Formal arylation of NH3 to produce diphenylamines over supported Pd catalysts

Article abstract of DOI:10.1039/c7cc06737b

In the presence of supported Pd nanoparticle catalysts, e.g., Pd/Al₂O₃, various diphenylamines could be synthesized through acceptorless formal arylation using NH₃ or its surrogates, e.g., urea, as nitrogen sources and cyclohexanones as arylation sources. The observed catalysis was truly heterogeneous, and the catalyst was reusable with retention of its high catalytic performance.

Full text of DOI:10.1039/c7cc06737b

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January 2016 Pages 1–216
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COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
N@C2n (2n
=
68 and 80). Synthesis of the
3
N@D5h-C80
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Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ
View Article Online
DOI: 10.1039/C7CC06737B
Journal Namꢀ
COMMUNICATIONꢀ
Formal arylation of NH
supportꢀd Pd catalysts†
3
to producꢀ diphꢀnylaminꢀs ovꢀr
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
a
a
b
a
b
YuꢀKoizumi, ꢀKentoꢀTaniguchi, ꢀXiongjieꢀJin,* ꢀKazuyaꢀYamaguchi,* ꢀKyokoꢀNozaki ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
andꢀNoritakaꢀMizuno*
DOI:ꢀ10.1039/x0xx00000xꢀ
www.rsc.org/
In thꢀ prꢀsꢀncꢀ of supportꢀd Pd nanoparticlꢀs catalysts, e.g., Pd/Al
various diphꢀnylaminꢀs could bꢀ synthꢀsizꢀd through accꢀptorlꢀss
formal arylation using NH or its surrogatꢀs, e.g., urꢀa, as thꢀ
2
O
3
,
ꢀ
X
(
X = NH
2
or OH)
NH2
(
a)
ꢀ
H
N
NO
2
[
O]
H2
3
ꢀ
NH3
HNO3
nitrogꢀn sourcꢀs and cyclohꢀxanonꢀs as thꢀ arylation sourcꢀs. Thꢀ
obsꢀrvꢀd catalysis was truly hꢀtꢀrogꢀnꢀous, and thꢀ catalyst was
rꢀusablꢀ with rꢀtꢀntion of its high catalytic pꢀrformancꢀ.
ꢀ
ꢀ
(
b)
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
OH
+
O
H2
[O]
H
N
Dehydrogenativeꢀ aromatizationꢀ hasꢀ recentlyꢀ emergedꢀ asꢀ aꢀ newꢀ
greenꢀ protocolꢀ toꢀ synthesizeꢀ functionalizedꢀ arenesꢀ fromꢀ six-
NH3
recycling
H2
1
memberedꢀ carbocyclicꢀ compounds. ꢀ Inꢀ theꢀ pastꢀ fewꢀ years,ꢀ manyꢀ
syntheticallyꢀ usefulꢀ catalyticꢀ reactionsꢀ haveꢀ beenꢀ reported,ꢀ whichꢀ Fig. 1ꢀSynthesisꢀofꢀdiphenylamineꢀfromꢀNH
3
ꢀandꢀbenzene.ꢀ(a)ꢀAꢀtraditionalꢀ
2
3
4
industrialꢀprocessꢀandꢀ(b)ꢀaꢀnewꢀgreenꢀprocessꢀthroughꢀformalꢀarylation.ꢀ
canꢀeffectivelyꢀaccessꢀphenols, ꢀarylꢀethers, ꢀN-substitutedꢀanilines, ꢀ
5
6
biaryls, ꢀandꢀheterocycles. ꢀTypically,ꢀmostꢀofꢀtheseꢀreactionsꢀutilizeꢀ
cyclohexanonesꢀ orꢀ cyclohexenonesꢀ asꢀ theꢀ arylationꢀ sources,ꢀ andꢀ oxidationꢀ toꢀ HNO
3
ꢀ isꢀ highlyꢀ desirableꢀ becauseꢀ ofꢀ theꢀ highꢀ atomꢀ
3
requireꢀ stoichiometricꢀ amountsꢀ ofꢀ hydrogenꢀ acceptors.ꢀ Althoughꢀ economicꢀ natureꢀ andꢀ theꢀ easyꢀ availabilityꢀ ofꢀ NH ꢀ (annuallyꢀ
8
acceptorlessꢀdehydrogenativeꢀaromatizationꢀwithꢀtheꢀliberationꢀofꢀ producedꢀca.ꢀ140ꢀmillionꢀtons ꢀbyꢀtheꢀwell-establishedꢀHaber–Boschꢀ
H
2
ꢀisꢀmoreꢀdesirable,ꢀtoꢀdateꢀthereꢀhaveꢀbeenꢀjustꢀaꢀfewꢀreportsꢀonꢀ process).ꢀ Inꢀ thisꢀ context,ꢀ theꢀ directꢀ arylationꢀ ofꢀ NH
theꢀ developmentꢀ ofꢀ catalyticꢀ acceptorlessꢀ dehydrogenativeꢀ cyclohexanoneꢀ wouldꢀ provideꢀ anotherꢀ promisingꢀ processꢀ forꢀ
aromatizationꢀsystems.2d,f,4h
productionꢀ ofꢀ diphenylamineꢀ becauseꢀ cyclohexanoneꢀ isꢀ aꢀ readilyꢀ
