catalysis mof-derived cobalt nanoparticles catalyze a ...catalysis mof-derived cobalt nanoparticles...

CATALYSIS

MOF-derived cobalt nanoparticlescatalyze a general synthesis of aminesRajenahally V Jagadeesh1 Kathiravan Murugesan1 Ahmad S Alshammari2

Helfried Neumann1 Marga-Martina Pohl1 Joumlrg Radnik1 Matthias Beller1dagger

The development of base metal catalysts for the synthesis of pharmaceutically relevantcompounds remains an important goal of chemical research Here we report that cobaltnanoparticles encapsulated by a graphitic shell are broadly effective reductive aminationcatalysts Their convenient and practical preparation entailed template assembly of cobalt-diamine-dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysisunder inert atmosphereThe resulting stable and reusable catalysts were active for synthesisof primary secondary tertiary andN-methylamines (more than 140 examples)The reactioncouples easily accessible carbonyl compounds (aldehydes and ketones) with ammoniaamines or nitro compounds and molecular hydrogen under industrially viable and scalableconditions offering cost-effective access to numerous amines amino acid derivativesand more complex drug targets

The development of nanostructured catalystsfor innovative organic synthesis is crucial forthe advancement of sustainable processesin the chemical pharmaceutical and agro-chemical industries (1ndash8) Howevermost of

the nanocatalysts known to date were developedfor the activation of structurally simple molecules(3ndash8) and are scarcely applied for more chal-lenging synthetic reactions or refinement of struc-turally complex compounds Among the differentclasses of nanomaterials supported metal par-ticles are particularly valued for their low energyconsumption and high activities and selectivities(1ndash14) which can be tuned by controlling thenature size distribution and stability of thenanoparticles as well as surface composition ofthe support (9ndash14) In general simple supportedmetal nanoparticles are prepared through thermal(via pyrolysis or calcination) or chemical reductionof the respective metal salts on heterogeneoussupports (1ndash10) To improve the activity of thesesimplematerialswell-definedorganometallic com-plexes have also recently been explored as pre-cursors for pyrolytic activation (13 14) Althoughthe resulting materials found application in cat-

alytic hydrogenations and oxidations (13 14) theylargely exhibit poor reactivity and selectivity forother challenging synthetic organic reactions Onekey to more rational preparation of active nano-particulate catalysts might be the use of structure-controlling templates which should strongly bindto the respectivemetal ions In this respect metalorganic frameworks (MOFs) represent a stableclass of porous compounds which can be as-sembled in a highly modular manner frommetalions and organic linkers (15ndash17) Recently theyhave been used as self-sacrificing compounds forproducing bulkmaterials via their direct pyrolysiswithout the use of external heterogeneous sup-ports (18ndash23) Here we describe the use of MOFsas specific precursors for producing highly activeand stable cobalt (Co) nanoparticles supportedon commercial carbon (C) In contrast to pre-vious works (18ndash23) the preformed material(Co-diamine-dicarboxylic acid MOF) acted as astructure-directing template for pyrolysis on car-bon Compared with more conventional routesto heterogeneous materials prepared by impreg-nation or immobilization in our procedure thepyrolysis precursor is better defined We applied

the resulting nanoparticles to reductive amina-tion of carbonyl compounds for the general syn-thesis of aminesAmines represent a privileged class of com-

pounds used extensively in fine andbulk chemicalspharmaceuticals and materials (24ndash29) In fact170 of the top 200drugs of 2015 containednitrogen(N) andor amino groups (26)Catalytic reductiveamination of carbonyl compounds withmolecularhydrogen is widely performed in research lab-oratories and industrial facilities (30ndash48) How-ever the preparation of primary amines by usingammonia relies on either precious metalndashbasedcatalysts (30 31 33ndash39) or Raney nickel (Ni)(30 31 40) which often remains nonselectiveor otherwise problematic (30 31 34ndash40) Hencethe development of more selective and earth-abundant metalndashbased catalysts continues toattract scientific interest

Preparation of MOF-derived cobaltnanoparticle-based catalysts

We initially exploredMOFs assembled in dimeth-ylformamide (DMF) at 150degC fromFemanganese(Mn) Co Ni and copper (Cu) nitrates and organiclinkers 14-diazabicyclo[222]octane (DABCO) andterephthalic acid (TPA) Next these in situndashgenerated MOFs were immobilized on com-mercial VulcanXC 72R carbon powder Upon slowevaporation of the solvent followed by drying ofthe resulting MOFs the template on C wasformed (Fig 1) Subsequent pyrolysis at 800degC for2 hours under argon atmosphere produced thefinal nanoparticles In addition the Co-DABCO-TPA MOF was separately prepared and isolatedbefore pyrolysis on carbon (detailed preparationis provided in the supplementary materials ma-terials and methods S22) Hereafter all thesematerials are labeled as M-L1-L2C-x whereM= FeMn Co Ni or Cu L1 = DABCO and L2 =TPA and x denotes the pyrolysis temperaturerespectively

