α,3-Didehydro-5-methyl-6-hydroxytoluene: Matrix isolation of a diradical related to the neocarzinostatin chromophore

Article abstract of DOI:10.1021/ja980792l

UV photolysis of 2,6-dimethylcyclohexa-2,5-dien-1-on-4-ylidene (4), matrix isolated in argon at 10 K, results in the formation of a labile species which is characterized as α,3-didehydro-5-methyl-6-hydroxybenzene (5) by comparison of the experimental IR s

Full text of DOI:10.1021/ja980792l

8480
J. Am. Chem. Soc. 1998, 120, 8480-8485
R,3-Didehydro-5-methyl-6-hydroxytoluene: Matrix Isolation of a
Diradical Related to the Neocarzinostatin Chromophore
Wolfram Sander,* Holger Wandel, G o1 tz Bucher, J u1 rgen Gr a1 fenstein, Elfi Kraka,* and
Dieter Cremer
Contribution from the Lehrstuhl f u¨ r Organische Chemie II der Ruhr-UniVersit a¨ t,
D-44780 Bochum, Germany, and Department of Theoretical Chemistry, G o¨ teborg UniVerity,
S-41296 G o¨ teborg, Sweden
ReceiVed March 9, 1998
Abstract: UV photolysis of 2,6-dimethylcyclohexa-2,5-dien-1-on-4-ylidene (4), matrix isolated in argon at 10
K, results in the formation of a labile species which is characterized as R,3-didehydro-5-methyl-6-
hydroxybenzene (5) by comparison of the experimental IR spectrum with calculations at the ROSS-BLYP/
6
-31G(d,p) level of theory. This assignment is confirmed by isotopic labeling and by investigating the
subsequent photochemistry of 5, which leads to 3-hydroxy-4-methylhepta-1,2,4-trien-6-yne (6). The ring opening
of diradical 5 to eneyne-allene 6 corresponds to the reversion of a Myers cyclization.
Introduction
1
In 1988 Myers and Proteau presented evidence that the
neocarzinostatin chromophore produces a highly reactive diradi-
cal upon reaction with methyl thioglycolate even at -38 °C.
The formation of diradicals of type R,3-dehydrotoluene 1 by
cyclization of eneyne-allene 2 is believed to be the key step
2,3
in the in vivo action of neocarzinostatin. Despite the current
interest in the Myers cycloaromatization reaction to yield
derivatives of 1, no isolation and direct spectroscopic charac-
terization of a derivative of 1 has been reported.
Results and Discussion
Visible light irradiation (λ > 475 nm) of quinone diazide 3,7
matrix isolated in argon at 10 K, quantitatively produces 2,6-
dimethylcyclohexa-2,5-dien-1-on-4-ylidene (4) with the carbonyl
-
1
stretching vibration at 1518 cm . The spectroscopic charac-
terization of 3 and 4 as well as the trapping of 4 by molecular
8
,9
oxygen was described earlier.
In contrast to most other
4
-oxocyclohexadienylidenes, which on irradiation with λ > 470
8,10-12
nm rearrange to highly strained 1,3-bridged cyclopropenes,
carbene 4 is completely stable toward visible light irradiation.
However, several hours of UV irradiation (λ > 360 nm, argon
10 K) of 4 results in the formation of at least three products
A-C with characteristic IR absorptions.
Recently, Squires and co-workers were able to generate 1 in
the gas phase and determine the heat of formation using
4
,5
collision-induced dissociation threshold measurements. The
diradical was found to be a ground-state singlet with the triplet
being 3 kcal/mol higher in energy. In another gas-phase study,
The highest stationary concentration of the primary product
A is obtained after 120 min of irradiation. A very intense IR
6
absorption at 3635 cm-1 indicates a phenolic OH stretching
Chen and co-workers were able to determine the photoelectron
-
1
spectrum of 1 and to estimate the singlet state to be ca. 5 kcal/
mol more stable than the triplet state. Here we report on the
matrix isolation, IR spectroscopic characterization, and photo-
chemical ring opening of a derivative of 1 starting from 4-diazo-
vibration (matrix-isolated phenol, 3634 cm ; cresol, 3638
-
1 13
cm
). If 4-d6 is irradiated, this vibration is red-shifted to
-1
2684 cm , which clearly confirms the assignment of a hydroxyl
group and also reveals that it is formed via H-abstraction from
one of the o-methyl groups. A medium intensity absorption of
compound A is found at 1173 cm ; the other vibrations of A
are of low intensity. The yield of A is much smaller if 4-d6 is
irradiated, and irradiation of 4-d3 preferentially results in the
formation of OH and not OD, which indicates a substantial
2
,6-dimethyl-cyclohexa-2,5-dienone (3) as a precursor.
-
1
(
1) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146-
1
1
3
147.
(2) Myers, A. G.; Dragovich, P. S.; Kuo, E. Y. J. Am. Chem. Soc. 1992,
14, 9369-86.
