Sodium dithionite initiated addition of CF2Br2 to β-pinene and reactions of the adduct. Synthesis and the reactivity of new 1,1-difluorodienes

Article abstract of DOI:10.1016/j.jfluchem.2007.07.004

Sodium dithionite effectively promotes the addition of dibromodifluoromethane to the exocyclic double bond of β-pinene. The reaction proceeded in a MeCN/H₂O system to give almost quantitatively an adduct, 1-(2-bromo-2,2-difluoroethyl)-4-(2-bromoisopropyl)-cyclohexene, as the sole product. On treatment of the adduct with 2,2,6,6-tetramethylpiperidine elimination of HBr only from the (CH₃)₂CHBr group occurred to give a mixture of regioisomeric dienes, while treatment with 50% KOH under phase transfer catalysis conditions or with K₂CO₃ in DMF resulted in total dehydrobromination to give trienes possessing an exocyclic CH{double bond, long}CF₂ group. Surprisingly, the main course of the reactions of the adduct with DBU (1,8-diazabicyclo[5.4.0]undece-7-ene) and also with t-BuOK in THF was elimination of HBr only from the CH₂CF₂Br group to afford 1-(2,2-difluorovinyl)-4-(2-bromoisopropyl)cyclohexene as the main product. Catalytic hydrogenation of the adduct followed by treatment with DBU afforded a conjugated diene, 1-(2,2-difluorovinyl)-4-isopropylcyclohexene. Compounds bearing the CH{double bond, long}CF₂ group are new 1,1-difluorodienes which readily reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to give cycloadducts, derivatives of triazolo[1,2-α]cinnoline.

Full text of DOI:10.1016/j.jfluchem.2007.07.004

Journal of Fluorine Chemistry 128 (2007) 1431–1438
www.elsevier.com/locate/fluor
Sodium dithionite initiated addition of CF2Br2 to b-pinene and
reactions of the adduct
Synthesis and the reactivity of new 1,1-difluorodienes
*
Wojciech Dmowski , Anna Jałmuz˙na, Z. Urbanczyk-Lipkowska
´
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
Received 24 May 2007; received in revised form 6 July 2007; accepted 9 July 2007
Available online 15 August 2007
Abstract
Sodium dithionite effectively promotes the addition of dibromodifluoromethane to the exocyclic double bond of b-pinene. The reaction
proceeded in a MeCN/H2O system to give almost quantitatively an adduct, 1-(2-bromo-2,2-difluoroethyl)-4-(2-bromoisopropyl)-cyclohexene, as
the sole product. On treatment of the adduct with 2,2,6,6-tetramethylpiperidine elimination of HBr only from the (CH3)2CHBr group occurred to
give a mixture of regioisomeric dienes, while treatment with 50% KOH under phase transfer catalysis conditions or with K2CO3 in DMF resulted in
total dehydrobromination to give trienes possessing an exocyclic CH CF2 group. Surprisingly, the main course of the reactions of the adduct with
DBU (1,8-diazabicyclo[5.4.0]undece-7-ene) and also with t-BuOK in THF was elimination of HBr only from the CH2CF2Br group to afford 1-(2,2-
difluorovinyl)-4-(2-bromoisopropyl)cyclohexene as the main product. Catalytic hydrogenation of the adduct followed by treatment with DBU
afforded a conjugated diene, 1-(2,2-difluorovinyl)-4-isopropylcyclohexene. Compounds bearing the CH CF2 group are new 1,1-difluorodienes
which readily reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to give cycloadducts, derivatives of triazolo[1,2-a]cinnoline.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Dibromodifluoromethane; Sodium dithionite; Pinene; Radical addition; Difluoromethyl terpenoids; 1,1-Difluorodienes; Cycloaddition
1. Introduction
conjugated diene, 4-isopropyl-1-(trans-3,3,3-trifluoroprope-
nyl)-cyclohexene, which has shown no activity in the Diels–
Alder type cycloadditions.
The reaction of perfluoroalkyl halides (RFI, RFBr) with
sodium dithionite in aqueous medium, known as ‘‘sulfinato-
dehalogenation’’, provides an easy way of generating
perfluoroalkyl radicals [1,2]. The addition of perfluoroalkyl
iodides, Cl(CF2)4I and Cl(CF2)6I, to a-pinene under such
conditions was reported to proceed with ring opening to give
unstable (not isolated) adducts, 4-(2-iodoisopropyl)-1-methyl-
6-perfluoroalkylcyclohexenes, which after in situ hydrodeio-
dination afforded 4-(isopropyl)-1-methyl-6-perfluoroalkylcy-
clohexenes in reasonable yields [3,4]. A stable adduct was
obtained in a similar reaction of b-pinene with 1,1,1-tribromo-
2,2,2-trifluoroethane [5] and more recently, in our laboratory,
with 1-bromo-1-chloro-2,2,2-trifluoroethane [6]. The latter
compound was transformed, with 50% overall yield, to a
In the present paper we report the sodium dithionite initiated
addition of dibromodifluoromethane to (1S,5S)-(ꢀ)-b-pinene
and transformations of the adduct 1 to various terpenoids
substituted with the –CH2CF2Br and –CH CF2 moieties. The
main goal of this work was, however, the synthesis of new
conjugated 1,1-difluorodienes 4–6 and 10 and investigation of
their behaviour in the Diels–Alder cycloaddition reactions. The
only 1,1-difluorodienes synthesized so far were 1-alkoxy-4,4-
difluoro-2-(trimethylsiloxy)-buta-1,3-dienes [7], 1,1-difluoro-
4-phenyl-1,3-butadiene [8–13] and its analogues substituted in
the aromatic ring [14]. The latter compounds, albeit in
unsatisfactory yields, were obtained in our laboratory by
addition of CF2Br2 to allylbenzenes and dehydrohalogenation
of the adducts [14]. All 1,1-difluorodienes were found to be
unstable and reactive towards strong dienophiles like benzy-
lidene-phenylamine [7] and 4-phenyl-3H-1,2,4-triazoline-3,5-
dione [13,14].
* Corresponding author. Fax: +48 22 632 66 81.
