The Newman-Kwart Rearrangement
FIGURE 1. Comparison of extent of reaction with time for conventional (red) and microwave (blue) heating in the rearrangement of 1a (0.25 M)
in NMP at 140 °C.
TABLE 1. Rate Constants (140 °C) and Activation Parameters for
1a in DCB at 0.25 M
SCHEME 1
heating method
k/s-1 at 140 °C
A/s-1
Ea/(kJ mol-1
)
microwave
thermal
1.35 × 10-4
5.1 × 1010
116.2
118.7
1.13 × 10-4
7.8 × 1010
Comparison Between Conventional Thermal and Micro-
wave Temperature Control/Heating. Although we were
confident that the NKR gave equivalent reaction rates under
both conventional and microwave heating in general synthetic
applications,7 we decided to establish a higher level of accuracy
before beginning this study. Therefore, experiments were
performed to confirm that reactions carried out under microwave
heating showed similar kinetic behavior to those carried out
under conventional convective heating (i.e., in a thermostatically
controlled silicon oil heating bath). The initial comparison was
performed on identical scale in microwave reaction tubes with
stirring bars. The oil bath reaction tube was sampled at multiple
time points, while each microwave data point was taken from
a single reaction tube. This avoids a possible cumulative error
in the microwave case for heating up the microwave tubes, since
they must be cooled each time before sampling (although control
studies show these effects to be negligible for reaction times of
>10 min, even at low conversions). Figure 1 shows the
comparison for the reaction of 2-nitrophenyl-O-thiocarbamate
(1a) at 0.25 M in NMP at 140 °C under conventional and
microwave heating. The solid lines are best-fit lines and show
that the rate constants for the reactions agree within 4%.
Reaction of the 2-nitro substrate 1a in dichlorobenzene (DCB)
over the temperature range of 120-180 °C at the same
concentration showed very similar rates and activation param-
eters using the two methods of heating (Table 1).
The difference in rate constants at 140 °C corresponds to an
effective temperature for microwave control of 3.5 °C above
that for thermal control. In other cases, apparent small increases
in effective temperature of between 2 °C and 4 °C at around
150 °C were observed for reactions in which microwave heating
was used to achieve and control reaction temperature; the effects
were smaller at higher temperatures. This difference, if real,
suggests a small extent of superheating associated with the
microwaves, depending upon the efficiency of the reaction
stirring, or possibly a slight systematic error in the temperature
measurement.
microwave effect, and which was reliable under a wide range
of known parameters (temperature, pressure, solvent, etc.). We
have already reported our findings on re-evaluating the New-
man-Kwart rearrangement (NKR)6 under both microwave and
conventional thermal heating, and have shown that there is no
difference between the two under easily achieved and well-
controlled conditions.7 The NKR has previously been shown
to be a first-order, unimolecular rearrangement converting an
O- to S-thiocarbamate (Scheme 1; 1 to 2).8 The rate of reaction
is also well-known to be strongly dependent on the aromatic
substituent,6a,8,9 and we have more recently shown a modest
solvent effect also.7,10
It is important to note that the reaction mixture must be a
well-stirred homogeneous solution to avoid the potential problem
of localized superheating due to inefficient agitation.10 It is
equally important to measure the temperature that accurately
reflects the contents of the reaction vessel. Although others have
rightly pointed out the potential concerns with relying on the
use of external IR pyrometers,11 compared to the more reliable
fiber optic probes or shielded thermocouples inserted in the
reaction mixture for example, we have found external IR
pyrometers to be reliable for this reaction when regularly
calibrated and in the hands of a competent user.7
(5) de la Hoz, A.; Diaz-Ortez, A.; Moreno, A. Chem. Soc. ReV. 2005,
34, 164-178.
(6) (a) Newman, M. S.; Karnes, H. A. J. Org. Chem. 1966, 31, 3980-
3984. (b) Kwart, H.; Evans, E. R. J. Org. Chem. 1966, 31, 410-412.
(c) Lloyd-Jones, G. C.; Moseley, J. D.; Renny, J. S. Synthesis 2008, 661-
689.
(7) (a) Moseley, J. D.; Sankey, R. F.; Tang, O. N.; Gilday, J. P.
Tetrahedron 2006, 62, 4685-4689. (b) Moseley, J. D.; Lenden, P.
Tetrahedron 2007, 63, 4120-4125.
(8) (a) Miyazaki, K. Tetrahedron Lett. 1968, 2793-2798. (b) Araki, Y.;
Kaji, A. Bull. Chem. Soc. Jpn. 1970, 43, 3214-3219. (c) Kaji, A,; Araki,
Y.; Miyazaki, K. Bull. Chem. Soc. Jpn. 1971, 44, 1393-1399.
(9) Relles, H. M.; Pizzolato, G. J. Org. Chem. 1968, 33, 2249-2253.
(10) Moseley, J. D.; Lenden, P.; Thomson, A. D.; Gilday, J. P.
Tetrahedron Lett. 2007, 48, 6084-6087.
Finally, we further tested this point by studying the rear-
rangement of 1a at a fixed bulk temperature (140 °C) using
(11) Nu¨chter, M.; Ondruschka, B.; Weiâ, D.; Beckert, R.; Bonrath, W.;
Gum, A. Chem. Eng. Technol. 2005, 28, 871-881.
J. Org. Chem, Vol. 73, No. 8, 2008 3131