A icles
h ps://doi.o g/10.1038/s41929-021-00722-x
1Leibniz-Ins i u ü Ka alyse e.V., Ros ock, Ge many. 2Regional Cen e o Ad anced Technologies and Ma e ials, Czech Ad anced Technology and Resea ch
Ins i u e, Palacky Uni e si y Olomouc, Olomouc, Czech Republic. 3Nano echnology Cen e, Cen e o Ene gy and En i onmen al Technologies, VŠB–
Technical Uni e si y o Os a a, Os a a-Po uba, Czech Republic. 4Depa men o Indus ial and Enginee ing Chemis y, Ins i u e o Chemical Technology
Mumbai-Ma a hwada Campus, Jalna, Maha ash a, India. ✉e-mail: [email p o ec ed]; mb.g[email p o ec ed].edu.in;
jagadeesh. [email p o ec ed]; [email p o ec ed]
Ca alysis plays a decisi e ole in many basic and applied
chemical p ocesses and is in ol ed in he indus ial p o-
duc ion o mo e han 90% o ine and bulk chemicals as
well as polyme ic ma e ials and many o he e e yday p oduc s1–5.
In addi ion, he syn hesis o bioac i e compounds o li e sciences
and he success o sus ainable ene gy echnologies, including g een
uels, depend on e icien ca aly ic p ocesses1–5. Indeed, he suc-
cess o o ganic syn hesis in he las 100 yea s elied o a la ge ex en
on he disco e y and applica ion o sui able ca alys s1–5. In his
espec , speci ically, he de elopmen o p ac ical and cos -e icien
hyd ogena ion s a egies cons i u es a key achie emen o he las
cen u y6. Nowadays, a ple ho a o molecula ly de ined me al com-
plexes as well as he e ogeneous ma e ials a e equen ly applied o
he selec i e hyd ogena ion o alkynes7,8, ole ins7,9,10, ca bonyl com-
pounds11,12, ni oa enes13,14 as well as (he e o)a enes7,15–17. Among
hese hyd ogena ion eac ions, he ans o ma ion o ni iles o p i-
ma y amines is pa icula ly aluable because he la e p oduc s a e
p i ileged compounds in chemis y, medicine and biology18–22. In
gene al, p ima y amines cons i u e impo an p ecu so s and cen-
al in e media es in he chemical, pha maceu ical, ag ochemical
and ma e ials indus ies18–22. A e he o iginal disco e y o benzo-
ni ile hyd ogena ion in he p esence o nickel in 1905 ( e . 23), many
ca alys s we e de eloped o his and ela ed eac ions (Fig. 1)24–42.
These achie emen s we e mainly possible due o he design o p e-
cious me al sys ems, which allow eac ions o be pe o med a low
empe a u e and p essu e24,30,31,33–38. Howe e , despi e hei emen-
dous success, hei limi ed a ailabili y and highe p ice cons i u e
majo d awbacks. Thus, s a e-o - he-a ca alys s o ni ile hyd o-
gena ion in indus y con inue o be Raney nickel26,27,31,33 and coppe
ch omi e29, which demand ha sh condi ions and su e om oxici y
issues. To sol e hese p oblems, al e na i e nickel- and cobal -based
he e ogeneous ca alys s ha e been epo ed in ecen yea s35,39–41.
F om a sus ainabili y poin o iew, i on would be an ideal ca a-
lys sys em o ni ile hyd ogena ion because o i s abundance (a
4.7% i is he second-mos abundan me al in he ea h c us ), low
p ice and low oxici y14,17,42–44. Indeed, in he las decade, using
sophis ica ed/syn he ically demanding PNP pince ligands, ac i e
i on complexes ha e been de eloped o hyd ogena e ni iles44. In
gene al, howe e , hese me al complexes a e less s able and di icul
o use. In con as , he e ogeneous ca alys s show imp o ed s abili y
and can be easily eused14,17,22,45–47. Un o una ely, o he bes o ou
knowledge, analogous suppo ed ac i e i on cen es o he hyd o-
gena ion o ni iles ha e no been c ea ed ye .
He e, we epo a s able and con enien i on-based nanoca alys
ob ained by he py olysis o i on ace a e on comme cial silica ha
shows excellen ac i i y and selec i i y o he hyd ogena ion o a
la ge numbe o ni iles o p oduce p ima y amines in he p esence
o ca aly ic amoun s o aluminium addi i es.
Resul s
Syn hesis and cha ac e iza ion o Fe-based nanoca alys s.
In he las decade, he excellen ca aly ic pe o mance o
ca bon-encapsula ed co e–shell 3d me al nanopa icles has been
demons a ed in a a ie y o hyd ogena ion eac ions14,16,17,22,39,40,46.
These ca alys s we e p epa ed by he immobiliza ion and py oly-
sis o me al complexes o me al o ganic amewo ks on ino ganic
suppo s ( o example, ca bon, SiO2 and Al2O3)14,16,17,22,39,40,46. In his
con ex , we de eloped ac i a ed Fe2O3 nanopa icles, su ounded by
Silica-suppo ed Fe/Fe–O nanopa icles o he
ca aly ic hyd ogena ion o ni iles o amines in he
p esence o aluminium addi i es
Vishwas G. Chand ashekha    1, Thi usangumu ugan Sen hama ai1, Ra ishanka G. Kadam   2,
Ondřej Malina2, Jose Kašlík   2, Radek Zbořil   2,3 ✉ , Manoj B. Gawande   2,4 ✉ ,
Rajenahally V. Jagadeesh   1 ✉ and Ma hias Belle    1 ✉
The hyd ogena ion o ni iles o amines ep esen s an impo an and equen ly used indus ial p ocess due o he b oad appli-
cabili y o he esul ing p oduc s in chemis y and li e sciences. Despi e he exis ing po olio o ca alys s epo ed o he
hyd ogena ion o ni iles, he de elopmen o i on-based he e ogeneous ca alys s o his p ocess is s ill a challenge. He e, we
show ha he imp egna ion and py olysis o i on(II) ace a e on comme cial silica p oduces a eusable Fe/Fe–O@SiO2 ca alys
wi h a well-de ined s uc u e comp ising he ayali e phase a he Si–Fe in e ace and α-Fe nanopa icles, co e ed by an ul a-
hin amo phous i on(III) oxide laye , g owing om he silica ma ix. These Fe/Fe–O co e–shell nanopa icles, in he p esence
o ca aly ic amoun s o aluminium addi i es, p omo e he hyd ogena ion o all kinds o ni iles, including s uc u ally challeng-
ing and unc ionally di e se a oma ic, he e ocyclic, alipha ic and a y ni iles, o p oduce p ima y amines unde scalable and
indus ially iable condi ions.
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ni ogen-doped g aphene, as selec i e ca alys s o he hyd ogena-
ion o ni oa enes o anilines14. In addi ion, suppo ed Fe-based
nanopa icles ha e also been ound ac i e o he hyd ogena ion
o quinolines17. Howe e , hese and ela ed Fe ma e ials showed
no ac i i y o mo e challenging subs a es, including ni iles
(Supplemen a y Table 1, en ies 1 and 2). To iden i y po en ial
i on-based he e ogeneous ca alys s o ni ile hyd ogena ion, we
p epa ed a se ies o i on nanopa icles suppo ed on a ious sup-
po s. Speci ically, comme cially a ailable neu al, acidic and basic
ino ganic suppo s, o example, Vulcan XC72R ca bon powde ,
Ae osil silica (SiO2), γ-Al2O3 and MgO, we e imp egna ed wi h
i on(II) ace a e. Subsequen ly, hese ma e ials we e py olysed a
800 °C unde educ i e (H2) condi ions. A schema ic illus a ion o
he syn he ic p ocedu e wi h he SiO2 suppo is p esen ed in Fig.