(
3) Myers, A. G.; Parrish, C. A. Bioconjugate Chem. 1996, 7, 322-
31.
4) Wenthold, P. G.; Wierschke, S. G.; Nash, J. J.; Squires, R. R. J. Am.
Chem. Soc. 1993, 115, 12611-12612.
5) Wenthold, P. G.; Wierschke, S. G.; Nash, J. J.; Squires, R. R. J. Am.
Chem. Soc. 1994, 116, 7378-7392.
6) Logan, C. F.; Ma, J. C.; Chen, P. J. Am. Chem. Soc. 1994, 116, 2137-
138.
7) Ried, W.; Dietrich, R. Chem. Ber. 1961, 94, 387-391.
(8) Bucher, G.; Sander, W. Chem. Ber. 1992, 125, 1851-9.
(9) Sander, W.; Bucher, G.; Komnick, P.; Morawietz, J.; Bubenitschek,
P.; Jones, P. G.; Chrapkowski, A. Chem. Ber. 1993, 126, 2101-9.
(10) Sander, W., Kirschfeld, A., Halton, B., Eds.; JAI Press: London,
1995; Vol. 4, Chapter 2; pp 1-80.
(11) Sander, W.; Bucher, G.; Reichel, F.; Cremer, D. J. Am. Chem. Soc.
1991, 113, 5311-22.
(12) Bucher, G.; Sander, W. J. Org. Chem. 1992, 57, 1346-51.
(
(
(
2
(
S0002-7863(98)00792-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/06/1998

Diradical Related to the Neocarzinostatin Chromophore
J. Am. Chem. Soc., Vol. 120, No. 33, 1998 8481
Scheme 1
(band 28), 1239 (band 26), 1087 (band 24), 925 (band 20), 809
(band 19), and 744 (band 18) do not appear in the spectrum of
the open form 6 (see Table 2) since all of these bands are typical
of an intact ring structure with an exocycylic methylene group
(CCH2 stretch, HCring bend, ring stretch, etc., Table 1). In turn,
the easily identified asymmetric allene stretching vibration of
-
1
6
(1947 cm , band 36, Table 2) is missing in the spectrum of
compound A, thus confirming that A does not possess an acyclic
structure with an allene group. On the other hand, those
vibrational modes which are normally considered as being
typical of phenol derivatives (phenol: OH stretching at 3637
-
1
-1
-1 23
cm , HOC bending at 1176 cm , OH torsion at 309 cm ;
see also ref 24) appear in the infrared spectrum of both 5 and
-
1
6
1
3
3
: OH stretch, 3635/3670 cm (exptl/calcd); HOC bend, 1173/
-1
-1
169 cm ; OH torsion, 318 cm cal. (5, Table 1); OH stretch,
637/ 3661 cm ; HOC bend, 1175/ 1151 cm ; OH torsion,
66 cm cal. (6, Table 2). Other intensive phenol ring
vibrations (1412 (band 32), 1546 cm (band 37), Table 1),
which according to ROSS-BLYP results could be used to
identify 5, coincide with bands of 4 and, therefore, cannot be
seen in the difference spectrum.
kinetic isotope effect. However, the yield of A formed from
-1
-1
4-d3 via the deuterium shift is too low to clearly assign IR
-1
absorptions other than the OD stretching vibration to this
isotopomer, and therefore, the isotope effect could not be
quantified. The opening of the benzene ring should result in
highly unsaturated molecules with characteristic IR absorptions
such as alkene, allene, or alkyne CC stretching vibrations. Since
no IR absorptions are observed in the 1700-2000 cm range,
it is reasonable to assume that the benzene ring in A is still
intact, and we thus assign A the structure of R,3-didehydro-5-
methyl-6-hydroxybenzene (5, Scheme 1).
-1
The second photoproduct B builds up on prolonged irradiation
6-12 h) of 5 with λ > 360 nm and was identified as 3-hydroxy-
-methylhepta-1,2,4-trien-6-yne (6) (Scheme 1). Hydroxyallene
-
1
(
4
6
3
exhibits several characteristic IR absorptions: OH stretch,
638 (band 45); alkyne CH stretch, 3333 (band 44); asymmetric
We carried out density functional theory (DFT) calculations
for several C8H8O isomers to verify the assignment made for
compound A. While carbene 4 (triplet state), hydroxyallene 6,
and vinyl ketone 7 are well described with standard DFT using
-1
allene stretch, 1947 cm (band 36, see Table 2). On deuteration
(
starting from 4-d6) band 44 is not affected, revealing that the
alkyne group is not deuterated, while band 36 is red-shifted by
-1
2
0 cm . The asymmetrical CCC stretching vibration of allene
the B3LYP energy functional1
4-17
and a 6-31G(d,p) basis,
18
-1
-1
25
at 1957 cm is shifted by 17 cm in H2CCCD2, and thus,
the investigation of diradical 5 cannot be carried out at the
single-determinant DFT level. Therefore, 5 has been treated
with the recently developed restricted-open-shell singlet DFT
-1
the observed shift of 20 cm in B is in accordance with a
doubly deuterated terminal allene group. The hydroxyl function
-1
is also deuterated and νOD of band 45 shifted to 2685 cm .
