Ambident reactivity of the cyanate anion

Article abstract of DOI:10.1002/chem.200800314

A study was conducted to investigate ambident reactivity of the cyanate anion. The study showed that the cyanate anion is an ambident nucleophile, which may react with electrophiles either at the oxygen terminus, to yield alkyl cyanates, or at the nitrogen terminus, to yield isocyanates. Equal amounts of alkyl cyanates and isocyanates were obtained, when secondary iodoalkynes were treated with silver cyanate and the formation of tert-butyl isocyanate, along with 2-methylpropene and cyanic acid. The study also investigated the possibility of S_N1 reactions of cyanates proceeding with charge control to give cyanates.

Full text of DOI:10.1002/chem.200800314

DOI: 10.1002/chem.200800314
Ambident Reactivity of the Cyanate Anion
[a]
Heike F. Schaller, Uli Schmidhammer,[b] Eberhard Riedle,[b] and Herbert Mayr*[a]
Dedicated to Professor Heinrich Nçth on the occasion of his 80th birthday
The cyanate anion is an ambident nucleophile, which may
react with electrophiles either at the oxygen terminus to
yield alkyl cyanates or at the nitrogen terminus to yield iso-
cyanates (Scheme 1).[1]
It cannot be excluded, however, that the selective forma-
tion of alkyl isocyanates under these conditions is due to a
cyanate ion catalyzed isomerization of an initially formed
alkyl cyanate into its thermodynamically more stable isomer
[Eq. (2)].[7]
R-OCN þ NCOÀ ! R-NCO þ NCOÀ
ð2Þ
Scheme 1. Ambident reactions of the cyanate anion.
Subsequent isomerization of the initial products may also
be responsible for the selective formation of alkyl isocya-
nates by the reaction of silver cyanate with primary alkyl
halides and trityl chloride. On the other hand, almost equal
amounts of alkyl cyanates and isocyanates were obtained
when secondary iodoalkanes were treated with silver cya-
nate, and the formation of tert-butyl isocyanate together
with 2-methylpropene and cyanic acid was also considered
as an indication for concomitant O- and N-attack.[4]
Because the charge density is higher at the more electro-
negative oxygen center while the larger HOMO coefficient
is at nitrogen,[2] the concept of charge and orbital control[3]
predicts hard electrophiles to attack at the oxygen side and
soft electrophiles to attack at the nitrogen. It was, therefore,
expected that alkyl cyanates should be formed in nucleophil-
ic substitution reactions with SN1 character while alkyl iso-
cyanates should be formed in nucleophilic substitution reac-
tions with SN2 character.[4]
In line with early work of Wurtz on the alkylation of po-
tassium cyanate with diethyl sulfate,[5] Slotta and Lorenz re-
ported that the reaction of dialkyl sulfates with alkali metal
cyanates is the best method for synthesizing alkyl isocya-
nates [Eq. (1)].[6]
In previous work,[8] kinetic investigations were employed
to demonstrate the change of regioselectivity in reactions of
the thiocyanate ion with benzhydrylium ions of variable
electrophilicity. A biexponential decay of the benzhydrylium
absorbances, a fast reversible attack at the sulfur terminus
and the slow irreversible attack at nitrogen side was ob-
served when morpholino-substituted benzhydrylium ions
were photolytically generated in the presence of SCNÀ ions
(Scheme 2).
KOCN þ ðROÞ2SO2 ! R-NCO þ ROSO3K
ð1Þ
[a] Dipl.-Chem. H. F. Schaller, Prof. Dr. H. Mayr
Department Chemie und Biochemie
Ludwig-Maximilians-Universität München
Butenandtstr. 5–13 (Haus F), 81377 München (Germany)
Fax : (+49)89-2180-77717
E-mail: Herbert.Mayr@cup.uni-muenchen.de
[b] Dipl.-Phys. U. Schmidhammer, Prof. Dr. E. Riedle
Lehrstuhl für BioMolekulare Optik
Ludwig-Maximilians-Universität München
Oettingenstr. 67, 80538 München (Germany)
Supporting information for this article is available on the WWW
under http://www.chemistry.org or from the author.
Scheme 2. Ambident reactivity of the thiocyanate anion (208C, acetoni-
trile).
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Chem. Eur. J. 2008, 14, 3866 – 3868