2. He ea e , hese ma e ials a e deno ed as Fe(OAc)2-suppo -x,
whe e x deno es he py olysis empe a u e.
As a benchma k eac ion, he hyd ogena ion o
4-chlo obenzoni ile (1) o 4-chlo obenzylamine (2) was chosen
(Fig. 3), no only o iden i y an ac i e ca alys sys em, bu also a
selec i e one. No ably, 1 easily unde goes educ i e dehalogena-
ion in he p esence o many known hyd ogena ion ca alys s. To
ou su p ise, du ing ini ial con ol expe imen s, we obse ed
some ac i i y (26% yield o 2) and high selec i i y (>90%) o he
p ima y amine in he p esence o Fe(OAc)2-SiO2-800 (Fig. 3). To
imp o e he con e sion and yield, we a ied he eac ion condi ions
( empe a u e, sol en , ca alys loading) and in es iga ed he in lu-
ence o addi i es (Supplemen a y Tables 1–3). Applying highe
ca alys loadings (up o 12.8 mol%), he p oduc yield inc eased up
o 50%, and he selec i i y o he p ima y amine emained e y
good. G a i yingly, in he p esence o aluminium iisop opoxide,
he yield o 4-chlo obenzylamine (2) d ama ically inc eased o 96%.
Following his excellen esul , se e al o he me al alkoxides, alu-
minium compounds as well as Lewis acids and bases we e es ed as
addi i es (Supplemen a y Table 2). Su p isingly, only a ew addi-
i es, o example, p- oluenesul onic acid, showed a posi i e e ec
on he eac ion, while mos , o example, bases, had a nega i e
impac . Op imal esul s, wi h an almos quan i a i e yield o 2, we e
achie ed in he p esence o inexpensi e aluminium oil (Fig. 3 and
Supplemen a y Fig. 1). In his case, he aluminium oil comple ely
dissol ed in he sol en (isop opanol), which explains he simila
posi i e e ec o aluminium oil and aluminium iisop opoxide.
Con ol expe imen s p o ed ha his dissolu ion only akes place in
he p esence o ammonia (Supplemen a y Table 4). To elucida e he
c ucial ole o aluminium addi i es, we pe o med kine ic in es iga-
ions o he model eac ion in he absence and p esence o aluminium
oil and aluminium iisop opoxide (Supplemen a y Figs. 2 and 3).
Su p isingly, all he eac ions needed a p eac i a ion ime (3–9 h) o
s a . Only in he p esence o aluminium iisop opoxide was his
p eac i a ion d as ically educed. Based on hese esul s and he
es ing o he di e en addi i es, we assume ha bo h aluminium
(2016 onwa ds)
Suppo ed Co and Ni NPs
de i ed om me al complexes
and MOFs
1905
(1905)
Ni
(1909)
Colloidal
Pd
(1923)
Raney Ni
(1925)
P O2
Cu2C 2O5
(1937)
(1937)
Raney Co
Suppo ed ca alys s
(Rh, Pd, P , Ru, Ni, Co)
(1946 onwa ds)
(A ound 1969)
Me al bo ides
(RhB, P B, RuB, NiB, CoB)
Me al alloys
(PdNi, NiAl, NiCo)
(A ound 1970)
His o y o ni ile hyd ogena ion using he e ogeneous ca alys s o e a cen u y
2021
Fe/FeÐO@SiO2
This wo k
Fig. 1 | His o ical o e iew o he e ogeneous ni ile hyd ogena ion ca alys s. The hyd ogena ion o ni iles using he e ogeneous ca alys s has a long
his o y ha co e s mo e han a cen u y.
Fe(OAc)2
Fe
FeO
FeII
immobilized on SiO2
Py olysis
1. S i , DMF, 150 ¡C
2. Addi ion o SiO2
3. S i , DMF, 150 ¡C, 4 h
4. Slow e apo a ion o
DMF and d ying
800 ¡C, 4 h, H2
Fe/FeÐO co eÐshell
nanopa icles suppo ed on SiO2
Fig. 2 | Ca alys p epa a ion. Syn hesis o Fe/Fe–O co e–shell nanopa icles by he imp egna ion and py olysis o i on(II) ace a e on SiO2. DMF,
N,N-dime hyl o mamide.
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iisop opoxide and aluminium oil a e con e ed unde he eac-
ion condi ions o an ac i e Lewis acid co-ca alys ha ac i a es he
ni ile g oup. These Lewis acidic cen es can p obably also be gene -
a ed on he silica suppo close o he nanopa icles by eac ion wi h
Si–OH si es on he su ace. No ably, ca aly ic (subs oichiome ic)
amoun s (20 mol%) o he aluminium addi i es we e su icien o
achie e imp o ed yields.
Unde he op imized condi ions, o he suppo ed ca alys s, such
as Fe(OAc)2-C-800, Fe(OAc)2-Al2O3-800 and Fe(OAc)2-MgO-800
(Supplemen a y Figs. 4–6), did no show any ac i i y (Fig. 3). In
hese samples we did no obse e needle-like well-de eloped α-Fe
nanopa icles g owing om he ma ix, as we did in he case o he
op imal ca alys , Fe(OAc)2-SiO2-800. In con as , he i on nanopa -
icles we e highly agg ega ed and/o encapsula ed wi hin he ma ix
(Supplemen a y Figs. 4–6). Simila ly, Fe(OAc)2 on SiO2 py olysed a
400 °C (Fe(OAc)2-SiO2-400) was comple ely inac i e (Fig. 3). This
is explained by a no ully de eloped ac i e Fe nanos uc u e a low
py olysis empe a u e, which is e iden om he powde X- ay
di ac ion (PXRD) pa e n (Supplemen a y Fig. 7) and ansmis-
sion elec on mic oscopy (TEM) image (Supplemen a y Fig. 8) o
he Fe(OAc)2-SiO2-400 sample. By con as , Fe(OAc)2-SiO2-600
and Fe(OAc)2-SiO2-1,000 exhibi ed compa able ac i i ies o ha
o Fe(OAc)2-SiO2-800, p o iding 93 and 94% yields o he desi ed
p oduc , espec i ely. This co ela es well wi h he simila size
and well-de eloped co e–shell s uc u e o he Fe(OAc)2-SiO2-600
and Fe(OAc)2-SiO2-1,000 samples (see he TEM images in
Supplemen a y Figs. 9 and 10) compa ed wi h Fe(OAc)2-SiO2-800
(Fig. 4c). As expec ed, i on(II) ace a e, unpy olysed Fe(OAc)2-SiO2
and Al addi i es alone we e comple ely inac i e in he eac ion
(Fig. 3). Addi ionally, we p epa ed con ol samples, including pu e
amo phous Fe2O3 nanopa icles (NPs), ayali e (Fe2SiO4) NPs and
ma ix- ee Fe–Fe2O3 co e–shell NPs wi h a e y hin oxidic shell
(Supplemen a y Figs. 11–13), and in es iga ed hei pe o mance
in he model eac ion. No ably, he ayali e and Fe2O3 NPs we e
comple ely inac i e, whe eas he Fe–Fe2O3 co e–shell NPs ga e
30% yield (Supplemen a y Table 5, en ies 1–3). This con i med he
c ucial ole o he Fe–Fe2O3 co e–shell supe s uc u e in igge ing
he ca aly ic p ocess. We belie e ha he ac i e ma e ial in ol es
Fe cen es and/o he Fe–O a omic in e ace48. The high ac i i y
o he ca alys inco po a ing he SiO2 ma ix (Fe(OAc)2-SiO2-800)
s ongly indica es ha he ma ix egula es he size o he i on oxide
c ys alli es49,50. Indeed, i has al eady been epo ed ha he Cu–O–
SiOx in e ace in a silica-suppo ed coppe (Cu@SiO2) ca alys plays
a key ole in H2 dissocia ion o o m Cu–Hδ− and SiO–Hδ+ species51.
