Hydrogenative Depolymerization of Nylons

Article abstract of DOI:10.1021/jacs.0c05675

The widespread crisis of plastic pollution demands discovery of new and sustainable approaches to degrade robust plastics such as nylons. Using a green and sustainable approach based on hydrogenation, in the presence of a ruthenium pincer catalyst at 150

Full text of DOI:10.1021/jacs.0c05675

Subscriber access provided by University of Birmingham
Article
Hydrogenative Depolymerization of Nylons
Amit Kumar, Niklas von Wolff, Michael Rauch, You-Quan Zou, Guy Shmul,
Yehoshoa Ben-David, Gregory Leitus, Liat Avram, and David Milstein
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c05675 • Publication Date (Web): 24 Jul 2020
Downloaded from pubs.acs.org on July 24, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 10
Journal of the American Chemical Society
1
2
3
4
5
6
Hydrogenative Depolymerization of Nylons
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
δ
2
1
1‡
3
3
Amit Kumar , Niklas von Wolff , Michael Rauch , You-Quan Zou , Guy Shmul , Yehoshoa Ben-David , Gre-
3
3
1
gory Leitus , Liat Avram , David Milstein *
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
Department of Organic Chemistry, Department of Chemical Research Support, The Weizmann Institute of Science, Rehovot 76100,
Israel. Laboratoire d'Electrochimie Moléculaire, UMR 7591, CNRS/University of Paris, 75013 Paris, France.
2
ABSTRACT: The widespread crisis of plastic pollution demands discovery of new and sustainable approaches to degrade robust plastics such
as nylons. Using a green and sustainable approach based on hydrogenation, in the presence of a ruthenium pincer catalyst at 150 C and 70 bar
H , we report here the first example of hydrogenative depolymerization of conventional, widely used nylons, and polyamides in general. Under
the same catalytic conditions, we also demonstrate the hydrogenation of a polyurethane to produce diol, diamine and methanol. Additionally,
we demonstrate an example where monomers (and oligomers) obtained from the hydrogenation process can be dehydrogenated back to a
poly(oligo)amide of approximately similar molecular weight, thus completing a closed loop cycle for recycling of polyamides. Based on the
experimental and DFT studies, we propose a catalytic cycle for the process that is facilitated by metal-ligand cooperativity. Overall, this unprec-
edented transformation, albeit at the proof of concept level, offers a new approach towards a cleaner route to recycling nylons.
o
2
6
INTRODUCTION
Nylons are commonly used plastics with a global market of more
than 8 million tons per annum, and is being expected to grow at the
rate of 2.2% reaching up to 10.4 million tons, equivalent to 47.0 bil-
lion USD by 2027
sources. In the past, we reported an efficient ruthenium pincer cat-
alyst (1’) for the hydrogenation of amides via C–N cleavage to form
alcohols and amines (Figure 1.A.i). Several other homogeneous cat-
alysts based on ruthenium, iron
7
8-17
18-21
22
and manganese have also
1
been reported for the hydrogenation of amides to form alcohols and
.
Inevitably, the ubiquity of nylons and their non-
23-24
amines.
Additionally, we also reported acceptorless dehydro-
biodegradable nature have resulted in the increased land and ocean
pollution posing a severe threat to our ecosystem. Therefore, it is
2
genative coupling of alcohols and amines to form amides catalyzed
by ruthenium pincer complex 2’ (Figure 1.A.ii). In this direction,
2
5
critical that efficient and sustainable technologies for the recycling of
plastics such as nylons are developed. The current plastic recycling
technologies are mostly based on mechanical recycling ‒ converting
one form of plastic to another by mechanical reprocessing (melting
and re-extrusion): for example, converting plastic bottles to fibres.
However, mechanical recycling produces poor quality of plastic and
the number of times a plastic can be mechanically recycled is also
limited. Distinct from mechanical recycling, chemical recycling in-
volves depolymerization of a plastic to produce the monomer raw
material from which the same virgin plastic can be made. Thus, only
chemical recycling closes the loop of plastic production and is a sus-
tainable mode of recycling. The reported chemical recycling meth-
ods for nylons are mainly based on pyrolysis, hydrolysis or aminoly-
sis – all of which require harsh reaction conditions (such as temper-
atures ≥ 250-300 C). Other methods based on glycolysis or amino-
glycolysis do not result in the efficient regeneration of nylons from
the degraded polymers. Thus, development of new, efficient and
2
6
27
Guan and we independently reported the synthesis of polyamides
via dehydrogenative coupling of diols and diamines using the ruthe-
nium pincer catalyst 2’ (Figure 1.A.iii). In order to develop a closed
loop cycle, we envisioned that it might be possible to achieve the very
challenging catalytic hydrogenative depolymerization of polyamides
to their monomers such as diols and diamines or amino alcohols
(Figure 1.A.iv). Saito and coworkers have briefly mentioned an ex-
ample of Ru-catalyzed hydrogenation of specialized, water soluble
functionalized polyamides, although the structures of the polyam-
ides and the hydrogenation products thereof were not reported.
Hydrogenative depolymerization of polyesters and polycarbonates
have also been reported earlier. However, we are not aware of any
report on the catalytic hydrogenation of conventional nylons such as
nylon 6, nylon 66, nylon 12 or related polyamides in general which
are highly robust and resistant to solvents. We report here our find-
ings on the depolymerization of nylons using a ruthenium catalyzed
hydrogenation process.
3
3
1
5
28
o
4
5
sustainable methods to depolymerize nylons for the purpose of recy-
cling are highly desirable.
Catalytic hydrogenation is an atom-economic, green and sustain-
able route for organic transformations as (a) it does not produce
stoichiometric waste as in the case of conventional reducing agents
and (b) hydrogen gas can potentially be produced from renewable
RESULTS AND DISCUSSION
A major challenge in the chemical reactivity of nylons is their
resistance to solvents and reagents due to the multiple, strong inter-
molecular hydrogen bonding interactions between the polymer
chains. We started our
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 10
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 1.A. (i) Hydrogenation of amides via C–N cleavage to form alcohols and amines; (ii) dehydrogenative coupling of alcohols and amines
to form amides; (iii) dehydrogenative coupling of diols and diamines to form polyamides and (iv) hydrogenation of polyamides via C–N cleav-
age to form monomers. Figure 1.B. Ruthenium complexes used in this study.