RESEARCH

Jagadeesh et al Science 358 326ndash332 (2017) 20 October 2017 1 of 6

1Leibniz-Institut fuumlr Katalyse eV an der Universitaumlt RostockAlbert-Einstein Strasse 29a Rostock D-18059 Germany2King Abdulaziz City for Science and Technology Post OfficeBox 6086 Riyadh 11442 Saudi ArabiaThese authors contributed equally to this work daggerCorrespondingauthor Email matthiasbellercatalysisde

Fig 1 Preparation of graphitic shellndashencapsulated Co nanoparticles supported on carbon by using MOF precursors

on June 4 2020

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Allof thesematerialswere tested in thebenchmarkreductive amination of 34-dimethoxybenzaldehydeby using ammonia and hydrogen to give veratryl-amine (34-dimethoxybenzylamine) which is pre-sent as a structural motif in several bioactivemolecules As shown in fig S1 materials resultingfrom pyrolysis of Fe- Mn- Cu- and Ni-DABCO-TPAC at 800degC showed no or only little cat-alytic activity Gratifyingly the corresponding Cocatalyst (Co-DABCO-TPAC-800) fromCo-MOFsgave a very good yield (88) of the desired amineThe pyrolyzed materials prepared from the insitundashgenerated and the isolated Co-MOFs ex-hibited similar activity Pyrolysis of cobalt nitratewith either DABCO (Co-DABCOC-800) or TPA(Co-TPAC-800) linkers alone led to less activecatalysts (15 to 20 yields) Apart from themetaland the linkers the pyrolysis temperature wasimportant for activity Specifically pyrolysis at400degC gave material with poor reactivity (16yield) whereas pyrolysis at 600degC and 1000degCresulted in active catalysts (75 and 83 yieldsrespectively) As expected the homogeneous cat-alyst and the pyrolyzed cobalt nitrate [Co(NO3)2C-800] were not active Similarly the Co-MOFswith and without support showed no productformation (fig S1)

Characterization of Co nanoparticle-based catalysts

We undertook detailed structural characterizationof these Co-based catalysts Aberration-correctedscanning transmission electronmicroscopy (STEM)analysis of the most active material (Co-DABCO-TPAC-800) revealed the formation of mainlymetallic Co particles with diameters rangingfrom lt5 to 30 nm (Fig 2) The energy-dispersivex-ray spectroscopy map (EDXS) (Fig 2A left)shows mainly the presence of metallic Co par-ticles within the carbon matrix Most of these


Fig 2 Catalyst characterization (A) EDXSmap and STEM images of Co-DABCO-TPAC-800 catalyst (Left) EDXS map Co red oxygenblue carbon green (Middle) Black arrowshighlight graphite-embedded metallic Co particles(Right) White circles represent single Co atoms atC (B) EELSEDXS study of Co-DABCO-TPAC-800 catalyst (Left) Parallel detectedspace-resolved C (EELS) N (EELS) and Co (EDX)signals (Middle) HAADF image overlaid by CNelemental map at the position of measurement(Right) N K-edge EELS spectrum of the white boxin the middle image

Fig 3 Co-DABCO-TPAC-800ndashcatalyzed reductive amination of aldehydes for the synthesis oflinear primaryaminesReaction conditions are 05mmol aldehyde 25mgcatalyst I [35mole (mol)Co] 5 to 7 bar NH3 40 bar H2 3 ml t-BuOH 120degC and 15 hours Isolated yields are reported unlessotherwise indicated Asterisk indicates GC yields by using n-hexadecane standard Dagger symbol (dagger)indicates reaction for 8 hours Isolated as free amines and converted to hydrochloride salts for measuringNMR and HRMS spectra

