Highly selective acylation of dimethylamine mediated by oxygen atoms on metallic gold surfaces

Article abstract of DOI:10.1002/anie.200905642

"Chemical Equation Presented" Completely coupled: The acylation of dimethylamine through coupling to formaldehyde occurs with almost 100 % selectivity at low coverage of adsorbed O atoms on metallic gold and with a low activation energy. Oxygen creates an active intermediate (CH₃) ₂N_(a), which attacks the carbonyl carbon of the aldehyde (see picture). A general mechanistic framework for efficient and selective acylation of amines promoted by Au is established.

Full text of DOI:10.1002/anie.200905642

Communications
DOI: 10.1002/anie.200905642
Gold Catalysis
Highly Selective Acylation of Dimethylamine Mediated by Oxygen
Atoms on Metallic Gold Surfaces**
Bingjun Xu, Ling Zhou, Robert J. Madix, and Cynthia M. Friend*
Throughout the ages, gold has been highly valued because of
its seeming chemical inertness, its luster and beauty resulting
from its resistance to bulk tarnishing reactions. However, the
surface of gold is not completely inert, particularly in the
presence of adsorbed oxygen. Indeed, there has been a
resurgence of research on heterogeneous catalysis by gold
recently due to its potential for developing environmentally
benign processes,[1–3] since Harutaꢀs breakthrough observa-
tion of low-temperature CO oxidation on gold nanoparticles
supported on reducible metal oxides.[4] Gold particles sup-
ported on oxide surfaces selectively promote a wide range of
reactions under various conditions, including aerobic oxida-
tion of alcohols[5–7] and amines,[8] as well as acylation of
amines[9,10] as does unsupported gold powder.[11] Herein, we
report for the first time the vapor-phase, surface mediated
acylation of an amine to an amide on metallic gold, and we
establish a molecular-level mechanism for this process based
on a specific characteristic of the adsorbed amide intermedi-
ate that provides a general basis for predicting such reactions.
Amides are widely used in chemical synthesis, in pharma-
ceutical production, and in the synthesis of polymers, includ-
ing nylon.[11] Conventional methods for synthesizing amides
use either activated acid derivatives, such as acid chlorides or
anhydrides, or rearrangement reactions induced by an acid or
base, which often produce toxic chemical waste.[12] Amine
acylation reactions catalyzed by homogeneous transition-
metal complexes[13–15] in solution have been reported along
with those on supported Au.[9,10] Ideally, direct synthesis of
amides through heterogeneous catalytic processes with high
selectivity under environmentally benign conditions would be
possible.
The performance of catalytic processes can be improved
through understanding the reaction mechanism at a molec-
ular level so that the kinetics and selectivity of the overall
process can be accurately predicted. A first step is to
deconvolute the roles of gold and the oxide support. Our
approach is to investigate O-covered Au(111), since without
oxygen, Au is inert towards many reactions, including those of
alcohols, aldehydes, and amines.[8,16–20]
The general concept for amine acylation on O/Au(111)
originates in the chemical nature of adsorbed oxygen and
other nucleophilic adsorbates formed by selective deproto-
nation of their conjugate acids. For example, adsorbed O on
Au surfaces activates alcohols,[17] ammonia,[19,20] and amines[8]
through Brønsted acid–base reactions:
RCH2OH þ OðaÞ ! RCH2OðaÞ þ OHðaÞ
RNH2 þ OðaÞ ! RNHðaÞ þ OHðaÞ
ð1Þ
ð2Þ
These same O-covered Au surfaces are active for self-
coupling of alcohols and cross-coupling between methanol
