Evidence for the cyclic CN2 carbene in the gas phase

Article abstract of DOI:10.1021/ol5027602

3-Halodiazirine-3-carboxylic acids (c-CN₂XCOOH, X = Cl or Br) were prepared from their esters and converted to the corresponding sodium salts. Collision-induced dissociation (CID) of the carboxylate ions led exclusively to the loss of CO_2<

Full text of DOI:10.1021/ol5027602

Letter
pubs.acs.org/OrgLett
Evidence for the Cyclic CN2 Carbene in the Gas Phase
Eva Hanzlova,†,∥ Jirí Vana,‡,∥ Christopher J. Shaffer,§ Jana Roithova,*,‡ and Tomas Martinu*,†
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†Department of Organic Chemistry, University of Chemical Technology, Technicka
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5, 166 28 Prague, Czech Republic
‡Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030/8, 128 43 Prague, Czech
Republic
§Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam
́
. 2, 166 10 Prague,
Czech Republic
S
* Supporting Information
ABSTRACT: 3-Halodiazirine-3-carboxylic acids (c-
CN2XCOOH, X = Cl or Br) were prepared from their esters
and converted to the corresponding sodium salts. Collision-
induced dissociation (CID) of the carboxylate ions led
exclusively to the loss of CO2 and the resulting c-CN2X− ions
dissociated to c-CN2 carbene at low energies. The bond dissociation energy (BDE) for c-CN2Br− was found to be less than 8
kcal/mol using CID of the anion generated by electrospray ionization of the carboxylate. The analogous difluoro system
(CF2XCOOH/CF2X−/CF2) exhibits similar dissociative behavior. All experimental BDEs are in very good agreement with MP4/
aug-cc-pVTZ calculations.
he cyclic CN2 carbene (diazirinylidene, c-CN2) is one of the
simplest experimentally elusive reactive intermediates.
proposed mechanism is supported by deuterium labeling and a
detailed computational study covering the selectivity of the initial
nucleophilic displacement, lability of c-CN2X− ions to dissoci-
ation, and basicity and kinetic stability of all proposed
intermediates to isomerization.
T
Despite its formal classification as an N-heterocyclic carbene
(NHC), the ground-state singlet c-CN2 is predicted to be
electrophilic and can be considered a single-carbon atom donor
due to its potential for the extrusion of N2.1 We have found
experimental and computational evidence for the intermediacy of
c-CN2 in the reactions of 3-bromo- or 3-chlorodiazirine-3-
carboxylates 1 with alkoxide ions in a DMF solution below 0
°C.1,2 The formation of dialkyl carbonates, dialkoxymethanes,
and 2-oxabicyclo[4.1.0]heptanes in these reactions, accompa-
nied by the evolution of N2, can be explained by a nucleophilic
displacement of the corresponding c-CN2X− ion, readily
dissociating to c-CN2 (Scheme 1). The electrophilic c-CN2
This is the only system available so far for the generation of c-
CN2 in solution. The electrophilic c-CN2 is scavenged by the
strongly nucleophilic environment, hindering attempts at
trapping the carbene by [2 + 1] cycloaddition. On the other
hand, the cycloaddition of the intermediate alkoxycarbene has to
be facilitated by allowing it to proceed in an intramolecular
fashion so that it can compete with the fast O−H insertion.
Given the limitations of solution chemistry, we set out to
exploit the well-defined conditions of gas phase experiments in
order to gain further evidence for the formation of c-CN2X− ions
and c-CN2 carbene.3 Initially, we subjected solutions of bromo
ester 1a and chloro ester 1b, respectively, to electrospray
ionization (ESI) and searched for the signals of the
corresponding c-CN2X− ions or the putative tetrahedral
intermediate ions (TIs) formed by the nucleophilic addition of
an alkoxide or hydroxide to the ester CO bond (Scheme 1).