E-mail address: dmowski@icho.edu.pl (W. Dmowski).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.07.004

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W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
2. Results and discussion
Addition of CF2Br2 to b-pinene was carried out under
typical sulfinatodehalogenation conditions (Na2S2O4/
NaHCO3/MeCN/H2O) by following, in general, the procedure
described earlier for the reaction of b-pinene with CF3CHClBr
[6]. Because of the volatility of CF2Br2 (bp ca. 22 8C), it was
added to the mixture of other reagents and solvents which was
pre-cooled to 15 8C and the reaction was controlled to maintain
the temperature within the range of 18–20 8C. The reaction was
completed within 30 min to give the adduct, 1-(2-bromo-2,2-
difluoroethyl)-4-(2-bromoisopropyl)cyclohexene (1) (Scheme
1), initially as yellow oil which after 1 h in a refrigerator
crystallized to form large colourless crystals. Elemental
analysis of this crude product gave almost theoretical values
Scheme 2.
with 2,2,6,6-tetramethylpiperidine resulted in total elimination
of HBr from the 2-bromoisopropyl group to give a mixture of
regioisomeric dienes, 1-(2-bromo-2,2-difluoroethyl)-4-isopro-
penylcyclohexene (2) and 1-(2-bromo-2,2-difluoroethyl)-4-
isopropenylidenecyclohexene (3), in a 87:13 ratio and in a
89% total yield (Scheme 2). No elimination of HBr from the
CH2CF2Br group was observed.
for all the elements indicating its high purity. 1H NMR and 19
F
NMR spectra have shown no impurities. In numerous
experiments yields of adduct 1 repeatedly exceeded 90%.
Similarly to the reaction of b-pinene with CF3CHClBr, as
little as 0.2 equiv. of Na2S2O4 was satisfactory for the reaction
with CF2Br2 to proceed with high rates and to give almost
quantitative yields. This suggests an effective free radical chain
mechanism as depicted previously [6].
Compounds 2 and 3 are stable at ambient temperature but
their attempted separation by distillation resulted in total
decomposition and therefore they were identified in their
mixtures. These mixtures gave correct elemental analyses,
identical mass spectra for both components, structures of which
1
The structure of compound 1 was unequivocally assigned by
spectral data. High magnetic non-equivalence of fluorine atoms
(2JFF = 155 Hz), appearance of two signals for the CH3 groups
and AB systems for all the CH2 groups reflects the asymmetric
structure of this molecule. High optical activity of adduct 1 and
the same sign of its optical rotation coefficient as of the starting
b-pinene gave evidence for the retention of absolute config-
uration S at the carbon atom C-4.
were unambiguously differentiated by the H NMR spectra.
The spectrum of 2 exhibited only one signal of the CH3 group
and two signals of vinylic protons of the isopropenyl group
while two CH3 group signals appeared in the spectrum of 3.
Additionally, the lack of asymmetry at carbon atom C-4 in
compound 3 resulted in simplification of both 1H NMR and 19
F
NMR spectra of the CH2CF2Br group; only one signal appeared
for the CH2 group protons and the CF2Br group fluorine atoms.
As compound 2 was the main component, the mixture of 2 and
3, similarly to 1, exhibited high optical activity.
Compound 1 is stable enough to be stored in an refrigerator
(4–6 8C) for long time but slowly decomposes at ambient
temperature with evolution of HBr and formation of brown tar.
Attempted distillation resulted in rapid decomposition. A
reason for the thermal instability of 1 is, most probably, the
presence of a bromine atom in the highly crowded isopropyl
group. Therefore, with the aim to obtain a more stable
compound, we carried out a number of attempts to remove this
bromine, either by controlled elimination of HBr or by
reductive debromination.
Treatment of compound 1 with 50% KOH under phase
transfer catalysis conditions or with K2CO3 in DMF at ambient
temperature resulted in elimination of both HBr molecules to
give a mixture of trienes, 1-(2,2-difluorovinyl)-4-isopropyli-
denecyclohexene (4) and 1-(2,2-difluorovinyl)-4-isopropenyl-
cyclohexene (5), respectively, in a 95% and 83% total yields.
The same compounds were obtained from the reaction of the
mixture of 2 and 3 with DBU (1,8-diazabicyclo[5.4.0]undece-
7-ene) in THF but in opposite proportion, similar to the 2:3 ratio
(Scheme 3).
In spite of the thermal instability of 1, this compound was
found to be reasonably stable against weak bases; no
dehydrobromination occurred by prolonged refluxing in
triethylamine/Et2O and only partial dehydrobromination took
place with pyridine in boiling toluene. However, treatment of 1
Scheme 1.
Scheme 3.

W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
1433
Scheme 4.
Surprisingly, the main course of the reactions of 1 with DBU
and also with t-BuOK in THF, even when an excess of the base
was used, was elimination of HBr from the CH2CF2Br group to
afford 1-(2,2-difluorovinyl)-4-(2-bromoisopropyl)cyclohexene
(6) as the main product; compounds 4 and 5 formed by the
elimination of two HBr molecules were only minor components
of the reaction mixtures (Scheme 4).
with zinc in refluxing THF and in ethanol complex mixture of
unidentified products was obtained. The most successful way to
derivatives bearing the (CH3)2CH group in position 4 of the
cyclohexenyl ring was catalytic hydrogenation of the mixture
of compounds 2 and 3. The best results were obtained when
hydrogenation was carried out in ethyl acetate under 0.17 MPa
pressure of hydrogen using 10% palladium on charcoal as a
catalyst; a mixture containing 60% of the required 1-(2-bromo-
2,2-difluoroethyl)-4-isopropylcyclohexene (7) together with
14% of isomeric compound 8 and 26% of fully hydrogenated
compound 9 was obtained in a 71% total yield (Scheme 5).
Higher pressure of hydrogen resulted in increased contents of
saturated compound 9.
The mixture of compounds 7–9 exhibited only small optical
activity. This suggests that compounds 7 and 8 exist in both
enantiomeric forms, that the hydrogenation proceeded not
stereoselectively and may involve a number of hydrogenation–
dehydrogenation processes. Surprisingly, only one diastereoi-
somer of 9 was detected by the NMR spectroscopy.