Thus, we belie e ha he silica in Fe(OAc)2-SiO2-800 would con-
ibu e o he ca aly ic ac i i y by o ming such an ac i e me al–sup-
po (Fe–O–SiOx) in e ace.
Nex , we conduc ed a de ailed cha ac e iza ion o he mos ac i e
ca alys Fe(OAc)2-SiO2-800. TEM analysis e ealed he o ma ion
o co e–shell s uc u es wi h globula and od-shape mo phologies,
wi h he needle diame e s anging om 10 o 30 nm and leng hs
up o 100 nm (Fig. 4a–c). Ene gy-dispe si e X- ay spec oscopy
(EDS) o his ma e ial showed he p esence o Si, O and Fe ele-
men s (Supplemen a y Fig. 14). The high- esolu ion TEM image
(HRTEM; Fig. 4d) con i ms ha he me allic pa o he ca alys is
composed o an α-Fe co e g owing om he SiO2 ma ix. Indeed,
he high-angle annula da k- ield scanning ansmission elec-
on mic oscopy (HAADF-STEM) and elemen al mapping images
clea ly e i y ha he Fe co e nanopa icles a e g owing om he
SiO2 ma ix and a e co e ed by a laye o ul a hin i on oxide wi h a
hickness o a ew nanome es (Fig. 4 –i). Based on his assignmen ,
he mos ac i e Fe(OAc)2-SiO2-800 ca alys is abb e ia ed o Fe/
Fe–O@SiO2 in he ollowing ex . A ep esen a i e HAADF-STEM
image o a globula pa icle and ypical dep h p o ile plo showing
he in ensi y dis ibu ion o he Si, O and Fe elemen s a a ious
dis ances om he su ace a e shown in Fig. 5a,b, espec i ely. The
dep h p o iles con i m ha he hickness o he oxidic Fe-O shell
is less han 5 nm. Clea ly, he ca alys su ace is composed o i on
nanopa icles, which g ow om he SiO2 ma ix, s abilized by an
ex emely hin i on oxide shell.
Fu he mo e, we pe o med e y de ailed chemical mapping
wi h a ocus on he i on-con aining su ace componen s ha a e
esponsible o he ca aly ic ac i i y. All he iden i ied Fe-bea ing
su ace-ac i e phase was composed o Fe nanopa icles co e ed
wi h a e y hin shell o i on oxide, i espec i e o he size and
mo phology (globula , needle-like) o he Fe NPs (Supplemen a y
Fig. 15).
To iden i y he chemical and s uc u al cha ac e o he ca a-
lys , we analysed he Fe/Fe–O@SiO2 sample by PXRD, Mössbaue
spec oscopy, X- ay pho oelec on spec oscopy (XPS) and elec on
pa amagne ic esonance (EPR) spec oscopy. The PXRD pa e n
o Fe/Fe–O@SiO2 (Supplemen a y Fig. 16) shows s ong me allic
α-Fe e lec ions a 2θ = 52.33, 77.16 and 99.60°, co esponding o
c ys alline ace s o he Fe (110), (200) and (211) planes, espec-
i ely (Join Commi ee on Powde Di ac ion S anda ds (JCPDS)
ca d numbe 04-012-6482). Thus, α-Fe is he dominan c ys alline
phase in ol ed in he ca alys supe s uc u e. The low-c ys alline
SiO2 ma ix is ep esen ed by a b oad peak a 2θ ≈ 26°, indica ing
he p esence o poo ly c ys alline c is obali e (JCPDS ca d num-
be 04-008-7643). The ul a hin i on oxide laye is, in acco d wi h
expec a ion, no iden i iable in he PXRD pa e n due o i s mos ly
amo phous na u e. Howe e , de ailed PXRD analysis clea ly showed
addi ional low-in ensi y di ac ion peaks co esponding o ayali e
(Fe2SiO4, JCPDS ca d numbe 04-002-3681) and c ys alline silicon
(Si(0), JCPDS ca d numbe 04-014-8844). In summa y, PXRD p o-
ided a complex pic u e o he high- empe a u e chemis y o he
Fe–Si–O sys em.
These obse a ions a e in line wi h he XPS analysis, which
con i med he p esence o jus Fe, Si and O elemen s in he su ey
spec um (Supplemen a y Fig. 17a). The high- esolu ion O1s spec-
um o Fe/Fe–O@SiO2 (Supplemen a y Fig. 17b) iden i ies peaks
26%
50%
96% 97%
<1% <1% <1% <1%
94% 93%
<1% <1% <1%
0
10
20
30
40
50
60
70
80
90
100
Yield o
4-chlo obenzylamine (%)
Ca alys
Fe(OAc)2-SiO2-800
Fe(OAc)2-SiO2-800 + AI(i-OP )3
b
Fe(OAc)2-SiO2-800 + AIc
Fe(OAc)2-C-800 + AIc
Fe(OAc)2-Al2O3-800 + AIc
Fe(OAc)2-MgO-800 + AIc
Fe(OAc)2-SiO2-400 + AIc
Fe(OAc)2-SiO2-600 + AIc
Fe(OAc)2-SiO2-1000 + AIc
Fe(OAc)2-SiO2 + AIc
Fe(OAc)2 + AIc
AIc
Fe(OAc)2-SiO2-800a
Fe ca alys
N
Cl Cl
NH2
50 ba H2, 5–7 ba NH3
i-P OH, 120 °C, 24 h
Fig. 3 | e alua ion o Fe ca alys s. Hyd ogena ion o 4-chlo obenzoni ile.
Reac ion condi ions: 0.5 mmol 4-chlo obenzoni ile, 40 mg ca alys
(8.5 mol% Fe), 50 ba H2, 5–7 ba NH3, 3 ml i-P OH, 120 °C, 24 h. Gas
ch oma og aphy (GC) yields a e gi en using n-hexadecane as s anda d.
aWi h 60 mg ca alys . bWi h 20 mol% Al(i-OP )3. cWi h 20 mol% (3 mg)
Al oil.
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a 530.72 and 533.14 eV, co esponding o Fe–O and Si–O bonds,
espec i ely. Mos impo an ly, he high- esolu ion Fe2p spec-
um (Supplemen a y Fig. 17d) e eals Fe 2p3/2 peaks a 710.27 and
712.73 eV, and Fe2p1/2 peaks a 723.37 and 725.83 eV, which can be
asc ibed o Fe3+ species52, along wi h wo sa elli e peaks a 717.41
and 730.51 eV. This is s ong p oo ha he amo phous i on oxide
phase co e ing he Fe(0) co e co esponds o amo phous Fe2O3. The
o ma ion o i on(III) oxide was con i med by he hype ine pa am-
e e s de i ed om oom- empe a u e Mössbaue spec oscopy (Fig.