Table 1. Catalyst screening for the hydrogenative depolymerization of resins of nylon 6.
t
Entry complex
2 mol%)
KOBu
conversion Aminoalcohol selec-
tivity (yield%)
Oligoamide detection
(monomer:dimer:trimer)
remark
(
1
4
5
6
7
8
9
1
2
8 mol%
8 mol%
8 mol%
2 mol%
2 mol%
2 mol%
0 mol%
0 mol%
0 mol%
77%
80%
66%
30%
22%
0%
24%
Yes (3:4:2)
Yes (3:4:2)
Yes (3:6:4)
Yes
No resins recovered
No resins recovered
26%
3
16%
No resins recovered
4
Not detected
Not detected
Not detected
Not detected
Not detected
Not detected
Resins recovered (broken)
Resins recovered (broken)
Resins recovered
5
Yes
6
No
7
0%
No
Resins recovered
10
1’
2’
22%
18%
Yes
Resins recovered (broken)
11
Yes
Resins recovered (broken)
a
t
Catalytic conditions: Nylon 6 (117 mg, 1 mmol relative to the mol wt of the monomer), complex (0.02 mmol), KO Bu (2-9 mg, 0.02-0.08
o
mmol) as specified, DMSO (2.5 mL), temperature 150 C, reaction time 48 h and H
materials after hydrogenation (see SI). Monomer means aminoalcohol. The ratio of monomer:dimer:trimer has been estimated by the LC-MS.
Resins recovered” means complete recovery of resins with the shape and size intact. “Resins recovered (broken)” means that the resins were
broken to small pieces after reaction.
2
(70 bars). Conversion is based on the weight of soluble
“
ACS Paragon Plus Environment

Page 3 of 10
1
Journal of the American Chemical Society
investigation by searching for a solvent that would (a) be capable of
comparable catalytic activity (Table 1), we used complex
1
for fur-
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
dissolving nylon 6 and (b) be compatible with Ru pincer complex-
catalyzed hydrogenation. We have previously reported that complex
(Figure 1.B) in the presence of two (or more) equivalents (relative
to ) of base is a highly active catalyst for the hydrogenation of esters
and amides.
ther studies as it is relatively easy to synthesize compared to complex
2
.
1
One of the reasons for the lower yield of 6-amino-1-hexanol could
1
be catalyst deactivation over time. Hence, in order to achieve better
yields of 6-amino-1-hexanol, we attempted sequential hydrogena-
tion of nylon 6. After the first hydrogenation in DMSO under the
2
9-30
Under the catalytic conditions using
1
(2 mol%),
t
o
KO Bu (8 mol%), H
2
(60 bar), for 48 h at 135 C, we screened sev-
eral solvents (2.5 mL) for the catalytic hydrogenation of nylon 6 (1
mmol, commercial resins of size 2-3 mm, Mw = ~10,000). As ruthe-
nium PNN complexes react with acids, resulting in their deactivation
optimized catalytic conditions, 2 mol% of complex
1
and 8 mol% of
t
KO Bu were added back to the mixture and the autoclave was pres-
o
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
surized with 70 bar of H and heated at 150 C for another 72 h. Fol-
2
3
1
as catalysts, we avoided using acids such as formic acid or acetic
acid as solvents even though they are known to dissolve nylons. No
conversion of nylon 6 was observed when toluene, THF, 1,4-diox-
ane, water or DMF were used under the catalytic conditions de-
scribed above and resins of nylon 6 were completely recovered un-
reacted, presumably due to the insolubility of nylon 6 in these sol-
vents (Table S1, see SI). We then employed DMSO as a solvent as it
can dissolve nylon 6 at elevated temperature (40 g per 100 mL at 130
lowing both hydrogenation steps, 99% of nylon 6 was depolymer-
ized to form 6-amino-1-hexanol (37%) and a mixture of oligoamides
b
(Table 2, entry 1 , see SI, section 9). We found that if not for a matter
of solubility, then THF or 1,4-dioxane are better solvents than
1
DMSO for hydrogenation of amides using complex (see SI, section
1
4.4). Thus, we developed an additional approach in which after the
first step of hydrogenation, we distilled off the DMSO and added
t
1
,4-dioxane along with complex
(70 bar) and the autoclave was heated at 150 C for additional 72
h. Interestingly, this resulted in a higher yield of 6-amino-1-hexanol
48%) although a lower conversion of nylon 6 (80%) was observed
1
(2 mol%), KO Bu (8 mol%) and
o
32
C). In addition to the ability of solubilizing nylons, DMSO has
o
H
2
also been claimed as an environmentally friendly solvent as it can be
prepared from renewable sources, exhibits lower toxicity compared
(
33
to several other polar solvents and is biodegradable. Because of
compared to the aforementioned process when DMSO was used for
such unique properties, coupled with low cost, DMSO has been uti-
both the steps, presumably due to a lower solubility of nylon 6 in di-
33
lized in several industrial processes as a solvent or reagent. Encour-
c
oxane (Table 2, entry 1
,
see SI, section 9).
agingly, in case of DMSO solvent, a mixture of a solution and a white
precipitate was obtained at the end of the hydrogenation, suggestive
of a partial solubilization or degradation of nylon 6. Indeed, analysis
of the reaction mixture by GC revealed the formation of 6-amino-1-
hexanol in 14% yield. Additionally, some other signals suggestive of
oligomers were observed by GC. HR-ESI-MS and MALDI-TOF
spectrometry as well as NMR spectroscopy confirmed the presence
of 6-amino-1-hexanol and oligoamides (dimer-tetramer). Addition-
ally, Diffusion Ordered Spectroscopy (DOSY) showed that the av-
erage size of the formed oligoamides is approximately three times
than that of 6-amino-1-hexanol. The conversion of nylon was deter-
mined by measuring the weights of the solid reaction mixture before
and after the reaction, as nylon 6 has no solubility in DMSO at room
temperature (see SI for details). Based on this method, the conver-
sion of nylon 6 was determined to be 65%. Additional solvents such
as anisole, hexamethylphosphoramide (HMPA), 1-butyl-3-methyl
In order to explore the generality of this depolymerization reac-
tion, we attempted the hydrogenation of other nylons. A powder
form of commercial nylon 6 (Mw ~11,000) was also depolymerized
(
85% conversion) under the optimized catalytic conditions (
1
, 2
t
o
mol% and KO Bu 8 mol%, 70 bar of H
2
and at 150 C) to produce 6-
amino-1-hexanol in 32% yield, the remainder being oligomers as ob-
served for the hydrogenation of nylon 6-resins. Under the same cat-
alytic conditions, but using complex
2
, a slightly better yield of 6-
amino-1-hexanol (36%) was observed (Table 1, entry 2). Interest-
t
ingly, when a catalytic combination of (5 mol%) and KO Bu (20
2
mol%) was used for 72 h, maintaining the remaining conditions,
99% conversion of nylon 6 was observed and 6-amino-1-hexanol was
detected in 55% yield based on GC analysis, the rest being the oligo-
d
mers (Table 1, entry 2 ). The products were also confirmed by the
HR-ESI-MS and NMR spectroscopy. LC-ESI-MS was used to esti-
mate the amount of formed oligomers, showing a ratio of monomer,
dimer and trimer of 3:4:2 (see SI for yields of the formed oligomers
estimated by the LC-ESI-MS).