(ROSS-DFT) approach, which will be described in more detail
The IR spectrum of 6 as well as that of 6-d6 is nicely reproduced
by B3LYP/6-31G(d,p) calculations (Table 2, Figure 2).
in the Experimental Section.
The ROSS-BLYP geometry of 5 (Figure 1a) is similar to the
The isotopic substitution pattern in 6-d6 confirms the mech-
anism outlined in Scheme 1. The primary step is the transfer
of one methyl-hydrogen atom of triplet carbene 4 to the carbonyl
oxygen atom to give diradical 5. Photochemical excitation is
required, however, it is not clear if the hydrogen transfer occurs
on an excited triplet surface or if this is rather a hot (triplet)
ground-state reaction.
5
MCSCF3-21G geometry of 1 and suggests that the CC bonds
adjacent to the radical centers are slightly shortened, which is
in line with the spin polarization pattern shown in Figure 1b.
In Table 1, calculated ROSS-BLYP/6-31G(d,p) vibrational
frequencies, relative intensities, and calculated isotope shifts are
compared with the available experimental data. Each vibrational
mode was characterized on the basis of an adiabatic analysis
see Table 1).22 The adiabatic stretching frequencies are
Recently we described the photochemistry of p-benzoquinone
diazide carboxylic acids as a route to 2,4-didehydrophenols.26
Thus, irradiation of 4-diazocyclohexa-2,5-diene-1-one-2-car-
boxylic acid with λ ) 435 nm cleanly yields 2,5-cyclohexadien-
(
included into Figure 1a and confirm the variation in the CC
bond as indicated in Figure 1b.
Comparison of calculated and experimental spectra provides
further proof for the existence of 5. The weak IR bands at 1249
1
-one-2-carboxylic acid-4-ylidene (8), which on 600-700-nm
irradiation eliminates CO2 and simultaneously transfers the
hydrogen atom of the carboxylic acid group to the carbonyl
oxygen atom. In contrast, the H-transfer in 4 to give diradical
5 requires UV irradiation. This difference in reactivity results
from the short nonbonding O-H distance of only 1.73 Å in 8
(
13) Gebicki, J.; Krantz, A. J. Chem. Soc., Perkin Trans. 2 1984, 1617-
1
621.
(
(
14) Becke, A. J. Chem. Phys. 1993, 98, 5648-5652.
15) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J.
Phys. Chem. 1993, 98, 11623.
(
16) Becke, A. D. Phys. ReV. A: Gen. Phys. 1988, 38, 3098-3100.
(
calculated at the B3LYP/6-31G(d) level of theory) compared
to 2.79 Å in the lowest energy conformation (C2V symmetry)
of 4 (Figure 3).
Photochemical ring cleavage of diradical 5 (Myers cyclo-
reversion) results in the formation of 6. Since the methylene
(
17) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B: Condens. Matter 1988,
3
7, 785-789.
(18) Hariharan, P. C.; Pople, J. A. Chem. Phys. Lett. 1972, 66, 217.
(19) Miehlich, B.; Stoll, H.; Savin, A. Mol. Phys. 1997, 91, 527-536.
(20) Andrews, J. S.; Murray, C. W.; Handy, N. C. Chem. Phys. Lett.
1
993, 201, 458-464.
(
21) Gr a¨ fenstein, J.; Kraka, E.; Cremer, D. Chem. Phys. Lett., in press.
22) (a) Konkoli, Z.; Cremer, D. Int. J. Quantum Chem. 1998, 67, 1-10.
(
(23) Michalska, D.; Bienko, D. C.; Abkowicz-Bienko, A. J.; Latajka, Z.
J. Phys. Chem. 1996, 100, 17786-17790.
(b) Konkoli, Z.; Larsson, J. A.; Cremer, D. Int. J. Quantum Chem. 1998,
6
2
1
7, 11-28. (c) Konkoli, Z.; Cremer, D. Int. J. Quantum Chem. 1998, 67,
9-40. (d) Konkoli, Z.; Larsson, J. A.; Cremer, D. Int. J. Quantum Chem.
998, 67, 41-55. (e) Cremer, D.; Larsson, J. A.; Kraka, E. In Theoretical
(24) Kraka, E.; Cremer, D.; Bucher, G.; Wandel, H.; Sander, W. Chem.
Phys. Lett. 1997, 268, 313-320.
(25) Eaton, D. R.; Thompson, H. Proc. R. Soc. A 1959, 250, 39.
(26) Bucher, G.; Sander, W.; Kraka, E.; Cremer, D. Angew. Chem. 1992,
104, 1225-1228; Angew. Chem., Int. Ed. Engl. 1992, 31, 1230-1233.
and Computational Chemistry, Vol. 5, Theoretical Organic Chemistry;
Parkanyi, C.; Ed.; Elsevier: Amsterdam, 1998; pp 259-327.