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are surrounded by a combination of some gra-phitic layers and short-range ordered graphiticshells (Fig 2A middle) In addition a smallerquantity of core-shell particles with cobalt oxide(Co3O4) shells at metallic Co is also present (figS2A) In regions of short-range ordered C we

detected single Co atoms as bright dots in high-angle annular dark field (HAADF) images (Fig 2Aright) To get information on the CoCN re-lation we performed the parallel mapping ofEDXS for all elements and electron energy lossspectroscopy (EELS) (Fig 2B) optimized for C N

and oxygen (O) Because the N signal is super-imposed on the C signal in EDXS we used thesemaps only for the Co distribution Shown in Fig2B are the maps of C N and Co (Fig 2B leftimage) in the neighborhood of ametallic particlewrapped by graphitic carbon The CN overlayin the HAADF image (Fig 2B middle image)gives evidence that N is not only located in thegraphitic shell on the Co particle but surprisinglyin short-range ordered C which is not part of thegraphitic shell and corresponds to features withsingle atoms shown in Fig 2A Co traces aredetectable everywhere in the N containing C atlow concentration In contrast the less activematerial Co-DABCOC-800 contained mainlyhollow Co3O4 particles (fig S2B) In addition toCo3O4 some CondashCo3O4 core-shell particles werealso present Although subnanometer Co struc-tures are found in this material no single Coatoms were detected Similarly Co-TPAC-800(fig S2C) also contained mainly Co3O4 particlesencapsulated within graphitic shells along witha small quantity of metallic cobalt in CondashCo3O4

core-shell structures No single Co atoms or sub-nanometer Co structures were detected in thismaterial Cobalt nitrateC-800 which was com-pletely inactive contained hollow Co3O4 with short-range ordered C from the support in the vicinity(fig S2D)In order to understand the formation mecha-

nism of the active catalyst materials pyrolyzedat lower temperatures were also characterized(fig S3) In Co-DABCO-TPAC-400 a minoramount ofmetallic Cowas present in the core ofCoCo oxide core-shell structures and no forma-tion of graphitic shells was observed Co-DABCO-TPAC-600 contained more metallic Co andincipient formation of graphitic shells envelop-ing themetallic Cowas evident Apparently thisstructural process is crucial for high activity andstability For themost active Co-DABCO-TPAC-800 single Co atoms within some of the gra-phitic structures were detected In the case ofCo-DABCO-TPAC-1000 most of the Co waspresent in metallic crystallite morphology com-pletely covered by graphitic structures In all ofthe active catalysts cloudy regions of Co speciesin the 1- to 2-nm range were detected The dif-ferent phases of Co in both active and less activecatalysts have been also confirmed with x-raypowder diffraction data (figs S7 and S8) thataccorded with the TEM analysisThe nature and quantity of nitrogen in these

materials was further explored with x-ray photo-electron spectroscopy (XPS) (fig S10 and S11)Surprisingly the combination of the two linkersincreased the quantity of N in the near-surfaceregion significantly compared with either linkeralone (fig S12) The N content in Co-DABCO-TPAC-800 was three times higher than in Co-DABCOC-800 whereas in Co-TPAC-800 onlytraces of N were observed In both Co-DABCO-TPAC-800 andCo-DABCOC-800 twoN-statescould be detected (fig S10) one correlating withimine-like N known from pyridine (~398 eV)(49 50) the other manifesting a higher bindingenergy corresponding to N bonded to the metal


Fig 4 Co-DABCO-TPAC-800ndashcatalyzed reductive amination of ketones Reaction conditionsare 05 mmol ketone 25 mg catalyst I (35 mol Co) 5 to 7 bar NH3 40 bar H2 3 ml tetrahydrofuran(THF) (dry) 120degC and 15 hours Isolated yields are reported unless otherwise indicated Asteriskindicates GC yields by using n-hexadecane standard Dagger symbol (dagger) indicates reaction for 20 hoursDouble dagger (Dagger) symbol indicates reaction for 24 hours Section symbol (sect) indicates reactionfor 30 hours with 35 mg catalysts Isolated as free amines and converted to hydrochloridesalts for measuring NMR and HRMS Parallel bars (||) indicate 5 to 50 g substrate 25 mg catalyst I(35 mol Co) for each 05 mmol substrate 5-7 bar NH3 40 bar H2 120-150 ml dry THF 120degC15 to 30 hours and isolated yields



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(49 50) For the former sample a clear separa-tion of both peaks was observed because of theslightly higher binding energy For Co-DABCO-TPAC pyrolyzed at different temperaturesiminic N was observed and the binding energyof the CondashN bond increased as pyrolysis tem-perature ascended up to 800degC (fig S11) Incomparison with all other samples the obser-vation of the two N states was specific to theseactive systems (fig S11) (49 50) It seems thatfor the optimal catalyst the bonding betweenCo and N is most pronounced In the materialpyrolyzed at 1000degC the formation of nitridescould be observed as well (fig S11) In the un-pyrolyzed and 1000degC samples the amount ofCo in the near-surface region was too low for areasonable peak fitting for all other samplesthe metal content was nearly the same