Given the satisfactory result of the hydrogenative depolymeriza-
tion of nylon 6, we explored the hydrogenation of other polyamides.
Commercial resins of Nylon 12 (purchased from Sigma Aldrich)
were also hydrogenated using the optimized catalytic condition to
obtain a mixture of 12-aminododecan-1-ol and smaller oligomers
imidazolium octyl sulfate (BMIm-OctSO ), diglyme and meta cre-
4
sol were also screened under the same catalytic conditions (Table
S1, see SI) but we did not obtain any better results than when using
DMSO.
Further, we optimized the catalytic conditions by varying base
loading, temperature, pressure, reaction time, ruthenium complexes
(see Table 1) and additives such as water, molecular sieves and
Lewis acids (see SI for the Table of optimization). Best results were
(
dimer and trimer, Table 2, entry 3). Additionally, we also prepared
t
obtained using
1
1
or
2
(2 mol%), KO Bu (8 mol%), 70 bar of H and
2
some polyamides using the dehydrogenative coupling route re-
o
50 C (oil bath temperature) for 48 h, which resulted in 77% con-
27
ported earlier by us and then attempted to depolymerize them. Un-
der the optimized catalytic conditions, 60% conversion of nylon 66
was observed and 1,6-hexane diol and hexamethylene diamine were
detected in 20% and 25%
version of nylon 6 (resins) and formation of 6-amino-1-hexanol in
24-26% yield (Table 1 and Table 2, entry 1), the remaining being
oligomers (dimer-tetramer). Since complexes
and exhibited
1 2
a
Table 2. Substrate scope for the catalytic hydrogenative depolymerization of polyamides
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 10
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
t
Catalytic conditions: Polyamide (1 mmol relative to the molecular weight of the monomer), complex (0.02 mmol), KO Bu (0.08 mmol),
1
o
b
DMSO (2.5 mL), H
2
(70 bar), temperature 150 C and reaction time 48 h. Two sequential hydrogenation steps both in DMSO (vide supra).
c
d
t
Two sequential hydrogenation steps first in DMSO and second in 1,4-dioxane (vide supra).
2
(0.05 mmol) and KO Bu (0.2 mmol), 72 h,
a
e
remaining conditions as above . Molecular weight could not be determined.
yields, respectively (entry 4). A low molecular weight polyamide
prepared by the dehydrogenative coupling of 1,4- phenylenedi-
methanol and 1,4-phenylenedimethanamine was hydrogenated to
afford 80% diol and 85% diamine (entry 5). Some other synthesized
poly(oligo)amides with the combination of aliphatic and aromatic
parts were also successfully hydrogenated to produce diols and dia-
mines (entries 6-8). Further, we extended this concept to the hydro-
genation of polyurethanes that is also a commonly used plastic and
(to diols, diamines and methanol) are beneficial not only for the re-
cycling purpose but also for the indirect conversion of CO to meth-
anol. Under the same catalytic conditions (Table 1, entry 9), using
2
t
complex (2 mol%) and KO Bu (8 mol%), commercial resins of a
1
polyurethane were hydrogenated to afford 1,4-butanediol (70%),
4,4'-methylenebis(cyclohexan-1-amine) (66%) and methanol
(45%). With the recent growth in the notion of circular chemistry
(economy), we also demonstrated, as a proof of concept that the
catalytic hydrogenation/dehydrogenation process can be utilized
3
5
3
4
can be prepared from CO . Thus, hydrogenation of polyurethanes
2
ACS Paragon Plus Environment

Page 5 of 10
Journal of the American Chemical Society
two amide moieties were found to coordinate to the two ruthenium
for the development of closed loop cycle for the polyamide synthe-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
sis/degradation. The monomers and oligomers obtained (after re-
moval of DMSO) from the reaction mixture described in Table 1,
centers, opening the amine side-arm of the pincer ligand. Hemilabil-
ity of the amine-side arms in case of PNNH pincer complexes of ru-
entry 5 were refluxed in 1,4-dioxane solvent containing complex
5
(1
thenium and manganese were proposed a few times in catalytic
t
29,38-40
mol%) and KO Bu (1 mol%) for 48 h to produce the corresponding
(de)hydrogenation reactions.
Notably, this is the first crystal
polyamide of 1600 mol. wt., similar to that used for hydrogenation
structure providing direct evidence for the hemilability of a PNNH
pincer complex relevant to catalysis. The size of complex as a di-
(entry 5, also see SI, section 13).
B
mer was also confirmed in the solution by DOSY NMR spectros-
copy.
Intrigued by the catalytic activity of the ruthenium pincer com-
1 2
plexes and for the hydrogenation of polyamides, we explored the
mechanism of the hydrogenative depolymerization process. The ex-
cellent ability of DMSO to disrupt the hydrogen bonding in amides
and peptides was reported earlier using NMR spectroscopy and
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
6,37
DFT studies.
We found that using complex
1
(2 mol%) and
t
KO Bu (8 mol%), only a trace amount of DMSO gets hydrogenated
under 70 bar of H
o
2
in THF (150 C, 24 h). We detected Me S only
2
in a trace quantity under the reaction conditions of hydrogenation
of nylons using DMSO as solvent. These experiments indicate that
complex
availing the catalyst for the hydrogenation of polyamides in DMSO
as solvent. Additionally, reaction of complex with 4 equivalents of
KO Bu in DMSO-d6 shows formation of a doubly-deprotonated an-
1
is not a good catalyst for the hydrogenation of DMSO,
1
t
30
1
ionic complex
trum in DMSO-d6 exhibited a hydride signal [δ -18.19 (d, JH,P
7.0 Hz, 1H)] very close to that observed in THF-d8 [δ -18.45 (d,
A
reported by us earlier in THF. The H NMR spec-
2
=
2
2
J
H,P = 28.0 Hz, 1H)] where the hydride is located trans to a vacant
t
Scheme 1. (i) Reaction of complex
of complexes and
; (iii) reaction of complex 1/KO Bu with the diamide N1,N2-
bis(4-methoxybenzyl)oxalamide.
