Preparation and characterization of the enol of acetamide: 1-aminoethenol, a high-energy prebiotic molecule

Article abstract of DOI:10.1039/d0sc04906a

Amide tautomers, which constitute the higher-energy amide bond linkage, not only are key for a variety of biological but also prebiotic processes. In this work, we present the gas-phase synthesis of 1-aminoethenol, the higher-energy tautomer of acetamide, that has not been spectroscopically identified to date. The title compound was prepared by flash vacuum pyrolysis of malonamic acid and was characterized employing matrix isolation infrared as well as ultraviolet/visible spectroscopy. Coupled-cluster computations at the AE-CCSD(T)/cc-pVTZ level of theory support the spectroscopic assignments. Upon photolysis at λ > 270 nm, the enol rearranges to acetamide as well as ketene and ammonia. As the latter two are even higher in energy, they constitute viable starting materials for formation of the title compound. This journal is

Full text of DOI:10.1039/d0sc04906a

View Article Online
View Journal
Chemical
Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: A. Mardyukov, F.
Keul and P. R. Schreiner, Chem. Sci., 2020, DOI: 10.1039/D0SC04906A.
Volume
Number
9
1
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
7
January 2018
Pages 1-268
Chemical
Science
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
rsc.li/chemical-science
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 2041-6539
EDGE ARTICLE
Xinjing Tang et al.
Caged circular siRNAs for photomodulation of gene
expression in cells and mice
rsc.li/chemical-science

Please do not adjust margins
Page 1 of 6
Chemical Science
View Article Online
DOI: 10.1039/D0SC04906A
ARTICLE
Preparation and Characterization of the Enol of Acetamide: 1-
Aminoethenol, a High-Energy Prebiotic Molecule
Received 00th January 20xx,
Accepted 00th January 20xx
Artur Mardyukov,a Felix Keul,a and Peter R. Schreinera*
DOI: 10.1039/x0xx00000x
Amide tautomers, which constitute the higher-energy amide bond linkage, not only are key for a variety of biological but
also prebiotic processes. In this work, we present the gas-phase synthesis of 1-aminoethenol, the higher-energy tautomer
of acetamide, that has not been spectroscopically identified to date. The title compound was prepared by flash vacuum
pyrolysis of malonamic acid and was characterized employing matrix isolation infrared as well as ultraviolet/visible
spectroscopy. Coupled-cluster computations at the AE-CCSD(T)/cc-pVTZ level of theory support the spectroscopic
assignments. Upon photolysis at   270 nm, the enol rearranges to acetamide as well as ketene and ammonia. As the latter
two are even higher in energy, they constitute viable starting materials for formation of the title compound.
ing meteoritic impact.18-23 To date, more than 180 molecules24
have been identified in the interstellar medium (ISM) through
their rotational and vibrational transitions and there is evidence
Introduction
Complex molecular structures typically form from thermody-
namically very stable and thus unreactive small molecules that
often have to be transformed first into more reactive isomers
before they can react. A prime example is ubiquitously available
formaldehyde (H2CO)1 that can only provide a path to forming
for the existence of larger structures that await their identifica-
tion.15, 25 The interstellar presence of (pre)biotic molecules sug-
gests that these may have extraterrestrial origin on earth as
well26. A number of these molecules have been detected in the
ISM, such as the simplest ‘sugar’ glycolaldehyde27 and precursor
molecules to the amino acid glycine such as methylamine28 and
aminoacetonitrile.29 Amino acids have been identified in some
meteorites10, 30 but not in interstellar clouds. However, only a
few species with a peptide moiety have been detected in inter-
stellar space,31-33 with acetamide being the largest.17 Acetam-
ide has been identified in the environments of Sagittarius B2
(SgrB2)17 and Orion KL34, and in comets35 (e.g., 67P/Churyumov-
Gerasimenko).36 This suggests that aqueous and ambient con-
ditions are not necessarily needed for the production of acet-
amide.34 Acetamide is one of the most abundant complex or-
ganic molecules on Sgr B2(N) and has been suggested to be a
source of larger peptidic molecules.34 The origin of acetamide
in the ISM remains unclear, as there is no established formation
mechanism that would allow its production in the gas phase.