5c). The 57Fe Mössbaue spec um o he sample shows a dominan
sex e (68% o he ela i e spec um a ea) and wo double compo-
nen s. Acco ding o he Mössbaue hype ine pa ame e s, he sex e
wi h ze o isome shi and a hype ine ield o 32.9 T can be unam-
biguously assigned o e omagne ic α-Fe. The double wi h high
isome shi (1.18 mm s–1) and quad upole spli ing (2.64 mm s–1)
clea ly belongs o Fe(II) ions in he ayali e s uc u e o med a
he Si–Fe in e ace53, in pe ec ag eemen wi h he esul s o he
PXRD measu emen s. Finally, he double wi h an isome shi o
0.35 mm s–1 is ypical o high-spin Fe(III) in amo phous i on(III)
oxide wi h diso de ed symme y o he i on en i onmen , as p o ed
by he ela i ely high quad upole spli ing (1.31 mm s–1)54. I is wo h
men ioning ha possible aces o Fe(III) ions usually in ol ed in
he ayali e s uc u e would o e lap he double o he i on(III)
oxide phase. Finally, he EPR spec um o Fe/Fe–O@SiO2 shows
b oad aniso opic signals wi h g ac o alues o gx = 2.72, gy = 2.04
and gz = 1.8 (ga e = 2.19) a 77 K (Fig. 5d), which indica es he p es-
ence o e omagne ic pa icles co esponding o Fe(0) wi h dis inc
size and mo phology. In summa y, HRTEM, HAADF-STEM, XPS,
PXRD, EPR and Mössbaue spec oscopy allowed us o explo e he
chemical and s uc u al cha ac e o he Fe/Fe–O@SiO2 ca alys ,
being composed o a SiO2 ma ix, a ayali e in e ace (Fe2SiO4) and
α-Fe–amo phous Fe2O3 co e–shell nanopa icles g owing om he
silica ma ix and ep esen ing he su ace-ac i e phase pa icipa ing
in he ca aly ic p ocess. The EPR and Mössbaue da a con i m he
e omagne ic cha ac e o he sample, p ede e mining he ca alys
o simple magne ic sepa a ion.
Hyd ogena ion o benzoni iles and he e ocyclic ni iles. Wi h an
ac i e Fe-based ca alys (Fe/Fe–O@SiO2) in hand, we demons a ed
i s gene al applicabili y o he selec i e hyd ogena ion o all kinds
o ni iles. Al hough in mos o he eac ions aluminium oil was
used as an inexpensi e addi i e, expe imen s pe o med o com-
pa ison in he p esence o aluminium iisop opoxide ga e simila
p oduc yields. Fi s , we ca ied ou he hyd ogena ion o a se ies
o a oma ic ni iles (Fig. 6). Simple benzoni iles as well as subs i-
u ed ones bea ing a oma ic o alkyl g oups ga e he co espond-
ing p ima y amines in yields o up o 96% (Fig. 6, p oduc s 3–7).
Fo he gene al applicabili y o any new ca alys , i s chemoselec i -
i y is an impo an aspec . Thus, om a syn he ic poin o iew, i
is impo an o no e ha his i on-based ca alys sys em is highly
selec i e o he hyd ogena ion o he ni ile g oup in unc ionalized
and mul isubs i u ed subs a es. As an example, amino-subs i u ed
and halogena ed benzylic amines we e p epa ed, which a e e sa ile
in e media es in o ganic syn hesis as well as o pha maceu icals
and ag ochemicals. Such p oduc s, including he mo e sensi i e
4-iodobenzylamine, we e easily p oduced om he co esponding
200 nm
20 nm
20 nm
10 nm
10 nm
10 nm
10 nm
10 nm
5 nm
abc
de
ghi
Fe
Fe
Fe
Fe O
Si
OSi
HAADF
Fig. 4 | TeM and HRTeM imaging o Fe(Oac)2-SiO2-800. a–i, TEM (a–c), HRTEM (d) and HAADF-STEM (e) images and elemen al mapping o i on ( ),
i on and oxygen (g), i on and silicon (h), and i on, silicon and oxygen (i) o he Fe(OAc)2-SiO2-800 ca alys .
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benzoni iles in yields o up o 97% (Fig. 6, p oduc s 8–16). In
addi ion, i luo ome hyl-subs i u ed benzylamines we e ob ained
in yields o 94 and 95% (Fig. 6, p oduc s 17 and 18, espec i ely).
We we e also pleased o ind ha he ni ile g oup was also selec-
i ely hyd ogena ed in he p esence o he mo e challenging C≡C,
es e , bo onic es e , amide, e he , i luo ome hoxy and hioe he
g oups (Fig. 6, p oduc s 19–30). Fu he mo e, when mul isubs i-
u ed ni iles we e subjec ed o hyd ogena ion, educ ion o he CN
g oup again ook place highly selec i ely owa ds he co esponding
benzylic amines in yields o up o 95% (Fig. 6, p oduc s 31–46).
He e ocyclic amines cons i u e e sa ile in e media es in he
pha maceu ical and ag ochemical indus ies. In his espec , he
selec i e hyd ogena ion o cyano-subs i u ed he e ocycles, o
example, quinolines, indoles, py oles, benzodioxoles, benzodiox-
anes, u ans, mo pholines and ph halanes, is o pa icula in e es .
The co esponding he e ocyclic amines we e ob ained (excep o
3-cyano u an) in yields o 85–94% (Fig. 6).
Hyd ogena ion o alipha ic ni iles. Compa ed wi h a oma ic
ni iles, he hyd ogena ion o alipha ic ni iles is in gene al mo e
challenging. Impo an ly, Fe/Fe–O@SiO2 exhibi ed high ac i i y and
selec i i y o hese subs a es, including dini iles, unde iden ical
condi ions (Fig. 7). Ini ially, se e al benzylic cyanides we e hyd o-
gena ed o he co esponding p ima y amines in excellen yields
(Fig. 7, p oduc s 57–72). In e es ingly, he 2-a yle hylamino mo i
is a common sca old in many cen al ne ous sys em-ac i e com-
pounds. He e, a a ie y o subs i u ed de i a i es we e smoo hly
hyd ogena ed and u nished he co esponding p ima y amines in
yields o up o 98% (Fig. 7, p oduc s 57–68). Phenylp opylamines
a e ano he impo an class o pha maceu ically ele an amines.
Fo example, he pa en compound (phenylp opylamine) is used in
he syn hesis o ca boxypep idase B- ype enzyme inhibi o s, mus-
ca inic ecep o an agonis s and po en ial an icance agen s. He e,
i was p epa ed in 94% yield om he co esponding ni ile (Fig. 7,
p oduc 69).
Al hough 3-(a ylamino)p opaneni iles a e p epa ed in a
s aigh o wa d manne om anilines and ac yloni ile, he hyd o-
gena ion o such subs a es is di icul because e o-Michael addi-
ions can occu . Howe e , his class o compounds was smoo hly
hyd ogena ed unde ou condi ions o gi e he espec i e p ima y
amines in good yields o up o 85% (Fig. 7, p oduc s 70–72). Finally,
a selec ion o alipha ic ni iles was es ed. G a i yingly, Fe/Fe–O@
SiO2 also showed good- o-excellen ac i i y and selec i i y o hese
demanding subs a es (Fig. 7, p oduc s 73–78). Pa icula ly in e -
es ing is he selec i e educ ion o 5-hexeneni ile (Fig. 7, p oduc
78). No ably, hexame hylenediamine (79), he key eeds ock o he
p oduc ion o nylon 66, was p epa ed in 85% yield by di ec hyd o-
gena ion o adiponi ile. Simila ly, o he diamines we e ob ained in
90–95% yield (Fig. 7, p oduc s 80 and 81).
Syn hesis o a y ni iles. Wi h a wo ldwide p oduc ion o a y
amines o >800,000 ons y –1, he hyd ogena ion o a y ni iles
cons i u es an impo an indus ial applica ion55. Fa y amines a e
aluable oleochemicals mainly used o p oduce ab ic so ene s,
lo a ion agen s, emulsi ie s, co osion inhibi o s and lub ica ing
addi i es55.