1
with KO Bu and H
2
, formation
30
coordination site (Scheme 1.i). This indicates that DMSO is likely
not coordinated to the ruthenium center, making the vacant coordi-
nate site available for the hydrogenation reaction.
A
C
; (ii) reaction of complex
A
with nylon 6 and
t
H
2
In order to gain further mechanistic insight, we studied the reac-
tion of nylon 6 (powder form, Mw = 11,000) with the in situ pre-
To get further insights into the mechanism, we employed DFT
calculations at the ωB97M-V/def2-
TZVPP/RIJCOSX/SMD//M06-L/def2TZVP/GD3/W06 level of
theory. We suggest that the first step involves deprotonation of the
pared complex
A
in DMSO-d6 using variable temperature NMR
spectroscopy (Scheme 1.ii). No reaction was observed when the
temperature was gradually increased from 298 K to 360 K, but inter-
1
estingly at 400 K, the hydride signal in the H NMR spectrum com-
3
1
1
precatalyst
1
at the benzylic position of the ligand P-arm to generate
pletely disappeared and the corresponding P{ H} NMR spectrum
30
the dearomatized complex
D
(as observed experimentally). In
showed a mixture of species. This might indicate insertion of one of
depth experimental thermodynamic analysis showed that for a simi-
lar PNP-Ru complex, the dearomatized form can be in equilibrium
with different Lewis or Brønsted acids to undergo reversible re-aro-
the carbonyl groups of nylon 6 into the Ru–H bond. Addition of H
5 bar) to the same NMR tube at 298 K resulted in the formation of
2
(
1
multiple ruthenium hydride species in the H NMR spectrum fea-
tured by broad signals at δ -5.56, -5.78, -10.30 and -11.34. The signals
at δ -5.56, -5.78 agree well with the ruthenium trans dihydride com-
plex
1
4
1
matization. From a computational point of view the amido N-H
bond of a simple test amide seems not to be acidic enough to gener-
ate higher concentrations of
F
(+9.1 kcal/mol) nor to be a good che-
late ( , +9.6 kcal/mol), in contrast to recent findings involving
formamides. On the other hand, other deprotonated species such
as N-arm dearomatized D’ (+5.9 kcal/mol) or N-H deprotonated
D’’ (-0.3 kcal/mol) should be accessible under the employed reac-
tion conditions.
C
that was independently prepared by the reaction of complex
(Scheme 1.i, hydride signals at δ -4.73 (d, JH,P
14.9 Hz) and -5.12 (d, JH,P = 17.6 Hz) in THF-d8 and at δ -5.23
t
2
E
with KO Bu and H
2
42
2
=
2
2
(d, JH,P = 15.7 Hz) and -5.42 (d, JH,P = 16.0 Hz) in DMSO-d6). The
31
1
P{ H} NMR spectrum of the reaction mixture after addition of H
2
also showed a mixture of complexes, including a signal at δ 123.9,
very close to that of complex
DMSO-d6).
C
(δ 123.5 in THF-d8, δ 122.93 in
Our calculations suggest that the hydrogenation reaction pro-
ceeds via two connected catalytic cycles involving the dearomatized
complex
gen activation of
temperature, which was shown to disfavor the H
D
and the trans dihydride complex
. Importantly, although the reaction is run at high
-splitting thermo-
is energetically
downhill (-9.7 kcal/mol). This emphasizes the importance of rela-
tively high pressures to generate high concentrations of in this
C
formed upon hydro-
A similar observation was made upon reaction of complex
N-benzyl benzamide (see SI, section 14.4). We also studied the re-
activity of complex with a diamide (Scheme 1.iii). Reaction of an
in situ prepared complex in THF or toluene-d8 with N1,N2-bis(4-
A
with
D
2
A
4
1
dynamics, formation of the dihydride species
C
A
methoxybenzyl)oxalamide (4 equivalents) resulted in the formation
of a mixture of complexes (See SI, section 14.5). Interestingly, a sin-
gle crystal obtained from this reaction mixture revealed a diruthe-
C
challenging amide hydrogenation. Previously reported experimental
and theoretical studies implicate an important role of proton relays
nium complex
B
(see SI, Figure S56) featuring N-H activation of
4
3-45
and solvation for this step.
both the amide groups. Significantly, both the C=O groups of the
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 10
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 2. Proposed mechanism for the hydrogenation of amides using DFT calculations.
As the reaction proceeds, both alcohols and amines are generated
and are very likely involved in this step. Although not rate-determin-
ing and over-simplified, we wish to emphasize that we find the lowest
clearly ruled out due to very high barriers (TS3B and TS3C, 39.7
and 37.4 kcal/mol, respectively). On the other hand, C-N bond
cleavage via O-coordination (TS3A, 30.7 kcal/mol), positions the
leaving amido group for protonation by the side-arm CH -group, as
barriers for H
2
-splitting from D’
(
TS1A, 19.4 kcal/mol), with the
2
4
2
test amide not acidic/basic enough to facilitate this step (TS1B, 26.2
kcal/mol). In the first catalytic cycle, hydrogen activation step is fol-
lowed by the hydrogenation of amide bond by the trans dihydride
observed also for the reverse reaction in a PNP-Ru complex. Alt-
hough significantly lower in energy than the other explored path-
ways, it would still be linked to an energetic span of around
40 kcal/mol. Anionic alkoxide species are amenable to expel very
weak leaving groups (e.g. hydrides in the case of alcohol dehydro-
complex
tized complex
bility in the presence of the diamide in
C
to form hemiaminal and regeneration of the dearoma-
. Given the experimental evidence for ligand hemila-
(Scheme 1.iii), we probed
D
5
1
B
genation). As amines are poor leaving groups, it might be suggested
that basic conditions will favor C-N bond cleavage. This is at least in
qualitative agreement with the above reported example of Beller’s
if this would be a viable pathway for amide hydrogenation. However,
we find a stepwise Noyori-type mechanism to be more favorable
with hydride transfer (TS2A1, 24.1 kcal/mol) preceding proton
transfer from the N-H group (TS2A2, 21.4 kcal/mol). Indeed, hy-
dride transfer via ligand hemilability is around 9 kcal/mol higher in
energy (TS2B, 33.0 kcal/mol).