We have explored the ionization and solvent conditions
(methanol, butan-1-ol, acetonitrile, addition of up to 50% v/v
water or DMF), but we only observed the corresponding halide
ions (free and water-solvated) to be the most abundant
fragments within the ESI source. These results may reflect the
expected metastability of both c-CN2X− ions1 and their parent
TIs4 under the employed conditions.
Scheme 1. Reaction of Esters 1 with Alkoxide Ions
reacts further with alkoxide ions in the presence of an alcohol,
eventually affording an alkoxymethylene, most probably by the
denitrogenation of a putative alkoxydiazirine. Final products arise
from the alkoxymethylene by an alcohol O−H insertion and
intramolecular [2 + 1] cycloaddition (when the alkoxy group
carries a suitably positioned and substituted CC bond). The
Therefore, we chose to use an alternative approach to the
generation of c-CN2X− and c-CN2 avoiding the intermediacy of
Received: September 18, 2014
Published: October 8, 2014
© 2014 American Chemical Society
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TIs, the collision-induced dissociation (CID) of halodiazirine
carboxylate ions c-CN2XCOO− (2). Graul and Squires found
decarboxylation to be the lowest energy fragmentation pathway
in CID of many different RCOO− ions.5 Importantly, this
process is known to be barrierless and continuously
endothermic. The measured bond dissociation energies
(BDEs) should thus match the theoretically predicted energy
demands for the formation of the separated R− ions and CO2. A
B3LYP/6-311+g(d) energy scan6 showed that the dissociation of
bromo ion 2a and chloro ion 2b to c-CN2X− and CO2 is indeed a
continuously endothermic process, and calculations at the MP4/
aug-cc-pVTZ//MP2/6-311+g(d) level7,8 predicted the BDEs of
24.5 and 27.8 kcal/mol, respectively. Subsequent dissociation of
c-CN2X− to c-CN2 and X− (X = Br, Cl) is less endothermic, with
calculated BDEs equal to 10.1 and 13.3 kcal/mol, respectively.
We have been able to prepare authentic samples of the
corresponding 3-halodiazirine-3-carboxylic acids 2-H and their
sodium salts 2-Na to be used in our CID experiments (Scheme
2). We obtained the bromo acid 2a-H by basic hydrolysis of the
Figure 1. IRMPD spectrum of an anion generated by ESI from
methanolic solution of 2a-Na (black line) and its comparison with the
theoretical B3LYP/6-311+G(d) IR spectra (lines represent the
theoretical spectra folded with the Gaussian function with full width
at half-maximum of 10 cm−1) calculated for 2a (red line) and 3a (blue
line) isomers; scaling factor was 0.975.
Scheme 2. Preparation of Acids 2-H and Salts 2-Na
n-butyl ester 1a in methanol9 or by dealkylation of the tert-butyl
ester 1c with trifluoroacetic acid; the chloro acid 2b-H can be
prepared by hydrolysis of the methyl ester 1b. Obtained in
moderate yields, the novel acids 2-H (formally trisubstituted
derivatives of acetic acid) are colorless low-melting crystalline
solids stable for hours at rt.10 The structural assignment of 2-H is
based on the 1H/13C NMR, IR, and HRMS spectra and
reactivity: (a) the quantitative conversion to the highly explosive
salts 2-Na using sodium methoxide in methanol; (b)
esterification with butan-1-ol using DCC/DMAP in dichloro-
methane affording the corresponding n-butyl esters (see the
Supporting Information (SI)).
We studied the structure of the ions generated by ESI from a
methanolic solution of the bromo carboxylate 2a-Na by infrared
multiphoton dissociation (IRMPD) spectroscopy.11 This
method provides infrared characteristics of isolated ions in the
gas phase.12,13 The IRMPD spectrum of the generated anions
shows two bands at 1700 and 1275 cm−1 that correspond well to
the predicted CO (1704 cm−1) and C−C (1268 cm−1)
stretching modes of ion 2a (Figure 1). In comparison, the
predicted C−C stretch of the alternative diazo isomer 3a is
suggested to be at significantly lower wavenumbers (1227 cm−1)
than found experimentally.