Foo and colleagues37 used computations to propose reaction
pathways towards the synthesis of acetamide in the ISM. Eight
bimolecular reaction paths were suggested that could lead to
the formation of acetamide. 1-Aminoethenol (1), the tautomer
of acetamide (3, Scheme 1), has been suggested to be a key in-
termediate for the formation of 3 in the ISM,37 but has never
been observed. To date, only indirect evidence for the experi-
mental preparation of 138, 39 and its enolate40 in the gas phase
comes from mass spectrometric experiments; there are no
spectroscopic data available for 1.
sugars2 through its hydroxymethylene tautomer (H–C
̈–OH), a
highly reactive carbene, that had long been elusive3 but
nevertheless had been deemed the “activated form of
formaldehyde” for a long time.4 Another example is the
hydrogenated form of HCN (a molecule abundant in space),
namely methanimine (H2C=NH) and its tautomer aminocarbene
(H–C̈–NH2), whose structure has only very recently been
revealed.5 That is, the higher-energy tautomers of biologically
relevant building blocks are likely to play a key role also for the
emergence of the molecules relevant to life, but many of these
have not been identified and fully characterized.6-9
As complex organic molecules including amino acids,10 sugars,11
purine bases,12, 13 short peptides,14 have been identified in me-
teorites, prebiotic organic reactions must take place in the in-
terstellar medium through the activation of thermodynamically
highly stable small molecules such as CO, CO2, H2O, CH4, HCN
but also formaldehyde, simple alcohols, and a variety of carbox-
ylic acids and, particularly relevant to the present study, their
amides.15-17 The formation of complex organic molecules has
been suggested to take place through various scenarios includ-
a. Artur Mardyukov, Felix Keul, and Peter R. Schreiner
Institute of Organic Chemistry, Justus Liebig University,
Heinrich-Buff-Ring 17, 35392 Giessen, Germany
E-mail: prs@uni-giessen.de
b. Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Amide 3 has been produced in various model ice experiments.41,
42
Henderson and Gudipati43 reported the synthesis of 3
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 2 of 6
ARTICLE
Chemical Science
through electron bombardment and/or UV irradiation of H2O, solution by addition of diethylamine to the corresponding aryl
View Article Online
NH3, and CH3OH ices at 5 and 70 K. Belloche et al.33 suggested substituted ketene.64
The isolation and spectroscopic
DOI: 10.1039/D0SC04906A
the formation of 3 to occur through H-abstraction from forma- characterization of unsubstituted enols of amides,57 however,
mide followed by methyl radical addition. Garrod et al.44 pro- has been elusive. To date, only conjugated amide enols were
61, 63
posed that the addition of CH3 to HNCO might be responsible identified using time-resolved spectroscopy.58,
Turecek
for the formation of 3 on grain surfaces. CH4-HNCO ice mixtures and coworkers65, 66 described several simple neutral enols that
at 20 K were irradiated with vacuum ultraviolet (VUV) photons were generated by flash pyrolysis from bicyclo[2.2.1]heptene
to produce the radicals required for the formation of the am- derivatives and characterized by high-resolution mass
ides, which then were identified by IR spectroscopy as well as spectrometry and ionization energy measurements in the gas
mass spectrometry.41 Recently, Haupa et al.45 found that the phase. Very recently, we reported the preparation of previously
reaction of atomic hydrogen with acetamide in solid p-H2 at 3.3 elusive 1,1-ethenediol (7), the enol of acetic acid, through flash
K produces the 2-amino-oxoethyl (•CH2CONH2) radical, which vacuum pyrolysis of malonic acid and subsequent product
further dissociates to ketene and •NH2 upon UV/Vis photolysis. trapping in argon matrices.67
As it is likely that amide enols are potentially detectable inter-
O
C
stellar molecules, we present here the generation and spectro-
scopic characterization of hitherto unreported parent amide
enol 1 and its deuterated isotopologue (d5-1) through flash vac-
uum pyrolysis of malonamic acid (3-amino-3-oxopropanoic
acid, 2) and d5-malonamic acid (d5-2), respectively. The pyroly-
sis products were isolated in argon matrices and characterized
by IR and UV/Vis spectroscopy by matching their spectra with
computations at the CCSD(T)/cc-pVTZ level of theory. Apart
from being a fundamentally important molecule, our results will
also aid the detection of 1 in interstellar space to provide a basis
for its involvement in the synthesis of larger biologically rele-
vant molecules.
H
N
+ NH3
H
H
O
H
O
 > 270 nm
OH
400 °C
H
H
4
Ar, 10 K
H2N
O
O
H
2
1
H2N
CH3
3
Scheme 1. 1-Aminoethenol (1) synthesized from malonamic acid (2) through
flash vacuum pyrolysis and trapping in an argon matrix. Subsequent
photorearrangement to acetamide (3) as well as ketene (4) and ammonia.