Diphenylamineꢀ andꢀ itsꢀ derivativesꢀ areꢀ anꢀ importantꢀ classꢀ ofꢀ availableꢀ industrialꢀ chemicalꢀ throughꢀ aꢀ well-establishedꢀ two-stepꢀ
chemicals,ꢀ whichꢀ haveꢀ widelyꢀ beenꢀ utilizedꢀ asꢀ pharmaceuticals,ꢀ processꢀ startingꢀ fromꢀ benzeneꢀ (Fig.ꢀ1b).ꢀ Therefore,ꢀ theꢀ
3
ꢀ withꢀ
ꢀ
ꢀ
3
agrochemicals,ꢀ dyes,ꢀ radical-trappingꢀ antioxidants,ꢀ andꢀ electronicꢀ developmentꢀofꢀefficientꢀcatalyticꢀsystemsꢀforꢀtheꢀarylationꢀofꢀNH ꢀ
7
materials. ꢀCurrently,ꢀdiphenylamineꢀisꢀmainlyꢀmanufacturedꢀbyꢀanꢀ withꢀ cyclohexanoneꢀ throughꢀ acceptorlessꢀ dehydrogenativeꢀ
onerousꢀ multi-stepꢀ processꢀ startingꢀ fromꢀ NH
involvingꢀ theꢀ Ostwaldꢀ processꢀ (three-stepꢀ oxidationꢀ ofꢀ NH
HNO ),ꢀtheꢀnitrationꢀofꢀbenzeneꢀtoꢀnitrobenzene,ꢀtheꢀreductionꢀofꢀ thisꢀprocess,ꢀH
nitrobenzeneꢀ toꢀ aniline,ꢀ andꢀ theꢀ deaminationꢀ ofꢀ anilineꢀ orꢀ theꢀ forꢀtheꢀbenzeneꢀhydrogenationꢀstep.ꢀ
3
ꢀ andꢀ benzene;ꢀ aromatizationꢀwouldꢀallowꢀaꢀnewꢀgreenꢀprocessꢀforꢀproductionꢀofꢀ
ꢀ toꢀ diphenylamineꢀstartingꢀformallyꢀfromꢀNH ꢀandꢀbenzeneꢀ(Fig.ꢀ1b).ꢀInꢀ
ꢀproducedꢀduringꢀtheꢀarylationꢀstepꢀcanꢀbeꢀrecycledꢀ
3
3
3
2
condensationꢀ ofꢀ anilineꢀ withꢀ phenolꢀ toꢀ produceꢀ diphenylamineꢀ
ꢀ
Quiteꢀ recently,ꢀ weꢀ successfullyꢀ developedꢀ severalꢀ catalyticꢀ
7
(
Fig.ꢀ1a). ꢀ Forꢀ productionꢀ ofꢀ nitrogen-containingꢀ compounds,ꢀ theꢀ acceptorlessꢀdehydrogenativeꢀaromatizationꢀreactionsꢀforꢀsynthesisꢀ
2
f
developmentꢀofꢀnewꢀcatalyticꢀprocessesꢀthatꢀcanꢀdirectlyꢀutilizeꢀNH
3
ꢀ
ofꢀ (i)ꢀ phenolsꢀ fromꢀ cyclohexanols/cyclohexanones, ꢀ (ii)ꢀ anilinesꢀ
2
f
(
orꢀitsꢀsurrogates)ꢀasꢀtheꢀnucleophilicꢀnitrogenꢀsourceꢀavoidingꢀitsꢀ fromꢀ cyclohexylamines, ꢀ andꢀ (iii)ꢀ diarylaminesꢀ fromꢀ variousꢀ
4
h
combinationsꢀ ofꢀ six-memberedꢀ carbocyclicꢀ compounds. ꢀ Asꢀ aꢀ
continuationꢀ ofꢀ ourꢀ interestꢀ inꢀ theꢀ developmentꢀ ofꢀ catalyticꢀ
acceptorlessꢀdehydrogenation,ꢀhereinꢀweꢀreport,ꢀforꢀtheꢀfirstꢀtime,ꢀ
a
Department of Applied Chemistry, School of Engineering,
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp; kyama@appchem.t.u-tokyo.ac.jp;
t-jin@mail.ecc.u-tokyo.ac.jp; Fax: +81-3-5841-7220
Department of Chemistry and Biotechnology, School of Engineering,
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
3
heterogeneouslyꢀPd-catalyzedꢀ“formal arylation of NH ”ꢀtoꢀproduceꢀ
diphenylamineꢀ andꢀ itsꢀ derivativesꢀ byꢀ meansꢀ ofꢀ dehydrogenativeꢀ
aromatizationꢀstrategy.ꢀTheꢀpresentꢀformalꢀarylationꢀutilizesꢀvariousꢀ
b
cyclohexanonesꢀasꢀtheꢀarylationꢀsourcesꢀandꢀNH ꢀorꢀitsꢀsurrogates,ꢀ
3
†ꢀElectronicꢀSupplementaryꢀInformationꢀ(ESI)ꢀavailable:ꢀExperimentalꢀdetails,ꢀdata
e.g.,ꢀurea,ꢀasꢀtheꢀnitrogenꢀsourcesꢀforꢀconstructionꢀofꢀareneꢀringsꢀ
ofꢀ diphenlylamineꢀ products,ꢀ TablesꢀS1–S5,ꢀ andꢀ Figs.ꢀS1–S6.ꢀ See
DOI:ꢀ10.1039/x0xx00000xꢀ
2
andꢀC–NꢀbondsꢀwithꢀtheꢀliberationꢀofꢀH .ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xx
J. Name.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Pleaseꢀd
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o
h
ꢀn
e
o
m
tꢀ
C
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us
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tꢀmarginsꢀ
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COMMUNICATIONꢀ
Journal Namꢀꢀ