Compounds 4–6 possessing structures of 1,1-difluorodienes
were not isolated because they are very unstable and may be
stored only in solutions for a rather short time; on removal of a
solvent they polymerise to form brown tar. Nevertheless,
structures of these compounds were unambiguously determined
from the NMR spectra. The existence of the CH CF2 group
was confirmed by appearance of two signals of fluorine atoms
with typical geminal coupling constants (2JFF = ca. 41 Hz) and
trans and cis coupling of fluorines to single hydrogen atom
(3JHF = 27 and 4 Hz, respectively).
The attempted reductive debromination of 2-bromoisopro-
pyl group in adduct 1 by typical methods failed. Treatment with
Bu3SnH in the presence of AIBN resulted mainly in
dehydrobromination to give 2 and 3. No reaction occurred
Treatment of the mixture of compounds 7–9 with
DBU resulted in dehydrobromination of alkene 7 to give
Scheme 5.

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W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
Scheme 6.
diene, 1-(2,2-difluorovinyl)-4-isopropylcycloxene (10), while
compounds 8 and 9 remain unchanged (Scheme 5).
3,5-dione gave as the major product cycloadduct 13 substituted
with 2-bromoisopropyl group (Scheme 7).
Because of the instability of compounds 4–6 and 10, their
attempted cycloadditions with common dienophiles, which
require elevated temperature or long reaction time, failed; only
polymeric products were formed. However, all these com-
pounds reacted immediately with 4-phenyl-3H-1,2,4-triazo-
line-3,5-dione, the most reactive dienophile known, to give in
good yields crystalline cycloadducts, derivatives of cinnoline.
Thus, addition of 4-phenyl-3H-1,2,4-triazoline-3,5-dione to a
solution containing compounds 4 and 5 (86 and 14%,
respectively) gave a product containing mainly cycloadduct
11 and small amount of cycloadduct 12. The later was obtained
as the main product from the analogous reaction with a solution
containing largely 5 (Scheme 6).
From among the compounds obtained by hydrogenation of a
mixture of 2 and 3 followed by treatment with DBU (Scheme 5)
only diene 10 is able to react with 4-phenyl-3H-1,2,4-
triazoline-3,5-dione, therefore, after column chromatography,
pure cycloadduct 14 was obtained (Scheme 8).
Cycloadducts 12, 13 and 14 possessing two asymmetric
carbon atoms, as found by the NMR spectrometry, were
mixtures of diastereoisomers in ratios of 1.8:1, 1.2:1 and 1.3: 1,
respectively. The NMR spectra of these compounds exhibited
double set of signals for the CH–CF2 group and for the CH
group neighbouring to nitrogen. Separation of the diastereoi-
somers was very difficult but a combination of crystallisation
and column chromatography allowed to obtained the major
1
Similarly, treatment of the mixture containing mainly
compound 6 (Scheme 4) with 4-phenyl-3H-1,2,4-triazoline-
diastereoisomer 12a in pure state. Careful analysis of the H
1
NMR spectra, including COSY and H{1H}NOE experiments
Scheme 7.
Scheme 8.

W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
1435
3.1. (4S)-1-(2-Bromo-2,2-difluoroethyl)-4-(2-
bromoisopropyl)-cyclohexene (1)
Sodium dithionite (0.4 g [85%], 2 mmol) and sodium
hydrogen carbonate (0.17 g, 2 mmol) were suspended in an
acetonitrile–water solution (1:1, 40 ml). The reaction mixture
was vigorously stirred and cooled to 15 8C, then b-pinene
(1.36 g, 10 mmol) and CF2Br2 (3.0 g, 14.3 mmol) were added
one by one. After few minutes gas evolution (CO2) began and a
noticeable exothermic effect occurred. The temperature was
kept at 18–20 8C (by cooling with an external water bath) for
about half an hour after which time the reaction ceased (no
more gas evolution) and most of inorganic salts dissolved.
Addition of water (50 ml) and removal of acetonitrile on a
rotary evaporator resulted in formation of an oily layer which
after 1 h in a refrigerator (ca. 4 8C) solidified to form colourless
crystals. The crystals were filtered off, washed few times with
cold water and dried over P4O10 under reduced pressure. Yield:
22
1
3.15 g (90%). mp 30–32 8C. ½aꢂD = ꢀ46.6 (1% in EtOH). H
Fig. 1. X-ray crystal structure of 12a. Thermal ellipsoids shown in 30%
probability.
NMR: 1.44 (ddd, JHH = 12.3, 11.8 and 5.6, 1H); 1.65 (tdd,
J
HH = ca. 11.5, 5.0 and 2.3, 1H); 1.75 (s, CH3); 1.80 (s, CH3);
2.00–2.35 (complex m, 5H); 3.04 (narrow AB system, JAB = ca.
3, 3JHH = 15.5 and 12.8, 2H, –CH2CF2Br); 5.70 (narrow m, 1H,
suggested that this diastereoisomer exists in a configuration in
which the proton of the methine group neighbouring to nitrogen
(C-10a) and that on the carbon atom bearing the isopropenyl
group (C-9) are mutually trans one to another. Since all
chemical transformations leading from b-pinene to 12
proceeded with retention of the (S)-conformation at the carbon
atom bearing the isopropenyl group, the conformation of the
new asymmetric centre in compound 12a (C-10a) should also
be assigned as (S). This was fully confirmed by the X-ray
analysis as shown in Fig. 1.
2
3
–CH ). 19F NMR: ꢀ42.8 (ddd, JFF = 155.0, JHF = 15.5 and
2
3
12.8, 1F); ꢀ43.6 (dt, JFF = 155.0, JHF = 15.5, 1F). MS (EI):
m/z (rel. int., ion): 348, 346, 344 (5, 10, 5, M+); 267, 265 [75, 77,
(M ꢀ Br)+]; 266, 244 [72, 64 (M ꢀ HBr)+]; 251, 249 [16, 17,
(M ꢀ HBr–CH3)+]; 225, 223 [11, 14, (M ꢀ C3H6Br)+]; 211,
209 (98, 100, C7H8F2Br+); 185 [9, (M ꢀ 2Br)+]; 141 (57,
C8H7F2 ); 129 (28, C7H7F2 ); 121 (20, C9H13+); 91 (18,
+
+
+
C7H7 ); 79 (21, C6H7 ); 69 (19, C5H9 ); 43 (19, C3H7 ); 41 (23,
+
+
+
+
C3H5 ). Analysis—found: C, 38.2; H, 4.5; Br, 46.3; F, 11.0%.