There is growing evidence that enols are building blocks in
prebiotic chemistry.46-48 Several enols have been postulated to
play a key role in the synthesis of carbohydrates in prebiotic
cycles.46 For instance, 1,2-ethenediol, the enol of glycolalde-
hyde, has been implied to contribute to the formation of carbo-
hydrates in early Earth environments.47 The interstellar detec-
tion of the simplest enol (vinyl alcohol, CH2=CHOH) in its syn and
anti forms through microwave emissions from Sagittarius B2
was reported in 2001.49 Laboratory experiments on plasma
discharged of alcohols showed the presence of several enols,
suggesting that enols can form from alcohols by high energy
(cosmic) irradiation.50 Ethenol was thereby generated in the gas
phase and characterized by microwave51, 52 and photoelectron
spectroscopy.53 Kable et al. showed that ethenol forms from
acetaldehyde upon UV (310–330 nm) irradiation.54 Hawkins
and Andrews reported the formation of acetaldehyde, ethylene
oxide, ketene, and ethenol as primary products by photolysis of
ozone in argon matrices containing ethene.55 Nunes et al.
showed that pyrolysis of isoxazole leads to the formation of (Z)-
3-hydroxypropenenitrile, which was subsequently photoiso-
merized by UV-irradiation to its (E)-isomer.56
Enols of simple amides are rather elusive species due to their
high thermodynamic instability and hence high reactivity com-
pared to their corresponding amide isomers, and so far, no clear
evidence has been presented regarding their existence.57 Only
a few examples are known in the literature.58-61 Hegarty et al.62
as well as Wagner et al.63 suggested the formation of amide
enols as intermediates in the hydration of arylketene imines
and amination of arylketenes by transient time-resolved
spectroscopy. Frey and Rappoport showed the synthesis and
NMR spectrum of a conjugated amide enol with bulky
substituents (Tip2=C(OH)NMe2, tip=2,4,6-triisopropylphenyl) in
Results and discussion
We prepared 1 by thermal extrusion of CO2 from 2, which was
evaporated from a storage bulb at 70 °C and passed through a
quartz pyrolysis tube, after which the pyrolysis products were
co-condensed with a large excess of argon on the surface of the
10 K matrix window. After various attempts, we determined
400 °C as the optimal pyrolysis temperature. Under these con-
ditions, the decarboxylation of 2 is facile as evident by the ap-
pearance of the very strong asymmetric stretching vibration of
CO2 at 2345 cm1. Along with CO2, H2O, and 3 (vide infra), we
observed a set of new IR bands that we assign to 1. The excel-
lent match in the direct comparison of the experimental and the
ab initio computed [AE-CCSD(T)/cc-pVTZ] IR spectrum confirms
this finding. Notably, a strong band at 1682 cm1 is attributed
to the C=C stretching mode in 1 (Figure 1, note that 1 is non-
planar due to pyramidalization around nitrogen) that agrees
well with previous IR measurements for conjugated
(amide)enols. Wagner and colleagues63 observed a transition
band at 1680 cm1 in the reaction of phenyl ketene with
diethylamine, which was attributed to the C=C stretch of the
corresponding enol amide. The very prominent bands at 3647,
3510, and 3413 cm1 can be assigned to the OH stretching mode
as well as the asymmetric and symmetric NH2 stretching modes
of 1, respectively (Figure S1). A less intense NH2 deformation
band mode was found at 1607 cm1 along with bands at 727 and
694 cm1 for the CH2 wagging and as well as out of plane rocking
modes. With the aid of the computations additional medium
and weakly intense bands were attributed to 1 (Table S1). We
also observed other intense bands at 1727, 1586, 1367, and
2 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 6
Chemical Science
Please do not adjust margins
Chemical Science
ARTICLE
1313 cm1 in the IR spectrum of the pyrolysis mixture, which The photolysis of 3 has been the subject of several VsiteuwdAireticsleinOntlhinee
70
71
were attributed to 3 that forms from 1 via 1,3[H] shift in the gas gas phase, solution,69, in low-temperature matrices, and
phase. Structure 3 was identified by comparison with matrix- computationally.72 In argon matrices, VUV irradiation of 3 has
isolated data of an authentic sample. A very prominent band at been shown to produce HNCOCH4 and COCH3NH2 molecular
DOI: 10.1039/D0SC04906A
2138 cm1 is assigned to ketene (4) (vide infra).68
complexes, and acetimidic acid;71 these results could readily be
The formation of 1 is also supported by isotopic labelling exper- reproduced here. Gas-phase UV-photolysis of 3 results in the
iments using d5-2 (Figure S2). Large isotope red-shifts are found formation of CO, •CH3 and •NH2 radicals and CH3CN through de-
for the OH as well as the NH2 asymmetric and symmetric hydration.73 Note that irradiation of 3 ( > 270 nm) does not
stretching modes of 955, 893, and 928 cm1, in good agreement result in rearrangements or decomposition.