Tablꢀ 1 Effectsꢀ ofꢀ catalystsꢀ andꢀ nitrogenꢀ sourcesꢀ onꢀ theꢀ formalꢀ arylationꢀ
(
Tableꢀ1,ꢀentryꢀ2).ꢀInꢀcontrast,ꢀwhenꢀtheꢀarylationꢀwaViseꢀwcAarrtricileedOꢀnoliunetꢀ
a
usingꢀ1a
ꢀ
DOI: 10.1039/C7CC06737B
withꢀsupportedꢀPdꢀcatalystsꢀpreparedꢀusingꢀbasicꢀsupports,ꢀsuchꢀasꢀ
ꢀ
O
2
Pd/CeO ꢀandꢀPd/LDHꢀ(LDHꢀ=ꢀMg‒Alꢀlayeredꢀdoubleꢀhydroxide),ꢀ 5aꢀ
Nitrogen
catalyst
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
+
ꢀ
source
wasꢀ formedꢀ asꢀ theꢀ majorꢀ productꢀ (Tableꢀ1,ꢀ entriesꢀ6ꢀandꢀ7).ꢀ Thisꢀ
phenolꢀformationꢀwasꢀconsistentꢀwithꢀourꢀpreviousꢀresultꢀwhereꢀtheꢀ
basicꢀnatureꢀofꢀcatalystsꢀplaysꢀaꢀcrucialꢀroleꢀforꢀtheꢀdehydrogenationꢀ
1a
H
N
H
N
NH2
OH
ofꢀ1aꢀtoꢀ5aꢀthroughꢀpromotingꢀtheꢀdeprotonativeꢀcoordinationꢀofꢀ1aꢀ
toꢀ theꢀ activeꢀ Pdꢀ center.2e,fꢀ Anotherꢀ possibleꢀ explanationꢀ forꢀ theꢀ
2
a
3a
4a
Yieldꢀ(%)ꢀ
5a
Nitrogenꢀ
sourceꢀ
Entryꢀ Catalystꢀ
phenolꢀformationꢀisꢀthatꢀtheꢀbasicꢀnatureꢀofꢀtheꢀcatalystsꢀinhibitsꢀ
ꢀ
ꢀ
2a
3a
3ꢀ
4a
2ꢀ
5a
5ꢀ
theꢀcondensationꢀofꢀNH
thatꢀ theꢀ useꢀ ofꢀ basicꢀ supportsꢀ isꢀ notꢀ suitableꢀ toꢀ produceꢀ
diphenylamines.ꢀRh/Al ꢀgaveꢀ2aꢀandꢀ3aꢀinꢀ16%ꢀandꢀ44%ꢀyields,ꢀ
respectivelyꢀ (Tableꢀ1,ꢀ entryꢀ8).ꢀ Otherꢀ supportedꢀ metalꢀ catalysts,ꢀ
suchꢀ asꢀ Cu/Al ,ꢀ Ru/Al ,ꢀ Pt/Al ,ꢀ andꢀ Au/Al ,ꢀ wereꢀ
completelyꢀinactiveꢀforꢀtheꢀpresentꢀarylationꢀ(Tableꢀ1,ꢀentriesꢀ9‒12).ꢀ
3
ꢀandꢀ1a.ꢀForꢀtheseꢀreasons,ꢀweꢀconcludedꢀ
1
2b
ꢀ
Pd/Al
2
2
O
O
3
ꢀ
ꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
Ureaꢀ
HCOONH
87ꢀ
69ꢀ
81ꢀ
77ꢀ
69ꢀ
12ꢀ
2ꢀ
ꢀ
Pd/Al
3
4ꢀ
8ꢀ
6ꢀ
2 3
O
3
4
5
6
7
8
9
1
1
1
1
1
1
1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Pd/TiO
2
ꢀ
12ꢀ
1ꢀ
3ꢀ
2ꢀ
Pd/Cꢀ
11ꢀ
6ꢀ
1ꢀ
2
O
3
2
O
3
2
O
3
2 3
O
Pd/ZrO
2
ꢀ
21ꢀ
11ꢀ
<1ꢀ
44ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
3ꢀ
1ꢀ
Pd/CeO
2
ꢀ
9ꢀ
51ꢀ
75ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
21ꢀ
5ꢀ
ꢀ
Besidesꢀ urea,ꢀ variousꢀ NH
COONH ,ꢀ andꢀ (NH CO ,ꢀ couldꢀ beꢀ utilizedꢀ asꢀ theꢀ nitrogenꢀ
-catalyzedꢀ arylationꢀ withꢀ 1a,ꢀ
therebyꢀ givingꢀ 2aꢀ inꢀ yieldsꢀ ofꢀ 72%,ꢀ 63%,ꢀ andꢀ 48%,ꢀ respectivelyꢀ
Tableꢀ1,ꢀentriesꢀ13‒15).ꢀItꢀshouldꢀbeꢀnotedꢀthatꢀaqueousꢀNH ꢀ(28%ꢀ
solution)ꢀ couldꢀ beꢀ directlyꢀ utilizedꢀ forꢀ theꢀ arylation;ꢀ whenꢀ theꢀ
reactionꢀ wasꢀ performedꢀ withꢀ aqueousꢀ NH ,ꢀ theꢀ desiredꢀ 2aꢀ wasꢀ
3 4
ꢀ surrogates,ꢀ suchꢀ asꢀ HCOONH ,ꢀ
Pd/LDHꢀ
4ꢀ
CH
3
4
4
)
2
3
Rh/Al
Cu/Al
Ru/Al
2
O
2
O
2
O
3
3
3
ꢀ
ꢀ
ꢀ
16ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
72ꢀ
63ꢀ
48ꢀ
46ꢀ
1ꢀ
2 3
sourcesꢀ forꢀ theꢀ presentꢀ Pd/Al O
<1ꢀ
<1ꢀ
<1ꢀ
<1ꢀ
1ꢀ
0ꢀ
1ꢀ
2ꢀ
3ꢀ
4ꢀ
5ꢀ
6ꢀ
(
3
2 3
Pt/Al O ꢀ
Au/Al
2
O
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
Pd/Al
Pd/Al
Pd/Al
Pd/Al
2
2
2
2
O
O
O
O
3
3
3
3
4
ꢀ
obtainedꢀinꢀ46%ꢀyieldꢀ(Tableꢀ1,ꢀentryꢀ16).ꢀTheꢀeffectꢀofꢀsolventsꢀonꢀ
theꢀ arylationꢀ wasꢀ notꢀ soꢀ significant.ꢀ Amongꢀ solventsꢀ examined,ꢀ
diglymeꢀ wasꢀ theꢀ bestꢀ solventꢀ (TableꢀS1,ꢀ entryꢀ1,ꢀ ESI†).ꢀ Also,ꢀ
mesitylene,ꢀ N,N-dimethylacetamideꢀ (DMA),ꢀ N-methylpyrrolidoneꢀ
CH
(NH
28%ꢀaq.ꢀNH
3
COONH
4
ꢀ
20ꢀ
2ꢀ
3ꢀ
4
) CO
2 3
ꢀ
<1ꢀ
<1ꢀ
43ꢀ
51ꢀ
3
ꢀ
1ꢀ
a
Reactionꢀconditions:ꢀCatalystꢀ(Metal:ꢀ1.6ꢀmol%),ꢀnitrogenꢀsourceꢀ(amountꢀ
(NMP),ꢀ andꢀ n-decaneꢀ gaveꢀ moderateꢀ yieldsꢀ ofꢀ 2aꢀ (TableꢀS1,ꢀ
○
ofꢀnitrogen:ꢀ1ꢀmmol),ꢀ1aꢀ(1ꢀmmol),ꢀdiglymeꢀ(2ꢀmL),ꢀArꢀ(1ꢀatm),ꢀ150ꢀ C,ꢀ24ꢀh.ꢀ