Un il oday, he indus ial hyd ogena ion o a y ni iles o
amines has elied on well-es ablished Raney Ni o Co ca alys s as
well as coppe ch omi e55. These ma e ials ha e conside able ox-
ici y issues o biological sys ems. Hence, al e na i e Ru-, Pd- and
100 Fe
g = 2.27
Da a
300 K/0 T
Fi
Fe(0)
Fe(II)
Fe(III)
g = 2.015
g = 1.80
Si
O
80
60
40
20
In ensi y (a.u.)
In ensi y (a.u.)
0
2
100.0
ab
cd
99.9
99.8
T ansmission (%)
99.7
–10 –5 0
Veloci y (mm s–1)
5 10
0
–2
–4
100 200 300 400
Magne ic ield (mT)
500
0
10 nm
5 10
Posi ion (nm)
15 20 25
Fig. 5 | Spec al da a o Fe/Fe–O@SiO2. a–d, HAADF-STEM image (a), dep h p o iles showing he in ensi y dis ibu ion o Fe, Si and O (b), Mössbaue
spec um eco ded a 300 K (c) and EPR spec um (X-band 9.090 GHz) eco ded a 77 K (d).
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Hyd ogena ion o benzoni iles
Fe/Fe–O@SiO2
AI, 50 ba H2, 5–7 ba NH3
i-P OH, 120 °C, 24 h
3: 96%a (93%)a
4: 90%
9: 92%
15: 89% (90%) 16: 80%b
21: 95%
26: 91%b
31: 80%c
27: 94%
32: 80%
37: 89%
43: 85%b
47: 91%b
53: 90% 54: 85% 55: 94%b56: 92%
48: 89% (91%) 49: 90% 50: 91% (93%) 51: 93% 52: 65%
44: 95% 45: 60%d46: 90%e
38: 93% 39: 91%
40: 94% 41: 87% (84%) 42: 89%
33: 70%b34: 95% (93%) 35: 90% 36: 95%
28: 95% 29: 92%b30: 94% (92%)
22: 90%g24: 97% 25: 97%
17: 94% 18: 95% 19: 91% 20: 85%
10: 95% (95%) 11: 97% (96%) 12: 96% 13: 97% 14: 91%
6: 96%a7: 96% (95%) 8: 90%
5: 88%b (89%)b
23: 98%a
Hyd ogena ion o he e ocyclic ni iles
Fig. 6 | Subs a e scope. Hyd ogena ion o (he e o)a oma ic ni iles. Reac ion condi ions: 0.5 mmol ni ile, 40 mg Fe/Fe–O@SiO2 (8.5 mol% Fe), 3 mg
Al oil (20 mol%), 5–7 ba NH3, 50 ba H2, 3 ml i-P OH, 120 °C, 24 h. Isola ed yields a e gi en. aYields we e de e mined by GC using n-hexadecane as
s anda d. bWi h 50 mg Fe/Fe–O@SiO2. cWi h 50 mg Fe/Fe–O@SiO2 and 5 mg Al oil. dA 135 °C. eWi h 60 mg Fe/Fe–O@SiO2 and 5 mg Al oil. Wi h 50 mg
Fe/Fe–O@SiO2 a 135 °C. gMe hyl 4-cyanobenzoa e was used as subs a e. T anses e i ica ion p oduc wi h i-P OH. Yields in pa en heses e e o he
eac ion pe o med in he p esence o 20 mol% Al(i-OP )3. P oduc s we e isola ed as ee amines and con e ed o hei hyd ochlo ide sal s o NMR and
high- esolu ion mass spec ome y (HRMS) analysis.
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P -based ca alys s we e de eloped55. Un o una ely, none o hese
sys ems is comme cially iable due o he high p ice o he p ecious
me als. G a i yingly, ou ca alys is capable o hyd ogena ing a y
ni iles in a highly selec i e manne . As a esul , se en di e en a y
amines we e p epa ed in excellen yields o 95–97% (Fig. 8, p od-
uc s 82–88).
To u he p o e he syn he ic u ili y and p ac icabili y o ou
Fe ca alys , we scaled up bo h he ca alys p epa a ion (up o 12 g;
Supplemen a y Table 6) and he ni ile hyd ogena ion p o ocol (up
o 20 g). Rega dless o he scale o p epa a ion (1–12 g), all he Fe
ma e ials exhibi ed simila ac i i y and selec i i y (Supplemen a y
Table 7). Nex , he ca aly ic hyd ogena ion eac ions o ou selec ed
a oma ic and alipha ic ni iles we e pe o med using quan i ies
o up o 20 g ni ile. Again, simila con e sions and yields we e
ob ained o hose achie ed wi h small-scale eac ions using up o
100 mg ni ile (Supplemen a y Fig. 18).
Finally, ca alys ecycling was in es iga ed a ull and hal con-
e sions, which is an impo an aspec o any he e ogeneous ca a-
lys . Indeed, he Fe/Fe–O@SiO2 ca alys could be eused up o he
ou h un. A e ha , a dec ease in he p oduc yield was obse ed.
Recycling es s pe o med a hal con e sion o 14 h showed a d op
in ac i i y om he hi d un onwa d (Supplemen a y Fig. 19).
Conclusions
We ha e p esen ed he e he de elopmen o a he e ogeneous
i on-based ca alys o he hyd ogena ion o ni iles. Key o success was
he use o silica-suppo ed Fe nanopa icles co e ed wi h an ul a hin
shell o amo phous i on(III) oxide (Fe/Fe–O@SiO2). These co e–shell
nanopa icles we e p epa ed by simple imp egna ion o i on(II) ace-
a e on comme cial silica and subsequen py olysis unde educ i e
condi ions. The low cos and en i onmen ally iendly cha ac e o
he ca alys , easy ecycling as well as upscaling o he syn he ic p ocess
ep esen key ad an ages and make he ma e ial a ac i e o many
applica ions. Impo an ly, he de eloped silica-suppo ed Fe/Fe–O
co e–shell ma e ial exhibi ed high chemoselec i i y o he educ ion
o unc ionalized and s uc u ally di e se a oma ic, he e ocyclic and
alipha ic ni iles, including indus ially ele an a y ni iles, o p o-
duce he co esponding p ima y amines in good- o-excellen yields.
Aluminium alkoxide species gene a ed in si u om aluminium oil o
aluminium iisop opoxide p o ed o be impo an o he co-ca aly ic
ac i a ion o he ni ile subs a e.
Me hods
Gene al conside a ions. All ni iles we e ob ained comme cially om a ious
chemical companies. Be o e using, he pu i y o all he ni iles was checked.
I on(II) ace a e (99.99%, ca no. 517933-25G) was ob ained om Sigma Ald ich.
Silica (Ae osil OX-50) was ob ained om E onik. Ca bon powde (VULCAN
XC72R, wi h code XVC72R) was ob ained om Cabo Co po a ion. γ-Al2O3 and
MgO we e ob ained om Sigma-Ald ich. Al oil was ob ained om Sigma-Ald ich
(Mini Bin, HS23534A). Fo compa ison pu poses, Al oil used o ood co e ing
was also pu chased om a local s o e (Kau land, ALUFOLIE; ICP). The pe cen age
o aluminium in Al- oil was de e mined by induc i ely coupled plasma (ICP) and
i was ound o be 99.97%. DMF was ob ained om Ac os Chemicals. Py olysis
expe imen s we e ca ied ou in a Len on ube u nace.