with the unscaled computed shifts of 1048, 957, and 985 cm1. The UV/Vis spectrum of enol 1 shows a strong absorption band
The shift of the C=C stretch is 51 cm1 (calc. 59 cm1). The at ~212 nm, in excellent agreement with the computed value of
scissoring vibration of the CH2 group shows an isotope shift of – 207 nm (f = 0.190) utilizing time-dependent (TD) density func-
349 cm1 (calc. 346 cm1). The CH2 in-plane and out of plane tional theory employing B3LYP/6-311++G(2d,2p). Moreover,
modes exhibit red shifts of 199 and 150 cm1, again in good TD-DFT computations showed weak transitions at 226 nm (f =
agreement with the computed shifts of 202 and 162 cm1, 0.026), 245 nm (f = 0.008), and 282 nm (f = 0.003). Unfortu-
respectively. Overall, the IR frequencies, intensities, and iso- nately, due to the low extinction coefficients, the UV/Vis transi-
topic shifts of two isotopologues (1 and d5-1) closely match the tions of 1 much above 212 nm could not be detected. The short-
computed data (Table S1), the only exception being the NCC out wavelength absorption at ~212 nm originates from a HOMO–
of plane and NOC in plane deformation modes, for which the LUMO+3 excitation, which corresponds to a -* transition (Fig-
computed intensities are higher than those measured; the NCC ure 2). In accordance with the IR experiments, irradiation of the
in plane vibrational frequency could not be ambiguously matrix with wavelength  > 270 nm leads to complete disap-
assigned in the IR spectrum because the low signal-to-noise pearance of the observed UV band. The computed bands of 3
ratio in this spectral region hampers its identification.
and 4 in the region at ~210–215 nm display low extinction
coefficients and therefore transitions of 3 and 4 could not be
detected (Figure S3).
Figure 1. IR spectrum showing the pyrolysis product of 2 with subsequent trapping in an
argon matrix at 10 K. (a) IR spectrum of 1 computed at AE-CCSD(T)/cc-pVTZ (unscaled).
(b) IR difference spectrum showing the photochemistry of 1 after irradiation with  > 270
nm in argon at 10 K. Downward bands assigned to 1 disappear while upward bands as-
signed to 3 and 4 appear after 30 min irradiation time. (c) IR spectrum of 3 computed at
AE-CCSD(T)/cc-pVTZ (unscaled).
Figure 2. Solid line: UV/Vis spectrum of 1 isolated at 10 K in Ar. Dashed lines: the pho-
tochemistry of 1 after irradiation at  > 270 nm for 1, 5, and 15 min in argon at 10 K.
Inset: computed [TD-B3LYP/6-311++G(2d,2p)] electronic transitions for 1.
We also computed the potential energy hypersurface surround-
ing 1. According to our CCSD(T)/cc-pVTZ computations, 1 exists
in two distinct conformations: anti-1 where the OH group has
an anti-orientation to the NH2 group, and syn-1 with a syn-ori-
entation of the OH group; anti-1 is 0.9 kcal mol1 (H0) more
stable than syn-1. The activation enthalpy for the anti-1  syn-
1 conformational isomerization is 3.9 kcal mol1. The effect of
nitrogen substitution on the electronic structure of 1 relative to
ethylene and other enols can be estimated from the HOMO-
LUMO energy differences (Figure S4). Substitution of one OH
group with NH2 leads to destabilization of the HOMO energy,
resulting in a smaller HOMO-LUMO gap in 1 (0.195 eV) com-
pared to 1,1-ethenediol (0.207 eV). This indicates that 1 is
more nucleophilic than 1,1-ethenediol but also that it can be ox-
Photolysis of the matrix-isolated pyrolysis products ( > 270 nm)
selectively bleached the IR bands of 1 (other species remained
unchanged) and simultaneously IR bands matching those of 3
appeared. The formation of 3 from 1 through 1,3[H]-migration
is also strongly supported by isotopic labelling experiments
using d5-1; irradiation the matrices of d5-1 produces d5-3. Along
with the IR bands of 3, UV irradiation ( > 270 nm) of matrix
isolated 1 resulted in the formation of a strong IR band at 2138
cm1 with an isotopic shift of 27 cm1 (calc.: 24 cm1 in d5-4)
that can readily be assigned to the C=O stretching mode of
ketene (4) as the deamination product of 1. No other product
bands appeared under these conditions.