In conclusion, sodium dithionite initiated addition of
dibromodifluoromethane to b-pinene provides a way to a
number of terpenic dienes with exocyclic CH CF2 group. These
compounds are new examples of conjugated 1,1-difluorodienes
and were found to be highly reactive towards strong dienophiles
like 4-phenyl-3H-1,2,4-triazoline-3,5-dione.
Calculated for C11H16Br2F2 (346.05): C, 38.2; H, 4.7; Br, 46.2;
F, 11.0%.
3.2. Dehydrohalogenation of 1
3.2.1. With 2,2,6,6-tetramethylpiperidine
Compound 1 (10 g, 28.9 mmol) and 2,2,6,6-tetramethyl-
piperidine (14.6 ml, 86.7 mmol) were refluxed in dry toluene
(100 ml) for 48 h. The precipitate of piperidine hydrobro-
mide was filtered off, the solution was washed with 5%
hydrochloric acid (3ꢄ 20 ml), followed with brine until
neutral, and dried over anhydrous MgSO4. Evaporation of the
solvent gave an oily liquid which was subjected to column
chromatography (silica gel, hexanes). Evaporation of the
solvent afforded 6.8 g (25.7 mmol, yield: 89%) of colourless
liquid composed of diene 2 (87%) and diene 3 (13%)
(estimated from the integrated NMR spectra). Analysis—
found: C, 49.2; H, 5.9; Br, 29.8; F, 15.0%. Calculated for
C11H15BrF2 (265.14): C, 49.8; H, 5.7; Br, 30.1; F, 14.3%.
3. Experimental
Melting points were determined in capillaries and are
1
uncorrected. H NMR, and 19F NMR spectra were recorded
with a Varian 400 spectrometer in CDCl3 solutions (or as
indicated otherwise). Chemical shifts are quoted in ppm from
internal TMS for H and from internal CFCl3 for 19F nuclei.
1
Coupling constants (J) values are in Hz. NOE and COSY
experiments were obtained with a Brucker AM-500 instrument.
Mass spectra were obtained with an AMD-604 spectrometer. IR
spectra were obtained with Perkin-Elmer 2000 spectrometer
(frequencies in cmꢀ1) and optical rotation coefficients were
measured with a JASCO-1020 polarimeter equipped with a
sodium lamp.
20
½aꢂD = ꢀ45.7 (1% in EtOH).
(4S)-1-(2-Bromo-2,2-difluoroethyl)-4-isopropenylcyclo-
1
hexene (2): H NMR: 1.43–1.55 (complex m, 1H); 1.74 (dm,
Dibromodifluoromethane and (1S,5S)-(ꢀ)-b-pinene [purity
20
ꢁ99%, ½aꢂD = ꢀ21 ꢃ 1 (neat)] were commercial reagents. 4-
2
J = ca. 1.0, CH3); 1.82 (dm, JHH = 13.5, 1H); 2.00 (dm,
Phenyl-3H-1,2,4-triazoline-3,5-dione was prepared according
to the literature procedure [15].
2JHH = 13.5, 1H); 2.25–2.10 (complex m, 4H); 3.02
3
(t, JHF = 14.8, 2H, –CH2CF2Br); 4.72 (sext, J = 0.9,

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W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
1H, CH2 ); 4.74 (qn, J = 1.5, 1H, CH2 ); 5.69 (narrow m, 1H,
2
1H NMR and 19F NMR signals of compound 4 in agreement
with given in Section 3.2.2.
3
–CH ). 19F NMR: ꢀ42.8 (dt, JFF = 155, JHF = 14.8, 1F);
2
3
ꢀ43.4 (dt, JFF = 155, JHF = 14.8, 1F).
Similar treatment of the mixture of compounds 2 and 3 gave
a mixture of 5 (87%) and 4 (13%) in 89% total yield.
1-(2,2-Difluorovinyl)-4-isopropenylcyclohexene (5)—1H
NMR: 1.43–1.55 (m, 1H); 1.74 (s, CH3); 1.82 (m, 1H); 2.00
(m, 1H); 2.10–2.35 (complex m, 4H); 4.71 (narrow m, 1H,
CH2 ); 4.73 (narrow m, 1H, CH2 ); 4.83 (dd, 3JHF = 27.4, 4.7,
1H, –CH CF2); 5.66 (narrow m, 1H, –CH ). 19F NMR: ꢀ85.1
(4S)-1-(2-Bromo-2,2-difluoroethyl)-4-isopropenylidenecy-
clohexene (3): 1H NMR: 1.66 (s, CH3); 1.69 (s, CH3); 2.13 (m,
3
2H); 2.33 (t, JHH = 6.2, 2H); 2.82 (broad s, 2H); 3.04 (t,
3JHF = 14.8, 2H, –CH2CF2Br); 5.72 (narrow m, 1H, –CH ). 19
F
3
NMR: ꢀ43.30 (t, JHF = 14.8, 2F).
2
3
2
3.2.2. With KOH
(dd, JFF = 41.0, JHF = 27.4, 1F); ꢀ88.5 (dm, JFF = 41.0 Hz,
Compound 1 (0.5 g, 1.45 mmol), 50% aqueous KOH
(0.42 ml, 8.7 mmol) and Bu4NHSO4 (0.49 g, 1.45 mmol) were
vigorously stirred at ambient temperature for 72 h. The reaction
was quenched with 5% aq. HCl (10 ml), extracted with ether
(3ꢄ 30 ml), the combined extracts were washed with water
until neutral and dried over MgSO4. Evaporation of the solvent
afforded 0.26 g (1.38 mmol, yield: 95%) of oily liquid
composed of triene 4 (86%) and triene 5 (14%) (estimated
from the integrated NMR spectra).
1F).
3.2.5. With t-BuOK
Compound 1 (0.5 g, 1.45 mmol) and t-BuOK (0.32 g,
2.9 mmol) in dry THF (5 ml) were vigorously stirred at
ambient temperature for 1.5 h. The reaction mixture was
acidified with 5% aq. HCl (15 ml), extracted with ether (3ꢄ
20 ml) and the combined extracts were washed with water and
dried over MgSO4. Evaporation of the solvent afforded 0.33 g
(1.33 mmol, yield: 92%) of oily liquid which by the integrated
NMR spectra was found to be composed of compounds 6
(72%), 4 (19%) and 5 (9%).