COMMUNICATION
In reactions with more electrophilic carbocations, the kS/
kN ratio decreased because both reactions approach diffu-
sion control.
We now set out to examine whether reactions with benz-
hydrylium ions (Table 1) can also be employed to elucidate
the ambident reactivity of cyanate ions.
absorption maxima) to yield the benzhydrylium ions 1g–j
and 1l as described previously.[12,13] The generated benzhy-
drylium ions then reacted with the cyanate anion, and the
change of absorbance due to the reaction of the benzhydry-
lium ions with the cyanate anions was monitored at appro-
priate timescales. As in the stopped-flow experiments, these
reactions were also performed under first-order conditions.
As depicted in the Supporting Information, plots of the
first-order rate constants kobs vs [OCNÀ] were linear, and the
resulting slopes gave the second-order rate constants k2
listed in Table 1.
Table 1. Second-order rate constants of the reactions of cyanate ions
with the benzhydrylium ions 1 (208C, acetonitrile).
Benzhydrylium ions
E[a]
k2
[mÀ1 sÀ1
]
Figure 1 shows that the second-order rate constants k2 for
1a–i correlate linearly with the electrophilicity parameters E
of the benzhydrylium ions as required by Equation (3),
where E is the electrophilicity parameter, N is the nucleo-
philicity parameter and s is the nucleophile-specific slope
parameter.
n=1
n=2
1a À10.04 1.11”103
1b À9.45 2.53”103
n=1
n=2
1c À8.76 1.33”104
1d À8.22 3.47”104
log k2 ¼ sðN þ EÞ
ð3Þ
R=
1e À7.69 1.09”105
R= NMe2
R= NMePh
R= N(Ph)2
1 f À7.02 3.21”105
1g À5.89 2.88”106
1h À4.72 3.48”107
R= NMe
A
1j À1.36 1.06”1010
[b]
R= OMe
R= Me
R= Cl
1k 0.00
1 l 3.63
1m 6.02
–
2.47”1010
[b]
–
[a] Electrophilicity parameters as defined previously.[9,10] [b] Only used
for product studies.
Exclusive formation of benzhydrylium isocyanates was
observed when benzhydrylium tetrafluoroborate 1h-BF4 or
chloro-bis(4-methoxyphenyl)methane 1k-Cl was treated
with tetraethylammonium cyanate in acetonitrile (for prod-
uct identification see Supporting Information). As in the ex-
amples quoted above, it was not clear whether the isolated
products resulted from kinetic or thermodynamic control.
The kinetics of the reactions of the less electrophilic benz-
hydrylium ions were followed photometrically by combining
acetonitrile solutions of (1a–f)-BF4 with solutions of Et4N+
OCNÀ in a stopped-flow instrument and monitoring the
decay of the absorbance at the absorption maxima[8,11] in the
visible as described previously.[9] The experiments were car-
ried out with an excess of Et4N+OCNÀ under first-order
conditions, resulting in an exponential decay of the absor-
bances of the benzhydrylium ions, from which the first-order
rate constants kobs were derived.
The reactions of the carbocations 1g–j and 1l were too
fast to be determined in this way. Therefore, the correspond-
ing diarylisocyanatomethanes, which were obtained by
mixing the benzhydrylium tetrafluoroborates (1g–i)-BF4 or
the chlorodiarylmethanes (1j,l)-Cl with an excess of Et4N+
OCNÀ, were irradiated by laser pulses (<1 ps, approx. 1 mJ,
center wavelengths between 265 and 300 nm matched to the
Figure 1. Plot of log k2 for the reactions of the cyanate ion with benzhy-
drylium ions 1a–j,l in acetonitrile at 208C versus their electrophilicity pa-
rameters E.
The flattening of the curve at log k2 >10 is due to diffu-
sion control, which is in the same order of magnitude as for
other reactions of benzhydrylium ions with anions in aceto-
nitrile.[12,14] The fact that the rate constants determined by
the stopped-flow and the Laser flash technique are on the
same correlation line shows the internal consistency of our
kinetic measurements, and from the linear part of this graph
we can derive N=13.60 and s=0.84 for OCNÀ in aceto-
nitrile.