entriesꢀ2‒5,ꢀESI†).ꢀTheꢀyieldꢀofꢀ2aꢀincreasedꢀwithꢀanꢀincreaseꢀinꢀtheꢀ
Whenꢀusingꢀureaꢀasꢀtheꢀnitrogenꢀsource,ꢀwaterꢀ(10ꢀμL)ꢀwasꢀalsoꢀaddedꢀtoꢀ
○
reactionꢀ temperatureꢀ (bathꢀ temperature)ꢀ upꢀ toꢀ 150ꢀ Cꢀ (TableꢀS2,ꢀ
theꢀreactionꢀmixture.ꢀYieldsꢀ(basedꢀonꢀ1a)ꢀwereꢀdeterminedꢀbyꢀGCꢀusingꢀ
b
biphenylꢀasꢀtheꢀinternalꢀstandard.ꢀ ꢀTheꢀreactionꢀwasꢀperformedꢀunderꢀO
atmosphereꢀ(1ꢀatm).ꢀ
2
ꢀ
ESI†).ꢀTheꢀeଏectꢀofꢀtheꢀamountꢀofꢀureaꢀonꢀtheꢀarylaꢁonꢀwithꢀ1aꢀisꢀ
summarizedꢀinꢀTableꢀS3ꢀ(ESI†).ꢀ
ꢀ
ꢀ
2 3
Toꢀ verifyꢀ whetherꢀ theꢀ observedꢀ catalysisꢀ withꢀ Pd/Al O ꢀ wasꢀ
ꢀ
Inꢀ ourꢀ previousꢀ studies,ꢀ weꢀ haveꢀ foundꢀ thatꢀ onlyꢀ Pd-basedꢀ trulyꢀheterogeneousꢀorꢀnot,ꢀtheꢀfollowingꢀcontrolꢀexperimentsꢀwereꢀ
catalystsꢀ exhibitedꢀ highꢀ performanceꢀ forꢀ severalꢀ dehydrogenativeꢀ conducted.ꢀTheꢀarylationꢀusingꢀureaꢀandꢀ1aꢀtoꢀproduceꢀ2aꢀwasꢀcarriedꢀ
aromatizationꢀreactions.2e,f,4f‒hꢀTherefore,ꢀtoꢀbeginꢀwith,ꢀweꢀcarriedꢀ outꢀunderꢀtheꢀconditionsꢀdescribedꢀinꢀFig.ꢀS1ꢀ(ESI†),ꢀandꢀafterꢀ5ꢀh,ꢀ
3
2 3
outꢀtheꢀformalꢀarylationꢀutilizingꢀanꢀeasilyꢀhandledꢀNH ꢀsurrogateꢀofꢀ Pd/Al O ꢀwasꢀremovedꢀfromꢀtheꢀreactionꢀmixtureꢀbyꢀhotꢀfiltration.ꢀ
ureaꢀasꢀtheꢀnitrogenꢀsourceꢀandꢀcyclohexanoneꢀ(1a)ꢀasꢀtheꢀarylationꢀ Then,ꢀureaꢀ(0.5ꢀmmol)ꢀandꢀwaterꢀ(10ꢀμL)ꢀwereꢀnewlyꢀaddedꢀtoꢀtheꢀ
○
sourceꢀtoꢀproduceꢀdiphenylamineꢀ(2a)ꢀinꢀtheꢀpresenceꢀofꢀvariousꢀPdꢀ filtrate,ꢀandꢀtheꢀresultingꢀmixtureꢀwasꢀagainꢀheatedꢀatꢀ150ꢀ C.ꢀInꢀthisꢀ
○
catalysts.ꢀ Theꢀ reactionsꢀ wereꢀ typicallyꢀ performedꢀ atꢀ 150ꢀ Cꢀ inꢀ case,ꢀnoꢀfurtherꢀproductionꢀofꢀ2aꢀandꢀnoꢀfurtherꢀconsumptionꢀofꢀ3aꢀ
diethyleneꢀ glycolꢀ dimethylꢀ etherꢀ (diglyme)ꢀ underꢀ acceptorlessꢀ wereꢀ observed,ꢀ asꢀ shownꢀ inꢀ Fig.ꢀS1ꢀ (ESI†).ꢀ Inꢀ addiꢁon,ꢀ itꢀ wasꢀ
conditionsꢀ (Arꢀ atmosphere)ꢀ describedꢀ inꢀ Tableꢀ1.ꢀ Underꢀ theseꢀ confirmedꢀ byꢀ theꢀ inductivelyꢀ coupledꢀ plasmaꢀ atomicꢀ emissionꢀ
conditions,ꢀ weꢀ confirmedꢀ thatꢀ 2aꢀ wasꢀ notꢀ producedꢀ atꢀ allꢀ inꢀ theꢀ spectroscopyꢀ (ICP-AES)ꢀ analysisꢀ thatꢀ Pdꢀ speciesꢀ wereꢀ hardlyꢀ
presenceꢀofꢀjustꢀAl
usingꢀsimpleꢀPdꢀsaltsꢀandꢀcomplexes,ꢀsuchꢀasꢀPdCl
acetate),ꢀPd(acac) ꢀ(acacꢀ=ꢀacetylacetonate),ꢀandꢀPd(PPh
failedꢀbecauseꢀofꢀtheꢀimmediateꢀformationꢀofꢀPdꢀblackꢀjustꢀafterꢀtheꢀ withꢀPd/Al O ꢀwasꢀundoubtedlyꢀheterogeneousꢀinꢀnature.
2
O
3
ꢀorꢀinꢀtheꢀabsenceꢀofꢀcatalysts.ꢀTheꢀarylationꢀ detectedꢀinꢀtheꢀfiltratesꢀafterꢀtheꢀcatalystꢀremovalꢀatꢀ5ꢀhꢀandꢀ24ꢀh,ꢀ
,ꢀPd(OAc) ꢀ(OAcꢀ=ꢀ respectivelyꢀ(belowꢀtheꢀinstrumentalꢀdetectionꢀlimit:ꢀ<0.06%).ꢀTheꢀ
Cl ꢀwereꢀ aforementionedꢀresultsꢀclearlyꢀindicateꢀthatꢀtheꢀobservedꢀcatalysisꢀ
2
2
2
3
)
2
2
1
0ꢀ
2
3
ꢀ
reactionsꢀ wereꢀ startedꢀ byꢀ heating.ꢀ Fortunately,ꢀ theꢀ arylationꢀ
efficientlyꢀproceededꢀtoꢀaffordꢀtheꢀdesiredꢀ2aꢀasꢀtheꢀmajorꢀproductꢀ retrievedꢀ fromꢀ theꢀ reactionꢀ mixtureꢀ byꢀ simpleꢀ filtration,ꢀ withꢀ
69‒87%ꢀ yields)ꢀ inꢀ theꢀ presenceꢀ ofꢀ severalꢀ supportedꢀ Pdꢀ greaterꢀ thanꢀ 85%ꢀ recovery.ꢀ Weꢀ performedꢀ repeatedꢀ reuseꢀ
nanoparticlesꢀ catalysts,ꢀ suchꢀ asꢀ Pd/Al ,ꢀ Pd/TiO ,ꢀ Pd/C,ꢀ andꢀ experimentsꢀ forꢀ theꢀ arylationꢀ usingꢀ ureaꢀ andꢀ 1aꢀ toꢀ produceꢀ 2aꢀ
Pd/ZrO ꢀ(Tableꢀ1,ꢀentriesꢀ1‒5);ꢀamongꢀthem,ꢀPd/Al ꢀwasꢀtheꢀbestꢀ underꢀtheꢀstandardꢀreactionꢀconditionsꢀusingꢀtheꢀretrievedꢀPd/Al O ꢀ
2 3
Afterꢀ theꢀ reactionꢀ wasꢀ completed,ꢀ Pd/Al O ꢀ couldꢀ easilyꢀ beꢀ
(
2
O
3
2
2
2 3