PXRD pa e ns we e measu ed a oom empe a u e wi h an Ae is
di ac ome e (PANaly ical) in B agg–B en ano geome y equipped wi h
Fe/Fe–O@SiO2
AI, 50 ba H2, 5–7 ba NH3
i-P OH, 120 °C, 24 h
57: 95% 58: 91% (93%)
59: 90%
62: 98%
67: 94%
72: 82% 73: 95%c
79: 85%d (89%)d80: 90%e (94%)e81: 95%e
74: 96%c75: 98%c
78: 65%c
77: 95%c
76: 97%a
68: 95% 69: 94% (92%) 70: 84% 71: 85%
63: 90%
64: 80%a
65: 89%b66: 91%
60: 90% 61: 91%
Fig. 7 | Subs a e scope. Hyd ogena ion o alipha ic ni iles. Reac ion condi ions: 0.5 mmol ni ile, 40 mg Fe/Fe–O@SiO2 (8.5 mol% Fe), 3 mg Al oil
(20 mol%), 5–7 ba NH3, 50 ba H2, 3 ml i-P OH, 120 °C, 24 h. Isola ed yields a e gi en. aWi h 50 mg Fe/Fe–O@SiO2. bA 135 °C. cYields we e de e mined
by GC using n-hexadecane as s anda d. dWi h 80 mg Fe/Fe–O@SiO2 and 6 mg Al oil a 135 °C. eWi h 80 mg Fe/Fe–O@SiO2 and 6 mg Al oil a 120 °C.
Yields in pa en heses e e o he eac ion pe o med in he p esence o 20 mol% Al(i-OP )3. P oduc s we e isola ed as ee amines and con e ed o hei
hyd ochlo ide sal s o NMR and HRMS analysis.
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an i on- il e ed Co Kα adia ion sou ce (40 kV, 15 mA, λ = 0.1789 nm) and
PIXcell de ec o . Some samples we e measu ed employing an X’Pe PRO MPD
di ac ome e (PANaly ical) in B agg–B en ano geome y equipped wi h a Co
Kα adia ion sou ce (40 kV, 30 mA, λ = 0.1789 nm), p og ammable di e gence,
di ac ed beam an i-sca e sli s and X’Cele a o de ec o . The angula ange
o measu emen was 5–105° 2θ (Fe/Fe–O@SiO2 was measu ed in he ange
10–105° 2θ) wi h a s ep size o 0.022 and 0.033° o Ae is and X’Pe PRO MPD
di ac ome e s, espec i ely. The c ys alline phases in he expe imen al PXRD
pa e ns we e iden i ied using he X’Pe High Sco e Plus so wa e56 in conjunc ion
wi h he PDF-4+57 and ICSD58 da abases. The comme cially a ailable silicon
s anda d e e ence ma e ial SRM 640 was used o e alua e he line posi ions.
Low- esolu ion TEM imaging o he ca alys mo phology was ca ied ou
wi h a JEOL mic oscope equipped wi h a LaB6 emission gun, ope a ing a 160 kV.
HRTEM images we e ob ained wi h a TITAN 60-300 HRTEM mic oscope
equipped wi h an X-FEG- ype emission gun, ope a ing a 80 kV. This mic oscope
was equipped wi h a Cs image co ec o and a HAADF-STEM ins umen . The
poin esolu ion was 0.06 nm in TEM mode. Elemen al mapping was pe o med
by STEM-EDS wi h an acquisi ion ime o 20 min. Fo he HRTEM analysis, he
powde samples we e dispe sed in e hanol and ul asonica ed o 5 min. One d op
o his solu ion was placed on a coppe g id suppo ing a holey ca bon ilm.
The XPS su ace in es iga ion was pe o med on a PHI 5000 Ve saP obe II
XPS sys em (Physical Elec onics) wi h a monoch oma ic Al Kα sou ce (15 kV,
50 W) and pho on ene gy o 1,486.7 eV. Dual beam cha ge compensa ion was used
o all measu emen s. All spec a we e eco ded in a acuum o 1.3 × 10−7 Pa a
21 °C. A 200-µm-diame e spo was analysed o each sample. The su ey spec a
we e measu ed wi h a pass ene gy o 187.850 eV and an elec on ol s ep o 0.8 eV,
whe eas he high- esolu ion spec a we e eco ded wi h a pass ene gy o 23.500 eV
and an elec on ol s ep o 0.2 eV. The spec a we e e alua ed wi h he Mul iPak
so wa e (ULVAC-PHI). All binding ene gies a e e e enced o he C1s ca bon peak
a 284.80 eV.
The ansmission 57Fe Mössbaue spec a we e collec ed employing a
Mössbaue MS96 spec ome e ope a ing in cons an accele a ion mode and
equipped wi h a 40 mCi 57Co(Rh) sou ce. The Mössbaue spec a we e i ed
wi h he MossWinn so wa e. The isome shi s a e e e enced o α-Fe a oom
empe a u e. EPR spec a we e eco ded on a JEOL JES-X-320 spec ome e ,
ope a ing a he X-band equency (~9.14 GHz) a 77 K, and equipped wi h a JEOL
ES 13060DVT5 a iable- empe a u e con ol appa a us.
All ca aly ic expe imen s we e ca ied ou in 300 o 100 ml au ocla es (PARR
Ins umen ). To a oid unspeci ic eac ions, all ca aly ic eac ions we e ca ied ou
ei he in glass ials, which we e placed inside he au ocla e, o in au ocla es i ed
wi h a glass/Te lon essel.
GC and GC-mass spec ome y (GC–MS) we e pe o med on an Agilen
Technologies 6890N ins umen . GC con e sions and yields we e de e mined by
GC using lame ioniza ion de ec ion (FID) on an Agilen 6890N ch oma og aph
equipped wi h Agilen HP-5MS 30m column (250 mm × 0.25 μm). The mass was
de e mined by GC-MS using Agilen 6890N ch oma og aph equipped wi h Agilen
HP-5MS 30m column (250 mm × 0.25 μm) and Agilen 5973N Mass Selec i e
De ec o (MSD).
1H and 13C NMR spec a we e eco ded on B uke ARX 300 and ARX 400
spec ome e s using [D6]DMSO and CDCl3 sol en s.
P epa a ion o Fe/Fe–O@SiO2 on he 1.5 g scale. A magne ic s i ing ba and
280.33 mg Fe(OAc)2 we e ans e ed o a 50- ml ound-bo omed lask and 30 ml
DMF was added. The eac ion mix u e was s i ed a 50 °C o dissol e he i on
ace a e. To his solu ion, 1.2 g SiO2 (Ae osil OX 50) was added, ollowed by 10 ml
DMF. Nex , a e lux condense was i ed o he ound-bo omed lask con aining
he eac ion mix u e, which was hen placed in an aluminium block p ehea ed
a 150 °C and s i ed o 4 h. Nex , he e lux condense was emo ed and he
ound-bo omed lask con aining he eac ion p oduc s was allowed o s and
wi hou s i ing o closing o 20 h a 150 °C o he slow e apo a ion o DMF.
A e e apo a ion o he sol en and ensu ing comple e d ying, he solid ma e ial
was cooled o oom empe a u e and g ound o a ine powde . This powde was
py olysed a a de ined empe a u e (400, 600, 800 o 1,000 °C) o 4 h in a ubula
u nace unde he low o 20% H2/N2 ( amp: 5 °C min–1, o al low: 3 l h–1) and hen
cooled o oom empe a u e.
Elemen al analysis o Fe/Fe–O@SiO2 by ICP and CHN analysis e ealed he
ollowing (w %) dis ibu ion: Fe = 6.09%; Si = 37.73%; C = 0.11%; H = 0.41%. The
B unaue –Emme –Telle su ace a ea was measu ed o be 46.04 m2 g–1.
The same p ocedu e was employed o he p epa a ion o Fe(OAc)2-C-800,
Fe(OAc)2-γ-Al2O3-800 and Fe(OAc)2-MgO-800.