and aldehydes.[16–18,21] Once the surface-bound alkoxy forms, a
fraction of it undergoes b-H elimination to form the
corresponding aldehyde:
RCH2OðaÞ þ OðaÞ ! RCðHÞ¼OðaÞ þ OHðaÞ
ð3Þ
Esterification subsequently proceeds by nucleophilic
attack on the aldehyde by the adsorbed alkoxy group at the
electron-deficient aldehydic carbon, resulting in the corre-
sponding ester through the hemiacetal intermediate (not
shown):
RCH2OðaÞ þ RCðHÞ¼OðaÞ þ OðaÞ ! RCð¼OÞOCH2RðgÞ þ OHðaÞ
ð4Þ
[*] B. Xu, Prof. C. M. Friend
Department of Chemistry and Chemical Biology
Harvard University
Cambridge, MA 02138 (USA)
Fax: (+1)617-496-8410
E-mail: cfriend@seas.harvard.edu
Homepage: http://www.seas.harvard.edu/friend/
The key steps in these reactions are the initial selective
ꢀ
activation of the RO H bond in the alcohol by adsorbed
oxygen and the nucleophilic attack of the adsorbed alkoxy on
the electron-deficient carbon in the aldehyde.[16,18]
Dr. L. Zhou, Prof. R. J. Madix, Prof. C. M. Friend
School of Engineering and Applied Sciences
Harvard University
Chemical analogy and understanding of the fundamental
mechanism of these reactions suggest that such reactions
should occur between other adsorbed nucleophiles and
electron-deficient carbon atoms. Hence, we anticipated that
Cambridge, MA 02138 (USA)
[**] We gratefully acknowledge the support of the U.S. Department of
Energy, Basic Energy Sciences, under Grant No. FG02-84-ER13289
(C.M.F.) and the National Science Foundation, Division of
Chemistry, Analytical and Surface Science (R.J.M.; CHE-0513936),
and the Division of Physics, through the Harvard Nanoscale Science
and Engineering Center grant.
ꢀ
activation of an N H bond in an amine [Eq. (2)] would yield
an amide intermediate that should also attack the electron-
deficient carbonyl carbon in aldehydes.
Here, we demonstrate the novel nucleophilic reactivity of
(CH3)2N, selectively formed from activation of dimethyl-
amine by adsorbed O on Au(111). The adsorbed (CH3)2N
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200905642.
394
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Angew. Chem. Int. Ed. 2010, 49, 394 –398

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Chemie
=
attacks the electron-deficient carbon in formaldehyde to yield
N,N-dimethylformamide with nearly 100% selectivity at low
initial oxygen coverage (qO = 0.15 ML (monolayers)). This
coupling reaction occurs at temperatures as low as 175 K,
indicating an extremely low activation barrier.
A single-crystal Au(111) surface was prepared in ultrahigh
vacuum, on which oxygen atoms were introduced by ozone
decomposition, due to the low dissociation probability of O2
on Au(111) (< 10ꢀ7 at 400 K).[22] The adsorption of O on
Au(111) using O3 decomposition induces formation of O-
containing Au nanoparticles,[23] which serves as an excellent
model for Au-based catalytic processes. The condition used
for oxidation produces nanoparticles of ca. 2 nm in diameter
and a low surface concentration with O bound primarily to
sites with local three-fold coordination.[24,25] These Au nano-
particles are remarkably selective and active.[16,26] At higher
[D6]dimethylamine exclusively yields (CD3)2NC(H) O,
based on the mass shift of the parent ion from 73 to 79 amu
(Figure 1b). Furthermore, [D2]formaldehyde reacts with
=
[D0]dimethylamine to form (CH3)2NC(D) O (74 amu) (Fig-
ure 1c). By using H2C18O, we established that the product
contains one oxygen derived from formaldehyde (see Fig-
ure S1 in Supporting Information). These results show that
the methyl groups in the amine and the carbonyl in the
ꢀ
formaldehyde are preserved and that only the aldehydic C H
bond is broken.