Synthesis of primary amines

With an activematerial (Co-DABCO-TPAC-800hereafter represented as catalyst I) in hand weinvestigated its substrate scope in the reductiveamination Initially various primary amineswhich are easily further functionalized and there-fore represent central building blocks were pre-pared starting from carbonyl compounds andsimple ammonia (Figs 3 and 4) A crucial problemfor the synthesis of primary amines has been thesubsequent formation of secondary and tertiaryamines The few catalysts known for the chemo-selective reductive amination of aldehydes and ke-tones to give primary amines are based onpreciousmetals (30 31 34ndash39) or Raney Ni (30 31 40)Although Raney nickel is available and compa-rably inexpensive it is highly flammable haz-ardous and less selective for functionalized andstructurally complex moleculesBy applying our Co catalyst we performed

selective reductive amination of 39 aldehydesto produce benzylic heterocyclic and aliphaticlinear primary amines in good to excellent yields(up to 92) (Fig 3) Sensitive functional groupsincluding halides esters as well as challengingCndashC double and triple bonds were well toleratedWe also prepared amino-salicin in 83 yieldfrom the O-glucoside helicin (Fig 3 product 41)to showcase the selective amination of bioactivecompounds Compared with benzaldehydes thereductive amination of aliphatic aldehydes ishampered by unproductive aldol condensationwhich can easily occur under basic conditionsNevertheless several aliphatic and araliphaticsubstrates gave the corresponding primary aminesin good yields (up to 92) and high selectivityThe hydrogenation of the in situndashgenerated

imine from aldehydes is faster than reductionof the corresponding ketone-derived imines Thusa more active catalyst or more drastic conditionstend to be required for efficient reductive amina-tion of ketones The generality of catalyst I wasfurther demonstratedby the synthesis of branchedprimary amines starting from diverse ketones(Fig 4) Gratifyingly both industrially relevantand structurally challenging ketones underwentsmooth amination and produced the correspond-ing primary amines in good to excellent yields


Fig 5 Co-DABCO-TPAC-800ndashcatalyzed synthesis of secondary and tertiary amines (A) Surveyof nitroarenes and amines Reaction conditions are 05 mmol nitroarene 075 to 1 mmol aldehyde 25 mgcatalyst I (35 mol Co) 20 mg amberlite IR-120 3 ml t-BuOH 120degC 24 hours and isolated yieldsAsterisk indicates 05 mmol amine 075 mmol aldehyde Dagger symbol indicates 30 mg catalystand 30 hours Double dagger symbol indicates 05 mmol amine and 075 mmol ketone (B) ReductiveN-alkylation of chiral amines Reaction conditions are 10 mmol amine 15 mmol benzaldehyde 500 mgcatalyst I (35 mol Co) 400 mg amberlite IR-120 15 ml t-BuOH 120degC 24 hours and isolated yields(C) Reductive N-alkylation of amino acid esters Reaction conditions are 05 mmol amino acid ester075 mmol aldehyde 25 mg catalyst (35 mol Co) 20 mg amberlite IR-120 3 ml t-BuOH 120degC24 hours and isolated yields (D) Preparation of existing drug molecules Reaction conditions are1 mmol amine 15 mmol aldehyde 50 mg catalyst I (35 mol Co) 3 ml t-BuOH 120degC 24 hoursand isolated yields Asterisk indicates 75 mg catalyst for 30 hours Dagger symbol (dagger) indicates 2 mmolamine and 1 mmol aldehyde Double dagger (Dagger) symbol indicates synthesis same as daggeredproducts followed by acylation with acid chlorides (detailed procedure is provided in the supplementarymaterials materials and methods S65)



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(Fig 4) Biologically active amphetamines (pro-ducts 77 to 79) which are potent central nervoussystem (CNS)ndashstimulating drugs were preparedin up to 91 yield In general amphetamines aresynthesized through reductive amination of thecorresponding phenyl-2-propanones by using am-monium formate at higher temperature (Leuckart-Wallach reaction) (51) More sensitive products areprepared through reductive amination reactionsby usingmore expensive platinum- andpalladium(Pd)ndashbased catalysts (51)We also explored amina-tion of nonsteroidal anti-inflammatory agents(80 to 82) and steroid derivatives (83 to 87)Introduction of amino groups into these bioactivemolecules has been scarcely explored so far Sulfur-containing compounds constitute a commonpoi-son for most heterogeneous catalysts although

they are found in more than 300 US Food andDrug Administrationndashapproved drugs (52) In thiscontext thioethers are the most common scaf-folds Gratifyingly catalyst I tolerated severalS-containing substrates including thiophenethioether and sulfone (Figs 3 and 4 products28 29 30 43 46 and 50)