P epa a ion o Fe/Fe–O@SiO2 on 6 and 12 g ba ches. The same p ocedu e was
used o he p epa a ion o Fe/Fe–O@SiO2 (Fe(OAc)2-SiO2-800) on he 6 and
12 g scale wi h a sligh modi ica ion o he py olysis p ocedu e, as desc ibed in
Supplemen a y Table 6.
Gene al p ocedu e o he hyd ogena ion o ni iles. A magne ic s i ing ba
and 0.5 mmol o he co esponding ni ile we e ans e ed o a 7-ml glass ial and
hen 3 ml i-P OH was added. Nex , 40 mg Fe/Fe–O@SiO2 (8.5 mol% Fe) and 3 mg
Al oil ( he Al oil was cu in o small pieces and used in he eac ions) o 20.42 mg
Al(i-OP )3 (20 mol%) we e added and he ial was i ed wi h a sep um, cap and
needle. Then, he eac ion ials we e placed in a 300-ml au ocla e (eigh ials
con aining di e en subs a es a a ime). The au ocla e was closed, lushed wice
wi h 20 ba hyd ogen and hen p essu ized wi h 5–7 ba ammonia gas and 50 ba
hyd ogen. The au ocla e was placed in an aluminium block p ehea ed a 133 °C
and he eac ions we e allowed o p oceed o he equi ed ime unde s i ing.
Fa s
and
oils
82: 97% (97%)
85: 96%b86: 95%b (95%) 87: 97%b
88: 95%b (94%)b
83: 97% 84: 97%a
Fa y amines
Fa y ni iles
P e iously used ca alys s
Raney Ni o Co, Cu ch omi e, Ru, Pd, P
This Fe ca alys
(Oc ylamine)
(My is ylamine) (S ea ylamine)
(Nonadecanamine)
(Hep adecylamine)
(Decylamine) (Lau ylamine)
Fe/Fe–O@SiO2
NH3, H2
120 °C, 24 h
Fig. 8 | Subs a e scope. Syn hesis o a y amines. Reac ion condi ions: 0.5 mmol ni ile, 40 mg Fe/Fe–O@SiO2 (8.5 mol% Fe), 3 mg Al oil (20 mol%),
5–7 ba NH3, 50 ba H2, 3 ml i-P OH, 120 °C, 24 h. Isola ed yields a e gi en. aA 135 °C. bWi h 50 mg Fe/Fe–O@SiO2. Yields in pa en heses e e o he
eac ion pe o med in he p esence o 20 mol% Al(i-OP )3. P oduc s we e isola ed as ee amines and con e ed o hei hyd ochlo ide sal s o NMR and
HRMS analysis.
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Du ing he eac ions, he inside empe a u e o he au ocla e was measu ed o
be 120 °C, and his empe a u e was conside ed o be he eac ion empe a u e.
A e comple ion o he hyd ogena ion eac ions, he au ocla e was cooled o
oom empe a u e. The emaining ammonia and hyd ogen we e discha ged and
he ials con aining he eac ion p oduc s we e emo ed om he au ocla e. The
solid ca alys was il e ed and washed ho oughly wi h e hyl ace a e. The eac ion
p oduc s we e analysed by GC–MS. The co esponding p ima y amines we e
pu i ied by column ch oma og aphy (silica, me hanol–dichlo ome hane). The
amines we e con e ed o hei espec i e hyd ochlo ide sal and cha ac e ized
by GC–MS and NMR analysis. To con e he amines o he hyd ochlo ide sal s,
1–2 ml me hanolic HCl (0.5 M HCl in me hanol) was added o he e hyl ace a e
solu ion o he espec i e amine and he mix u e s i ed a oom empe a u e o
4–5 h. Then, he sol en was emo ed and he esul ing hyd ochlo ide sal was
d ied unde high acuum. Fo selec ed amines, he yields we e de e mined by
GC using he ollowing p ocedu e. A e comple ing he eac ion, n-hexadecane
(100 µl) was added as s anda d o he eac ion ials and he eac ion p oduc s
we e dilu ed wi h e hyl ace a e ollowed by il a ion using a plug o silica and hen
analysed by GC.
G am-scale eac ions. A magne ic s i ing ba and he co esponding ni ile
we e ans e ed o a glass- i ed 300-ml Pa au ocla e and 15–50 ml i-P OH was
added. Nex , he equi ed amoun o ca alys (Fe/Fe–O@SiO2, 8.5–10 mol%) and
Al oil (20 mol%; he Al oil was cu in o small pieces and used in he eac ions)
we e added. Then, he au ocla e was closed, lushed wice wi h 20 ba hyd ogen
and hen p essu ized wi h 5–7 ba NH3 ollowed by 50 ba hyd ogen. The au ocla e
was placed in an aluminium block p ehea ed a 133–147 °C (placed 30 min be o e
coun ing he eac ion ime o achie e he eac ion empe a u e) and he eac ions
we e s i ed o 24 h. Du ing he eac ions, he inside empe a u e o he au ocla e
was measu ed o be 120–135 °C. A e comple ion o he eac ions, he au ocla e
was cooled o oom empe a u e. The emaining ammonia and hyd ogen we e
discha ged, and he eac ion p oduc s we e emo ed om he au ocla e. The solid
ca alys was il e ed and washed ho oughly wi h me hanol and e hyl ace a e. The
eac ion p oduc s we e analysed by GC–MS and he co esponding p oduc s we e
pu i ied by column ch oma og aphy (silica, dichlo ome hane–me hanol) and
cha ac e ized by NMR and GC–MS analysis.
Ca alys ecycling. A magne ic s i ing ba and 10 mmol benzoni ile we e
ans e ed o a 100-ml au ocla e and hen 20 ml i-P OH was added. Nex , 900 mg
ca alys (Fe/Fe–O@SiO2) and 408.50 mg Al(i-OP )3 we e added. The au ocla e was
closed, lushed wi h 20 ba hyd ogen and hen p essu ized wi h 5–7 ba NH3 and
50 ba H2. The au ocla e was placed in a p ehea ed aluminium block a 130 °C and
he eac ions we e s i ed o he equi ed ime. Du ing he eac ions, he inside
empe a u e o he au ocla e was measu ed o be 120 °C. A e comple ion o he
eac ions, he au ocla e was cooled o oom empe a u e. The emaining ammonia
and hyd ogen we e hen discha ged, and he eac ion p oduc s we e emo ed om
he au ocla e. Nex , 250 µl n-hexadecane was added as s anda d o he eac ion
p oduc s. The ca alys was sepa a ed by il a ion and he il a e con aining
he eac ion p oduc s was subjec ed o GC analysis o de e mine he yield o
benzylamine. The sepa a ed ca alys was washed wi h e hyl ace a e, d ied unde
acuum and used wi hou u he pu i ica ion o eac i a ion o he nex un.
Da a a ailabili y
All da a a e a ailable om he au ho s upon easonable eques .
Recei ed: 31 Ma ch 2021; Accep ed: 10 No embe 2021;
Published online: 30 Decembe 2021
Re e ences
1. Belle , M. & Bolm, C. T ansi ion Me als o O ganic Syn hesis (Wiley-VCH,
2008).
2. Negishi, E.-I. Magical powe o ansi ion me als: pas , p esen , and u u e
(Nobel lec u e). Angew. Chem. In . Ed. 50, 6738–6764 (2011).
3. Hagen, J.Indus ial Ca alysis: A P ac ical App oach (Wiley‐VCH, 2006).
4. Ca low, C. R., Da idson, M., Ha dac e, C. & Hu chings, G. J. Ca alysis
making he wo ld a be e place. Philos. T ans. R. Soc. A 374, 20150089
(2016).