By analogy to previous studies, we assert that the first step
in the amine acylation reaction is deprotonation of the
dimethylamine to form adsorbed (CH3)2N(a)
:
ðCH3Þ2NHðaÞ þ OðaÞ ! ðCH3Þ2NðaÞ þ OHðaÞ
ð5Þ
The experiments with the different deuterated species
show that (CH3)2N(a) must attack the aldehydic carbon in
formaldehyde, presumably to form the hemiaminal:
ꢀ
coverage, less reactive, larger Au O islands form a two-
dimensional “oxide”.[26]
Dimethylamine was initially reacted with O/Au(111) at
120 K, and then formaldehyde was adsorbed onto the surface.
The selective coupling product, N,N-dimethylformamide
ðCH3Þ2NðaÞ þ H2C¼OðaÞ ! ðCH3Þ2NCH2OðaÞ
ð6Þ
=
(CH3)2NC(H) O (m/z 73), evolves at ca. 175 K into the gas
Subsequent b-hydride elimination yields N,N-dimethyl-
formamide:
phase while heating the surface (Figure 1a) along with water
and unreacted dimethylamine. There is no detectable CO2
(m/z 44) or NO2 (m/z 46). A small amount of N-methyl
formamide (m/z 59) was also observed at ca. 350 K.
ðCH3Þ2NCH2OðaÞ þ OðaÞ ! ðCH3Þ2NCðHÞ¼OðgÞ þ OHðaÞ
ð7Þ
The product was unequivocally identified by detection of
the parent ion and by comparison of its fragmentation pattern
to that of an authentic sample of N,N-dimethylformamide,
obtained by subliming the condensed amide. Isotopic labeling
was used to confirm product identification and to clarify
the mechanism. Reaction of [D0]formaldehyde with
This reaction is analogous to the esterification reaction
[Eq. (4)].
At high oxygen coverage, that is, qo = 1 ML, secondary
oxidation products form: NO2, CO2, H2O, methyl isocyanate
(m/z 57), and N-methylformamide were identified by quanti-
tative mass fragmentation analysis. These products appear to
form through direct oxidation of dimethylamine, as they also
appear at the same temperatures in the oxidation of dimethyl-
amine on O/Au(111) (data not shown). Apparently, at high O
coverage, combustion of dimethylamine competes directly
with acylation.
The selectivity for N,N-dimethylformamide from coupling
between dimethylamine and formaldehyde thus decreases
with initial oxygen coverage employed (Figure 2). At low
initial oxygen coverage, the selectivity approaches 100%. As
the initial oxygen coverage increases, the selectivity drops to
30% at qo = 1 ML, where combustion reactions dominate,
consistent with the general trend observed in self-coupling
reactions of alcohols.[16,17]
The reaction steps involved in the selective acylation of
dimethylamine, including those suggested for secondary
oxidation, are summarized in Scheme 1. Evidence for specific
intermediates is obtained using X-ray photoelectron spec-
troscopy. The evolution of the N(1s) and C(1s) X-ray
photoelectron peaks with heating show that dimethylamine
is first converted to (CH3)2N(a) by abstraction of the amino
hydrogen (Figure 3). Secondary oxidation leads to the
formation of N-methylformamide and methylisocyanate.
(Figure 3 and Table S1, complementary reactivity data is
shown in Figure S2).
Figure 1. Reaction of dimethylamine and formaldehyde on O/Au(111)
yields N,N-dimethylformamide in temperature-programmed reaction
spectra obtained after introducing: a) [D0]dimethylamine (9 L) and
b) [D6]dimethylamine ((CD3)2NH) (9 L) both followed by
[D0]formaldehyde (27 L) on O/Au(111) (qo =0.15 ML) at 120 K. In
c) [D0]dimethylamine (9 L) and [D2]formaldehyde (27 L) were sequen-
tially dosed onto O/Au(111) (qo =0.15 ML) at 120 K. The contributions
from fragmentation of dimethylamine and N,N-dimethylformamide to
the m/z 44 and m/z 46 signals were subtracted for clarity in (a). No
Dimethylamine condensed on clean Au(111) is charac-
terized by a single N(1s) peak with a binding energy (BE) of
reaction is detected on clean Au(111). The heating rate was 4 Ksꢀ1
.