O
2
3
catalystꢀ andꢀgaveꢀ 2aꢀ inꢀ 87%ꢀ yieldꢀ togetherꢀ withꢀ theꢀ formationꢀ ofꢀ catalyst.ꢀ Theꢀ transmissionꢀ electronꢀ microscopyꢀ (TEM)ꢀ analysisꢀ
smallꢀ amountsꢀ ofꢀ side-products,ꢀ suchꢀ asꢀ N-cyclohexylanilineꢀ (3a),ꢀ confirmedꢀ thatꢀ theꢀ averageꢀ particleꢀ sizeꢀ ofꢀ Pdꢀ nanoparticlesꢀ
anilineꢀ (4a),ꢀ andꢀ phenolꢀ (5a),ꢀ underꢀ theꢀ conditionsꢀ describedꢀ inꢀ graduallyꢀ increasedꢀ duringꢀ theꢀ repeatedꢀ reuseꢀ experiments;ꢀ theꢀ
9
Tableꢀ1. ꢀInꢀtheꢀpresenceꢀofꢀPd/Al
2
O
3
,ꢀtheꢀreactionꢀalsoꢀefficientlyꢀ averageꢀparticleꢀsizeꢀinꢀtheꢀfreshlyꢀpreparedꢀPd/Al O ꢀcatalystꢀwasꢀ
2
3
proceededꢀ evenꢀ underꢀ aerobicꢀ conditionsꢀ thoughꢀ theꢀ yieldꢀ ofꢀ 2aꢀ 2.7ꢀnmꢀandꢀincreasedꢀupꢀtoꢀ3.5ꢀnmꢀafterꢀtheꢀfifthꢀreuseꢀexperimentꢀ
wasꢀ somewhatꢀ lowerꢀ thanꢀ thatꢀ underꢀ acceptorlessꢀ conditionsꢀ (Fig.ꢀS2,ꢀESI†).ꢀAlthoughꢀtheꢀgradualꢀincreaseꢀinꢀtheꢀparꢁcleꢀsizeꢀwasꢀ
2
ꢀ|ꢀJ. Name.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
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Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ
ChemComm
Journal Namꢀ
COMMUNICATION
observed,ꢀPd/Al
2
O
3
ꢀcouldꢀbeꢀreusedꢀatꢀleastꢀfiveꢀtimesꢀwithꢀkeepingꢀ (1f),ꢀtheꢀproductꢀdistributionꢀwasꢀsimilarꢀtoꢀthatꢀusinVgieꢀw1bAꢀrt(iTclaebOlneliꢀn2e,ꢀ
DOI: 10.1039/C7CC06737B
itsꢀ highꢀ catalyticꢀ performance;ꢀ 87%ꢀ yieldꢀ ofꢀ 2aꢀ withꢀ theꢀ freshꢀ entryꢀ6).ꢀInꢀtheꢀcaseꢀofꢀaꢀmoreꢀstericallyꢀcrowdedꢀsubstrateꢀ(1g),ꢀtheꢀ
catalyst,ꢀ89%ꢀyieldꢀforꢀtheꢀ1stꢀreuse,ꢀ90%ꢀyieldꢀforꢀtheꢀ2ndꢀreuse,ꢀ correspondingꢀprimaryꢀanilineꢀwasꢀselectivelyꢀobtainedꢀwithoutꢀtheꢀ
9
0%ꢀyieldꢀforꢀtheꢀ3rdꢀreuse,ꢀ87%ꢀyieldꢀforꢀtheꢀ4thꢀreuse,ꢀandꢀ88%ꢀ formationꢀ ofꢀ theꢀ correspondingꢀ diphenylamineꢀ (Tableꢀ2,ꢀ entryꢀ7).ꢀ
yieldꢀforꢀtheꢀ5thꢀreuseꢀ(Fig.ꢀS3,ꢀESI†).ꢀ
Cyclohexanonesꢀpossessingꢀanꢀetherꢀ(1hꢀandꢀ1i)ꢀorꢀanꢀesterꢀgroupꢀ
(1j)ꢀcouldꢀalsoꢀactꢀasꢀtheꢀarylationꢀsourcesꢀ(Tableꢀ2,ꢀentriesꢀ8‒10).ꢀInꢀ
ꢀ
ꢀ
theꢀcaseꢀofꢀ3-trifluoromethylcyclohexanoneꢀ(1k),ꢀtheꢀmajorꢀproductꢀ
Tablꢀ 2 Substrateꢀ scopeꢀ forꢀ theꢀ Pd/Al
2 3
O -catalyzedꢀ formalꢀ arylationꢀ usingꢀ wasꢀ theꢀ correspondingꢀ N-cyclohexylaniline,ꢀ whichꢀ isꢀ likelyꢀ dueꢀ toꢀ
a
ureaꢀandꢀvariousꢀcyclohexanones
ꢀ
theꢀ slowꢀ amineꢀ dehydrogenationꢀ (Tableꢀ2,ꢀ entryꢀ11).ꢀ Aꢀ substrateꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
O
possessingꢀ tert-butyldimethylsilylꢀ (TBS)ꢀ groupꢀ alsoꢀ yieldedꢀ theꢀ
Pd/Al O
2
3
Urea
+
R
correspondingꢀ diphenylamine,ꢀ andꢀ theꢀ TBSꢀ deprotectionꢀ hardlyꢀ
1
proceededꢀ duringꢀ theꢀ reactionꢀ (Tableꢀ2,ꢀ entryꢀ12).ꢀ Notably,ꢀ aꢀ 1:1ꢀ
H
N
H
N
NH2
mixtureꢀ ofꢀ cyclohexanolꢀ andꢀ 1aꢀ (K/Aꢀ oil)ꢀ couldꢀ beꢀ utilizedꢀ asꢀ theꢀ
R
R
R
R
R
startingꢀmaterial;ꢀwhenꢀtheꢀreactionꢀwasꢀcarriedꢀoutꢀinꢀtheꢀpresenceꢀ
ofꢀPd‒Fe/Al O
2 3
,11ꢀ2aꢀwasꢀobtainedꢀinꢀ80%ꢀyieldꢀ(Fig.ꢀ2).ꢀ
2
3
4
O
O
O
O
O
ꢀ
ꢀ
H
N
1a
1b
1c
1d
1ꢀ
OH
+
O
tBu
Pd−Fe/Al2O
3
ꢀ
ꢀ
Urea
+
O
O
O
O
1a
2a
1
g
1
f
1h
OMe
1i
8
0%ꢀyield
O
EtO
ꢀ
O
F3C
O
2 3
Fig. 2 Synthesisꢀ ofꢀ 2aꢀ fromꢀ K/Aꢀ oil.ꢀ Reactionꢀ conditions:ꢀ Pd‒Fe/Al O ꢀ (Pd:ꢀ
EtO
2.5ꢀmol%ꢀ withꢀ respectꢀ toꢀ K/Aꢀ oil),ꢀ ureaꢀ (0.6ꢀmmol),ꢀ waterꢀ (12ꢀμL),ꢀ K/Aꢀ oilꢀ
1
j
1k
1l
○
O
TBSO
(1ꢀmmol),ꢀdiglymeꢀ(2ꢀmL),ꢀArꢀ(1ꢀatm),ꢀ150ꢀ C,ꢀ24ꢀh.ꢀYieldꢀ(basedꢀonꢀK/Aꢀoil)ꢀ
wasꢀdeterminedꢀbyꢀGCꢀusingꢀbiphenylꢀasꢀtheꢀinternalꢀstandard.