50
anionic Mo-alkoxo complex, that can deprotonate the hemiaminal
and facilitate subsequent C-N cleavage via H-bonding, or the exam-
ple from the Bernskoetter group where the strongly basic co-catalyst
TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) generates the highest
4
8
catalytic activity. In another Ru-catalyzed amide hydrogenation
An intriguing aspect of amide hydrogenation is the fate of the in-
termediate hemiaminal. We calculate its dissociation to the amine
and aldehyde to be strongly favorable (DG = -7.1 kcal/mol). A com-
mon notion is thus, that the hemiaminal dissociates easily as also im-
5
2
system, basic conditions were needed to promote C-N cleavage. Fi-
nally, an analogy to the cleavage to the hemiaminal might be the scis-
sion of C-N bonds in oxaziridines, which was shown to be base-cat-
53
t
4
6
alyzed. In our case, indeed excess KO Bu is needed for a successful
turnover. Moreover, as the reaction proceeds, the reaction medium
will become more basic. The generated amines and alcohols could
further provide a stabilizing H-bond network. A preliminary surface
scan of the potassium salt of the hemiaminal showed that in the ab-
sence of an H-bonding network, the C-N cleavage is uphill in energy
but without any sizeable transition state (see SI). Clearly a more pro-
found analysis, possibly involving explicit solvation, would be
needed to assess with certainty the true nature of the C-N bond
cleaving transition state in such amide hydrogenation reactions.
plied by a mechanistic proposal by Sanford and co-workers. Simi-
larly, Prakash and co-workers could not detect any hemiaminal in-
4
7
termediate during CO hydrogenation via formamides. In contrast,
2
recent work from the Bernskoetter group indicates that hemiaminal
dissociation is kinetically hindered and relies on proton-relay cataly-
4
8
sis to occur readily. This is in agreement with earlier DFT calcula-
tions from the same group, highlighting the TOF-limiting nature of
this step, that is facilitated either by the employed iron complex, or
49
via proton-relay by a solvent/reactant molecule. We were thus in-
terested how these observations translate to our system. Again, the
test amide seems not to be acidic enough to serve as efficient proton-
Finally, the aldehyde from the decomposition of hemiaminal gets
relay for the generation of the labile zwitterion (TS3D1
,
hydrogenated by
C
to form alcohol and regenerates the dearoma-
43.1 kcal/mol). Interestingly, for Fe and for Mo-complexes in the
tized complex ’’, that would again be in rapid equilibrium with .
D
D
5
0
absence of alcohols, a C-N bond cleavage might be promoted via
an N-coordinated intermediate. In our case, such a pathway can be
ACS Paragon Plus Environment

Page 7 of 10
CONCLUSION
Journal of the American Chemical Society
https://www.reportlinker.com/p03993523/Global-Nylon-Indus-
try.html.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
In conclusion, we report here the hydrogenative depolymeriza-
tion of conventional nylons such as nylon 6, other polyamides and a
polyurethane. The reaction is catalyzed by ruthenium pincer com-
plexes using DMSO as a solvent which plays a critical role in the pro-
cess, by disrupting the hydrogen bonding of the polyamide and at
the same time remaining uncoordinated to the metal-center, thus al-
lowing the catalysis to occur. We also demonstrate an example where
the diols and diamines obtained from the hydrogenative depolymer-
ization process are used to synthesize the original polyamide via a
ruthenium catalyzed dehydrogenative coupling process, thus closing
the loop of polyamide production. DFT calculations confirm the
important role of metal-ligand cooperativity where the hydrogena-
tion of amide bonds take place via an outer-sphere mechanism.
Methods for chemical recycling of nylons have been reported earlier,
however this is the first time that a process based on hydrogenation,
which is a green, sustainable and atom-economic reaction, has been
used to depolymerize conventional and robust nylons such as nylon
2. Geyer, R.; Jambeck, J. R.; Law, K. L. Production, use, and fate of all
plastics ever made. Sci. Adv.
2
017
,
3, e1700782.
3
. (a) The New Plastics Economy — Rethinking the Future of Plastics,
https://www.ellenmacarthurfoundation.org/assets/downloads/publi-
cations/NPEC-Hybrid_English_22-11-17_Digital.pdf, (2016). (b) La
Mantia, F. P. Mechanical Propoerties of Recycled Nylons. Macromol.
Symp. 1999, 147, 167–172. (c) Ragaert, K.; Delva, L.; Geem, V. K. Me-
chanical and Chemical Recycling of Solid Plastic Waste. Waste Manag.
2017, 69, 24–58. (d) Singh, N.; Hui, D.; Singh, R.; Ahuja, I. P. S.; Feo,
L.; Fraternali, F. Recycling of Plastic Solid Waste: A state of Art Review
and Future Applications. Compos. Part B Eng. 2017, 115, 409–422. (e)
Rahimi, A.; García, J. M. Chemical Recycling of Waste Plastics for New
Materials Production. Nat. Rev. Chem. 2017, 1, 0046. (f) Lu, X.-B.; Liu,
Y.; Zhou, H. Learning Nature: Recyclable Monomers and Polymers.
Chem. Eur. J. 2018, 24, 11255-11266. (g) Coates, G. W.; Getzler, Y.D.
Y. L. Chemical recycling to monomer for an ideal, circular polymer
economy. Nat. Rev. Mater. 2020, 5, 501-516.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4. (a) Mihut, C.; Captain, D. K.; Gadala-Maria, F.; Amiridis, M. D. Re-
6. We believe that this unprecedented transformation, although not
view: Recycling of nylon from carpet waste. Polym. Eng. Sci. 2001, 41,
1457-1470. (b) Dimitis, S.; Andriotis, L. A.; Koutsidis, I. A.; Louka, D.
A.; Nianias, N. P.; Siafaka, P.; Tsagkalias, I.; Tsintzou, G. Recent Ad-
vances in the Chemical Recycling of Polymers (PP, PS, LDPE, HDPE,
PC, Nylon, PMMA). material recycling – trends and perspectives 2012.
at a practical level yet, provides a new promising direction aimed at
the highly desirable depolymerization of waste nylons, as well as hy-
drogenation of other polyamides.
ASSOCIATED CONTENT
(c) Alberti, C.; Figueira, R.; Hofmann, M.; Koschke, S.; Enthaler, S.