8482 J. Am. Chem. Soc., Vol. 120, No. 33, 1998
Sander et al.
Figure 1. Calculated geometries and adiabatic frequencies of biradical 5 (a, ROSS-BLYP/6-31G(d,p)) and 6 (c and d, B3LYP/6-31G(d,p)). Bond
-
1
lengths are in Å, and angles are in deg (all normal print). Adiabatic stretching frequencies are in cm (italics). Dihedral angles τ are given for 6
to show its degree of planarity. The oxygen atom is denoted by a gray ball. (b) Spin polarization pattern of 5. The spin of the single electrons are
indicated by thick arrows. Thin arrows give the spin polarization pattern according to the intraatomic Hund rule (see text).
group of 5 is transformed into the terminal methylene group of
the allene moiety in 6, this group is dideuterated in 6-d6. The
DFT calculations confirm that 6 is formed in the s-Z conforma-
tion (Scheme 1) with a distortion of the butadiene unit from
planarity by 34° and with the OH bond being located syn to
the allene CdC bond (Figure 1d).
Siemens Sichromat equipped with glass capillary columns (29.5 m,
OV1, 140 °C). Deuterated compounds were obtained from Deutero
GmbH (deuterium oxide, isotopic purity 99.9%) and Acros Chimica
(
methyl iodide 99+ atom % D). 2-Chloro-6-methylphenol was obtained
from Aldrich and used without further purification.
-Diazo-2,6-dimethyl-1-oxo-2,5-cyclohexadiene (3). The synthesis
4
of 3 was carried out according to a procedure described by Ried and
Dietrich.7 Purification of the product was accomplished by column
chromatography (basic alumina, dichloromethane).
Irradiation of 6 at slightly shorter wavelengths (1 h with λ >
50) results in the formation of a complex mixture of products.
3
Some of these products might be conformers or stereoisomers
4
-Diazo-2-methyl-6-(trideuteriomethyl)-1-oxo-2,5-cyclohexadi-
of 6. One of the final photoproducts C exhibits a strong
ene (3-d ). 2-Chloro-6-methylphenol was methylated with dimethyl
3
-1
carbonyl absorption at 1724.8 cm . Other vibrations are found
32
sulfate in aqueous sodium hydroxide. The phenyl methyl ether was
added to a suspension of lithium in diethyl ether. After heating for 2
-
1
at 1445.6 and 1324.3 cm . Due to the low intensities of the
other IR absorptions, product C was not further characterized.
However, it is reasonable to assume that a photochemically
induced 1,3-H shift to vinyl ketone 7 takes place, which
according to B3LYP/6-31G(d,p) calculations is 24.0 kcal/mol
more stable than 6. A similar rearrangement was described for
3
h, the solution was cooled; a solution of CD I (Aldrich; 99.5% atom
% D) in diethyl ether was added dropwise, and the mixture was heated
for 2 h. Water and diluted hydrochloric acid were added, and the
4
reaction mixture was extracted with ether. After drying with MgSO ,
the solvent was removed and the crude 2-methyl-6-(trideuteriomethyl)-
phenyl methyl ether used for the next step without further purification.
The phenyl methyl ether was refluxed in 48% HBr/acetic acid until
complete ether cleavage (GC analysis). Purification of the product was
accomplished by dissolving the phenol in diluted sodium hydroxide
solution and extraction of the aqueous phase with ether; acidifying the
aqueous phase with diluted hydrochloric acid and extraction with ether
hydroxyallene, which at -50 °C thermally rearranges to
acrolein.27
In summary, diradical 5 is the first derivative of a R,3-
dehydrotoluene that has been isolated and characterized by IR
spectroscopy. UV irradiation of 5 results in the Myers cyclo-
reversion to give allene 6. The scope of this reaction is currently
being investigated in our laboratory.
yielded the 2,6-dimethylphenol isotopomer in good purity. The phenol
was azo-coupled with phenyldiazonium chloride33 and the azo com-
pound subsequently reduced with sodium dithionite34 to the corre-
sponding amine.
Experimental Section
The amine was dissolved in cold HCl-saturated ethanol and treated
with isoamyl nitrite. After stirring for 1 h, the diazonium chloride was
quantitatively precipitated by addition of diethyl ether to the reaction
mixture. The salt was dissolved in ethanol, cooled, and treated with
ammonia-saturated ethanol; the color of the reaction mixture changed
rapidly from colorless to orange, and after removal of the solvent, the
The NMR spectra were recorded with a Bruker AM-400 spectrom-
eter; chemical shifts are reported in δ relative to TMS unless otherwise
indicated. Gas chromatography (GC) was performed by the use of a
(
27) Hakiki, A.; Ripoll, J. L.; Thuillier, A. Bull. Soc. Chim. Fr. 1985,
9
11-920.
(28) Mullholland, T. P. C. J. Chem. Soc. 1965, 4939-4953.
3
crude 3-d was purified by column chromatography (basic alumina,
(29) Namura, E.; Taniguchi, H.; Otsuji, Y. Bull. Chem. Soc. Jpn. 1993,
6
9
1
6, 3797-3801.
30) Hakiki, A.; Ripoll, J. L.; Thuillier, A. Bull. Soc. Chim. Fr. 1985,
(
(32) Mullholland, T. P. C. J. Chem. Soc. 1965, 4939-4953.
(33) Namura, E.; Taniguchi, H.; Otsuji, Y. Bull. Chem. Soc. Jpn. 1993,
66, 3797-3801.
11-920.
(31) Jackman, L. M.; Petrei, M. M.; Smith, B. D. J. Am. Chem. Soc.
991, 113, 3451-3458.
(34) Smith, I. J. Am. Chem. Soc. 1941, 63, 1036-1040.

Diradical Related to the Neocarzinostatin Chromophore
J. Am. Chem. Soc., Vol. 120, No. 33, 1998 8483
Table 1. Measured and Calculated Vibrational Frequencies ω and Infrared Intensities I of R,3-Didehydro-5-methyl-6-hydroxytoluene (5)
exptl
ω (cm-1
ROSS-BLYP/6-31G(d,p)
band no.a
sym
)
I
b
ω (cm-1
)
I
b
ω
/ωc
ω
/ωd
assignmente
rel
rel
i
i
45
44
43
42
41
40
39
38
37
36
35
34
33
32
31
30
29
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
a′
a′
a′
a′
a′
a′
a′′
a′
a′
a′
a′
a′′
a′
a′
a′
a′
a′
a′
a′
a′
a′
a′
a′′
a′
a′
a′
a′′
a′
a′′
a′′
a′′
a′
a′′
a′
a′′
a′
a′′
a′
3635
100
3670
3204
3105
3098
3096
3051
2976
2934
1546
1493
1471
1465
1461
1412
1402
1378
1302
1259
1253
1224
1169
1078
1024
1018
956
917
821
784
779
719
679
666
536
528
522
485
472
471
330
318
296
36
4
7
7
5
0.728
1.000
1.0
1.0
1.0
1.0
1.0
1.0
0.728
0.745
0.726
1.000
1.000
0.738
0.740
0.720
0.994
0.985
0.958
0.720
0.949
0.915
0.910
0.887
0.916
0.887
0.855
0.866
0.731
0.969
0.832
0.967
0.885
0.824
0.995
0.935
0.984
0.965
0.836
0.944
0.957
0.958
0.917
0.956
0.760
0.925
0.903
0.751
0.844
0.871
0.914
0.869
0.750
OH stretch
CH
CH
2
stretch
stretch
2
HCring stretch
HCring stretch
9
CH
CH
CH
3
3
3
stretch
stretch
stretch
22
31
13
3
4
5
6
69
1
4
7
15
14
25
100
11
1
13
3
11
6
8
19
6
25
0
1
0.996
0.997
0.999
0.999
1.0
0.999
0.998
0.998
0.991
0.998
0.958
1.0
0.743
0.994
1.000
1.053
1.009
1.029
1.000
0.988
1.000
0.999
1.000
0.945
1.000
0.987
0.998
0.990
1.000
0.989
0.976
0.764
1.000
0.996
0.960
0.993
0.992
CC stretch, ring
CH
CH
CH
CH
3
2
3
3
bend; ring stretch
bend; CCH
bend
bend; ring stretch
2
stretch
ring stretch; CO stretch
ring stretch; HOC bend; HCring bend
1375
1249
1
5
CH
ring stretch; HOC bend
CCH stretch
3
bend
2
HOC bend; HCring bend; ring stretch
HCring bend; CO stretch
HOC bend; CO stretch
ring stretch; HCring bend
HCCMe bend
HCCMe bend; CMe C stretch
2
CH bend; HCCMe bend
ring stretch; CMe C stretch
HCring oop
ring bend; CO stretch
HCring oop
2
H C oop; ring torsion
O oop; ring torsion
1239
1173
1087
6
39
2
1020
4
925
809
744
708
8
7
1
2
ring stretch; CO stretch
ring torsion; H C oop
2
ring bend; OCring bend
ring torsion; CMe and CH
ring bend; OCring bend
3
1
0
0
2
3
77
0
0
2
oop
ring torsion; CMe and OCring oop
H
H
2
CCring bend; ring bend
CCring bend; OCring bend; CMe Cring bend
a′
2
a′′
a′′
a′
a′′
a′′
a′′
HOCring torsion
O oop; CMe oop; CH
CMe CCring bend; H
ring torsion; HOCring torsion
ring torsion; CMe oop
ring torsion
2
oop
287
199
138
120
2
CCring bend
4
1
0
a
Number of vibration. Relative intensities based on the most intense band (100). c Ratio of H/ H isotopic frequencies for the d
b
2
1
1
isotopomer
d
2
1
6 2 3
isotopomer (CD ; CD
; OD). e Assignments according to adiabatic analysis; diabatic ordering.
(
OD). Ratio of H/ H isotopic frequencies for the d
See ref 22.
CH
2
Cl
2
). IR (Ar, 10 K): 2101.7 (9), 2067.5 (100), 2052.7 (6), 1648.6
Computational Methods
(
<1), 1614.7 (20), 1609.4 (19), 1598.7 (4), 1595.3 (1), 1589.6 (3),
The triplet (4) and closed-shell singlet (6 and 7) systems were treated
with standard DFT. For 5, however, conventional (single-reference)
DFT is not appropriate, since here one has to use at least a
two-determinant description of the form Ψ ) σR(1) πâ(2) + πR(2)
σâ(1) (ignoring paired electrons and normalization) to account for a
single electron in a σ orbital and another single electron in a π orbital.
1
451.4 (<1), 1428.8 (<1), 1380.7 (3), 1366.4 (1), 1262.9 (11), 1258.1
(10), 1218.4 (1), 1150.7 (2), 1078.7 (1), 1036.8 (<1), 1006.5 (2), 953.7
-
1
(
1), 905.6 (0), 868.6 (2), 521.2 (<1) cm (relative intensity).
-Diazo-2,6-bis(trideuteriomethyl)-1-oxo-2,5-cyclohexadiene (3-
). Starting material for the synthesis of 3-d was 2,6-bis(trideuteri-
4
d
6
6
omethyl)phenol, which was prepared according to a procedure by
Jackman et al. 2,6-Dimethylphenol was refluxed in D O with a nickel
2
on Kieselguhr catalyst. The hydrogen exchange at the methyl positions
was nearly quantitative (>99%, determined by NMR). 2,6-Bis-
19
This leads to MC DFT, which is at the focus of current research and
still bears a number of unsolved problems. We have avoided these
31
problems by retreating to restricted open shell theory for low-spin
20
(ROSS) cases as it was discussed by Andrews, Murray, and Handy
(trideuteriomethyl)phenol was oxidized with Fremy’s salt to the
for Hartree-Fock and second-order perturbation theory. At the ROSS-
DFT level the two-determinant problem is reformulated in a way that
one can essentially remain within the realm of single-configuration
theory at the cost of building up a more complicated Fock matrix. Also,
a new exchange correlation (XC) functional has to be constructed for
the ROSS case, which was solved by starting from the one for the
corresponding high-spin open shell case and adding an extra term to
the exchange energy so that the correlation energy is described properly
in the low-spin situation. With this new XC functional, a self-consistent
corresponding 2,6-bis(trideuteriomethyl)-1,4-benzoquinone. The fol-
lowing steps were carried out analoguos to the synthesis of 3.
7
1
H
13
NMR (CDCl
3
): δ 7.21 (s, 2H), 2.1 (s, <0.035 H).
): δ 181.9, 134.1, 125.6, 71.7; IR (Ar, 10 K): 2087 (26), 2074.1
18), 2065.5 (31), 2061.7 (100), 1614.2 (25), 1608 (34), 1605 (47),
C NMR
(
(
CDCl
3
1
1
590.5 (6), 1373 (5), 1350.3 (2), 1259.1 (13), 1257.8 (3), 1156.7 (5),
096.2 (2), 929.8 (8), 907.1 (1), 881.6 (2), 862.7 (4) cm- (relative
1
intensity).

8484 J. Am. Chem. Soc., Vol. 120, No. 33, 1998
Sander et al.
Table 2. Measured and Calculated Vibrational Frequencies ω and Infrared Intensities I of 3-Hydroxy-4-methylhepta-1,2,4-triene-6-yne (6)
argon matrix
B3LYP/ 6-31G(d,p) (scaled by 0.96)
no.a
ω (cm-1
)
I
b
ω
i
/ωc
ω (cm-1
)
I
b
ω
/ωc
assignmentd,e
rel
rel
i
45
44
43
42
41
40
39
38
37
36
35
34
33
32
31
30
29
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
3637.5
3333.4
31
100
0.738
1.000
3661
3352
3045
3025
3012
2981
2980
2923
2122
1973
1607
1451
1442
1427
1369
1368
1291
1213
1151
1042
1027
1021
988
943
875
824
705
646
609
596
569
564
546
471
436
366
345
317
277
30
70
8
13
14
15
17
23
1
22
3
16
20
6
0.728
1.000
0.744
1.000
0.741
0.740
0.735
0.719
1.000
0.985
0.996
0.944
0.898
0.839
0.820
0.758
0.799
0.795
0.735
0.987
0.981
0.863
0.846
0.847
0.802
0.958
0.940
0.958
0.998
0.921
0.959
0.945
0.880
0.927
0.923
0.727
0.936
0.942
0.913
0.905
0.864
0.943
0.792
0.944
0.930
OH stretch
alkyne CH stretch
asym allene CH
alkene CH stretch
asym CH stretch
sym allene CH stretch; CH
asym CH stretch; CH
sym CH stretch
2
stretch
3
2
3
stretch
2976.6
1946.7
15
15
3
2
stretch
3
alkyne CC stretch; C4C5 stretch
asym allene stretch
alkene CdC stretch
0.990
1450.5
1443.9
11
2
CH
H15C9C3 bend; CH
CH deform; H15C9C3C2 torsion
C2C3 stretch; H11C4C3 bend; HOC bend
CH deform
2
sciss; C7C8 + C2C7 allene stretch; C2C3 stretch
2
scissor
3
2
1
1380.2
1305.3
1222.9
1174.7
1057.2
1044.7
1036.6
6
22
7
10
99
56
11
0.996
0.994
0.987
0.762
0.984
3
44
53
86
82
45
35
0
H11C4C3 bend; HOC bend
C-O stretch; allene CC stretch
HOC bend; C3C9 stretch; C2C3 stretch
C4C5 stretch; CH3 deform
C3C9 stretch; C4C5 stretch
CH
allene CH
H15C9C3 bend; C4C5 stretch; C3C4C5 bend
allene CH oop
3
deform
2
wag
3
880.5
819.1
35
10
0.800
0.965
30
12
3
2
alkene CH oop
CO stretch; C2C3 stretch
O and C2 oop; C2C3C4C5 torsion
alkyne CC-H def and torsion
6
630.3
597.1
93
34
1.000
47
12
5
13
45
0
1
100
1
4
5
6
2
2
allene CH wag
C3C4C5 bend; C3C9 stretch; OC2C3 bend
C2C3 stretch; C3C2C7 bend
alkyne C-H oop; alkyne C-H def
C3C4C5C6 torsion
OC2C3 bend; C9 oop
OH torsion
C4C3C9 bend; C4C5C6 bend; C4C13C2 bend
C9 and O oop; OC2C3 bend
OCC bend; CCC bends
591.4
569.6
9
26
1.008
0.973
213
184
152
143
104
40
C8C7C2 bend; C8C7C2C3 torsion
C-CH
C8C7C2C3 torsion; CCC bends
torsion; CCCC torsions
3
torsion
0
1
0
0
C-CH
3
CCC bends
C7C2C3C4 torsion; CCC bend
a
Number of vibrations. Relative intensities based on the most intense band (100). c Ratio of H/ H isotopic frequencies for the d
b
2
1
6
isotopomer
; OD). Assignments according to adiabatic analysis; diabatic ordering. See ref 22. e For numbering of atoms see Figure 1.
d
(
CD
2
; CD
3
procedure was derived to determine the Kohn-Sham orbitals for ROSS-
1366.4 (3), 1269.3 (2), 1254.9 (55), 1135.4 (4), 1037.3 (1), 1010.7
(7), 942.8 (2), 932.6 (2), 872.4 (6), 767.2 (<1), 531.2 (4) cm (relative
intensity).
2
1
-1
DFT. The ROSS-DFT XC functional was tested in connection with
standard DFT procedures, and ROSS-BLYP results turned out to be
the best for small test systems (for more details, see ref 21).
2,6-Dimethyl-1-oxo-2,5-cyclohexadien-4-ylidene (4). IR (Ar, 10
K): 1518.3 (100), 1501.3 (28), 1438.6 (9), 1434.5 (37), 1426.9 (13),
Matrix Isolation. Standard techniques with an APD CSW-202
Displex closed-cycle helium cryostat were used. Matrices were
produced by deposition of argon (Linde, 99.9999%) on top of CsI (IR)
or sapphire (UV-vis) window with a rate of approximately 0.15 mmol/
min. Infrared spectra were recorded by using a Bruker IFS66 FTIR
1
404.5 (7), 1371.9 (8), 1330.4 (2), 1263.4 (28), 1204.8 (2), 1028.8
(
5
4), 1026.5 (5), 977.4 (8), 907.9 (1), 840.3 (33), 795 (3), 755.5 (5),
-
1
44.9 (15) cm (relative intensity).
-Methyl-r,4-didehydrocresol (5). IR (Ar, 10 K): 3634.9 (100),
374.9 (1), 1253.4 (<1), 1249.7 (5), 1238.8 (6), 1172.6 (39), 1087.3
6
1
-
1
spectrometer with a standard resolution of 1 cm in the range 400-
-1
(2), 1020.5 (4), 925.1 (8), 809.5 (7), 744.1 (1), 708.3 (2) cm (relative
-
1
4
000 cm
. Irradiations were carried out with use of Ushio HBO
intensity).
5
00-W mercury high-pressure arc lamps in Oriel housings equipped
3
-Hydroxy-4-methylhepta-1,2,4-trien-6-yne (6). IR (Ar, 10 K):
with quartz optics. IR irradiation from the lamps was absorbed by a
0-cm path of water. For broad-band irradiation, Schott cutoff filters
3637.5 (31), 3333.4 (100), 2976.6 (15), 1946.7 (15), 1450.5 (11), 1443.9
1
(
(
(
2), 1380.2 (6), 1305.3 (22), 1222.9 (7), 1174.7 (10), 1057.2 (99), 1044.7
were used (50% transmission at the wavelength specified), and for
narrow-band irradiation, interference filters in combination with dichroic
mirrors (“cold mirrors”) and cutoff filters were used.
56), 880.5 (35), 819.1 (10), 630.3 (93), 597.1 (34), 591.4 (9), 569.6
-1
26) cm (relative intensity).
2
-Methyl-6-(trideuteriomethyl)-1-oxo-2,5-cyclohexadien-4-
4
-Diazo-2,6-dimethyl-1-oxo-2,5-cyclohexadiene (3). IR (Ar, 10
K): 2068.7 (94), 2062.1 (100), 2053.4 (3), 2010.6 (1), 1671.8 (1),
617.8 (93), 1608.8 (49), 1456 (1), 1428.6 (2), 1382.6 (4), 1379.1 (1),
ylidene (4-d ). IR (Ar, 10 K): 1515.4 (34), 1510.8 (100), 1459.4
(6), 1438.4 (10), 1435.3 (9), 1408.1 (17), 1371.4 (2), 1325.1 (2),
1261.5 (30), 1220.6 (1), 1197.7 (2), 1074.9 (2), 1039.6 (7), 1024
3
1

Diradical Related to the Neocarzinostatin Chromophore
J. Am. Chem. Soc., Vol. 120, No. 33, 1998 8485
Figure 2. Difference matrix IR spectra in absorbance showing the photochemistry of carbene 4. (a) Bands of carbene 4 disappearing and bands
of diradical 5 and allene 6 appearing after 120 min of 360-nm irradiation. (b) Bands of 5 and remaining 4 disappearing and more allene 6 as well
as other photoproducts (X) appearing after 12 h of 360-nm irradiation. (c) IR spectrum of 6 calculated at the B3LYP/6-31G(d,p) level of theory.
2
,6-Bis(trideuteriomethyl)-1-oxo-2,5-cyclohexadien-4-ylidene (4-
). IR (Ar, 10 K): 1510.5 (100), 1493.7 (3), 1442.7 (1), 1414.3 (22),
324.4 (14), 1268 (17), 1221 (5), 1089.1 (7), 1044.3 (13), 1037.3 (29),
d
1
8
6
-
1
95.7 (8), 857 (5), 829.5 (46), 797.1 (1), 524.1 (9) cm (relative
intensity).
-(Trideuteriomethyl)-r,r,O-trideutero-r,4-didehydrocresol (5-
6
-
1
d
6
). IR (Ar, 10 K): 2683.6 (100) cm (relative intensity).
-Hydroxy-1,1,O-trideutero-4-(trideuteriomethyl)hepta-1,2,4-
trien-6-yne (6-d ). IR (Ar, 10 K): 3334.3 (100), 2684.7 (35), 1926.6
20), 1374.7 (15), 1297.6 (45), 1207.3 (50), 1190.6 (50), 1141.3 (20),
3
6
(
1
052.9 (5), 1040.8 (-), 983.6 (15), 895.6 (40), 790.8 (4), 704.8 (10),
-
1
Figure 3. Structures of carbenes 4 and 8 (B3LYP/6-31G(d)) showing
the distance of the carbonyl oxygen atom toward the closest hydrogen
atom and the CdO bonding distance.
630.1 (75), 596.4 (39), 554.0 (14) cm (relative intensity).
Acknowledgment. This work was financially supported by
the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie. At the University of G o¨ teborg, research
was supported by the Swedish Natural Science Research Council
(NFR). Calculations were done one the CRAY C94 of the
Nationellt Superdatorcentrum (NSC), Link o¨ ping, Sweden. J.G.,
E.K., and D.C. thank the NSC for a generous allotment of
computer time.
(
(
(
3), 1021.5 (2), 996.1 (2), 902.9 (4), 894.4 (4), 838.7 (45), 836.7
-), 811 (1), 808.7 (2), 757.4 (1), 718.3 (1), 534.4 (12), 472.0
-
1
1) cm (relative intensity).
4
-Diazo-2,6-bis(trideuteriomethyl)-1-oxo-2,5-cyclohexadiene (3-
d
1
1
8
6
). IR (Ar, 10 K): 2087 (26), 2074.1 (18), 2065.5 (31), 2061.7 (100),
614.2 (25), 1608 (34), 1605 (47), 1590.5 (6), 1373 (5), 1350.3 (2),
259.1 (13), 1257.8 (3), 1156.7 (5), 1096.2 (2), 929.8 (8), 907.1 (1),
81.6 (2), 862.7 (4) cm-1 (relative intensity).
JA980792L