Figure 2. CID spectra of carboxylate ions (a) 2a and (b) 2b (79Br and
35Cl isotopomers) obtained using an Orbitrap mass spectrometer. The
intensities of the parent ions were normalized to 100 (off-scale); the
signals at nominal m/z 53 and 91 in (b) are scaled by a factor of 10.
ion, possibly formed by the loss of N2 (Figure 2b). These results
attest to the kinetic stability of the CN2 ring to opening in our
experiments as we have pointed out previously for our chemistry
in solution.1b
We continued in the characterization of ions 2a and 2b by CID
with the aim to extract their experimental BDEs for
decarboxylation. We have used two fundamentally different
mass spectrometers (triple quadrupole and ion trap instruments)
and thus two independent approaches for evaluation of the
obtained data. The results obtained with the triple quadrupole
instrument were evaluated using Chen’s L-CID procedure.17 The
energy-dependent CID curves were measured at several collision
gas pressures. The obtained threshold energies were extrapolated
to zero pressure (see the SI). The dissociation threshold for
decarboxylation of the bromo carboxylate 2a was determined as
22.3 0.4 kcal/mol, and that of the chloro carboxylate 2b as 27.6
0.3 kcal/mol. These values are in excellent agreement with the
predicted BDEs (Table 1). We note in passing that
decarboxylation was always accompanied by subsequent
dehalogenation, and for the determination of the threshold
energy for the CO2 loss from 2a and 2b, the sum of the
Having confirmed the structure of bromo ion 2a isolated in the
gas phase, we have performed its CID and determined the exact
masses of its fragment ions. We have observed that 2a dissociates
CO2 as expected, resulting in a mixture of CN2Br−, Br−, and
H2OBr− ions, with no other fragmentations competing (Figure
2a). It should be pointed out that the possibility of
denitrogenation of the diazirine ring in 2a was of concern.14,15
Analogously, CID of the chloro ion 2b afforded a mixture of
CN2Cl− and H2OCl− ions16 containing ca. 5% of the C2O2Cl−
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Letter
a
the isomeric 1CNN carbene and 1NCN nitrene in the rearranged
BrCNN− and BrNCN− ions are above 50 and 65 kcal/mol,
respectively.7,8 We have also attempted to determine the BDEs of
c-CN2 in c-CN2X− by an MS3 experiment using the ion trap
instrument. The fragment ions were, however, formed with a
sufficient internal energy to undergo spontaneous dehalogena-
tion even at zero collision energy.
Table 1. Calculated and Experimental BDEs
experimental (CID)
b
c
d
reaction
calcd
QOQ
IT
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
2a → c-CN2Br− + CO2
2b → c-CN2Cl− + CO2
4a → CF2Br− + CO2
24.5
27.8
22.1
26.3
10.1
13.3
7.3
22.3 0.4
27.6 0.3
20.0 0.1
26.9 0.8
19.1 1.2
29.6 1.2
18.0 0.9
4b → CF2Cl− + CO2
c-CN2Br− → c-CN2 + Br−
c-CN2Cl− → c-CN2 + Cl−
CF2Br− → CF2 + Br−
27.6 0.7
The very good mutual accordance between the calculated and
experimentally determined BDEs allowed us to explore other
related systems. Based on calculations we previously predicted
remarkable analogies between the electron affinities and
ionization potentials of c-CN2 and the fluoro carbenes FCX (X
= F or Cl).1a There are also close similarities between the
geometries, expected basicities, and BDEs of c-CN2X− and
CF2X− (X = Cl or Br) ions. Thus, we extended our CID
experiments to bromodifluoro- and chlorodifluoroacetate ions
(4a and 4b), introduced as sodium salts, and we have found that
their observed BDEs for the loss of CO2 indeed closely parallel
those of diazirine carboxylates 2a and 2b, in very good agreement
with theory (Table 1 and Figure 3). In addition, the weakly
bonded CF2X− ions20 eluded our experimental determination of
the BDE for the loss of CF2 carbene, likely for the same reasons as
given above for the c-CN2X−/c-CN2 pair. It should be
emphasized that the similar behavior of carboxylates 2 and 4 in
our CID experiments can be considered as indirect evidence for
the validity of the structural assignments of the c-CN2X− and c-
CN2 species.