Supporting Information. Supporting information is available free of
Chemical Recycling of End-of-Life Polyamide 6 via Ring Closing Depol-
ymerization. ChemistrySelect, 2019, 4, 12638– 12642 and references
therein. (d) Corbin, T. F.; Davis, E. A.; Dellinger, J. A. Reclaiming ε-ca-
prolactam from nylon 6 carpet. US Patent: US5169870A, 1991. (e)
Commercial nylon-carpet recycling to ε-caprolactam or virgin nylons is
charge
via
the
Internet
at
http://pubs.acs.org.
Experimental details of catalytic hydrogenation, mechanistic studies,
NMR, GC, ESI-MS and X-ray data, and computational details, Crystal-
lographic data for .
B
operated
by
Shaw
Industries
AUTHOR INFORMATION
Corresponding Author
(https://www.energy.gov/eere/amo/nylon-carpet-recycling), Aquafil
(
https://www.aquafil.com/where-we-are/usa/acr-1/) and DOMO
chemicals
(https://www.domochemicals.com/en/markets-
*
david.milstein@weizmann.ac.il
brands/econamid).
5. Datta, J.; Błażek, K.; Włoch, M.; Bukowski, R. A. New Approach to
Present Addresses
Chemical Recycling of Polyamide 6.6 and Synthesis of Polyurethanes
with Recovered Intermediates. J. Polym. Environ. 2018, 26, 4415-4429.
δ
‡
School of Chemistry, University of St. Andrews, KY169ST, UK; De-
partment of Chemistry, University of Cambridge, CB21EW, UK.
6. Rylender, P. N. Hydrogenation Methods. (Academic Press, 1985).
7. Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W; Milstein, D. Di-
rect Hydrogenation of Amides to Alcohols and Aminesunder Mild Con-
Notes
The authors declare no competing financial interest.
ditions. J. Am. Chem. Soc. 2010
,
132, 16756-16758.
ACKNOWLEDGMENT
8
. Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T. Chemoselective Hy-
This research was supported by the European Research Council (ERC
AdG 692775). D. M. holds the Israel Matz Professorial Chair of Organic
Chemistry. A. K. is thankful to the Planning and Budgeting Committee
of Israel and Feinberg Graduate School for a (senior) postdoctoral fel-
lowship. Y.-Q. Z. acknowledges the Sustainability and Energy Research
Initiative (SAERI) foundation for a research fellowship. Computations
were performed using HPC resources from GENCI-CINES (Grant
drogenation of ImidesCatalyzed by Cp*Ru(PN) Complexes and Its Ap-
plication to the Asymmetric Synthesis of Paroxetine. J. Am. Chem. Soc.
2007
,
129,
290-291.
9. Ito, M.; Kobayashi, C.; Himizu, A.; Ikariya, T. Highly Enantioselective
Hydrogenative Desymmetrization of Bicyclic Imides Leading to Multi-
ply Functionalized Chiral Cyclic Compounds. J. Am. Chem. Soc. 2010
132, 11414-11415.
,
2019
AP010811227).
10. Ito, M.; Ootsuka, T.; Watari, R.; Shiibashi, A.; Himizu, A.; Ikariya, T.
Catalytic Hydrogenation of Carboxamides and Esters by Well-Defined
Cp*Ru Complexes Bearing a Protic Amine Ligand. J. Am. Chem. Soc.
REFERENCES
1. (a) Kind, S.; Neubauer, S.; Becker, J.; Yamamoto, M.; Volkert, M.;
Abendroth, G. v.; Zelder, O.; Wittmann, C. From zero to hero – Produc-
tion of bio-based nylon from renewable resources using engineered
Corynebacterium glutamicum. Metab. Eng. 2014, 25, 113-123. (b) Ny-
lon Market Size, Share & Trends Analysis Report by Product (Nylon 6,
Nylon 66), by Application (Automobile, Electrical & Electronics, Engi-
neering Plastics, Textile), by Region, and Segment Forecasts, 2020 –
2
1
011, 133, 4240-4242.
1. Takebayashi, S.; John, J. M.; Bergens, S. H. Desymmetrization of
meso-Cyclic Imides via Enantioselective Monohydrogenation. J. Am.
Chem.
Soc.
2010
,
132,
12832-12834.
12. John, J. M.; Bergens, S. H. A Highly Active Catalyst for the Hydro-
genation of Amides to Alcohols and Amines. Angew. Chem. Int. Ed.
2011, 50, 10377-10380.
13. John, J. M.; Loorthuraja, R.; Antoniuk, E.; Bergens, S. H. Catalytic
2
027, https://www.researchandmarkets.com/reports/4375423/ny-
lon-market-size-share-and-trends-analysis. (c) Global Nylon Industry,
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 10
hydrogenation of functionalized amides under basic and neutral condi-
tions. Catal. Sci. Technol. 5, 1181-1186.
2015
14. Cabrero-Antonino, J. R.; Alberico, E. ; Drexler, H.-J.; Baugmann, W.;
Junge, K.; Junge, H.; Beller, M. Efficient Base-Free Hydrogenation of
Amides to Alcohols and Amines Catalyzed by Well-Defined Pincer Im-
idazolyl–Ruthenium Complexes. ACS Catal. 2016, 6, 47-54.
Z.; Rong, L.; Wu, J.; Zhang, L.; Wang, Z.; Ding, K. Catalytic Hydrogena-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
,
tion of Cyclic Carbonates: A Practical Approach from CO2 and Epox-
ides to Methanol and Diols. Angew. Chem., Int. Ed. 2012, 51,
13041−13045. (f) Kumar, A.; Janes, T.; Espinosa-Jalapa, N. A.; Milstein,
D. Manganese Catalyzed Hydrogenation of Organic Carbonates to
Methanol and Alcohols. Angew. Chem. Int. Ed. 2018, 57, 12076−
12080. (g) Zubar, V.; Lebedev, Y.; Azofra, L. M.; Cavallo, L.; El-Sepelgy,
O.; Rueping, M. Hydrogenation of CO2 -Derived Carbonates and Pol-
ycarbonates to Methanol and Diols by Metal-Ligand Cooperative Man-
ganese Catalysis. Angew. Chem., Int. Ed. 2018, 57, 13439−13443.
1
5. Miura, T.; Naruto, M.; Toda, K.; Shimomura, T.; Saito, S. Multifac-
eted catalytic hydrogenation of amides via diverse activation of a steri-
cally confined bipyridine–ruthenium framework. Sci. Rep. 2017, 7,
1586.