1
1-(2,2-Difluorovinyl)-4-isopropylidenecyclohexene (4): H
NMR: 1.69 (s, CH3), 1.73 (s, CH3); 2.31 (m, 2H); 2.37 (d,
3
HH = 6.4, 2H); 2.87 (broad s, 2H); 4.86 (dd, JHF = 27.3,
J
3JHF = 4.6 H, 1H, –CH CF2); 5.66 (narrow m, 1H, –CH ). 19
F
2
3
NMR: ꢀ85.4 (ddm, JFF = 41.0, JHF = 27.3, 1F), ꢀ88.7 (dm,
3.3. Hydrogenation of the mixture of 2 and 3 and
dehydrobromination of products
2JFF = 41.0, 1F).
1-(2,2-Difluorovinyl)-4-isopropenylcyclohexene (5): 1H
NMR and 19F NMR signals in agreement with given in
Section 3.2.4.
Mixture of compounds 2 and 3 (87 and 13%, respectively,
Section 3.2.1) was dissolved in ethyl acetate (150 ml) and
hydrogenated in the presence of 10% Pd/C catalyst (0.1 g) in a
Parr apparatus for 4 h at ambient temperature under 0.17 MPa
pressure of hydrogen. The catalyst was filtered off through a
layer of Celite then the eluent was evaporated and the oily
residue which was purified by column chromatography (silica
gel, hexanes) to give colourless liquid (0.71 g, yield 71%)
composed of compounds 7, 8 and 9 (60, 14 and 26%,
respectively; estimated from the integrated NMR spectra).
Analysis—found: C, 50.0; H, 7.0; Br, 29.5; F, 13.5%.
Calculated for C11H17Br F2 (267.16): C, 49.5; H, 6.4; Br,
3.2.3. With K2CO3
Compound 1 (0.5 g, 1.45 mmol) and K2CO3 (0.8 g,
5.8 mmol) in DMF (5 ml) were vigorously stirred at ambient
temperature for 72 h. The reaction mixture was diluted with
water (5 ml), extracted with ether (3ꢄ 10 ml) and the combined
extracts were washed with water and dried over MgSO4.
Evaporation of the solvent afforded 0.22 g (1.2 mmol, yield:
83%) of oily liquid composed of triene 4 (77%), triene 5 (17%)
and compound 3 (6%) (estimated from the integrated NMR
spectra).
23
29.9; F, 14.2%. ½aꢂD = ꢀ8.9 (1% in ethanol).
1-(2-Bromo-2,2-difluoroethyl)-4-isopropylcyclohexene (7):
1H NMR: 0.88 (d, 3JHH = 4.4, CH3); 0.90 (d, 3JHH = 4.4, CH3);
1.16–1.34 (complex m, 2H); 1.46 (q, 3JHH = 6.6, 2H); 1.78 (m,
2H); 2.10 (m, 2H); 3.00 (t, 3JHF = 14.4, 2H, –CH2CF2Br); 5.68
3.2.4. With DBU
Compound 1 (0.5 g, 1.45 mmol) and DBU (0.87 ml,
5.8 mmol) in dry THF (5 ml) were vigorously stirred at
ambient temperature for 3 h. Precipitate of DBU hydrobro-
mide was filtered off, the eluent was washed with 5% aq. HCl
(3ꢄ 10 ml) followed with brine until neutral and dried over
MgSO4. Evaporation of the solvent afforded 0.37 g (1.4 mmol,
yield: 96%) of oily liquid containing 93% of compound 6 and
7% of compound 4 (estimated from the integrated NMR
spectra).
2
(narrow m, 1H, –CH ). 19F NMR: ꢀ42.6 (dt, JFF = 154,
2
3
3JHF = 14.4, 1F); ꢀ43.4 (dt, JFF = 154, JHF = 14.4, 1F).
1H NMR and 19F NMR signals of compounds 8 and 9 in
agreement with given in Section 3.4.3.
The above mixture of compounds 7–9 was treated with DBU
and worked up as in Section 3.2.4 to give a mixture containing
60% of diene 10 (91% yield in relation to 7) and unchanged
compounds 8 and 9.
1-(2,2-Difluorovinyl)-4-(2-bromoisopropyl)cyclohexene
(6): 1H NMR: 1.42 (ddd, 2JHH = 24.6, 3JHH = 12.0 and 5.3, 1H);
1.64 (tdd, 3JHH = 11.4, 4.9 and 2.4, 1H); 1.75 (s, CH3); 1.80 (s,
CH3); 2.00–2.15 (m, 2H); 2.20–2.44 (complex m, 3H); 4.83
1-(2,2-Difluorovinyl)-4-isopropylcyclohexene (10): 1H
NMR: 0.82 (complex m, 6H, 2xCH3); 1.10–1.25 (complex
3
AB system, 2H); 1.42 (q, JHH = 6.5, 2H); 1.74 (m, 2H); 2.02
3
3
(m, 2H); 4.74 (dd, JHF = 27.5 and 4.7, 1H, CH CF2); 5.56
(dd, JHF = 27.3, 4.4, 1H, –CH CF2); 5.63 (narrow m, 1H, –
2
3
2
CH ). 19F NMR: ꢀ84.9 (dd, JFF = 40.2, JHF = 27.3, 1F);
(narrow m, 1H, CH ). 19F NMR: ꢀ85.40 (dd, JFF = 41.3,
2
2
ꢀ88.2 (dm, JFF = 40.2, 1F).
3JHF = 27.5, 1F); ꢀ88.92 (dm, JFF = 41.3, 1F).

W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
1437
3.4. Reactions of dienes 4–6 and 10 with 4-phenyl-3H-
1,2,4-triazoline-3,5-dione
1H); 1.80 (td, JHH = 13.89 and 5, 1H); 1.84 (s, CH3); 2.28–2.46
(complex m, 3H); 2.63 (narrow m, 1H); 2.85 (dm, JHH = 12.5,
1H); 4.64 (dm, JHH = ca. 12, 1H, N–CH–); 5.08 (narrow m, 2H,
CH2 ); 5.70 (d, 3JHF = 6.6, 1H, CH–CF2); 7.37–7.54 (m, 5H,
Mixtures of compounds obtained as described in Sections
3.2.2 and 3.2.4 (4.0 mmol) were dissolved in CH2Cl2 (7 ml)
then 4-phenyl-3H-1,2,4-triazoline-3,5-dione (ca. 4.5 mmol)
was added portionwise. Immediate colour change, from red
to pale-yellow, occurred after addition of each portion of the
dienophile. After addition of the last portion, colour did not
changed during 10 min. Solid material obtained after evapora-
tion of the solvent was purified by column chromatography
(silica gel, hexanes/ethyl acetate 1:1).