e
<8.0
−
−
−
−
−
−
−
CF2Cl− → CF2 + Cl−
10.1
a
b
Values are in kcal/mol. Calculated at the MP4/aug-cc-pVTZ//
MP2/6-311+g(d) level (refs 7 and 8). Triple quadrupole. Ion trap.
c
d
e
Confidence interval not determined.
corresponding c-CN2X− and X− fragment abundances was
evaluated.
Analogous measurements were also performed with the ion
trap instrument, and the data were evaluated according to
Schroder’s procedure.18 Hence, the energy-dependent CID
̈
curves were fitted with sigmoid functions, and the extrapolation
of their tangent at the inflex to the baseline gave the threshold
energy (see the SI). The calibration of the collision energy scale
in the ion trap was made via decarboxylation of trifluoroacetate,
dichloroacetate, trichloroacetate, and benzoate ions as standards
(Figure 3).19 The BDEs for decarboxylation of 2a and 2b
In summary, we have prepared the novel halodiazirine
carboxylic acids 2-H and their sodium salts 2-Na. Carboxylate
ions 2 underwent the dissociation of CO2 during CID at low
energies, while no competing loss of N2 was observed for the
bromo anion 2a and only minor denitrogenation occurred with
the chloro anion 2b. The resulting c-CN2X− ions readily
dissociated to c-CN2 carbene, and the BDE for c-CN2Br− was
found to be less than 8 kcal/mol. The related system of
difluorohaloacetic carboxylates 4a,b, CF2X− ions, and CF2
carbene exhibited almost identical behavior, as predicted
previously. The structural assignments were based on very
good agreement between the calculated and experimental BDEs.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, spectroscopic data for all new
compounds, mass spectrometry and computational details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 3. Experimental vs calculated BDEs for decarboxylation of R−
COO− ions. Experimental values were obtained using an ion trap mass
spectrometer; calculations were done at the MP4/aug-cc-pVTZ//MP2/
6-311+g(d) level (refs 7 and 8). Squares and solid line correspond to
calibration species, triangles corresponds to studied species, and the
dotted line shows the correlation of all data points.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: martinut@vscht.cz.
determined using this simple ion-trap approach are 19.1 1.2
and 29.6 1.2 kcal/mol, respectively, in good agreement with
those theoretically predicted and obtained from the triple
quadrupole experiments (Table 1).
*E-mail: jana.roithova@natur.cuni.cz.
Author Contributions
∥E.H. and J.V. contributed equally.
In order to further confirm the cyclic structure of the CN2X−
fragment ions, we attempted to generate these species under
harder ionization/decarboxylation conditions in the ion source
and to determine the energy of their fragmentation to c-CN2
carbene. This approach was successful only for the bromo
derivative 2a in the triple quadrupole instrument with water as
the sheath liquid. The obtained BDE of c-CN2 in c-CN2Br−
amounts to less than 8.0 kcal/mol, which is again in very good
agreement with theory (Table 1), while the predicted BDEs of
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the European Research Council (StG
ISORI, No: 258299) and the Ministry of Education, Youth, and
Sports of the Czech Republic (Specific University Research
Grant MSMT 20/2014) is gratefully acknowledged. Mr. Philippe
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Letter
̂
Maitre and Mr. Vincent Steinmetz (CLIO) as well as Ms. Kvet
Bartova (ICT) are acknowledged for their help and assistance.
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a
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REFERENCES
■
(1) (a) Martinu, T.; Bohm, S.; Hanzlova,
́
E. Eur. J. Org. Chem. 2011,
̊
̈
̌
́ ́
6254. (b) Hanzlova, E.; Navratil, R.; Cejka, J.; Bohm, S.; Martinu, T. Org.
̈ ̊
Lett. 2014, 16, 852.