16. Shi, L.; Tan, X.; Long, J.; Xiong, X.; Yang, S.; Xue, P.; Lv, H; Zhang,
X. Direct Catalytic Hydrogenation of Simple Amides: A Highly Efficient
Approach from Amides to Amines and Alcohols. Chem. Eur. J. 2017, 23,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
29. (a) Kumar, A.; Janes, T.; Espinosa-Jalapa, N. A.; Milstein, D. Selec-
tive Hydrogenation of Cyclic Imides to Diols and Amines and Its Appli-
cation in the Development of a Liquid Organic Hydrogen Carrier. J. Am.
Chem. Soc. 2018, 140, 7453-7457. (b) Kar, S.; Rauch, M.; Kumar, A.;
Leitus, G.; Ben-David, Y.; Milstein, D. Selective Room-Temperature
Hydrogenation of Amides to Amines and Alcohols Catalyzed by a Ru-
5
46-548.
1
7. Kita, Y.; Higuchi, T.; Mashima, K. Hydrogenation of amides cata-
lyzed by a combined catalytic system of a Ru complex with a zinc salt.
Chem. Commun. 2014, 50, 11211-11213.
1
8. Jayarathne, U.; Zhang, Y.; Hazari, N.; Bernskoetter, W. H. Selective
thenium Pincer Complex and Mechanistic Insight, ACS Catal., 2020
,
Iron-Catalyzed Deaminative Hydrogenation of Amides. Organometal-
lics 2017, 36, 409-416.
10, 5511-5515. (c) Hu, P.; Fogler, E.; Diskin-Posner, Y.; Iron, M. A.;
Milstein, D. A novel liquid organic hydrogen carrier system based on cat-
alytic peptide formation and hydrogenation. Nat. Commun. 2015, 6,
6859.
19. Schneck, F.; Assmann, M.; Balmer, M.; Harms, K.; Langer, R. Selec-
tive Hydrogenation of Amides to Amines and Alcohols Catalyzed by Im-
proved Iron Pincer Complexes. Organometallics 2016, 35, 1931-1943.
30. Fogler, E.; Garg, J. A.; Hu, P.; Leitus, G.; Shimon, L. J. W.; Milstein,
D. System with Potential Dual Modes of Metal–Ligand Cooperation:
Highly Catalytically Active Pyridine-Based PNNH–Ru Pincer Com-
2
0. Rezayee, N. M.; Samblanet, D. C.; Sanford, M. S. Iron-Catalyzed Hy-
drogenation of Amides to Alcohols and Amines. ACS Catal 2016, 6,
plexes.
Chem.
Eur.
J.
2014
,
20,
15727-15731.
6
377-6383.
31. Balaraman, E.; Khaskin, E.; Leitus, G.; Milstein, D. Catalytic trans-
formation of alcohols to carboxylic acid salts and H2 using water as the
2
1. Garg, J. A.; Chakraborty, S.; Ben-David, Y.; Milstein, D. Unprece-
dented iron-catalyzed selective hydrogenation of activated amides to
amines and alcohols. Chem. Commun. 2016, 52, 5285-5288.
22. Papa,V.; Cabrero-Antonino, J. R.; Alberico, E.; Spanneberg, A.;
Junge, K.; Junge H.; Beller M. Efficient and selective hydrogenation of
amides to alcohols and amines using a well-defined manganese–PNN
oxygen atom source. Nat. Chem. 2013
,
5, 122-125.
32.
https://www.gaylordchemical.com/literature/dmso-solubility-
data/.
33. (a) Byrne, F. P.; Jin, S.; Paggiola, G.; Petchey, T. H. M.; Clark, J. H.;
Farmer, T. J.; Hunt, A. J.; Robert McElroy, C.; Sherwood, J. Tools and
techniques for solvent selection: green solvent selection guides. Sustain-
able Chem. Processes 2016, 4, 1−24. (b) Vignes, R. Dimethyl sulfoxide
(DMSO) , a new, clean, unique, superior solvent, ACS Annual Meeting,
2000. (c) Xiang, J.-C.; Gao, Q.-H.; Wu, A.-X. The Applications of
DMSO. Solvents as Reagents in Organic Synthesis: Reactions and Ap-
plications, 2017, 315-353.
pincer
3. Smith, A. M.; Whyman, R. Review of Methods for the Catalytic Hy-
drogenation of Carboxamides. Chem. Rev. 2014, 114, 5477−5510.
4. Chardon, A.; Morisset, E.; Rouden, J.; Blanchet, J. Recent Advances
in Amide Reductions. Synthesis, 2018
50, 984−997.
5. Gunanathan, C.; Ben-David, Y.; Milstein, D. Direct Synthesis of Am-
complex.
Chem.
Sci.
2017
,
8,
3576-3585.
2
2
,
2
ides from Alcohols and Amines with Liberation of H
317, 790-792.
2
. Science 2007
,
34. Langanke, J.; Wolf, A.; Hofmann, J.; Bo ̈h m, K.; Subhani, M. A.;
Muller, T. E.; Leitner, W.; Gurtler, C. Carbon dioxide (CO2) as sustain-
̈
̈
26. Zeng, H.; Guan, Z. Direct Synthesis of Polyamides via Catalytic De-
hydrogenation of Diols and Diamines. J. Am. Chem. Soc. 2011, 133,
able feedstock for polyurethane production. Green Chem. 2014, 16,
1865−1870.
1
159-1161.
35. Keijer, T.; Bakker, V.; Slootweg, J. C. Circular chemistry to enable a
2
7. Gnanaprakasam, B.; Balaraman, E.; Gunanathan, C.; Milstein, D.
circular economy. Nat. Chem. 2019
,
11, 190−195.
Synthesis of polyamides from diols and diamines with liberation of H2.
J. Polym. Sci. A 2012, 50, 1755-1765.
36. Molchanov, S.; Gryff-Keller, A. Solvation of Amides in DMSO and
CDCl3: An Attempt at Quantitative DFT-Based Interpretation of 1H
and 13C NMR Chemical Shifts. The Journal of Physical Chemistry A
2017, 121, 9645-9653.
28. (a) Milstein, D.; Balaraman, E.; Gunanathan, C.; Gnanaprakasam B.;
Zhang, J. Novel ruthenium complexes and their uses in processes for for-
mation and/or hydrogenation of esters, amides and derivatives thereof
US Pat. Ap., US20130281664A1, 2013. (b) Krall, E. M.; Klein, T. W.;
Andersen, R. J.; Nett, A. J.; Glasgow, R. W.; Reader, D. S.; Dauphinais,
B. C.; McIlrath, S. P.; Fischer, A. A.; Carney, M. J.; Hudson, D. J.; Rob-
ertson, N. J. Controlled hydrogenative depolymerization of polyesters
and polycarbonates catalyzed by ruthenium(II) PNN pincer complexes.