Synthesis of secondary andtertiary amines

We next explored the synthesis of secondaryand tertiary amines (Fig 5) which are found ina large number of biologically active natural pro-ducts (26ndash29) In contrast to the preparation ofprimary amines by using ammonia (vide supra)a few non-noble-metalndashbased catalysts have al-ready been used for reductive aminations to pre-

pare secondary and tertiary amines however insuch cases functional group tolerance and broadsubstrate scope have been limited (41ndash48) Bothnitroarenes and amines reacted with aldehydesto give the corresponding secondary amines selec-tively in up to 92 yields (Fig 5A products 88 to103) Compared with the traditional reaction ofanilines the one-pot reductive amination of nitro-arenes and carbonyl compounds is straightforwardand ensures a better step economy This directprocess shows that the Co nanocatalyst can alsobe used for the selective hydrogenation of nitro-arenes to anilines which are of additional in-terest for dye formation andmaterials synthesisThe reductive alkylation ofN-containing hetero-cycles as well as primary and secondary aminesgave the corresponding derivatives in 81 to 88yields To demonstrate the amination of ke-tones phenyl-2-propanone was reacted with4-aminocyclohexane or 4-aminocyclohexanol(aliphatic amines) and produced the correspond-ing secondary amines in 84 and 89 respectively(Fig 5A products 104 and 105) Further we alsotried the reductive amination of acetophenoneusing nitroarenes or aromatic amines but didnot observe any substantial desired productformation in this case Competition reactions ofaniline with 4-bromobenzaldehyde and aceto-phenone were examined Here reductive ami-nation of the aldehyde occurred with excellentconversion and high selectivity whereas theketone remained untouched Similarly the re-action of 4-bromobenzaldehyde with anilineproceeded selectively in the presence of phenyl-2-propanone Thus this catalyst allows for selec-tive amination of aldehydes in the presence ofketones In general for the majority of reduc-tive amination reactions high chemoselectivityis obtained However in a few cases we observedminor amounts of the corresponding alcohol(lt5) andor secondary imineamine (lt10) Inthe preparation of secondary amines up to 10of the imine was observed In bromo-substitutedsubstrates (products 6 7 89 112 117 122 and125) we also observed small amounts of dehal-ogenation In general we did not detect any over-alkylation productsTo demonstrate compatibility with preexisting

stereochemistry we performed the reductiveN-alkylation with chiral amines A plethora of chiralamines is available from biological and industrialsources As shown in Fig 5B the N-alkylationsof (S)-(minus)-1-methylbenzylamine and (R)-(+)-a-methylbenzylamine proceeded efficiently andoffered the corresponding chiral amine derivativeswith retention of the original stereochemistry(Fig 5B products 106 to 108) as assessed withchiral high-performance liquid chromatography(HPLC) [procedure andHPLC data are availablein the supplementary materials materials andmethods S64(a)] Further the reductive alkyla-tion of two amino acid esters (phenylalanine andtyrosine) was performed in 82 to 89 yields (Fig5C products 109 to 114) However the chirality ofthese N-alkylated amino acid esters was notretained and we obtained the correspondingracemic mixtures


Fig 6 Co-DABCO-TPAC-800ndashcatalyzed preparation of N-methylamines (A) Reactions ofaldehydes with dimethylamine Conditions are 05 mmol aldehyde 100 ml aqueous dimethylamine (40)25 mg catalyst I (35 mol Co) 3 ml t-BuOH 120degC and 24 hours Isolated yields are reportedunless otherwise indicated Asterisk indicates GC yields by using n-hexane standard (B) Reactions ofnitroarenes or amines with formaldehyde Conditions are 05 mmol nitroarene 100 to 200 ml aqueousformaldehyde (37) 11 THF- H2O (3ml) and isolated yields Asterisk indicates 05 mmol amine100 to 200 ml aqueous formaldehyde (37) and 11 THF- H2O (3 ml)