2
Ph). 19F NMR: ꢀ77.44 (dm, JFF = 216.3, 1F); ꢀ85.3 (dd,
3
2JFF = 216.3, JHF = 6.6, 1F). IR (in KBr): n(C O) = 1794 (s)
24
and (vs), n(C C) = 1684 (m). ½aꢂD = ꢀ91.8 (1% in CH2Cl2).
Minor diastereoisomer (12b): 1H NMR: 1.43 (ddd, 2JHH = 25.7,
3JHH = 13.2 and 4.01, 1H); ca. 1.60 (overlapped m, 1H); 1.74 (s,
CH3); ca. 2.35 (overlapped m, 3H); 2.58 (m, 2H); 4.53 (dm,
J
HH = ca. 12, 1H, N–CH–); 4.75 (d, JHH = ca. 0.7, 1H, CH2 );
3
4.78 (qn, JHH = 1.5, 1H, CH2 ); 5.75 (d, JHF = 6.7, J = 1.51,
1H, CH–CF2); 7.37–7.54 (m, 5H, Ph). 19F NMR: ꢀ77.3 (ddd,
3
2
3.4.1. Reaction of the mixture of 4 and 5
2JFF = 216.6, JHF = 6.7, 4.3, 1F); ꢀ85.8 (dd, JFF = 216.6,
Mixture containing 86% of 4 and 14% of 5 (Section 3.2.2)
gave crystalline product (1.1 g, 3.07 mmol, total yield 77%)
composed of 95% of cycloadduct 11 and 5% of cycloadduct 12
(integrated NMR estimate). mp 189–190 8C. Analysis—found:
C, 63.7; H, 5.2; F, 10.8; N, 11.7%. Calculated for C19H19F2N3O2
(359.38): C, 63.5; H, 5.3; F, 10.6; N, 11.7%. MS (EI): m/z (rel.
int., ion): 359 (11, M+); 316 [3, (M ꢀ C3H7)+]; 220 (1,
C12H13FN2O+); 197 (3, C9H7F2N2O+); 183 (100, C9H7F2NO+);
178 (11, C9H7FN2O+); 159 (4, C9H7N2O+); 119 [4, (PhNCO)+];
3JHF = 6.7, 1F).
X-ray crystallographic studies of compound. 12a:
C19H19F2N3O2, Fw = 359.37. Suitable crystal of dimensions
0.63 mm ꢄ 0.38 mm ꢄ 0.27 mm was mounted on a glass fiber.
Data collection was performed at 295 on a Nonius BV MACH
diffractometer with graphite monochromated Cu Ka
˚
(l = 1.54178 A). Unit cell dimensions: a = 7.1650 (6),
˚
b = 15.6390 (10), c = 8.1820 (7) A, b = 105.550 (7)8,
3
V = 883.3 (1) A , Z = 2, dx = 1.351 Mg mꢀ3, F(000) = 376, m
˚
91 [3, PhN+]; 77 (2, C6H5 ); 41 [3, (C3H5)+]. ½aꢂ24 = ꢀ8.7 (1% in
(Cu Ka) = 0.870 mmꢀ1, monoclinic system, space group P21.
Thousand nine hundred and sixty one reflections were collected
in the u-range 5.61–74.058, 1823 unique [R(int) = 0.0339] were
used for structure elucidation.
+
D
CH2Cl2). 5,5-Difluoro-8,9,10,10a-tetrahydro-9-isopropylideno-
2-phenyl-2H-[1.2,4]-triazolo-[1,2-a]cinnoline-1,3(5H,7H)-
dione (11)—1H NMR: 1.74 (s, CH3); 1.76 (s, CH3); 1.85 (t,
JHH = 12.4, 1H); 2.01 (t, JHH = 12.4, 1H); 2.17 (sept., JHH = ca.
6.2, 1H); 2.55 (ddd, JHH = 13.1, 4.5 and 2.5, 1H); 2.93 (dm,
Structure was solved with direct methods using the
SHELXS97 [16] and refined with SHELXL97 [17] software.
Refinement was performed anisotropically for all non-
hydrogen atoms using the full-matrix least-squares method.
In general, hydrogen atoms were assigned to idealized
positions and were allowed to ride with thermal parameters
fixed at 1.2Ueq of the parent atom. The residual electron
densities were of no chemical significance. Final R indices
[1823 reflections with I > 2s(I)]: R1 = 0.0453, wR2 = 0.1191,
and for all data R1 = 0.0984, wR2 = 0.1483. CCDC-644964
contains the supplementary crystallographic data for this paper
[18].
J
HH = 13.6, 1H); 3.54 (ddd, JHH = 12.5, 4.7 and 2.2, 1H); 4.63
(dm, JHH = ca. 12, 1H, N–CH–);5.75 (dd, 3JHF = 6.6, 4JHH = 1.5,
1H, CH–CF2); 7.38–7.55 (m, 5H, Ph). 19F NMR: ꢀ77.8 (dm,
2JFF = 216.6 Hz, 1F); ꢀ84.8 (dd, JFF = 216.6 Hz,
2
3JHF = 6.6 Hz, 1F). IR (in KBr): n(C O) = 1722 (vs) and
1787 (vs), n(C C) = ca. 1670 (overlapped). ½aꢂ2D4 = ꢀ91.8 (1%
in CH2Cl2).