ꢀ
ꢀ
Entryꢀ Substrateꢀ
Conv.ꢀ(%)ꢀ
ꢀ
Yieldꢀ(%)ꢀ
ꢀ
ꢀ
2
3
4
ꢀ
Phenolꢀ isꢀ aꢀ readilyꢀ availableꢀ chemicalꢀ producedꢀ byꢀ theꢀ well-
establishedꢀcumeneꢀprocess.ꢀTheꢀsynthesisꢀofꢀdiphenylamineꢀfromꢀ
NH ꢀ andꢀ phenolꢀ isꢀ alsoꢀ aꢀ desirableꢀ andꢀ environmentally-friendlyꢀ
process.ꢀ Herein,ꢀ weꢀ attemptedꢀ toꢀ synthesizeꢀ diphenylamineꢀ fromꢀ
1
2
3
4
5
6
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1a
>99ꢀ
74ꢀ
87(73)ꢀ
24ꢀ
3ꢀ
2ꢀ
1b
1c
1d
1ꢀ
1f
5ꢀ
16ꢀ
2ꢀ
3
>99ꢀ
>99ꢀ
>99ꢀ
83ꢀ
90ꢀ
3ꢀ
84ꢀ
2ꢀ
1ꢀ
1
2
3 4
anꢀ NH ꢀ surrogateꢀ andꢀ phenol. ꢀ Weꢀ choseꢀ HCOONH ꢀ asꢀ theꢀ
66ꢀ
<1ꢀ
9ꢀ
2ꢀ
reductantꢀ (forꢀ phenol)ꢀ andꢀ theꢀ nitrogenꢀ source.ꢀ Afterꢀ severalꢀ
screeningꢀ experimentsꢀ (TableꢀS4,ꢀ ESI†),ꢀ weꢀ foundꢀ theꢀ optimalꢀ
38ꢀ
20ꢀ
37ꢀ
7ꢀ
7b
8c
ꢀ
1g
1h
1i
51ꢀ
<1ꢀ
<1ꢀ
16ꢀ
5ꢀ
2
conditions;ꢀ inꢀ theꢀ presenceꢀ ofꢀ Pd/CeO ,ꢀ theꢀ desiredꢀ 2aꢀ wasꢀ
ꢀ
>99ꢀ
>99ꢀ
>99ꢀ
>99ꢀ
>99ꢀ
61(50)ꢀ
59ꢀ
4
obtainedꢀ inꢀ 73%ꢀ yieldꢀ byꢀ theꢀ reactionꢀ ofꢀ HCOONH ꢀ andꢀ 5aꢀ inꢀ
9
1
1
1
ꢀ
10ꢀ
4ꢀ
mesityleneꢀatꢀ140ꢀºCꢀ(Fig.ꢀ3).ꢀ
ꢀ
c
0 ꢀ
1j
40(30)ꢀ
30ꢀ
5ꢀ
c,d
1 ꢀ
1k
1l
63ꢀ
4ꢀ
2ꢀ
H
N
ꢀ
d
OH
2 ꢀ
57(56)ꢀ
<1ꢀ
ꢀ
ꢀ
ꢀ
Pd/CeO
2
a
HCOONH4
+
2 3
Reactionꢀ conditions:ꢀ Pd/Al O ꢀ (Pd:ꢀ 1.6ꢀmol%ꢀ withꢀ respectꢀ toꢀ 1),ꢀ ureaꢀ
5
a
2a
(
0.5ꢀmmol),ꢀwaterꢀ(10ꢀμL),ꢀcyclohexanoneꢀ1ꢀ(1ꢀmmol),ꢀdiglymeꢀ(2ꢀmL),ꢀ Arꢀ
○
73%ꢀyield
(
1ꢀatm),ꢀ 150ꢀ C,ꢀ 24ꢀh.ꢀ Yieldsꢀ (basedꢀ onꢀ 1)ꢀ wereꢀ determinedꢀ byꢀ GCꢀ usingꢀ
biphenylꢀ asꢀ theꢀ internalꢀ standard.ꢀ Besidesꢀ anilines,ꢀ phenolsꢀ wereꢀ alsoꢀ
formedꢀasꢀtheꢀbyproducts.ꢀValuesꢀinꢀtheꢀparenthesesꢀindicateꢀtheꢀisolatedꢀ
Fig. 3 Synthesisꢀ ofꢀ 2aꢀ throughꢀ theꢀ formalꢀ arylationꢀ usingꢀ HCOONH
phenolꢀ(5a).ꢀReactionꢀconditions:ꢀPd/CeO ꢀ(Pd:ꢀ10ꢀmol%ꢀwithꢀrespectꢀtoꢀ5a),ꢀ
HCOONH ꢀ(0.6ꢀmmol),ꢀ5aꢀ(0.4ꢀmmol),ꢀmesityleneꢀ(2ꢀmL),ꢀArꢀ(1ꢀatm),ꢀ140ꢀ C,ꢀ
4ꢀh.ꢀ Yieldꢀ (basedꢀ onꢀ 5a)ꢀ wasꢀ determinedꢀ byꢀ GCꢀ usingꢀ biphenylꢀ asꢀ theꢀ
4
ꢀ andꢀ
2
b
c
yields.ꢀ ꢀMesityleneꢀ (2ꢀmL)ꢀ wasꢀ usedꢀ insteadꢀ ofꢀ diglyme.ꢀ ꢀPd/Al
2
O
3
ꢀ (Pd:ꢀ
.2ꢀmol%ꢀ withꢀ respectꢀ toꢀ 1).ꢀ ꢀAꢀ halfꢀ scaleꢀ reactionꢀ withꢀ respectꢀ toꢀ theꢀ
standardꢀconditions.ꢀ
○
4
d
3
2
internalꢀstandard.ꢀ
ꢀ
ꢀ
ꢀ
Withꢀ theꢀ optimizedꢀ reactionꢀ conditionsꢀ utilizingꢀ ureaꢀ asꢀ theꢀ
ꢀ
Theꢀ reactionꢀ profileꢀ forꢀ theꢀ transformationꢀ ofꢀ 1aꢀ withꢀ ureaꢀ
nitrogenꢀsource,ꢀweꢀnextꢀinvestigatedꢀtheꢀscopeꢀandꢀlimitationꢀofꢀ
theꢀ arylationꢀ sourcesꢀ forꢀ theꢀ presentꢀ Pd/Al -catalyzedꢀ formalꢀ
arylation.ꢀ Asꢀ above-mentioned,ꢀ 1aꢀ wasꢀ theꢀ goodꢀ arylationꢀ sourceꢀ
Tableꢀ2,ꢀentryꢀ1).ꢀTheꢀeffectꢀofꢀstericꢀcrowdingꢀaroundꢀtheꢀcarbonylꢀ
groupꢀofꢀarylationꢀsourcesꢀwasꢀveryꢀsignificant.ꢀTheꢀreactionsꢀwithꢀ
-methylcyclohexanoneꢀ (1c),ꢀ 4-methylcyclohexanoneꢀ (1d),ꢀ andꢀ 4-
showedꢀthatꢀ3aꢀandꢀ4aꢀwereꢀproducedꢀinꢀreasonableꢀamountsꢀatꢀ
theꢀonsetꢀandꢀthatꢀtheyꢀdecreasedꢀtoꢀrelativelyꢀsmallꢀamountsꢀatꢀ
theꢀendꢀofꢀtheꢀreactionꢀ(Fig.ꢀS1,ꢀESI†).ꢀInꢀaꢀseparateꢀexperiment,ꢀweꢀ
confirmedꢀ thatꢀ 3aꢀ wasꢀ efficientlyꢀ convertedꢀ intoꢀ 2aꢀ underꢀ theꢀ
2 3
O
(
standardꢀ conditionsꢀ inꢀ theꢀ presenceꢀ ofꢀ Pd/Al
WhenꢀtheꢀPd/Al -catalyzedꢀreactionꢀofꢀ1aꢀandꢀ4-tert-butylanilineꢀ
4ꢀ)ꢀ wasꢀ carriedꢀ outꢀ underꢀ theꢀ standardꢀ conditions,ꢀ theꢀ ketone-
2 3
O ꢀ (Fig.ꢀS4,ꢀ ESI†).ꢀ
3
2 3
O
tert-butylcyclohexanoneꢀ (1ꢀ)ꢀ asꢀ theꢀ arylationꢀ sourcesꢀ efficientlyꢀ