(2) The previously unpublished reaction of chloro ester 1b is slower
and lower yielding than that of bromo ester 1a, but both reactions afford
the same types of products; see the SI.
(3) The formation of c-CN2 in the gas phase from the diazirinyl anion
c-CN2H− has been implicated by S. Kass: (a) Kroeker, R. L.; Kass, S. R. J.
Am. Chem. Soc. 1990, 112, 9024. (b) Tian, Z.; Kass, S. R. Chem. Rev.
2013, 113, 6986.
(4) TIs of this type are known to be metastable in the gas phase: Haas,
G. W.; Giblin, D. E.; Gross, M. L. Int. J. Mass Spectrom. 1998, 172, 25.
(5) Graul, S. T.; Squires, R. R. J. Am. Chem. Soc. 1990, 112, 2517.
(6) All calculations in this work have been done using Gaussian 09,
Revision D.01; Gaussian, Inc.: Wallingford, CT, 2013. See the SI for the
complete reference.
(7) BDEs (i.e., loss of CO2 or X− ion) were obtained as the difference
between the sum of electronic energies of completely separated product
fragments and the BSSE-corrected energy of a reactant calculated at the
MP4 level; all energies include a zero-point correction calculated at the
MP2 level.
(8) The wave functions of some species were found to exhibit an RHF
→ UHF instability at the B3LYP, MP2, MP4, and CCSD(T) levels. We
determined using the T1 diagnostic at the CCSD(T)//aug-cc-pVTZ
level whether a single-reference-based electron correlation procedure is
appropriate for the treatment of such species: Lee, T. J.; Taylor, P. R. Int.
J. Quant. Chem. Symp. 1989, 23, 199. The test was passed (T1 < 0.020)
by c-CN2Br− (T1 = 0.015) and c-CN2Cl− ions (T1 = 0.016); their
dissociation energies at the CCSD(T) level are nearly identical to those
at the MP4 level. On the other hand, the calculated energies of the
1
BrCNN− ion (T1 = 0.021), CNN singlet carbene (T1 = 0.026), and
1NCN singlet nitrene (T1 = 0.026) are expected to be less accurate. The
singlet−triplet gap for the latter two species calculated at the MP4 level
is, however, still in good agreement with experimental values (within 1
and 4 kcal/mol, respectively), indicating sufficient accuracy of the
calculations for our purposes. See the SI for details.
(9) Reactions of 1 with nucleophiles in methanol do not result in the
expulsion of the c-CN2X moiety (ref 1b).
(10) There is only one other diazirine-3-carboxylic acid (the 3-methyl
derivative) reported in the literature: Church, R. F. R.; Weiss, M. J.
(American Cyanamid Co., USA). Substituted diaziridines and diazirines.
U.S. Patent 3,525,736, August 25, 1970.
(11) Ortega, J. M.; Glotin, F.; Prazers, R. Infrared Phys. Technol. 2006,
49, 133.
(12) Mac Aleese, L.; Maître, P. Mass Spectrom. Rev. 2007, 26, 583.
(13) Roithova,
(14) Moss, R. A. Acc. Chem. Res. 2006, 39, 267.
́
J. J. Chem. Soc. Rev. 2012, 41, 547.
̌
(15) Marek, A.; Turecek, F. J. Am. Soc. Mass. Spectrom. 2014, 25, 778.
(16) The mass corresponding to the Cl− ion was below the cutoff of
our instrument.
(17) Narancic, S.; Bach, A.; Chen, P. J. Phys. Chem. A 2007, 11, 7006.
(18) Zins, E. L.; Pepe, C.; Schroder, D. J. Mass Spectrom. 2010, 45,
̈
1253.
(19) The collision energy in the ion trap instrument is given in % of a
“normalized collision energy” scale, and it has to be transformed into
standard energy units by a calibration.
(20) (a) Paulino, J. A.; Squires, R. R. J. Am. Chem. Soc. 1991, 113, 1845.
(b) Moss, R. A.; Zhang, M.; Krogh-Jespersen, K. Org. Lett. 2009, 11,
5702.
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