5. Busacca, C. A., Fand ick, D. R., Song, J. J. & Senanayake, C. H. The g owing
impac o ca alysis in he pha maceu ical indus y. Ad . Syn h. Ca al. 353,
1825–1864 (2011).
6. Rylande , P. N.Ca aly ic Hyd ogena ion in O ganic Syn heses (Academic P ess,
1979).
7. Alonso, D. A. e al. in Science o Syn hesis: Wa e in O ganic Syn hesis (ed.
Kobayashi, S.) 95–119 (Thieme, 2012); h ps://doi.o g/10.1055/
sos-SD-206-00075
8. Oge , C., Balas, L., Du and, T. & Galano, J.-M. A e alkyne educ ions
chemo-, egio-, and s e eoselec i e enough o p o ide pu e (Z)-ole ins
in poly unc ionalized bioac i e molecules? Chem. Re . 113, 1313–1350
(2013).
9. Massa o, L., Zheng, J., Ma ga i a, C. & Ande sson, P. G. Enan iocon e gen
and enan iodi e gen ca aly ic hyd ogena ion o isome ic ole ins. Chem. Soc.
Re . 49, 2504–2522 (2020).
10. Chi ik, P. J. I on- and cobal -ca alyzed alkene hyd ogena ion: ca alysis
wi h bo h edox-ac i e and s ong ield ligands. Acc. Chem. Res. 48,
1687–1695 (2015).
11. Magano, J. & Dune z, J. R. La ge-scale ca bonyl educ ions in he
pha maceu ical indus y. O g. P ocess Res. De . 16, 1156–1184 (2012).
12. Zhong, R., Wie, Z., Zhang, W., Liu, S. & Liu, Q. A p ac ical and
s e eoselec i e in si u NHC-cobal ca aly ic sys em o hyd ogena ion o
ke ones and aldehydes. Chem 5, 1552–1566 (2019).
13. Fo men i, D., Fe e i, F., Scha nagl, F. K. & Belle , M. Reduc ion
o ni o compounds using 3d-non-noble me al ca alys s. Chem. Re . 119,
2611–2680 (2019).
14. Jagadeesh, R. V. e al. Nanoscale Fe2O3-based ca alys s o selec i e
hyd ogena ion o ni oa enes o anilines. Science 342, 1073–1076 (2013).
15. Wiesen eld , M. P., Nai oukh, Z., Dal on, T. & Glo ius, F. Selec i e a ene
hyd ogena ion o di ec access o sa u a ed ca bo- and he e ocycles. Angew.
Chem. In . Ed. 58, 10460–10476 (2019).
16. Mu ugesan, K. e al. Cobal -nanopa icles ca alyzed e icien and selec i e
hyd ogena ion o a oma ic hyd oca bons. ACS Ca al. 9, 8581–8591 (2019).
17. Sahoo, B. e al. A obus i on ca alys o he selec i e hyd ogena ion o
subs i u ed (iso)quinolones. Chem. Sci. 9, 8134–8141 (2018).
18. Law ence, S. A. Amines: Syn hesis, P ope ies and Applica ions (Camb idge
Uni . P ess, 2004).
19. Ricci, A. Amino G oup Chemis y: F om Syn hesis o he Li e Sciences
(Wiley-VCH, 2008).
20. Qu eshi, M. H. Top 200 Pha maceu icals by Re ails Sales in 2020 (Uni e si y
o A izona, 2020); h ps://nja da son.lab.a izona.edu/si es/nja da son.lab.
a izona.edu/ iles/Top%20200%20Pha maceu icals%20By%20Re ail%20
Sales%202020V3.pd
21. Mu ugesan, K. e al. Ca aly ic educ i e amina ions using molecula
hyd ogen o syn hesis o di e en kinds o amines. Chem. Soc. Re . 49,
6273–6328 (2020).
22. Hahn, G., Kunnas, P., de Jonge, N. & Kempe, R. Gene al syn hesis o p ima y
amines ia educ i e amina ion employing a eusable nickel ca alys . Na .
Ca al. 2, 71–77 (2019).
23. Saba ie , P. & Sende ens, J. B. Applica ion aux ni iles de la me hode
d’hyd ogena ion di ec e pa ca alyse: syn hese d’amines p imai es, secondai es
e e iai es. C. R. Hebd. Séances Acad. Sci. 140, 482–484 (1905).
24. Paal, C. & Ge um, J. Übe ka aly ische Wi kungen kolloidale Me alle de
Pla ing uppe. VI. Reduk ionska alysen mi kolloidalem Palladium. Be . D sch.
Chem. Ges. 42, 1553–1560 (1909).
25. B aun, V. J., Blessing, G. & Zobel, F. Ka aly ische hyd ie ungen un e D uck
bei Gegenwa on nickelsalzen. VI.: ni ile. Be . D sch. Chem. Ges. A 56,
1988–2001 (1923).
26. Raney, M. Me hod o p epa ing ca aly ic ma e ial. US pa en 1563587A
(1925).
27. Ca o he s, W. H. & Jones, G. A. The p epa a ion o some p ima y amines by
he ca aly ic educ ion o ni iles. J. Am. Chem. Soc. 47, 3051–3057 (1925).
28. Alle , B. V. Raney cobal hyd ogena ion ca alys s. I. The p epa a ion o he
ca alys . J. Appl. Chem. 7, 130–134 (2007).
29. Ad kins, H. Reac ions o Hyd ogen wi h O ganic Compounds O e
Coppe -Ch omium Oxide and Nickel Ca alys s 53 (Uni . Wisconsin P ess,
1937).
30. F ei elde , M. A low p essu e p ocess o he educ ion o ni iles. Use o
hodium ca alys . J. Am. Chem. Soc. 82, 2386–2389 (1960).
31. F eidlin, L. K. & Sladko a, T. A. Ca aly ic educ ion o dini iles. Russ. Chem.
Re . 33, 319–330 (1964).
32. Ba ne , C. Hyd ogena ion o alipha ic ni iles o e ansi ion me al bo ides.
Ind. Eng. Chem. P od. Res. De . 8, 145–149 (1969).
33. de Belle on, C. & Fouilloux, P. Homogeneous and he e ogeneous
hyd ogena ion o ni iles in a liquid phase: chemical, mechanis ic, and
ca aly ic aspec s. Ca al. Re . 36, 459–506 (1994).
34. López-De Jesús, Y. M., Johnson, C. E., Monnie , J. R. & Williams, C. T.
Selec i e hyd ogena ion o benzoni ile by alumina-suppo ed I –Pd ca alys s.
Top. Ca al. 53, 1132–1137 (2010).
35. Lé ay, K. & Hegedűs, L. Recen achie emen s in he hyd ogena ion o ni iles
ca alyzed by ansi ional me als. Cu . O g. Chem. 23, 1881–1900 (2019).
36. Yoshimu a, M. e al. Selec i e syn hesis o p ima y amines om ni iles
unde hyd ogena ion condi ions. Ad . Syn h. Ca al. 360, 1726–1732 (2018).
37. Liu, Y. e al. Mild palladium-ca alysed highly e icien hyd ogena ion o C≡N,
C–NO2, and C=O bonds using H2 o 1 a m in H2O. G een Chem. 21, 830–838
(2019).
38. Wang, H. e al. Quasi Pd1Ni single-a om su ace alloy ca alys enables
hyd ogena ion o ni iles o seconda y amines. Na . Commun. 10, 4998
(2019).
39. Ryabchuk, P. e al. In e me allic nickel silicide nanoca alys —a non-noble
me al–based gene al hyd ogena ion ca alys . Sci. Ad . 4, eaa 0761 (2018).
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