proceededꢀ (Tableꢀ2,ꢀ entriesꢀ3‒5),ꢀ whileꢀ theꢀ reactionꢀ rateꢀ ofꢀ 2-
methylcyclohexanoneꢀ(1b)ꢀwasꢀsmallerꢀthanꢀthoseꢀofꢀ1cꢀandꢀ1d,ꢀandꢀ
aꢀsignificantꢀamountꢀofꢀtheꢀcorrespondingꢀprimaryꢀanilineꢀwasꢀalsoꢀ
producedꢀ(Tableꢀ2,ꢀentryꢀ2).ꢀWhenꢀusingꢀaꢀ2,5-dimethylꢀderivativeꢀ
(
anilineꢀcross-couplingꢀproductꢀwasꢀproducedꢀinꢀ98%ꢀyieldꢀ(Fig.ꢀS5,ꢀ
ESI†).ꢀ Therefore,ꢀ weꢀ consideredꢀ thatꢀ 3a,ꢀ 4a,ꢀ andꢀ N-
phenylcyclohexylimineꢀ (6a)ꢀ areꢀ possibleꢀ intermediatesꢀ forꢀ theꢀ 2aꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xx
J. Name.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Pleaseꢀd
C
o
h
ꢀn
e
o
m
tꢀ
C
ad
o
j
m
us
m
tꢀmarginsꢀ
Page 4 of 5
COMMUNICATIONꢀ
Journal Namꢀꢀ
production.ꢀInꢀaddition,ꢀweꢀhaveꢀfoundꢀinꢀtheꢀpreviousꢀstudyꢀthatꢀ
ThisꢀworkꢀwasꢀsupportedꢀinꢀpartꢀbyꢀJSPSꢀKAKENHIꢀGVierawnAtrꢀtNicluemOnblienerꢀ
DOI: 10.1039/C7CC06737B
theꢀ Pd-catalyzedꢀ aromatizationꢀ ofꢀ 3aꢀ toꢀ 2aꢀ proceedsꢀ throughꢀ theꢀ 15H05797ꢀ inꢀ Preciselyꢀ Designedꢀ Catalystsꢀ withꢀ Customizedꢀ
acceptorlessꢀ amineꢀ dehydrogenationꢀ ofꢀ 3aꢀ toꢀ 6aꢀ followedꢀ byꢀ theꢀ ScaffoldingꢀandꢀGrantꢀNumberꢀ17K14860.ꢀ
disproportionationꢀtoꢀ2aꢀandꢀ3aꢀandꢀthatꢀtheꢀdisproportionationꢀisꢀ
4
h
muchꢀfasterꢀthanꢀtheꢀamineꢀdehydrogenation. ꢀ
Notꢀs and rꢀfꢀrꢀncꢀs
ꢀ
Takingꢀ theꢀ aforementionedꢀ piecesꢀ ofꢀ experimentalꢀ evidenceꢀ
4
h
andꢀ ourꢀ previousꢀ results ꢀ intoꢀ consideration,ꢀ weꢀ proposeꢀ twoꢀ
plausibleꢀ reactionꢀ pathwaysꢀ (PathwayꢀAꢀ andꢀ PathwayꢀBꢀ inꢀ Fig.ꢀ4).ꢀ
1
(a)ꢀS.ꢀA.ꢀGirard,ꢀH.ꢀHuang,ꢀF.ꢀZhou,ꢀG.-J.ꢀDengꢀandꢀC.-J.ꢀLi,ꢀOrg.
Chem. Front.,ꢀ2015,ꢀ2,ꢀ279;ꢀ(b)ꢀA.ꢀV.ꢀIosubꢀandꢀS.ꢀS.ꢀStahl,ꢀACS.
Catal.,ꢀ2016,ꢀ6,ꢀ8201.ꢀ
3
Theꢀ reactionꢀ isꢀ initiatedꢀ byꢀ theꢀ condensationꢀ ofꢀ NH ꢀ andꢀ 1aꢀ toꢀ
2
(a)ꢀY.ꢀIzawa,ꢀD.ꢀPunꢀandꢀS.ꢀS.ꢀStahl,ꢀScience,ꢀ2011,ꢀ333,ꢀ209;ꢀ(b)ꢀY.ꢀ
Izawa,ꢀC.ꢀZhengꢀandꢀS.ꢀS.ꢀStahl,ꢀAngew. Chem. Int. Ed.,ꢀ2013,ꢀ52,ꢀ
produceꢀcyclohexylimineꢀ(7a).ꢀSubsequently,ꢀtheꢀdisproportionationꢀ
ofꢀ 7aꢀ takesꢀ placeꢀ toꢀ giveꢀ 4aꢀ andꢀ cyclohexylamineꢀ (8a).ꢀ Theꢀ
dehydrogenationꢀofꢀ8aꢀproceedsꢀtoꢀreproduceꢀ7a.ꢀAlternatively,ꢀtheꢀ
condensationꢀ ofꢀ 8aꢀ withꢀ 1aꢀ orꢀ 7aꢀ affordsꢀ N-
cyclohexylidenecyclohexanamineꢀ (9a).ꢀ Inꢀ PathwayꢀA,ꢀ theꢀ
condensationꢀ ofꢀ 4aꢀ withꢀ 1aꢀ orꢀ 7aꢀ affordsꢀ 6aꢀ followedꢀ byꢀ theꢀ
disproportionationꢀtoꢀaffordꢀ2aꢀtogetherꢀwithꢀtheꢀformationꢀofꢀ3a.ꢀ
Then,ꢀ theꢀ dehydrogenationꢀ ofꢀ 3aꢀ proceedsꢀ toꢀ reproduceꢀ 6a.ꢀ Inꢀ
PathwayꢀB,ꢀtheꢀdisproportionationꢀofꢀ9aꢀtakesꢀplaceꢀtoꢀformꢀ3aꢀandꢀ
dicyclohexylamineꢀ (10a).ꢀ Then,ꢀ 2aꢀ isꢀ producedꢀ throughꢀ theꢀ
dehydrogenationꢀ(3a→6a)/disproportionationꢀ(6a→2a and 3a)ꢀsequence.ꢀ
Althoughꢀ theꢀ amineꢀ intermediatesꢀ 8aꢀ andꢀ 10aꢀ hardlyꢀ observedꢀ
duringꢀ theꢀ reaction,ꢀ PathwayꢀBꢀ shouldꢀ beꢀ consideredꢀ becauseꢀ 2aꢀ
wasꢀproducedꢀwhenꢀusingꢀ8aꢀorꢀ10aꢀasꢀtheꢀstartingꢀmaterial.ꢀDuringꢀ
theꢀ reaction,ꢀ theꢀ imineꢀ intermediatesꢀ wereꢀ hardlyꢀ detected,ꢀ thusꢀ
suggestingꢀ thatꢀ theꢀ disproportionationꢀ stepsꢀ areꢀ veryꢀ fast.ꢀ Theꢀ
reactionꢀprofileꢀ(Fig.ꢀS1,ꢀESI†)ꢀsuggestedꢀthatꢀtheꢀdehydrogenaꢁonꢀ
ofꢀ3aꢀtoꢀ6aꢀisꢀlikelyꢀtheꢀrate-limitingꢀstepꢀforꢀtheꢀpresentꢀarylation.ꢀ
ꢀ
3
672;ꢀ(c)ꢀD.ꢀPun,ꢀT.ꢀDiaoꢀandꢀS.ꢀS.ꢀStahl,ꢀJ. Am. Chem. Soc.,ꢀ2013,ꢀ
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4