Can all observed second-order rate constants be assigned
to N-attack as suggested by the product studies? The
smooth correlation line shown in Figure 1 indicates that the
rate-determining step does not change throughout this reac-
tion series. If N-attack would be accompanied by a fast and
reversible O-attack, one should be able to observe a biexpo-
nential decay as in the previous studies with SCNÀ.[8] From
the fact that all kinetics investigated in this work show mono-
exponential decays, one can derive that the equilibrium con-
stants for O-attack - if it occurs at all - must be so small that
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H. Mayr et al.
the low concentrations of the intermediate benzhydryl cyan-
ates are kinetically irrelevant. This argument does not hold
when N- and O-attack proceed with comparable rates,
which may occur in the diffusion-controlled range. One can
assume that highly electrophilic carbocations which do not
meet a barrier when approaching OCNÀ from either side
will give mixtures of R-NCO and R-OCN. However, when
the benzhydryl chloride 1m-Cl was treated with AgOCN in
diethyl ether or nitromethane following a procedure report-
ed by Holm and Wentrup,[4] the corresponding benzhydryl
isocyanate 1m-NCO was isolated exclusively (Scheme 3).
We cannot specify whether the isocyanate 1m-NCO is the
result of kinetic or thermodynamic control because even pri-
mary alkyl cyanates have been reported to rearrange into
alkyl isocyanates under mild conditions.[7]
are the fourth example of prototype ambident anions, the
behavior of which cannot be explained by the HSABcon-
cept or the concept of charge and orbital control. Other
cases can be expected to follow.
Acknowledgements
The authors thank Dr. A. A. Tishkov and Dr. A. R. Ofial for helpful dis-
cussions. This work was supported by the Deutsche Forschungsgemein-
schaft through the SFB749 (Dynamik und Intermediate molekularer
Transformationen).
Keywords: alkyl cyanates · carbocations · kinetics · linear
free energy relationships
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Scheme 3.
The fact that NCOÀ reacts quantitatively even with 1a
and 1b, that is, with carbocations of low Lewis acidity, while
the ionization equilibrium is on the side of the ions for (1a–
f)-NCS[8] indicates that NCOÀ is a much stronger Lewis base
towards carbocations than NCSÀ. A direct comparison of
the N-nucleophilicities of NCOÀ and NCSÀ can be derived
from their reactions with the benzhydrylium ions 1g and 1i:
The nitrogen of NCOÀ is 500–1000 times more reactive than
the nitrogen of NCSÀ.
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We finally want to come back to the question of orbital
and charge control: Do SN1 reactions of cyanates proceed
with charge control to give alkyl cyanates? Figure 1 shows
that carbocations with electrophilicity parameters E> À1,
that is, carbocations which are less stabilized than the diani-
sylcarbenium ion 1k or the tritylium ion undergo diffusion-
controlled reactions with NCOÀ. Those types of carbocations
which are typically generated as intermediates of SN1 reac-
tions will therefore undergo barrier-less reactions with the
cyanate anion without passing through a transition state,
and reactivity concepts which are based on relative activa-
tion energies cannot be employed. Because similar situa-
[14] J. Bartl, S. Steenken, H. Mayr, J. Am. Chem. Soc. 1991, 113, 7710–
7716.
[15] A. A. Tishkov, H. Mayr, Angew. Chem. 2005, 117, 145–148; Angew.
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tions have recently been reported for the reactions of carbo-
Received: February 20, 2008
Published online: March 28, 2008
À [12]
cations with SCNÀ,[8] CNÀ,[15] and NO2 ,
cyanate anions
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Chem. Eur. J. 2008, 14, 3866 – 3868