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Synthesis of N-methylamines

Among the various alkylated amines N-methylamines are of special interest becauseof their role in regulating biological functions(53 54) In general this class of amines is pre-pared either through PdCndashcatalyzed reductiveamination with formaldehyde or by using active(toxic) methylation reagents By applying our Cocatalyst I we prepared selectedN-methylaminesstarting from aldehydes andNN-dimethylamine(DMA) which is also a readily available bulkchemical (Fig 6A) In addition the direct re-ductive methylation of nitroarenes or amineswith aqueous formaldehyde produced selectivelythe corresponding N-methylamines (Fig 6B)Compared with traditional alkylations by usingmethyl-X compounds advantageously the pre-sented Co-catalyzed synthesis of N-methylaminesis either more cost effective or waste-free

Demonstrating catalyst recyclingand gram-scale reactionsStability and recyclability are crucial featuresfor any heterogeneous catalyst In addition to theobvious cost advantages the use of recyclableheterogeneous catalyst can considerably facili-tate product purification As shown in the re-ductive aminationof phenylacetone our supportedCo nanoparticles are highly stable and are con-veniently recycled up to six times without anysignificant loss of catalytic activity (fig S14) Afterthat slight decrease of activity is observedNext gram-scale reactions were performed for

several interesting substrates Apart from ampheta-mine related 4(-4-hydroxyphenyl)-2-amino-butaneand 11-diphenyl-2-amino-propane as well as17-amino-estronewere synthesized in up to 50-gscale (Fig 4) In all the cases similar yields to thoseof 50- to 100-mgndashscale reactions were obtained

Preparation of existing drug molecules

Last we undertook preparation of 10 existingdrug molecules (Fig 5D) These syntheses show-case the applicability of the supported Co nano-particles for selective preparation of amine-baseddrugs Previously thesemolecules were preparedvia the reductive amination reactions by usingeither precious metalndashbased catalysts or sodiumborohydride (55ndash59) In addition some have alsobeen prepared through nucleophilic substitutionreactions of corresponding amines with halogen-ated compounds (55ndash60) Here the correspondingaromatic aldehydes were treated with piperazine

and morpholine derivatives or primary amines togive the desired products in 82 to 92 yields ac-cording to our standard procedure which furtherdemonstrates the general utility of this single Condashbased catalyst

REFERENCES AND NOTES

1 Nanotechnologies Principles Applications Implications andHands-on Activities (European Commission 2012)

2 V Polshettiwar T Asefa Nanocatalysis Synthesis andApplications (Wiely 2013)

3 A Corma P Serna Science 313 332ndash334 (2006)4 M Sankar et al Chem Soc Rev 41 8099ndash8139 (2012)5 H M Torres Galvis et al Science 335 835ndash838 (2012)6 W Luo et al Nat Commun 6 6540 (2015)7 J Zečević G Vanbutsele K P de Jong J A Martens Nature

528 245ndash248 (2015)8 M D Hughes et al Nature 437 1132ndash1135 (2005)9 P Munnik P E de Jongh K P de Jong Chem Rev 115

6687ndash6718 (2015)10 F Tao Metal Nanoparticles for Catalysis Advances and

Applications (Royal Society of Chemistry 2014)11 E M van Schrojenstein Lantman T Deckert-Gaudig

A J G Mank V Deckert B M Weckhuysen Nat Nanotechnol7 583ndash586 (2012)

12 G Prieto J Zečević H Friedrich K P de Jong P E de JonghNat Mater 12 34ndash39 (2013)

13 R V Jagadeesh et al Science 342 1073ndash1076 (2013)14 R V Jagadeesh H Junge M Beller Nat Commun 5 4123 (2014)15 H Furukawa K E Cordova M OrsquoKeeffe O M Yaghi Science

341 1230444 (2013)16 A Corma H Garciacutea F X Llabreacutes i Xamena Chem Rev 110

4606ndash4655 (2010)17 H Wang Q-L Zhu R Zou Q Xu Chem 2 52ndash80 (2017)18 P Pachfule D Shinde M Majumder Q Xu Nat Chem 8

718ndash724 (2016)19 J Tang Y Yamauchi Nat Chem 8 638ndash639 (2016)20 W Xia A Mahmood R Zou Q Xu Energy Environ Sci 8

1837ndash1866 (2015)21 K Shen X Chen J Chen Y Li ACS Catal 6 5887ndash5903 (2016)22 X Ma Y-X Zhou H Liu Y Li H-L Jiang Chem Commun

(Camb) 52 7719ndash7722 (2016)23 B Liu H Shioyama T Akita Q Xu J Am Chem Soc 130

5390ndash5391 (2008)24 S A Lawrence Amines Synthesis Properties and Applications

(Cambridge Univ Press 2004)25 A Ricci Amino Group Chemistry From Synthesis to the Life