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2020, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 4 of 6
ARTICLE
Chemical Science
idized more readily. Nitrogen as a superior -donor leads to containing 1 in the dark at 10 K the IR bands Voiefw A1rticrleemOnalinine
DOI: 10.1039/D0SC04906A
even larger destabilization of the HOMO with (EHOMO – ELUMO
)
unchanged over the course of six days.
value of 0.190 eV in 1,1-diaminoethylene (Figure S4). The C=C The spectroscopic proof for the existence of 1 is important in
bond of 1.337 Å in 1 is slightly shorter than that in 1,1-eth- the context of the abiotic formation of heteroatomic organic
enediol (1.343 Å, Figure S5).67 This is also evident from the ex- molecules that are relevant for the formation of biologically
perimentally observed C=C stretching vibration of 1 that is red- relevant building blocks. Our studies can aid the identification
shifted by 30 cm1 in comparison to the C=C stretching vibration of 1 in interstellar media. As both ketene and ammonia have
of 1712 cm1 in the diol.67 By comparison of the experimentally been detected in interstellar clouds,76, 77 the discovery of 1 is
observed IR spectrum with the computed spectra of anti-1 and only a matter of time because this bimolecular reaction is ca. –
syn-1, we conclude that only conformer anti-1 is present in the 18 kcal mol–1 exothermic. The barrier of this amination is too
argon matrix. Indeed, the syn-1 to anti-1 conformational high to occur under interstellar conditions, it may well be
transformation is associated with a very fast computed significantly lowered through NH3 and/or H2O catalysis on ices
quantum mechanical tunnelling (QMT) half-life of 2.72  108
s
or dust grains, as evident from numerous studies78, 79 showing
(for additional information please see the supporting that the activation energy for the addition of NH3 to ketene can
information).
be significantly lowered through a second ammonia molecule
The enol to amide (13) interconversion proceeds through that acts as a bifunctional catalyst.78
non-planar transition structure (TS2) and requires activation of
39.1 kcal mol1 (Figure 3), which is similar to [1,3]H-shift in 1,1-
ethenediol to acetic acid.67 Generally speaking, such [1,3]H-
shifts are highly unfavourable because they involve 4-
electron/4-center transition structures. The related [1,3]H-shift
from syn-1 to acetimidic acid (6) is characterized by an even
higher barrier (TS5) of 54.1 kcal mol1. The formation of
ketenimine 8 and water from anti-1 is associated with a similarly
high barrier (TS4) of 59.7 kcal mol1; 5 has been detected in the
star-forming region Sagittarius B2(N).74 We did not observe 5
and 6 in our FVP experiments, in accordance with our
computations that render these two reactions rather unlikely at
FVP temperature of ~400 °C due to the excessively high
activation barriers. We do observe the characteristic peaks of 3
and 4 directly after FVP, suggesting that the energy in the
pyrolysis zone is sufficiently high for 1 to undergo a [1,3]H-shift
Conflicts of interest
No competing financial interests have been declared.
Acknowledgements
This work was supported by the Volkswagen Foundation (“What
is Life” grant 92 748). We thank Bastian Bernhardt for help with
the QMT computations.
Author Contributions
A. M. and P. R. S. conceived the idea. A. M. carried out all ex-
perimental and computational studies. F. K. synthesized the
starting material. A. M. and P. R. S. analysed and discussed all
data. A. M. and P. R. S. co-wrote the manuscript.
‡
to 3 (∆H0 =39.1 kcal mol–1) and decomposition to produce 4 and
ammonia (∆H0 =35.6 kcal mol–1). Formation of acetimidic acid
‡
(6, two conformers are shown in Fig. 3) from 1 is exothermic by
–11 to –12 kcal mol1 but requires 55 kcal mol1 activation. In
contrast to 1, 4, and 6 have been synthesized and characterized
in argon matrices by vacuum ultraviolet irradiation of 3 by
Duvernay et al.71
Notes and references
1.
2.
3.
L. E. Snyder, D. Buhl, B. Zuckerman and P. Palmer, Phys.
Rev. Lett., 1969, 22, 679.
A. K. Eckhardt, M. M. Linden, R. C. Wende, B. Bernhardt
and P. R. Schreiner, Nat. Chem., 2018, 10, 1141-1147.