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Communications
Figure 2. Selectivity for production of N,N-dimethylformamide (the
ratio of m/z 73 signal to the sum of m/z 44 and m/z 73 signals,
corrected for fragmentation) vs. initial oxygen coverage.
Figure 3. X-ray photoelectron spectra. a) N(1s) region following:
i) condensation of dimethylamine multilayers on Au(111) at 120 K,
ii) adsorption of dimethylamine on O/Au(111) (qo =0.15 ML) at 120 K
and subsequently heated to iii) 200 K and iv) 300 K. b) O(1s) region
for: i) as-prepared O/Au(111) (qo =0.15 ML) and ii–iv) after the same
treatment as in (a), plots ii–iv. All spectra were obtained after cooling
to 120 K.
399.7 eV (Figure 3a, plot i). When dimethylamine is adsorbed
onto O-covered Au(111) at 120 K (qo = 0.15 ML), the N(1s)
peak broadens and shifts to lower binding energy, which is
deconvoluted into a peak at 399.7 eV, assigned to molecular
dimethylamine, and one at 398.7 eV, ascribed to (CH3)2N(a),
(Figure 3a, plot ii). The (CH3)2N(a) formed from deprotona-
tion of dimethylamine by the adsorbed O [Eq. (5)], is
signified by a N(1s) peak at 398.7 eV, in excellent agreement
with the previous identification of (CH3)2N(a) on Cu(211).[27]
When the surface is heated to 200 K, the N(1s) spectrum
broadens, ultimately leading to a new feature at 398.5 eV that
persists when the surface is heated to 300 K (Figure 3a,
plots iii and iv), and which is attributed to CH3NCH2O(a) , the
decrease to 40% and 80%, respectively, of their amounts at
120 K after heating to 200 K. The decrease in the amount of
(CH3)2N(a) is attributed to its conversion to the precursor for
secondary oxidation products. This argument is supported by
reactivity experiments. If after adsorbing dimethylamine on
O/Au(111) (qo = 0.15 ML) at 120 K, the surface was heated to
200 K, 250 K or 300 K and then cooled back to 120 K, very
little N,N-dimethylformamide was formed after subsequent
exposure to formaldehyde. These observations are supporting
evidence that the (CH3)2N(a) is the key intermediate for the
coupling to form the N,N-dimethylformamide. Nearly the
same amount of methylisocyanate and N-methylformamide
was formed after each of these heat treatments, consistent
with the formation of the precursor
= =
=
precursor to CH3N C O and CH3N(H)C(H) O.
The concentrations of adsorbed (CH3)2NH(a) and
(CH3)2N(a) decrease substantially following heating of the
surface (Figure 3), based on the decrease in their character-
istic N(1s) peak intensities. The (CH3)2NH(a) and (CH3)2N(a)
to secondary oxidation below
200 K.
The O(1s) feature supports our
identification of the precursor to
secondary oxidation. At a coverage
of 0.15 ML the O(1s) peak for
adsorbed O is at 529.7 eV (Fig-
ure 3b, plot i). After dimethyla-
mine is dosed onto the surface at
120 K, a shoulder appears at higher
binding energy. When the surface is
heated to 200 K, water desorbs,[28]
and a peak appears at 531.6 eV
(Figure 3b, plot iii), which is
assigned to the precursor for the
secondary oxidation products.
Accordingly, this peak persists to
300 K (Figure 3b, plot iv). The
atomic ratio of C:N:O in this pre-
cursor was calculated as 2:1:1 using
Scheme 1. Proposed mechanisms for the coupling of dimethylamine with formaldehyde and the
secondary oxidation of dimethylamine promoted on O/Au(111).