Sciences (Wiley-VCH 2008)26 httpnjardarsonlabarizonaedusitesnjardarsonlabarizonaedu

filesTop200PharmaceuticalProductsRetailSales2015LowRespdf27 S D Roughley A M Jordan J Med Chem 54 3451ndash3479 (2011)28 P M Dewick Medicinal Natural Products A Biosynthetic

Approach (Wiley ed 3 2008)29 C Joyce W F Smyth V N Ramachandran E OrsquoKane

D J Coulter J Pharm Biomed Anal 36 465ndash476 (2004)30 S Gomez J A Peters T Maschmeyer Adv Synth Catal 344

1037ndash1057 (2002)31 H Alinezhad H Yavari F Salehian Curr Org Chem 19

1021ndash1049 (2015)32 V N Wakchaure J Zhou S Hoffmann B List Angew Chem

Int Ed 49 4612ndash4614 (2010)33 D Chusov B List Angew Chem Int Ed 53 5199ndash5201 (2014)34 S Ogo K Uehara T Abura S Fukuzumi J Am Chem Soc

126 3020ndash3021 (2004)

35 Y Nakamura K Kon A S Touchy K-i Shimizu W UedaChemCatChem 7 921ndash924 (2015)

36 T Gross A M Seayad M Ahmad M Beller Org Lett 42055ndash2058 (2002)

37 P Ryberg R Berg US patent WO2015178846 A1 201538 J Gallardo-Donaire M Ernst O Trapp T Schaub Adv Synth

Catal 358 358ndash363 (2016)39 G Liang et al Angew Chem Int Ed 56 3050ndash3054 (2017)40 Z Wang Ed Mignonac Reaction in Comprehensive

Organic Name Reactions and Reagents (Wiley 2010)41 F Mao et al RSC Advances 6 94068ndash94073 (2016)42 F Santoro R Psaro N Ravasio F Zaccheria ChemCatChem

4 1249ndash1254 (2012)43 T Stemmler A-E Surkus M-M Pohl K Junge M Beller

ChemSusChem 7 3012ndash3016 (2014)44 R V Jagadeesh et al Nat Protoc 10 548ndash557 (2015)45 S Pisiewicz T Stemmler A-E Surkus K Junge M Beller

ChemCatChem 7 62ndash64 (2015)46 T Stemmler et al Green Chem 16 4535ndash4540 (2014)47 P Zhou et al Appl Catal B 210 522ndash532 (2017)48 J W Park Y K Chung ACS Catal 5 4846ndash4850

(2015)49 F Buchner et al J Phys Chem C 112 15458ndash15465

(2008)50 F Jaouen et al ACS Appl Mater Interfaces 1 1623ndash1639

(2009)51 A Allen R Ely Synthetic methods for amphetamine

wwwnwafsorgnewslettersSyntheticAmphetaminepdf52 M Feng B Tang S H Liang X Jiang Curr Top Med Chem

16 1200ndash1216 (2016)53 E J Barreiro A E Kuumlmmerle C A M Fraga Chem Rev 111

5215ndash5246 (2011)54 J Chatterjee F Rechenmacher H Kessler Angew Chem Int Ed

52 254ndash269 (2013)55 R Quanqing Z Tingjian W Shaojie China patent CN

101735201A (2010)56 Y Zhang Y Liu Z Song Y Zhu G Gao China patent CN

104788326 (2016)57 E W Baxter A B Reitz lsquolsquoReductive Aminations of Carbonyl

Compounds with Borohydride and Borane Reducing Agentsrsquorsquo inOrganic Reactions (Wiley 2004)

58 S A Forsyth H Q N Gunaratne C Hardacre A McKeownD W Rooney Org Process Res Dev 10 94ndash102 (2006)

59 J-C Souvie US patent US5142053A (1992)60 B Lal S Lahiri C P Bapat R S Kulkarni D K Mulla

A Y Hawaldar US patent WO2010046908A2 (2010)

ACKNOWLEDGMENTS

We gratefully acknowledge the support of the EuropeanResearch Council (ERC) Federal Ministry of Education andResearch (BMBF) the State of Mecklenburg-Vorpommern andKing Abdulaziz City for Science and Technology (KACST) Wethank the analytical staff of the Leibniz-Institute for CatalysisRostock for their excellent service All data are availablein the supplementary materials

SUPPLEMENTARY MATERIALS

wwwsciencemagorgcontent3586361326supplDC1Materials and MethodsFigs S1 to S14NMR and HRMS Spectra