P. R. Schreiner, H. P. Reisenauer, F. C. Pickard, A. C.
Simmonett, W. D. Allen, E. Matyus and A. G. Csaszar,
Nature, 2008, 453, 906-909.
4.
5.
R. Breslow, Tetrahedron Lett., 1959, 22-26.
A. K. Eckhardt and P. R. Schreiner, Angew. Chem., Int. Ed.,
2018, 57, 5248-5252.
6.
7.
8.
S. L. Miller and H. C. Urey, Science 1959, 130, 245-251.
J. L. Bada, Chem. Soc. Rev., 2013, 42, 2186-2196.
G. M. Muñoz Caro, U. J. Meierhenrich, W. A. Schutte, B.
Barbier, A. Arcones Segovia, H. Rosenbauer, W. H. P.
Thiemann, A. Brack and J. M. Greenberg, Nature, 2002,
416, 403-406.
Figure 3. Potential energy profile (H0) in kcal mol1 of the reactions of enol 1 at AE-
CCSD(T)/cc-pVTZ + ZPVE at 0 K.
9.
K. Ruiz-Mirazo, C. Briones and l. E. A. de, Chem. Rev.,
2014, 114, 285-366.
10.
K. Kvenvolden, J. Lawless, K. Pering, E. Peterson, J. Flores,
C. Ponnamperuma, I. R. Kaplan and C. Moore, Nature,
1970, 228, 923-926.
Apart from fast C–O bond rotation, 1 does not display QMT
reactivity because the barriers are generally too high and too
wide.75 This is evident from the fact that when keeping matrices
4 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 6
Chemical Science
Please do not adjust margins
Chemical Science
ARTICLE
11.
Y. Furukawa, Y. Chikaraishi, N. Ohkouchi, N. O. Ogawa, D.
P. Glavin, J. P. Dworkin, C. Abe and T. Nakamura, Proc.
Natl. Acad. Sci. , 2019, 116, 24440-24445.
M. P. Callahan, K. E. Smith, H. J. Cleaves, II, J. Ruzicka, J. C.
Stern, D. P. Glavin, C. H. House and J. R. Dworkin, Proc.
Natl. Acad. Sci. , 2011, 108, 13995.
Meierhenrich, G. M. M. Caro, F. Raulin, R. Roll, A. Steele,
View Article Online
H. Steininger, R. Sternberg, C. Szopa, W. Thiemann and S.
DOI: 10.1039/D0SC04906A
Ulamec, Science, 2015, 349, 497.
12.
37.
L. Foo, A. Surányi, A. Guljas, M. Szőri, J. J. Villar, B.
Viskolcz, I. G. Csizmadia, A. Rágyanszki and B. Fiser, Mol.
Astrophys., 2018, 13, 1-5.
13.
14.
P. G. Stoks and A. W. Schwartz, Nature 1979, 282, 709.
A. Shimoyama and R. Ogasawara, Origins Life Evol.
Biosphere, 2002, 32, 165-179.
C. R. Arumainayagam, R. T. Garrod, M. C. Boyer, A. K. Hay,
S. T. Bao, J. S. Campbell, J. Wang, C. M. Nowak, M. R.
Arumainayagam and P. J. Hodge, Chem. Soc. Rev., 2019,
48, 2293-2314.
W. M. Irvine, Origins Life Evol. Biosphere, 1998, 28, 365-
383.
J. M. Hollis, F. J. Lovas, A. J. Remijan, P. R. Jewell, V. V.
Ilyushin and I. Kleiner, Astrophys. J., 2006, 643, L25.
P. Ehrenfreund and S. B. Charnley, Annu. Rev. Astron.
Astrophys., 2000, 38, 427-483.
G. Danger and L. Le Sergeant d'Hendecourt, Actual. Chim.,
2012, 363, 31-35.
C. F. Chyba, P. J. Thomas, L. Brookshaw and C. Sagan,
Science, 1990, 249, 366.
B. Menez, C. Pisapia, C. Pisapia, F. Jamme, P. Dumas, M.
Refregiers, M. Andreani, Q. P. Vanbellingen, A. Brunelle
and L. Richard, Nature, 2018, 564, 59-63.
U. J. Meierhenrich, Cell. Origin Life Extreme Habitats
Astrobiol., 2004, 7, 183-186.
38.
39.
M. A. Trikoupis, P. C. Burgers, P. J. A. Ruttink and J. K.
Terlouwa, Int. J. Mass Spectrom., 2001, 210/211, 489-502.
D. Schröder, J. Loos, R. Thissen, O. Dutuit, P. Mourgues,
H.-E. Audier, C. Lifshitz and H. Schwarz, Angew. Chem.,
Int. Ed., 2002, 41, 2748-2751.