From the mixture containing 87% of 5 and 13% of 4 (Section
3.2.4 bottom) gave a product (0.54 g, 3.1 mmol, total yield
62%) composed of 89% of 12 and 11% of 11 (integrated NMR
estimate). mp 135–137 8C. Cycloadduct 12 was found to be a
mixture of two diastereoisomers in a 1.8: 1 ratio. The major
diastereoisomer 12a was isolated by repeated crystallisation
from hexenes/ethylacetate (2:1). The minor isomer 12b was
3.4.2. Reaction of the mixture of 6 and 4
Mixture containing 93% of 6 and 7% of 4 (§ 3.2.4) gave
crystalline product (1.16 g, 2.64 mmol, total yield 66%)
composed of 87% of cycloadduct 13 and 13% of cycloadduct
11 (integrated NMR estimate). Mp 110–111 8C. Analysis –
found: C, 52.0; H, 5.0; Br, 18.1; F, 8.6; N, 9.7%. Calculated for
C19H20BrF2N3O2 (440.29): C, 51.8; H, 4.9; Br, 18.2; F, 8.6; N,
9.5%. MS (EI): m/z (rel. int., ion): 441, 439 (7, 8, M+); 359 [34,
(M ꢀ HBr)+]; 339 [9, (M ꢀ HBr–HF)+]; 316 [79, (M ꢀ HBr–
1
identified in the mixture of diastereoisomers by H NMR and
19F NMR spectroscopy.
5,5-Difluoro-8,9,10,10a-tetrahydro-9-isopropenylo-2-
phenylo-2H-[1.2,4]triazolo[1,2-a]cinnoline-1,3(5H,7H)-
dione: major diastereoisomer (12a): Analysis—found: C, 63.7;
H, 5.2; F, 10.8; N, 11.7%. Calculated for C19H19F2N3O2
(359.38): C, 63.5; H, 5.3; F, 10.6; N, 11.7%. MS (EI): m/z (rel.
int., ion): 359 (43, M+); 344 [3, (M ꢀ CH3)+]; 339 [4,
(M ꢀ HF)+]; 331 [2, (M ꢀ CO)+]; 316 [100, (M ꢀ C3H7)+];
C3H7)+]; 290 (6, C15H12F2N2O2 ); 197 [42, (M ꢀ PhNCO–
+
C3H7)+]; 183 (100, C9H7F2NO+); 159 (7, C9H7N2O+); 141 (6,
+
+
C8H7F2 ); 119 (24, PhNCO+); 91 (21, PhN+); 77 (10, C6H5 );
+
+
41 (28, C3H5 ). IR (in KBr): n(C O) = 1795 (s) and 1733 (vs),
303 [5, (M ꢀ 2CO)+]; 290 (10, C15H12F2N2O2 ); 197 [73,
24
(M ꢀ PhNCO–C3H7)+]; 183 (31, C9H7F2NO+); 171 (16,
n(C C) = 1684 (m). ½aꢂD = ꢀ157.1 (1%
w
CH2Cl2).
24
C8H6F2NO+); 159 (6, C9H7N2O+); 141 (6, C8H7F2 ); 128 (6,
½aꢂD = ꢀ157.1 (1% in CH2Cl2). Cycloadduct 13 was found
to be a mixture of two diastereoisomers, 13a and 13b, in a 1.2: 1
ratio (not separated).
+
C9H6N+); 119 (4, PhNCO+); 91 (3, C7H7 , PhN+); 77 (2,
+
C6H5 ); 41 (3, C3H5 ). 1H NMR: 1.70 (tt, JHH = 13.30, and 5,
+
+

1438
W. Dmowski et al. / Journal of Fluorine Chemistry 128 (2007) 1431–1438
+
9-(2-Bromoisopropyl)-5,5-difluoro-8,9,10,10a-tetrahydro-
2-phenyl-2H-[1.2,4]-triazolo-[1,2-a]cinnoline-1,3-(5H,7H)-
214 (7, C11H16F2N2 ); 199 [5, (M ꢀ PhNCO–C3H7)+]; 184 (14,
C11H14F2 ); 178 (18, C9H7FN2O+); 159 (6, C9H7N2O+); 143
(17, C8H9F2 ); 129 (17, C9H7N+); 119 (20, PhNCO+); 91 (12,
+
1
dione (13): major diastereoisomer (13a): H NMR: 1.68–1.92
+
+
+
+
+
(complex m, 2H); 1.76 (s, CH3); 1.79 (s, CH3); 1.99 (m, 2H);
2.52 (dt, JHH = 13.3 Hz, 3.8, 2H); 2.74 (m, 1H), 4.82 (m, 1H,
C7H7 , PhN+); 77 (8, C6H5 ); 43 (8, C3H7 ); 41 (12, C3H5 ). IR
(in KBr): n(C O) = 1792 (s) and 1728 (vs), n(C C) = 1680
(m). Major diastereoisomer (14a)—1H NMR: 0.98 (d,
3
N–CH–); 5.78 (d, JHF = 6.0, 1H, CH–CF2); 7.37–7.54 (m,
3
5H, Ph). 19F NMR: ꢀ77.87 (dm, 2JFF = 217,1F); ꢀ85.82 (dm,
2JFF = 217, 1F). Minor diastereoisomer (13b): 1H NMR: 1.22–
1.36 (complex AB system, 2H); 1.48 (m, 1H), 1.61 (q,
3JHH = 12, 1H); 1.78 (s, CH3); 1.80 (s, CH3); 2.28 (m, 2H); 2.60
(dm, 3JHH = ca. 11, 1H); 4.53 (dm, JHH = ca. 12, 1H, N–CH–);
3JHH = 6.6 Hz, CH3); 1.07 (d, JHH = 6.6, CH3); 1.55 (m,
2H); 1.68 (td, JHH = 12.4 and 4.4, 1H); 1.86 (dq, JHH = 10.5 and
6.6, 1H); 2.10 (dm, JHH = 14.7, 1H); 2.38 (narrow m, 2H); 2.68
(dm, JHH = 12.7, 1H); 4.75 (dm, JHH = 12.4, 1H, N–CH–); 5.70
(d, JHF = 6.6, 1H, CH–CF2); 7.36–7.55 (m, 5H, Ph). 19F
3
2
2
5.75 (d, 3JHF = 6.7, 1H, CH–CF2); 7.37–7.54 (m, 5H, Ph). 19
F
NMR: ꢀ77.75 (dm, JFF = 216, 1F); ꢀ85.04 (dd, JFF = 216,
2
2
NMR: ꢀ77.6 (dm, JFF = 217, 1F); ꢀ85.8 (dd, JFF = 217,
3JHF = 6.6 Hz, 1F). Minor diastereoisomer (14b)—1H NMR:
2
3
3JHF = 6.7, 1F).