10 May 2017 accepted 7 September 2017Published online 21 September 2017101126scienceaan6245




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MOF-derived cobalt nanoparticles catalyze a general synthesis of amines

Radnik and Matthias BellerRajenahally V Jagadeesh Kathiravan Murugesan Ahmad S Alshammari Helfried Neumann Marga-Martina Pohl Joumlrg

originally published online September 21 2017DOI 101126scienceaan6245 (6361) 326-332358Science

this issue p 326 see also p 304Sciencegraphitic shell The catalyst could be conveniently separated from products and recycled up to six timesXu) The cobalt was first embedded in a metal-organic framework (MOF) which upon heating transformed into abroad range of substrates including complex molecules of pharmaceutical interest (see the Perspective by Chen and

report a class of nonprecious cobalt nanoparticles that catalyze this reaction across a veryet alhydrogen Jagadeesh often requires precious metal catalysts couples ammonia or other amines with carbonyl compounds and then with

Reductive amination is a common method that chemists use to make carbon-nitrogen bonds The reaction whichA MOF sets the stage to make amines

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REFERENCES

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is a registered trademark of AAASScienceScience 1200 New York Avenue NW Washington DC 20005 The title (print ISSN 0036-8075 online ISSN 1095-9203) is published by the American Association for the Advancement ofScience

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Allof thesematerialswere tested in thebenchmarkreductive amination of 34-dimethoxybenzaldehydeby using ammonia and hydrogen to give veratryl-amine (34-dimethoxybenzylamine) which is pre-sent as a structural motif in several bioactivemolecules As shown in fig S1 materials resultingfrom pyrolysis of Fe- Mn- Cu- and Ni-DABCO-TPAC at 800degC showed no or only little cat-alytic activity Gratifyingly the corresponding Cocatalyst (Co-DABCO-TPAC-800) fromCo-MOFsgave a very good yield (88) of the desired amineThe pyrolyzed materials prepared from the insitundashgenerated and the isolated Co-MOFs ex-hibited similar activity Pyrolysis of cobalt nitratewith either DABCO (Co-DABCOC-800) or TPA(Co-TPAC-800) linkers alone led to less activecatalysts (15 to 20 yields) Apart from themetaland the linkers the pyrolysis temperature wasimportant for activity Specifically pyrolysis at400degC gave material with poor reactivity (16yield) whereas pyrolysis at 600degC and 1000degCresulted in active catalysts (75 and 83 yieldsrespectively) As expected the homogeneous cat-alyst and the pyrolyzed cobalt nitrate [Co(NO3)2C-800] were not active Similarly the Co-MOFswith and without support showed no productformation (fig S1)

Characterization of Co nanoparticle-based catalysts

We undertook detailed structural characterizationof these Co-based catalysts Aberration-correctedscanning transmission electronmicroscopy (STEM)analysis of the most active material (Co-DABCO-TPAC-800) revealed the formation of mainlymetallic Co particles with diameters rangingfrom lt5 to 30 nm (Fig 2) The energy-dispersivex-ray spectroscopy map (EDXS) (Fig 2A left)shows mainly the presence of metallic Co par-ticles within the carbon matrix Most of these


Fig 2 Catalyst characterization (A) EDXSmap and STEM images of Co-DABCO-TPAC-800 catalyst (Left) EDXS map Co red oxygenblue carbon green (Middle) Black arrowshighlight graphite-embedded metallic Co particles(Right) White circles represent single Co atoms atC (B) EELSEDXS study of Co-DABCO-TPAC-800 catalyst (Left) Parallel detectedspace-resolved C (EELS) N (EELS) and Co (EDX)signals (Middle) HAADF image overlaid by CNelemental map at the position of measurement(Right) N K-edge EELS spectrum of the white boxin the middle image

Fig 3 Co-DABCO-TPAC-800ndashcatalyzed reductive amination of aldehydes for the synthesis oflinear primaryaminesReaction conditions are 05mmol aldehyde 25mgcatalyst I [35mole (mol)Co] 5 to 7 bar NH3 40 bar H2 3 ml t-BuOH 120degC and 15 hours Isolated yields are reported unlessotherwise indicated Asterisk indicates GC yields by using n-hexadecane standard Dagger symbol (dagger)indicates reaction for 8 hours Isolated as free amines and converted to hydrochloride salts for measuringNMR and HRMS spectra



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catalysis mof-derived cobalt nanoparticles catalyze a ...catalysis mof-derived cobalt nanoparticles...

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