396
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Angewandte
Chemie
integrated areas of C(1s), N(1s), and O(1s) peaks, corrected
for their corresponding sensitivity factors. Since, aside from
combustion products, the only species that evolve above
300 K are methylisocyanate and N-methylformamide, it is
hydes.[18] We are currently generalizing this process to other
reaction combinations to firmly extend this generality.
reasonable to identify the N-containing surface species at Experimental Section
Clean Au(111) was prepared as described previously.[26] All temper-
300 K as CH3NCH2O(a), the precursor to these secondary
oxidation products. We suggest this species is formed by:
ature programmed reaction data were obtained with well-established
protocols.[26] The reaction products were identified by quantitative
mass spectrometry (Balzers Prisma QMS 200) using fragmentation
patterns obtained from authentic samples. The initial surface
concentration of oxygen atoms was reproducibly varied by controlling
the ozone flux. Following exposure of the oxygen-covered Au(111) to
dimethylamine and formaldehyde at 120 K, temperature pro-
grammed reaction was employed to identify reaction products and
to interrogate the mechanism of the reactions. The X-ray photo-
electron spectra were acquired with an analyzer passing energy of
17.9 eVand a multiplier voltage of 3 kVusing MgKa X-rays (300 W) as
the excitation source. The binding energy (BE) calibration was
referenced to the Au 4f7/2 peak at 83.8 eV. The N(1s) and O(1s)
spectra were acquired by multiple scans (300 and 100 cycles,
respectively) to enhance the signal-to-noise ratio.
ðCH3Þ2NðaÞ þ OðaÞ ! CH3NCH2OðaÞ þ OHðaÞ
ð8Þ
The work reported here establishes a general mechanistic
framework for anticipating an entire class of amine acylation
reactions using aldehydes promoted by O-covered Au
(Scheme 1). The strong parallels with the esterification of
alcohols, the pattern of products formed using deuterium
labeling, and the spectroscopic evidence for the key
(CH3)2N(a) intermediate are strong evidence for the nucleo-
philic attack on the aldehydic carbon by this intermediate.
Our work also has implications for selective amine
acylation over supported Au catalysts: the mechanism
established here for unsupported Au in the vapor phase
may also contribute to the reactive chemistry even in the
liquid phase using formaldehyde as the acylation agent (e.g.,
in aqueous solution). The mechanism proposed is general and
not limited to acylation of dimethylamine; other aldehydes
may also be used. The key factor reported herein in
determining selectivity is abstraction of a single H atom
Received: October 8, 2009
Published online: December 3, 2009
Keywords: acylation · cross-coupling · gold catalysis ·
.
heterogeneous catalysis · reaction mechanism
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ꢀ
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activation, to form an adsorbed amide. Molecular species,
including water, are weakly bound to Au, so that even in
solution their steady-state coverages will be low. Recent
studies of benzyl amine acylation in methanol solution were
explained by a combination of Au-mediated oxidative
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oxygen-assisted esterification is facile on Au surfaces, both in
the vapor and liquid phases. Importantly, we observe that
methyl formate does not react with dimethylamine on
Au(111) to any significant extent with or without adsorbed
oxygen on Au(111) under our conditions (Figure S3), lending
support to the acylation mechanism suggested by Haruta
et al. in methanol solution.
In conclusion, we have established that the cross-coupling
between dimethylamine and formaldehyde occurs with selec-
tivity approaching 100% at low coverage of adsorbed O on
metallic gold to form N,N-dimethylformamide through a
pathway with a low activation energy. The coupling reaction
occurs through the attack of nucleophilic (CH3)2N(a) on the
carbonyl carbon of the aldehyde. Such reactions appear
general to the coupling of alcohols and amines with aldehydes
to form esters and amides, through adsorbed alkoxides and
amides, respectively. Both nucleophilic reaction intermedi-
ates are formed selectively by reaction of their conjugate
acids with adsorbed oxygen. We anticipate that this principle
will apply to coupling of other amines and aldehydes,
analogous to the the cross-coupling of alcohols and alde-
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