0.89 (s, CH3); 0.91 (s, CH3); 1.23 (ddd, JHH = 25, JHH = 13
and 4.0, 1H); 1.38 (q, 3JHH = 11.5 Hz, 1H); 1.55 (overlapped m,
1H); 1.96 (dm, JHH = ca. 13, 1H); 2.23 (m, 1H); 2.52 (tdd,
3JHH = 13, 4.03 and 2.8, 1H); 4.75 (dm, JHH = 11.7 1H, N–CH–
3.4.3. Reaction of the mixture of 10, 8 and 9
Mixture containing 60% of 10, 14% of 8 and 26% 9 (Section
3.3) gave an oil which was separated by column chromato-
graphy in two fractions. The first fraction (oil, 0.19 g,
0.73 mmol) consisted of 34% compound 8 and 66% of
3
); 5.72 (d, JHF = 6.9, 1H, CH–CF2); 7.36–7.55 (m, 5H, Ph).
19F NMR: ꢀ77.14 (ddd, 2JFF = 216, 3JFH = 6.0 and 4.3 Hz, 1F);
2
3
ꢀ85.52 (dd, JFF = 216, JHF = 6.9, 1F).
23
compound 9 (19F NMR estimate). ½aꢂD = ꢀ1.75 (1% in
ethanol). The second, crystalline fraction (0.57 g, 1.47 mmol)
was found by integrated 19F NMR to be a mixture of
diastereoisomers 14a and 14b in a 1.3:1 ratio. Yield: 61%
relative to 10. mp 119–121 8C. Repeated column chromato-
graphy (silica gel, hexanes/ethyl acetate 4:1) allowed to obtain
References
[1] W.Y. Huang, J. Fluorine Chem. 58 (1992) 1–8.
[2] W.Y. Huang, F.H. Wu, Israel J. Chem. 39 (1999) 167–170.
[3] W.Y. Huang, W. Wang, B.N. Huang, Acta Chim. Sin. (Engl Ed.) (1986)
178–184.
24
a fraction containing 81% of 14a. ½aꢂD = ꢀ8.38 (1% in
[4] B.N. Huang, J.T. Liu, Chin. J. Chem. (1990) 358–361.
[5] W.Y. Huang, W. Wang, Acta Chim. Sin. (Chinese Ed.) 47 (1986) 141–146.
[6] W. Dmowski, J. Ignatowska, K. Piasecka-Maciejewska, J. Fluorine Chem.
125 (2004) 1147–1151.
ethanol).
4-(2-Bromo-2,2-difluoroetylo)-1-isopropylcyclohexene
(8)—1H NMR: 0.98 (s, CH3); 0.99 (s, CH3); 1.50 (complex m,
2H); 1.67(complex m, 1H); 1.83–1.94 (complex m, 2H); 2.01
(m, 2H); 2.13–2.46 (complex m, 3H, 1H-CH(CH3)2, 2H –
CH2CF2); 5.34 (narrow m, 1H, CH ). 19F NMR: ꢀ40.90 (ddd,
2JFF = 154, 3JHF = 16.1 and 14.0, 1F); ꢀ41.50 (dm, 2JFF = 154,
1F).
[7] H. Amii, T. Kobayashi, H. Teresawa, K. Uneyama, Org. Lett. 3 (2001)
3103–3105.
[8] T. Fuchigami, M. Yatoba, Synthesis 5 (1981) 365–366.
[9] N. Kamigata, T. Fukushima, Y. Terakawa, M. Yoshidu, H. Sawada, J.
Chem. Soc. Trans. I 3 (1991) 627–633.
[10] S. Furuta, M. Kuroboshi, T. Hiyama, Bull. Chem. Soc. Jpn. 72 (1999) 805–
819.
4-(2-Bromo-2,2-difluoroetylo)-1-isopropylcyclohexane
(9)—1H NMR: 0.86 (d, 3JHH = 6.8, 6H, 2xCH3); 1.01 (narrow
m, 3H); 1.26 (narrow m, 3H); 1.42 (complex m, 1H); 1.54 (m,
1H); 1.63–1.76 (complex m, 2H); 1.83–1.94 (complex m, 1H);
[11] T. Kobayashi, T. Exda, O. Tamura, H. Ishibashi, J. Org. Chem. 67 (2002)
3156–3159.
[12] I. Nowak, M.J. Robins, Org. Lett. 7 (2005) 721–724.
[13] S. Elsheimer, C.J. Foti, M.D. Bartberger, J. Org. Chem. 61 (1996) 6252–
6255.
3
3
3.00 (dt, JHF = 15.5 Hz, JHH = 6.2 Hz, 2H, CH2CF2). 19F
[14] I. Ignatowska, W. Dmowski, J. Fluorine Chem. 128 (2007) 997–1006.
[15] M.J. Baush, B. David, J. Org. Chem. 57 (1992) 1118–1124.
[16] G.M. Sheldrick, SHELS-97, Program for Crystal Structure Solution,
3
NMR: ꢀ40.95 (t, JHF = 15.5 Hz, 2F).
5,5-Difluoro-8,9,10,10a-tetrahydro-9-isopropyl-2-phenyl-
2H-[1.2,4]triazolo[1,2-a]cinnoline-1,3(5H,7H)-dione (14):
Analysis—found: C, 63.2; H, 5.9; F, 10.5%, N, 11.6%.
Calculated for C19H21F2N3O2 (361.39): C, 63.2; H, 5.9; F, 10.5;
N, 11.6%. MS (EI)—m/z (rel. int., ion): 361 (100, M+); 341 [3,
(M ꢀ HF)+]; 318 [100, (M ꢀ C3H7)+]; 291 (3, C14H11
¨
University of Gottingen, Germany, 1997.
[17] G. M. Sheldrick, SHELXL97, Program for Crystal Structure Refinement,
¨
University of Gottingen, Germany, 1997.
[18] These data can be obtained free of charge at ‘‘http://www.ccdc.cam.ac.uk/
conts/retrieving.html’’ [or from the Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB2 1EZ, UK; CCDC-644964. E-
mail: deposit@ccdc.cam.sc.uk.
+
+
+
F2N3O2 ); 278 (4, C13H8F2N3O2 ); 277(5, C13H7F2N3O2 );