M.ꢀSutter,ꢀN.ꢀSotto,ꢀY.ꢀRaoul.ꢀE.ꢀMétayꢀandꢀM.ꢀLemaire,ꢀGreen
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2
012,ꢀ 14,ꢀ 1692;ꢀ (f)ꢀ K.ꢀ Taniguchi,ꢀ X.ꢀ Jin,ꢀ K.ꢀ Yamaguchiꢀ andꢀ N.ꢀ
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Jin,ꢀK.ꢀYamaguchiꢀandꢀN.ꢀMizuno,ꢀCatal. Sci. Technol.,ꢀ2016,ꢀ6,ꢀ
3
929;ꢀ (h)ꢀ K.ꢀ Taniguchi,ꢀ X.ꢀ Jin,ꢀ K.ꢀ Yamaguchi,ꢀ K.ꢀ Nozakiꢀ andꢀ N.ꢀ
Mizuno,ꢀChem. Sci.,ꢀ2017,ꢀ8,ꢀ2131.ꢀ
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(a)ꢀ F.ꢀ Zhou,ꢀ M.-O.ꢀ Simonꢀ andꢀ C.-J.ꢀ Li,ꢀ Chem. Eur. J.,ꢀ 2013,ꢀ 19,ꢀ
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151;ꢀ(b)ꢀS.ꢀChen,ꢀY.ꢀLiao,ꢀF.ꢀZhao,ꢀH.ꢀQi,ꢀS.ꢀLiuꢀandꢀG.-J.ꢀDeng,ꢀ
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ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Initiation
NH
O
NH
Org. Lett.,ꢀ2014,ꢀ16,ꢀ1618.ꢀ
+
+ H O
2
3
1
a
7a
NH2
(a)ꢀF.ꢀXiao,ꢀY.ꢀLiao,ꢀM.ꢀWuꢀandꢀG.-J.ꢀDeng,ꢀGreen Chem.,ꢀ2012,ꢀ14,ꢀ
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Org. Lett.,ꢀ2013,ꢀ15,ꢀ2604;ꢀ(d)ꢀX.ꢀCao,ꢀX.ꢀCheng,ꢀY.ꢀBai,ꢀS.ꢀLiuꢀandꢀ
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N.ꢀYang,ꢀQ.ꢀJiangꢀandꢀR.ꢀLiu,ꢀAdv. Synth. Catal.,ꢀ2016,ꢀ358,ꢀ1731.ꢀꢀ
(a)ꢀ S.ꢀ A.ꢀ Lawrence, Amines: Synthesis Properties and
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Z.ꢀ Rappoport, The Chemistry of Anilines,ꢀ Johnꢀ Wileyꢀ &ꢀ Sons,ꢀ
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NH
+
2[A]
+
2[A]H2
7
a
4a
Aminꢀ dꢀhydrogꢀnation
2[A]H2
2[A]
+
H2
Pathway A
O
7
NH2
N
H O
1
NH
a
2
+ or
+
or
4
a
6a
NH3
H
N
7
a
N
2
008.ꢀ
+
2[A]
+
2[A]H
2
6
a
2a
8
9
Dataꢀ fromꢀ Unitedꢀ Stateꢀ Geologicalꢀ Surveyꢀ (USGS),ꢀ Mineralꢀ
Commodityꢀ Summaries,ꢀ Nitrogenꢀ(Fixed)‒Ammonia.ꢀ See:ꢀ
https://minerals.usgs.gov/minerals/pubs/commodity/nitrogen/.ꢀ
Forꢀtheꢀreactionꢀofꢀ1aꢀunderꢀtheꢀconditionsꢀdescribedꢀinꢀTableꢀ1,ꢀ
weꢀ confirmedꢀ byꢀ theꢀ MSꢀ analysisꢀ ofꢀ theꢀ gas-phaseꢀ thatꢀ
hydrogenꢀgasꢀwasꢀformedꢀduringꢀtheꢀreaction.ꢀTheꢀvolumetricꢀ
analysisꢀ revealedꢀ theꢀ formationꢀ ofꢀ reasonableꢀ amountsꢀ ofꢀ
hydrogenꢀgas.ꢀ
Pathway B
O
NH2
N
H O
1a
NH
2
+ or
+
or
8
a
9a
NH3
7a
H
N
N
+
+
2[A]
+
+
2[A]H
2
10 R.ꢀA.ꢀSheldon,ꢀM.ꢀWallau,ꢀI.ꢀW.ꢀC.ꢀE.ꢀArendsꢀandꢀU.ꢀSchuchardt,ꢀ
Acc. Chem. Res.,ꢀ1998,ꢀ31,ꢀ485.ꢀ
11 QuiteꢀRecently,ꢀweꢀfoundꢀthatꢀ3dꢀmetals,ꢀsuchꢀasꢀFe,ꢀCo,ꢀandꢀNi,ꢀ
couldꢀeffectivelyꢀpromoteꢀtheꢀPd-catalyzedꢀdehydrogenationꢀofꢀ
cyclohexanolsꢀtoꢀcyclohexanones:ꢀSeeꢀref.ꢀ2f.ꢀ
9
a
3a
H
N
N
2[A]
2[A]H
2
6a
Fig. 4 PlausibleꢀreactionꢀpathwaysꢀforꢀtheꢀPd/Al
Inꢀtheꢀdisproportionationꢀsteps,ꢀiminesꢀ6a,ꢀ7a,ꢀandꢀ9aꢀcanꢀactꢀasꢀtheꢀhydrogenꢀ
2a
1
2 Z.ꢀChen,ꢀH.ꢀZeng,ꢀS.ꢀA.ꢀGirard,ꢀF.ꢀWang,ꢀN.ꢀChen,ꢀC.-J.ꢀLi,ꢀAngew.
Chem. Int. Ed.,ꢀ2015,ꢀ54ꢀ,14487.ꢀ
2 3
O -catalyzedꢀformalꢀarylation.ꢀ
2
acceptors.ꢀ[A]ꢀ=ꢀacceptorꢀ(6a,ꢀ7a,ꢀ9a),ꢀ[A]H ꢀ=ꢀamineꢀ(3a,ꢀ8a,ꢀ10a).ꢀ
ꢀ
4
ꢀ|ꢀJ. Name.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

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ChemComm
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DOI: 10.1039/C7CC06737B
Graphical abstract
H
N
H2
O
Pd/Al O
2 3
NH3
+
urea)
R
R
R
(
2 3
In the presence of Pd/Al O , various diphenylamines could be synthesized through
acceptorless formal arylation using urea as the nitrogen sources and cyclohexanones as the
arylation sources.