M. C. Hare, S. S. Marimanikkuppam and S. R. Kass, Int. J.
Mass Spectrom., 2001, 210/211, 153-163.
N. F. W. Ligterink, J. T. van Scheltinga, V. Taquet, J. K.
Joergensen, S. Cazaux, E. F. vanDishoeck and H. Linnartz,
Mon. Not. R. Astron. Soc., 2018, 480, 3628-3643.
M. P. Bernstein, S. A. Sandford, L. J. Allamandola, S. Chang
and M. A. Scharberg, Astrophys. J., 1995, 454, 327.
B. L. Henderson and M. S. Gudipati, Astrophys. J., 2015,
800, 66/61.
R. T. Garrod, S. L. Widicus Weaver and E. Herbst,
Astrophys. J., 2008, 682, 283-302.
K. A. Haupa, W.-S. Ong and Y.-P. Lee, Phys. Chem. Chem.
Phys., 2020, 22, 6192-6201.
H.-J. Kim, A. Ricardo, H. I. Illangkoon, M. J. Kim, M. A.
Carrigan, F. Frye and S. A. Benner, J. Am. Chem. Soc.,
2011, 133, 9457-9468.
A. Ricardo, M. A. Carrigan, A. N. Olcott and S. A. Benner,
Science, 2004, 303, 196.
A. J. Coggins and M. W. Powner, Nat. Chem., 2017, 9, 310-
317.
B. E. Turner and A. J. Apponi, Astrophys. J., 2001, 561,
L207-L210.
J. Wang, Y. Li, T. Zhang, Z. Tian, B. Yang, K. Zhang, F. Qi, A.
Zhu, Z. Cui and C.-Y. Ng, Astrophys. J., 2008, 676, 416-419.
S. Saito, Chem. Phys. Lett., 1976, 42, 399-402.
M. Rodler and A. Bauder, J. Am. Chem. Soc., 1984, 106,
4025.
G. Y. Matti, O. I. Osman, J. E. Upham, R. J. Suffolk and H.
W. Kroto, J. Electron Spectrosc. Relat. Phenom., 1989, 49,
195-201.
D. U. Andrews, B. R. Heazlewood, A. T. Maccarone, T.
Conroy, R. J. Payne, M. J. T. Jordan and S. H. Kable, Science
2012, 337, 1203-1206.
M. Hawkins and L. Andrews, J. Am. Chem. Soc., 1983, 105,
2523.
C. M. Nunes, I. Reva, T. M. V. D. Pinho e Melo, R. Fausto,
T. Solomek and T. Bally, J. Am. Chem. Soc., 2011, 133,
18911-18923.
15.
40.
41.
16.
17.
18.
19.
20.
21.
42.
43.
44.
45.
46.
22.
23.
47.
48.
49.
50.
V. K. Pearson, M. A. Sephton, A. T. Kearsley, P. A. Bland, I.
A. Franchi and I. Gilmour, Meteorit. Planet. Sci., 2002, 37,
1829-1833.
http://www.astrochymist.org/astrochymist_ism.html.
A. Belloche, H. S. P. Mueller, K. M. Menten, P. Schilke and
C. Comito, Astron. Astrophys., 2013, 559, A47/41.
A. Brack, Chem. Biodiversity, 2007, 4, 665-679.
24.
25.
26.
27.
J. M. Hollis, F. J. Lovas and P. R. Jewell, Astrophys. J., 2000, 51.
540, L107.
52.
28.
29.
N. Kaifu, M. Morimoto, K. Nagane, K. Akabane, T. Iguchi
and K. Takagi, Astrophys. J., 1974, 191, L135.
A. Belloche, K. M. Menten, C. Comito, H. S. P. Mueller, P.
Schilke, J. Ott, S. Thorwirth and C. Hieret, Astron.
Astrophys., 2008, 482, 179-196.
J. E. Elsila, D. P. Glavin and J. P. Dworkin, Meteorit. Planet.
Sci., 2009, 44, 1323-1330.
R. H. Rubin, G. W. Swenson, Jr., R. C. Benson, H. L. Tigelaar 55.
and W. H. Flygare, Astrophys. J., 1971, 169, L39.
B. E. Turner, A. G. Kislyakov, H. S. Liszt and N. Kaifu,
Astrophys. J., 1975, 201, L149.
A. Belloche, A. A. Meshcheryakov, R. T. Garrod, V. V.
53.
54.
30.
31.
32.
33.
56.
