k under p = 249 atm ( for ethyl acetate ), following the approach of martin and co - workers . [ r . l . martin , p . j . hay , l . r . pratt , j . phys . chem . a 1998 , 102 , 3565 ; n . sieffert , m . bühl , inorg . chem . 2009 , 48 , 4622 ]. all publications , patents and patent applications mentioned in this specification are indicative of the level of skill of those skilled in the art to which this invention pertains and are herein incorporated by reference to the same extent as if each individual publication , patent , or patent applications was specifically and individually indicated to be incorporated by reference . the invention being thus described , it will be obvious that the same may be varied in many ways . such variations are not to be regarded as a departure from the spirit and scope of the invention , and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims .