o-fluoranil chemistry: Diels-Alder versus hetero-Diels-Alder cycloaddition

Article abstract of DOI:10.1021/jo7026678

(Chemical Equation Presented) The title quinone undergoes [4 + 2] cycloadditions in two ways, Diels-Alder on the ring and hetero-Diels-Alder by attack at the oxygens. The latter mode of reaction is strongly favored thermodynamically, but there is a kinetic bias favoring the normal Diels-Alder addition that often prevails, especially with cycloaddends that are not electron-rich.

Full text of DOI:10.1021/jo7026678

o-Fluoranil Chemistry: Diels–Alder versus Hetero-Diels–Alder
Cycloaddition
David M. Lemal,* Sudharsanam Ramanathan, and John Shellito
Department of Chemistry, Dartmouth College, HanoVer, New Hampshire 03755
daVid.m.lemal@dartmouth.edu
ReceiVed December 14, 2007
The title quinone undergoes [4 + 2] cycloadditions in two ways, Diels–Alder on the ring and hetero-
Diels–Alder by attack at the oxygens. The latter mode of reaction is strongly favored thermodynamically,
but there is a kinetic bias favoring the normal Diels–Alder addition that often prevails, especially with
cycloaddends that are not electron-rich.
Introduction
Aside from a brief description of its electrochemistry,1 the
literature contains only a single paper on the chemistry of the
title compound, o-fluoranil (tetrafluoro-o-benzoquinone, 1). This
1967 report by Shteingarts et al.2 showed that the quinone can
undergo [4 + 2] cycloaddition either by Diels–Alder reaction
on the ring diene to give an R-diketone (2) or by hetero-
Diels–Alder addition on the carbonyl oxygens to give a dioxene
(3) (or dioxin). o-Fluoranil is potentially useful as a (CF)4
synthon, because we have found that normal Diels–Alder
reaction followed by 2-fold photodecarbonylation of the R-di-
ketone adduct incorporates a [-CFdCFsCFdCF-] fragment
into a molecule.3 However, it was guesswork as to which of
the modes of cycloaddition would occur with a given substrate.
The main objective of the present study was to shed light on
that issue.
interaction with most substrates, the very low-lying LUMO
offers little basis for choice between the two reaction pathways.
The HOMO would favor normal Diels–Alder addition, and
should be important with electron-deficient substrates.
Atomic charges calculated at the B3LYP/6-31G/ level of
theory5 appear below. If charge distribution were the only factor
involved, electron-rich cycloaddends would undergo Diels–
Alder reaction preferentially, and electron-poor ones react at
the oxygens.
Thermodynamics provides a strong bias toward the latter
mode of reaction, mostly because it generates an aromatic ring.
For a variety of cycloaddends, Table 1 presents calculated
energy changes for both reaction types, together with the product
found experimentally. The ∆∆E column shows the invariably
Results and Discussion
Competing Pathways. The quinone’s frontier orbitals
(AM1)4 are depicted below. Expected to be the key orbital for
(1) Stallings, M. D.; Morrison, M. M.; Sawyer, D. T. Inorg. Chem. 1981,
20, 2655.
(2) Shteingarts, V. D.; Budnik, A. G. IzV. Sibi. Otd. Akad. Nauk SSSR, Ser.
Khim. Nauk 1967, 124.
(4) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. J. Am.
Chem. Soc. 1985, 107, 3902.
(3) Bogachev, A. A.; Kobrina, L. S. Russ. J. Org. Chem. 1997, 33, 681–3.
3392 J. Org. Chem. 2008, 73, 3392–3396
10.1021/jo7026678 CCC: $40.75 2008 American Chemical Society
Published on Web 03/21/2008

o-Fluoranil Chemistry
TABLE 1. Calculated Reaction Energiesa for o-Fluoranil and
Observed Products
cycloaddend
∆EDA
∆EDiox.
∆∆E
product
furan
-7.20b -22.18
-15.0 dioxene
-17.3 dioxene2
-33.2 dioxene2
-14.3 dioxene
1,4-diphenylbutadienec
diphenylketene
cyclohexene
norbornene
-9.59d -26.91
-10.68
-43.85
-21.25b -35.56
-30.59e
-20.02f
-42.07f -11.5 DA adduct
-36.78
styrene
R-methylstyrene
indene
methyl acrylate
3-hexyne
-16.8 DA adduct2
-18.8 DA adduct2
-11.3 DA adduct2
-10.5 DA adduct
-15.4 DA adduct
-16.1 DA adduct2
-23.3 DA adduct
-21.63g -40.43
-22.58f
-33.86
-22.46b -32.94
-36.43
-37.00
-28.74
-51.85
-53.06
-52.04
phenylacetylene
DMADh
a In kcal/mol, calculated at the B3LYP/6-31G/ level of theory (0 K,
without zeropoint energy corrections). b Endo. c Trans, trans. d Styryl
exo, phenyl endo. e Exo, exo. f Exo. g Phenyl exo. h Dimethyl acety-
lenedicarboxylate.
large energetic advantage of the hetero-Diels–Alder reaction.
Distinction between the two types of adduct is easily made with
19F NMR. The dioxenes display two multiplets in the δ –165
to –170 region for the four fluorines, but the Diels–Alder adducts
give rise to peaks in the –150 ppm region for the vinyl fluorines
and the -200 ppm region for the bridgehead fluorines. The table
makes it clear that charge distribution in the quinone has little
influence on the course of the reaction, as some of the most
electron-rich cycloaddends (e.g., furan) attack at oxygen, and
most electron-deficient ones undergo Diels–Alder reaction.
It is remarkable that Diels–Alder reaction takes place so
frequently in the face of unfavorable thermodynamics, most
notably in the case of dimethyl acetylenedicarboxylate, where
the dioxin (4) is >20 kcal/mol more stable than the Diels–Alder
adduct (5).
FIGURE 1. Reaction profiles for phenylacetylene/o-fluoranil cycload-
ditions, calculated at the B3LYP/6-31G/ level of theory. Enthalpy
changes are given in kcal/mol. The entropies of activation and of
reaction are large and negative, but very similar for the two reaction
types.
The strong kinetic bias toward Diels–Alder reaction is also
apparent in the case of phenylacetylene, and Figure 1 shows
calculated enthalpy changes in both its Diels–Alder reaction and
the unobserved dioxin formation. The two transition states,
shown in Figure 2, are quite unsymmetrical, but the net transfer
of charge from the acetylene to the quinone is only 0.13 and
0.31 units in the Diels–Alder and dioxin transition states,
respectively.
The fact that the reaction is strongly exothermic means that
the transition state comes early and is thus less influenced than
otherwise by the enthalpy difference between the two possible
FIGURE 2. Transition states for reactions of phenylacetylene with
o-fluoranil: Diels–Alder addition (a) and dioxin formation (b), calculated
at the B3LYP/6-31G/ level of theory.
products.6 However, the question remains as to the origin of
the kinetic bias favoring Diels–Alder reaction. The following
three factors probably all contribute to that bias. The increase
in transition state energy arising from filled orbital repulsion
should be greater for attack at the electron-rich oxygens of the
quinone than at the electron-deficient carbons. Rehybridization
at carbon of the C-F bonds from sp2 toward sp3 should help to
(5) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratman,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.;
Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson,
G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.;
Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez,
C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.;
Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; and Pople, J. A. Gaussian 98,
Revision A.5; Gaussian, Inc.: Pittsburgh, PA, 1998.
(6) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334.
J. Org. Chem. Vol. 73, No. 9, 2008 3393

Lemal et al.
acid gave quinonitrole 6, which decomposed spontaneously to
an inseparable mixture of o- and p-fluoranil (7).13 Because the
ortho isomer is far more reactive than the para, it is often
practical to use this easily prepared mixture for reactions of the
o-quinone, with its isomer 7 remaining unchanged for separation
in the workup. The quinone mixture was used exclusively in
the present work.
When the reaction product is a dioxene, quinone 7 can be
removed by extraction with sodium bisulfite solution. As electron-
deficient R-diketones, Diels–Alder adducts of o-fluoranil react
with water voraciously, and the Russian workers isolated them
by taking advantage of the insolubility in benzene of their highly
polar hydrates.2 In the present work, we have derivatized the
Diels–Alder adducts with o-phenylenediamine, forming qui-
FIGURE 3. Frontier orbital interactions (AM1) in the dimethyl
acetylenedicarboxylate/o-fluoranil Diels–Alder reaction. HOMO sta-
bilization is 0.022 (ꢀ′)2 for o-fluoranil and 0.020 (ꢀ′)2 for DMAD.
stabilize a Diels–Alder transition state (Bent’s rule7), and finally
the much larger coefficient at carbon than at oxygen in the
quinone HOMO favors that mode of reaction. The HOMO
presumably plays an especially important role in determining
the reaction course for the electron-poor substrates methyl
acrylate and dimethyl acetylenedicarboxylate, which might not
have been expected to react at all with the electron-deficient
quinone. For DMAD, the quinone HOMO-acetylene LUMO
interaction is as large as the acetylene HOMO-quinone LUMO
interaction, as illustrated in Figure 3.
Regarding other entries in Table 1, formation of a dioxene
from diphenylketene may be a consequence of the huge
difference in reaction energies for the competing pathways,
together with steric hindrance to Diels–Alder reaction from the
twisted phenyls. One might have anticipated that cyclohexene
and norbornene (just a bridged cyclohexene) would react
similarly with o-fluoranil, but instead they present a sharp
contrast. Both react at room temperature, but whereas nor-
bornene yields a pair of stereoisomeric Diels–Alder adducts,
cyclohexene gives none. In a messy reaction, it affords the
dioxene in roughly 5% yield, and also undergoes slow oxidation
to benzene with comcomitant formation of tetrafluorocatechol.9
Most of the aryl-substituted alkenes in Table 1 yield Diels–Alder
adducts, but trans,trans-1,4-diphenylbutadiene gives a dioxene.
Thus, the behavior of alkenes is not completely predictable, but
alkynes with substituents ranging from alkyl to methoxycarbonyl
afford Diels–Alder adducts. Smaller steric demand in the case
of alkynes may be responsible at least in part for the difference.
Synthetic Considerations. o-Fluoranil has been prepared by
nitric acid oxidation of tetrafluorocatechol.2 The catechol was
originally synthesized from hexafluorobenzene in three steps,10,11
and recently from pentafluorophenol in better yield, again in
three steps.12
noxalines such as 9 from dione 8.14 p-Fluoranil is reduced by
the diamine to tetrafluorohydroquinone (10), identified by
comparison with an authentic sample, and the diamine forms
highly colored oxidation products. Extraction with sodium
carbonate solution removes the hydroquinone.
The two diones formed in the ratio 4:1 from the reaction of
o-fluoranil with norbornene behaved differently toward the
diamine. The major isomer reacted readily but the minor one
with reluctance, presumably for steric reasons. Their configura-
tions have not been established, but the reactivity difference
supports assignment of the major isomer as 11 and the minor
one as 12, endo and exo, respectively, on the new 6-membered
ring (both probably exo with respect to the norbornene ring,
again for steric reasons).
We have made further improvements in the rather labor-
intensive synthesis of the quinone, to be published elsewhere.
Shteingarts found that oxidaton of pentafluorophenol with nitric
(7) Bent, H. A. Chem. ReV. 1961, 61, 275.
(8) This orbital is actually the HOMO-3, as the slightly higher lying top
three occupied orbitals are concentrated on the oxygens.
(9) Both Diels-Alder and hetero-Diels-Alder reaction are much more
exothermic with norbornene, so again an earlier transition state helps to explain
the contrasting behavior. The product energy difference favoring dioxene is also
somewhat smaller in the case of norbornene (Table 1).
(10) Burdon, J.; Damodaran, V. A.; Tatlow, J. C. J. Chem. Soc. 1964, 763.
(11) Macdonald, C.; Tomlinson, A. J.; Willis, C. J. Can. J. Chem. 1971, 49,
2578.
Surprisingly, the reaction of o-phenylenediamine with the
Diels–Alder adduct 13 derived from dimethyl acetylenedicar-
boxylate gave only a small yield of the quinoxaline, the major
product being dimethyl tetrafluorophthalate (14). Under very
mild conditions, the diamine had induced loss of the dicarbonyl
bridge, perhaps via the mechanism shown in Scheme 1,
3394 J. Org. Chem. Vol. 73, No. 9, 2008

o-Fluoranil Chemistry
SCHEME 1
extracted with 10 mL of 10% aqueous NaHSO3 solution to remove
the unreacted p-quinone, followed by 10 mL of brine. Dried over
MgSO4, the organic phase was filtered and evaporated to leave a
dark brown syrup. A 0.5 g portion of this syrup was chromato-
graphed on 12.5 g of silica gel with CH2Cl2 as eluent, giving 211
mg of orange crystals of the dioxene (37% yield based on total
product). Purification by low-temperature recrystallization from
hexane followed by sublimation gave white needles, mp 68–69 °C.
19F NMR (CDCl3): δ -162.5 (ddd, J ) 21.7, 7.6, 3.1 Hz, C5 or
C8, 1F), -163.3 (ddd, J ) 21.7, 7.6, 3.9 Hz, C5 or C8, 1F), -165.8
(td, J ) 21.7, 3.1 Hz, C6 or C7, 1F), -166.8 (td, J ) 21.7, 3.9 Hz,
C6 or C7, 1F). 1H NMR (CDCl3): δ 6.57 (dd, J ) 2.82, 1.41, C2H),
6.22 (d, J ) 6.49, C9aH), 5.64 (ddd, J ) 2.82, 1.98, 1.41 Hz, C3aH),
5.15 (dd, unresolved, J )1.98, 1.41 Hz, C3H). 13C NMR (19F
1
decoupled, CDCl3): δ 151.2 (dm, JCH ) 196 Hz, vinyl C), 139.5
(aryl CO), 138.55 (CF), 138.52 (CF), 137.5 (CF), 136.7 (CF), 136.5
concerted or stepwise. Stabilization of developing negative
charge by a methoxycarbonyl group presumably explains why
bridge loss occurred here but not when the 3-hexyne and
phenylacetylene adducts were treated with o-phenylenediamine.
1
(aryl CO), 130.3 (dd, JCH ) 233, 6.4 Hz, vinyl C), 100.4 (ddm,
1
1JCH ) 183, 38 Hz, bridgehead C), 79.4 (dm, JCH ) 164 Hz,
bridgehead C). IR (C2Cl4): 2963, 1750, 1616, 1510, 1464, 1357,
1261, 1103, 1046 cm-1. Anal. Calcd for C10H4F4O3: C, 48.40; H,
1.62; F, 30.63. Found: C, 48.39; H, 1.61; F, 30.49.
1,4-Dihydro-2,3-diethyl-1,4,11,12-tetrafluoro-1,4-ethenophena-
zine (9). In a 25 mL round-bottomed flask were placed 2.94 g of
quinone mixture (1.78 g of o-quinone, 9.89 mmol), 4.0 mL (2.9 g,
35 mmol) of 3-hexyne, and 15 mL of benzene. The mixture, which
rapidly became black, was refluxed for 31 h, after which no
o-quinone remained. 19F NMR (CDCl3): δ –152.9 (vinyl F, 2F),
-209.6 (bridgehead F, 2F) for the dione adduct, NMR yield 65%.
A solution of 1.08 g (10 mmol) of o-phenylenediamine in 5 mL of
warm benzene was added and the mixture was boiled for 3 min.
The 19F NMR spectrum showed only three significant signals, two
for the desired quinoxaline and one for tetrafluorohydroquinone.
Evaporation of the solvent left 4.88 g of dark brown residue. A
portion (26%) of this product was dissolved insofar as possible in
20 mL of CH2Cl2, and extraction with 10 mL of 5% NaOH resulted
in copious precipitation of brown solid. The organic layer was
separated, washed with 10 mL of water, and dried over MgSO4.
Filtration and evaporation of the solvent gave 404 mg of brown
solid, which was chromatographed on 12 g of silica gel with 20%
ethyl acetate/hexanes as eluent. The resulting quinoxaline (350 mg,
41% crude yield) was sublimed (∼90 °C, 20 mTorr) and finally
recrystallized from methanol to afford 230 mg of colorless blocks,
Conclusions
Thermodynamics greatly favors dioxene (or dioxin) formation
over Diels–Alder addition in the reactions of o-fluoranil with a
broad spectrum of cycloaddends. Nonetheless, there exists a
strong kinetic preference for the latter mode of reaction that
often overcomes the thermodynamic bias, particularly in the
case of substrates that are not electron-rich. Alkynes in general
undergo Diels–Alder reaction, but prediction about reaction
pathways for some other cycloaddends is risky because coun-
tervailing factors are closely balanced. The fact that Diels–Alder
addition occurs with a variety of substrates bodes well for use
of o-fluoranil as a (CF)4 synthon.
Experimental Section
Tetrafluorobenzoquinones (1, 7).14 Pentafluorophenol (6.00 g,
32.6 mmol), melted with a heat gun, was added rapidly dropwise
with stirring to concentrated nitric acid (20 mL) that had been cooled
in an ice bath. The mixture became yellow and set to a crystalline
mass. After several minutes the solid was collected by filtration,
washed well with ice–water, and sucked dry. Initially pale yellow,
this quinonitrole became yellower as it began to decompose to the
quinones, so it was quickly dissolved in 20 mL of CH2Cl2 and dried
with MgSO4 followed by a little P4O10 to preclude destruction of
the sensitive o-quinone by water. After filtration, the solution was
refluxed for 40–50 min to complete conversion to the quinone
mixture. The solution was then decanted or filtered to leave behind
a small amount of white solid derived from the extruded nitrosyl
fluoride. Evaporation of the solvent left 5.28 g (29.3 mmol, 90%
yield) of orange-red crystals. 19F NMR (CDCl3): ortho-isomer δ
-135.7 (s, 2F), -150.2 (s, 2F); para-isomer δ -140.0 (s, 4F). No
other signals were present in the spectrum, and the 1H NMR
spectrum showed no proton-containing impurities. The ortho/para
ratio was 61:39, representing a yield of 55% for the o-quinone.
cis-5,6,7,8-Tetrafluoro-3a,9a-H-furo[2,3-b][1,4]benzodioxin. In
a 25 mL round-bottomed flask were combined 1.00 g of the quinone
mixture (61:39 o/p ratio, 3.39 mmol of o-fluoranil), 3 mL of freshly
distilled furan (2.8 g, 41 mmol), 10 mL of benzene, and a spatulaful
of CaCO3 to scavenge adventitiously formed HF. The mixture,
which rapidly darkened, was stirred at rt for 40 h, at which time
very little o-fluoranil remained. The dark brown mixture was
1
mp 155–157.5 °C. H NMR (CDCl3): δ 8.09, 7.78 (A2X2, aryl H,
4H), 2.45 (m, CH2, 4H), 1.07 (t, J ) 7.7 Hz, CH3, 6H). 19F NMR
(CDCl3): δ –155.0 (s, vinyl F, 2F), –212.6 (s, bridgehead F, 2F).
13C NMR (CDCl3): δ 150.8 (“CdN”); 142.8 (CsCH2); 141.5 (vinyl
1
CsF, JCF ) 292 Hz), 137.7 (“CsN”), 130.4, 128.9 (aryl CH),
91.4 (bridgehead CF, 1JCF ) 219 Hz), 19.0 (CH2), 13.4 (CH3). IR
(C2Cl4): 2966, 1749, 1508, 1461, 1331, 1290, 1232, 1190, 1061,
950, 855 cm-1. Anal. Calcd for C18H14F4N2: C, 64.66; H, 4.22; N,
8.38. Found: C, 64.74; H, 4.19; N, 8.41.
Dimethyl 1,4-Dihydro-1,4,11,12-tetrafluoro-1,4-ethenophena-
zine-2,3-dicarboxylate. In a 25 mL round-bottomed flask were
placed 2.01 g of the quinone mixture (1.31 g o-quinone, 7.28 mmol),
1.17 g (8.20 mmol) of dimethyl acetylenedicarboxylate, and 5 mL
of freshly distilled toluene. Reaction was complete after the dark
red solution had been refluxed for 19 h. 19F NMR (CDCl3): δ
-148.5 (vinyl f, 2F), -206.2 (bridgehead F, 2F) for the dione
adduct. A solution of o-phenylenediamine (0.80 g, 7.4 mmol) in 8
mL of warm CH2Cl2 was added portionwise by pipet to the cooled
reaction mixture. After filtration to remove 1.5 g of insoluble
material and evaporation of the solvent, the resulting brown tar
(2.65 g) was redissolved in 35 mL of CH2Cl2 and extracted with
20 mL of 5% Na2CO3 solution. A second extraction with 10 mL
of 10% Na2CO3 followed to ensure complete removal of the
tetrafluorohydroquinone. The organic layer was dried over MgSO4,
filtered, and evaporated. The residue was chromatographed on silica
gel (24 g) with 20% ethyl acetate/hexanes as eluent. Early fractions
yielded dimethyl tetrafluorophthalate (836 mg, 43% crude yield),
(12) Barthel, J.; Bustrich, R. German patent DE 19633027, 1988.
(13) Shteingarts, V. D.; Budnik, A. G.; Yakobson, G. G.; Vorozhtsov, N. N.,
Jr. Zh. Obsch. Khim. 1967, 37, 1537.
(14) The Russian group also prepared quinoxalines from their hydrates (ref
2).
J. Org. Chem. Vol. 73, No. 9, 2008 3395

Lemal et al.
and later ones the quinoxaline (153 mg, 5.3% crude yield).
Recrystallizations from hexanes with charcoal treatment gave pure
phthalate as fine, white crystals, mp 72–73.5 °C (lit.15 73–73.5 °C).
1H NMR (CDCl3): δ 3.94. 19F NMR (CDCl3): δ -137.0, -149.2.
Recrystallizations of the quinoxaline from methanol with charcoal
treatment yielded white crystals melting at 190–191 °C. 19F NMR
(CDCl3): δ -151.1 (s, vinyl F, 2F), -209.8 (s, bridgehead F, 2F).
1H NMR (CDCl3): δ 8.16 (m, aryl H, 2H), 7.84 (m, aryl H, 2H),
2.91 (m, CH3, 6H). 13C NMR (CDCl3): δ 160.3 (CdO), 148.3
6,6a,7,8,9,10,10a,11-Octahydro-6,11,13,14-tetrafluoro-6,11-
etheno-7,10-methanobenzo[b]phenazine. A quinone mixture (266
mg of ortho-isomer, 1.48 mmol), norbornene (190 mg, 2.02 mmol),
and CH2Cl2 (4 mL) were combined in a 10 mL round-bottom flask,
and the solution was refluxed. Complete after a few hours, the
reaction gave two Diels–Alder adducts in a ratio of ca. 4:1. The
19F NMR spectrum (CDCl3) showed signals at δ –146.2 (vinyl Fs),
–195.6 (bridgehead Fs) for the major adduct, and at –147.9 (vinyl
Fs), –194.7 (bridgehead Fs) for the minor one. o-Phenylenediamine
(168 mg, 1.56 mmol) was added, and the resulting black mixture
was refluxed for 20 min. The major adduct was converted
completely to its quinoxaline derivative, but much of the minor
one survived. After evaporation of the solvent, the dark residue
was heated and triturated with CHCl3, but some black polymeric
material remained undissolved. The slurry was placed on a column
of silica gel (12 g), and elution followed with 20% ethyl acetate/
hexanes. Successive fractions of 238 mg (major quinoxaline) and
59 mg (ca. 2:1 major/minor quinoxaline) were obtained (58% total
yield). 19F NMR (CDCl3) for the minor isomer: δ –147.9 (s, vinyl
F, 2F), -194.7 (s, bridgehead F, 2F). The first fraction was
recrystallized from hexanes, then from methanol to give the major
isomer as colorless needles, mp 181–181.5 °C. 19F NMR (CDCl3):
δ -151.3 (s, vinyl F, 2F), -201.68 (s, bridgehead F, 2F). 1H NMR
(CDCl3): δ 8.25 (m, aryl H, 2H), 7.83 (m, aryl H, 2H), 2.85 (s,
bridgehead H proximal to F, 2H), 2.33 (s, distal bridgehead H, 2H),
2.10 (d, J ) 11.7 Hz, one-C bridge H, 1H), 1.70 (m, two-C bridge
H, 2H), 1.26 (d, J ) 11.7 Hz, one-C bridge H, 1H), 1.19 (m, two-C
bridge H, 2H). 13C NMR (CDCl3): δ 149.4 (“CdN”), 139.0
(“CsN”), 134.1 (vinyl CF, 1JCF ) 288 Hz), 130.7, 129.4 (aryl CH),
(“CdN”), 143.6 (CsCO), 141.6 (vinyl CF, 1JCF ) 295 Hz), 138.0
1
(“CsN”), 131.5, 129.3 (aryl CH), 90.0 (bridgehead CF, JCF
)
228 Hz), 53.5 (CH3). IR (C2Cl4): 2960, 1750, 1718, 1700, 1514,
1433, 1318, 1263, 842 cm-1. Anal. Calcd for C18H10F4 N2O4: C,
54.83; H, 2.56; N, 7.11. Found: C, 55.00; H, 2.50; N, 6.99.
Methyl 1,4-Dihydro-1,2,3,4-tetrafluoro-1,4-ethanophenazine-
11-carboxylate. In a 25 mL round-bottomed flask were placed a
quinone mixture (1.23 g of ortho-isomer, 6.84 mmol), benzene (10
mL), and 1.0 mL (0.96 g, 11 mmol) of methyl acrylate. Reaction
was complete after the resulting solution was refluxed for 18 h.
The 19F NMR spectrum (CDCl3), showed signals for the Diels–
Alder adduct at δ -144.6, -147.4 (vinyl Fs) and –193.8, –194.8
(bridgeheads Fs). o-Phenylenediamine (0.8 g, 7 mmol) was added
in 6 mL of benzene, and the orange solution instantly became black.
After 5 min at reflux, the mixture was evaporated to a dark brown
tar. A sample of the tar (1.495 g, 45.0% of the total) was
chromatographed on 20 g of silica gel with 20% ethyl acetate/
hexanes as eluent, giving 686 mg of crude quinoxaline (66% yield).
Recrystallization from methanol followed by sublimation at 100
°C and 30 mTorr gave analytically pure, microcrystalline product,
mp 167.5–168 °C. Its stereochemistry has not been determined.
19F NMR (CDCl3): δ -149.4 (s, vinyl F, 1F), -152.6 (s, vinyl F,
1F), -198.8 (s, bridgehead F, 1F), -200.1 (s, bridgehead F, 1F).
1H NMR (CDCl3): δ 8.21 (m, aryl, 2H), 7.88 (m, aryl, 2H), 3.89
(s, methyl, 3H), 3.31 (m, 3° H, 1H), 2.76 (m, methylene, 1H), 2.62
(m, methylene, 1H). 13C NMR (CDCl3): δ 169.8 (CdO), 148.7,
148.6 (“CdN”), 140.1 (“CsN”), 137.0 (vinyl CF, 1JCF ) 287 Hz),
1
90.5 (bridgehead CF, JCF ) 217 Hz), 51.1 (bridgehead CH,
proximal to F), 37.2, 33.7, 30.1 (CH, CH2). IR (C2Cl4): 2968, 1740,
1504, 1359, 1323, 1220, 1184, 1093, 1039, 997, 954 cm-1. Anal.
Calcd for C19H14F4 N2: C, 65.89; H, 4.07; N, 8.09. Found: C, 65.88;
H, 4.06; N, 8.09. in.
Acknowledgment. The authors thank the National Science
Foundation for support of this work.
1
135.3 (vinyl CF, JCF ) 290 Hz), 131.1, 129.4 (aryl CH), 89.9
(bridgehead CF, 1JCF ≈ 218 Hz), 88.2 (bridgehead CF, 1JCF ≈ 218
Hz), 52.7 (CH3), 44.1 (CH), 35.9 (CH2). IR (C2Cl4): 3033, 2956,
1739, 1506, 1439, 1350, 1272, 1244, 1211, 1172, 1094, 1033, 956
cm-1. Anal. Calcd for C16H10F4 N2O2: C, 56.81; H, 2.98; N, 8.28.
Found: C, 56.81; H, 2.93; N, 8.29.
Supporting Information Available: Total energies at the
B3LYP/6-31G/ level of theory, general experimental informa-
1
tion, and H and 13C NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
(15) Yakobson, G. G.; Odinokov, V. N.; Yorozhtsov, N. N., Jr. Zh. Obsch.
Khim. 1966, 36, 139.
JO7026678
3396 J. Org. Chem. Vol. 73, No. 9, 2008