Chem. Commun. 2014, 50, 4884−4887. (c) Fuentes, J. A.; Smith, S. M.;
Scharbert, M. T.; Carpenter, I.; Cordes, D. B.; Slawin, A. M. Z.; Clarke,
M. L. On the Functional Group Tolerance of Ester Hydrogenation and
Polyester Depolymerisation Catalysed by Ruthenium Complexes of
Tridentate Aminophosphine Ligands. Chem. - Eur. J. 2015, 21,
10851−10860. (d) Westhues, S.; Idel, J.; Klankermayer, J. Molecular
catalyst systems as key enablers for tailored polyesters and polycar-
bonate recycling concepts. Sci. Adv. 2018, 4, eaat9669−9676. (e) Han,
37. Chand, A.; Chowdhuri, S. Effects of dimethyl sulfoxide on the hy-
drogen bonding structure and dynamics of aqueous N-methylacetamide
solution.
J.
Chem.
Sci.
2016
,
128,
991-1001.
38. Kumar, A.; Espinosa-Jalapa, N. A.; Leitus, G.; Diskin-Posner, Y.; Av-
ram, L.; Milstein, D. Direct Synthesis of Amides by Dehydrogenative
Coupling of Amines with either Alcohols or Esters: Manganese Pincer
Complex as Catalyst. Angew. Chem. Int. Ed. 2017, 56, 14992-14996.
39. Espinosa-Jalapa, N. A.; Kumar, A.; Leitus, G.; Diskin-Posner, Y.; Mil-
stein, D. Synthesis of Cyclic Imides by Acceptorless Dehydrogenative
Coupling of Diols and Amines Catalyzed by a Manganese Pincer Com-
plex. J. Am. Chem. Soc. 2017
,
139, 11722-11725.
40. Kumar, A.; Janes, T.; Espinosa-Jalapa, N. A.; Milstein, D. Manganese
Catalyzed Hydrogenation of Organic Carbonates to Methanol and Al-
cohols. Angew. Chem. Int. Ed. 2018
,
57, 12076-12080.
ACS Paragon Plus Environment

Page 9 of 10
Journal of the American Chemical Society
4
1. Mathis, C. L.; Geary, J.; Ardon, Y.; Reese, M. S.; Philliber, M. A.;
Hazari, N.; Jaraiz, M.; Nova, A. Rational selection of co-catalysts for the
deaminative hydrogenation of amides. Chem. Sci., 2020, 11, 2225-2230.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
VanderLinden, R. T.; Saouma, C. T. Thermodynamic Analysis of Metal-
Ligand Cooperativity of PNP Ru Complexes: Implications for CO2 Hy-
drogenation to Methanol and Catalyst Inhibition. J. Am. Chem. Soc.
49. Artus Sua ́ rez, L.; Culakova, Z.; Balcells, D.; Bernskoetter, W. ̀ H.;
2
4
019
2. Bruffaerts, J.; von Wolff, N.; Diskin-Posner, Y.; Ben-David, Y.; Mil-
,
141,
14317−14328.
Eisenstein, O.; Goldberg, K. I.; Hazari, N.; Tilset, M.; Nova, A. The Key
Role of the Hemiaminal Intermediate in the Iron-Catalyzed Deamina-
tive Hydrogenation of Amides. ACS Catal., 2018, 8, 8751− 8762.
stein, D. Formamides as Isocyanate Surrogates: A Mechanistically
Driven Approach to the Development of Atom-Efficient, Selective Cat-
alytic Syntheses of Ureas, Carbamates, and Heterocycles. J. Am. Chem.
50. Leischner, T.; Artus Suarez, L.; Spannenberg, A.; ́ Junge, K.; Nova,
Soc
.
2019
,
141,
16486-16493.
A.; Beller, M. Highly selective hydrogenation of amides catalysed by a
43. Dub, P. A.; Gordon, J. C. Metal-Ligand Bifunctional Catalysis: The
“Accepted” Mechanism, the Issue of Concertedness, and the Function
of the Ligand in Catalytic Cycles Involving Hydrogen Atoms. ACS
molybdenum pincer complex: scope and mechanism. Chem. Sci. 2019
,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
10, 10566−10576.
51. Gusev, D. G. Revised Mechanisms of the Catalytic Alcohol Dehy-
drogenation and Ester Reduction with the Milstein PNN Complex of
Ruthenium. Organometallics 2020, 39, 258− 270.
Catal.
2017
,
7,
6635−6655.
44. Sinha, V.; Govindarajan, N.; de Bruin, B.; Meijer, E. J. How Solvent
Affects C-H Activation and Hydrogen Production Pathways in Homo-
geneous Ru-Catalysed Methanol Dehydrogenation Reactions. ACS
Catal. 2018, 8, 6908−6913.
52. John, J. M.; Loorthuraja, R.; Antoniuk, E.; Bergens, S. H. Catalytic
hydrogenation of functionalized amides under basic and neutral condi-
tions. Catal. Sci. Technol. 2015
,
5, 1181 −1186.
4
5. Smith, N. E.; Bernskoetter, W. H.; Hazari, N. The Role of Proton
Shuttles in the Reversible Activation of Hydrogen via Metal−Ligand Co-
operation. J. Am. Chem. Soc., 2019
141, 17350-17360.
53. Rastetter, W. H.; Wagner, W. R.; Findeis, M. A. Mechanism of oxa-
ziridine fragmentation by amines. J. Org. Chem. 1982, 47, 419-422.
,
46. Rezayee, N. M.; Samblanet, D. C.; Sanford, M. S. Iron-Catalyzed Hy-
drogenation of Amides to Alcohols and Amines. ACS Catal. 2016, 6,
6
377−6383.
4
7. Kar, S.; Sen, R.; Kothandaraman, J.; Goeppert, A.; Chowdhury, R.;
Munoz, S. B.; Haiges, R.; Prakash, G. K. S. Mechanistic Insights into Ru-
theniumPincer-Catalyzed Amine-Assisted Homogeneous Hydrogena-
tion of CO
2
to Methanol. J. Am. Chem. Soc. 2019, 141, 3160−3170.
48. Suàrez, L. A.; Jayarathne, U.; Balcells, D.; Bernskoetter, W. H.;
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 10
Insert Table of Contents artwork here
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
0
ACS Paragon Plus Environment