Ilyushin, E. A. Alekseev, R. A. Motiyenko, L. Margules, H. S. 57.
P. Mueller and K. M. Menten, Astron. Astrophys., 2017,
J. P. Richard, G. Williams, A. C. O'Donoghue and T. L.
Amyes, J. Am. Chem. Soc., 2002, 124, 2957-2968.
A. W. Acton, A. D. Allen, L. M. Antunes, A. V. Fedorov, K.
Najafian, T. T. Tidwell and B. D. Wagner, J. Am. Chem.
Soc., 2002, 124, 13790-13794.
601, A49/41.
58.
34.
35.
D. T. Halfen, V. Ilyushin and L. M. Ziurys, Astrophys. J.,
2011, 743, 60/61.
K. Altwegg, H. Balsiger, J. J. Berthelier, A. Bieler, U.
Calmonte, S. A. Fuselier, F. Goesmann, S. Gasc, T. I.
Gombosi, L. Le Roy, J. de Keyser, A. Morse, M. Rubin, M.
Schuhmann, M. G. G. T. Taylor, C. Y. Tzou and I. Wright,
Mon. Not. R. Astron. Soc., 2017, 469, S130.
F. Goesmann, H. Rosenbauer, J. H. Bredehoeft, M.
Cabane, P. Ehrenfreund, T. Gautier, C. Giri, H. Krueger, L.
Le Roy, A. J. MacDermott, S. McKenna-Lawlor, U. J.
59.
60.
61.
62.
M. R. M. Badal, M. Zhang, S. Kobayashi and M. Mishima, J.
Phys. Org. Chem., 2013, 26, 1071-1076.
A. D. Allen and T. T. Tidwell, J. Org. Chem., 1999, 64, 266-
271.
G. Raspoet, M. T. Nguyen, S. Kelly and A. F. Hegarty, J.
Org. Chem., 1998, 63, 9669-9677.
36.
A. F. Hegarty, J. G. Kelly and C. M. Relihan, J. Chem. Soc.,
Perkin Trans. 2, 1997, 1175-1181.
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2020, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 6 of 6
ARTICLE
63.
Chemical Science
B. D. Wagner, B. R. Arnold, G. S. Brown and J. Lusztyk, J.
View Article Online
DOI: 10.1039/D0SC04906A
Am. Chem. Soc., 1998, 120, 1827-1834.
J. Frey and Z. Rappoport, J. Am. Chem. Soc., 1996, 118,
3994-3995.
64.
65.
66.
F. Turecek, Tetrahedron Lett., 1984, 25, 5133.
F. Turecek, L. Brabec and J. Korvola, J. Am. Chem. Soc.,
1988, 110, 7984.
67.
68.
69.
70.
71.
A. Mardyukov, A. K. Eckhardt and P. R. Schreiner, Angew.
Chem., Int. Ed., 2020, 59, 5577-5580.
C. B. Moore and G. C. Pimentel, J. Chem. Phys., 1963, 38,
2816-2829.
S. R. Bosco, A. Cirillo and R. B. Timmons, J. Am. Chem.
Soc., 1969, 91, 3140.
G. H. Booth and R. G. W. Norrish, J. Chem. Soc., 1952, 188-
198.
F. Duvernay, P. Chatron-Michaud, F. Borget, D. M. Birney
and T. Chiavassa, Phys. Chem. Chem. Phys., 2007, 9, 1099-
1106.
72.
73.
74.
75.
X.-B. Chen, W.-H. Fang and D.-C. Fang, J. Am. Chem. Soc.,
2003, 125, 9689-9698.
B. C. Spall and E. W. R. Steacie, Proc. R. Soc. London, Ser.
A, 1957, 239, 1-15.
F. J. Lovas, J. M. Hollis, A. J. Remijan and P. R. Jewell,
Astrophys. J., 2006, 645, L137.
D. Ley, D. Gerbig and P. R. Schreiner, Org. Biomol. Chem.,
2012, 10, 3781-3790.
76.
77.
B. E. Turner, Astrophys. J., 1977, 213, L75-L79.
A. C. Cheung, D. M. Rank, C. H. Townes, D. D. Thornton
and W. J. Welch, Phys. Rev. Lett., 1968, 21, 1701.
K. Sung and T. T. Tidwell, J. Am. Chem. Soc., 1998, 120,
3043-3048.
C. K. Kim, K. A. Lee, J. Chen, H. W. Lee, B.-S. Lee and C. K.
Kim, Bull. Korean Chem. Soc., 2008, 29, 1335-1343.
78.
79.
6 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins