Polyhalogenated heterocyclic compounds: Part 46. Multifunctional heterocycles from bromofluoropyridine derivatives

Article abstract of DOI:10.1016/S0022-1139(01)00534-6

2,4,6-Tribromo-3,5-difluoro-pyridine 1 was used as the starting material for the synthesis of a variety of multifunctional pyridine derivatives. For example, nucleophilic substitution reactions involving appropriate difunctional nucleophiles gave products resulting from intramolecular cyclisation processes and the organolithium derivative 9, readily prepared from 1, could be trapped by various of electrophilic reagents.

Full text of DOI:10.1016/S0022-1139(01)00534-6

Journal of Fluorine Chemistry 112 ?2001) 349±355
Polyhalogenated heterocyclic compounds
Part 46. Multifunctional heterocycles from
bromo¯uoropyridine derivatives$
Hadjar Benmansoura, Richard D. Chambersa,*, Graham Sandforda,1, Graham McGowana,
Slimane Dahaouia,b, Dmitrii S. Yu®ta,b, Judith A.K. Howarda,b
aDepartment of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK
bChemical Crystallography Group, Durham DH1 3LE, UK
Received 8 June 2001; accepted 31 August 2001
Dedicated to Prof. Karl Christe on the occasion of his 65th birthday
Abstract
2,4,6-Tribromo-3,5-di¯uoro-pyridine 1 was used as the starting material for the synthesis of a variety of multifunctional pyridine
derivatives. For example, nucleophilic substitution reactions involving appropriate difunctional nucleophiles gave products resulting from
intramolecular cyclisation processes and the organolithium derivative 9, readily prepared from 1, could be trapped by various of
electrophilic reagents. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Bromo¯uoropyridine; Heterocyclic compounds; Nucleophilic substitution
1. Introduction
bromine, respectively [7]. In preliminary experiments, we
also demonstrated that sites attached to bromine can be
activated in palladium catalysed processes [7].
Polysubstituted pyridine derivatives are notoriously dif®-
cult to synthesise and the problem grows with the number
and different substitution patterns of the substituents [2].
Nevertheless, relatively little attention has been focused on
the use of polyhalogenated pyridine derivatives as appro-
priate starting compounds for the synthesis of multifunc-
tional derivatives and this paper demonstrates the relevance
of some of the chemistry of 2,4,6-tribromo-3,5-di¯uoro-
pyridine 1 in this context.
There is a considerable chemistry derived from nucleo-
philic substitution in penta¯uoro- and pentachloro-pyridine
that has already been described [3±6], but comparatively
little that is directed to the synthesis of multifunctional
compounds. However, recently we reported that 1 could
be used for this purpose and highlighted the different pre-
ferences for reaction of 1 with various hard and soft nucleo-
philes which led to attack at sites attached to ¯uorine and
2. Results and discussion
Reaction of sodium phenoxide with 1 led exclusively to
attack at carbon attached to the 3- and 5-¯uorine substituents
to give products 2 and 3 ?Scheme 1) depending on the
proportion of phenoxide used ?one and two equivalents,
respectively). However, when resorcinol was used the dis-
ubstituted derivative 4, arising from reaction of resorcinol
and two equivalents of the pyridine derivative 1, was isolated
as the major product. It is clear, however, that the remaining
sites attached to ¯uorine also compete for resorcinol,
because a signi®cant amount of intractable material was
formed which we assume to be polyaryl ethers.
Using catechol, the situation is more interesting because
cyclic systems 5 and 6 are produced ?Scheme 2). It is
reasonable to assume that 5 and 6 are formed by ®rst reaction
at the 3-position, displacing ¯uoride ion, but then intramo-
lecular displacement of bromine occurs and this process
obviously competes favourably with intermolecular displa-
cement of ¯uorine from another molecule of 1. However,
$ For part 45, see [1].
* Corresponding author. Tel.: ‡44-191-374-3120;
fax: ‡44-191-384-4737.
E-mail address: r.d.chambers@durham.ac.uk ?R.D. Chambers).
1 Co-corresponding author.
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ? 0 1 ) 0 0 5 3 4 - 6

350
H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
Scheme 1. Reagents and conditions: ?i) PhONa ?two equivalents), THF, reflux, 24 h; ?ii) 1,3-NaO±C6H4±ONa, THF, reflux, 24 h.
Scheme 2. Reagents and conditions: ?i) n-BuLi, Et2O, À78 8C; ?ii) H2O, À78 8C to room temperature; ?iii) Me3SiCl, À78 8C to room temperature; ?iv) CO2
gas, À78 8C to room temperature; ?v) PhCOCl, À78 8C to room temperature; ?vi) CH3C6H4COCl, À78 8C to room temperature.

H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
351
some intractable material is formed which is attributed to
polymer formation. It could be argued that a 2:1 ratio for
intramolecular displacement of bromine at the 2- versus 4-
sites, giving 5 and 6, respectively, re¯ects a less crowded site
at the 2-position, because the directing effect of nitrogen
would normally slightly favour attack at the 4-position. A
similar effect is observed in reactions of 3-methyl catechol
and 4-methyl catechol with 1; each gave mixtures of pro-
ducts 7a±d and 8a±d, respectively, where, again, the cycli-
sation step appears to slightly favour attack at the 2-position.
Reaction of 1 with n-butyllithium in diethylether at
À78 8C gives rapid bromine±lithium exchange and the lithio
derivative 9 is suf®ciently stable at low temperature to react
with a variety of electrophiles ?Scheme 3). Reaction of 9
with water gave 10, which demonstrated that bromine±
lithium exchange proceeds quantitatively while silylation
and carboxylation, giving 11 and 12, respectively, may also
be achieved.
Surprisingly, however, reactions of lithio derivative 9
with aroyl chlorides stopped at the ketone stage and 13
and 14 were isolated as crystalline solids, suitable for X-ray
structural analysis. The most reasonable explanation of this
unusual result is that approach of nucleophiles to the car-
bonyl group in both 13 and 14 is sterically impeded by the
attached aryl groups and this is supported by the crystal
structure of 14 ?Fig. 1).
More convincing, however, is the fact that reaction of 9
with acetyl chloride does indeed proceed beyond the ketone
Scheme 3. Reagents and conditions: ?i) n-BuLi, Et2O, À78 8C; ?ii) CH3COCl, room temperature.
Fig. 1. X-ray crystal structure of 2,6-dibromo-3,5-difluoro?4-pyridyl) methylphenyl ketone 14.

352
H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
Scheme 4.
15 stage giving the acyl ester 16 of the corresponding
alcohol by a mechanism outlined in Scheme 4. Obviously,
in this case, 15 is much less sterically hindered to further
nucleophilic attack. A similar process involving a lithiated
per¯uoroheterocyclic system was reported by Coe and Rees
during the course of this work [8].
In summary, 9 may be trapped by a range of electrophiles
leading to various products depending on the electrophilic
system, thus extending the synthetic utility of perbromo-
¯uoro heterocycles such as 1.
A single crystal of 14 was grown that was suitable for
X-ray crystallography. We expected to observe signi®cant
face-to-face p±p interaction between the electron poor
pyridine ring and the relatively electron rich aryl ring, as
is observed in many systems involving a combination of
highly ¯uorinated aromatic derivatives and hydrocarbon
aromatic systems [9]. However, as shown in Figs. 1 and 2,
the molecules in the crystal form stacks along the a-direction
that are arranged in a `herring bone' con®guration in which
the pyridine subunits adopt an edge-to-face con®guration
Fig. 2. Crystal stacking arrangement of 2,6-dibromo-3,5-difluoro?4-pyridyl) methylphenyl ketone 14.

H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
353
‡
?s, C-2), 148.0 ?s, C-3), 155.8 ?s, Aripso); m/z ?EI ) 503
with the aromatic ring of the adjacent molecule. Further-
more, at ®rst sight, it appears that face-to-face p±p inter-
actions between adjacent pyridine rings is occurring but the
‡
‡
‡
‡
?M , 2%), 501 ?M , 7), 499 ?M , 7), 498 ?M , 7), 497
?M , 2), 77 ?100).
‡
Ê
calculated interplanar distance ?3.68 A) is too large for any
such interaction to be signi®cant. Consequently, the crystal
structure observed is probably due to the adoption of the
most favourable stacking arrangement and the minimisation
of unfavourable electron pair interactions.
3.1.3. Reaction with resorcinol
Sodium ?0.07 g, 3 mmol), resorcinol ?0.16 g, 10 mmol)
and 2,4,6-tribromo-3,5-di¯uoro-pyridine ?1.5 g, 4.3 mmol)
in THF ?50 ml) gave a white solid ?1.9 g) which, after
puri®cation by column chromatography on silica gel using
dichloromethane/hexane ?1:1) as eluant, gave 2,4,6-tri-
bromo-3-¯uoro-5-[3-?2,4,6-tribromo-5-¯uoro?3-pyridylox-
y))phenoxy]pyridine 4 ?0.55 g, 17%) as a white crystalline
solid; mp 239.5±245.3 8C; ?found: C, 26.0; H, 0.7; N, 3.4.
C15H4Br6F2N2O2 requires: C, 24.8; H, 0.5; N, 3.6%); dH
6.44 ?2H, m, H-4,6), 7.16 ?2H, m, H-2,5); dC 104.4 ?s, Ar-2),
110.0 ?s, Ar-4), 118.0 ?d, 2JCF 21.3, C-4), 124.4 ?d, 2JCF 25.9,
C-2), 130.6 ?s, C-6), 130.9 ?s, Ar-5), 147.3 ?s, C-5), 154.2 ?d,
3. Experimental
All solvents were dried before use by literature proce-
dures. NMR spectra were recorded on a Varian VXR 400S
NMR spectrometer with tetramethylsilane and trichloro-
¯uoromethane as internal standards and deuteriochloroform
as solvent, unless otherwise stated. In 19F NMR spectra,
up®eld shifts are quoted as negative. Coupling constants are
given in Hz. Mass spectra were recorded a Fisons VG Trio
1000 spectrometer coupled with a Hewlett-Packard 5890
series II gas chromatograph. IR spectra were recorded on a
Perkin-Elmer 1600 FTIR spectrometer using KBr plates
while elemental analyses were obtained on either a Per-
kin-Elmer 240 or a Carlo Erba elemental analyser. Melting
points were recorded at atmospheric pressure and are uncor-
rected. Column chromatography was performed on silica
gel ?Merck No. 1-09385) and TLC analysis was performed
on silica gel TLC plates ?Merck). 2,4,6-Tribromo-3,5-
di¯uoro-pyridine was synthesised according to the literature
procedure [7].
‡
1JCF 262, C-3), 156.7 ?s, Ar-1); dF À104.0 ?s); m/z ?EI ) 780
‡
‡
‡
‡
‡
‡
?M , 3%), 778 ?M , 17), 776 ?M , 44), 774 ?M , 60), 772
?M , 45), 770 ?M , 18), 768 ?M , 3); and intractable
material.
‡
3.1.4. Reaction with catechol
Sodium ?0.22 g, 9.5 mmol), catechol ?0.47 g, 4.3 mmol)
and 2,4,6-tribromo-3,5-di¯uoro-pyridine ?1.5 g, 4.3 mmol)
in THF ?50 ml) gave a white solid ?2.05 g) which, after
puri®cation by column chromatography on silica gel using
dichloromethane/hexane ?1:1) as eluant, gave a mixture
consisting of 2,4-dibromo-3-¯uorobenzo[e]pyridino[3,2-b]-
1,4-dioxin 5 and 1,3-dibromo-4-¯uorobenzo[e]pyridino-
[4.3-b]1,4-dioxane 6 ?0.63 g, 41%) in the ratio 2:1 ?mea-
sured by 19F NMR integration of the crude reaction mixture)
as a white crystalline solid; ?found: C, 36.6; H, 1.1; N, 3.7.
C11H4Br2FNO2 requires: C, 36.6; H, 1.1; N, 3.9%); dH 6.96
3.1. Reactions with oxygen nucleophiles
3.1.1. General procedure
‡
Sodium metal was added to a solution of the alcohol or
diol in THF ?50 ml) and the mixture was heated at re¯ux
temperature until complete dissolution of the sodium.
2,4,6-Tribromo-3,5-di¯uoro-pyridine was added and the
reaction mixture heated at re¯ux temperature for a further
24 h. On cooling, THF was removed by distillation and the
residue added to water. Extraction into dichloromethane,
drying ?MgSO4) and evaporation of the solvent gave a
solid which was puri®ed by column chromatography on
silica gel.
?m, ArH); dF À111.2 ?s, 5), À133.5 ?s, 6); m/z ?EI ) 363
‡
‡
‡
?M , 39%), 361 ?M , 75%), 359 ?M , 39), 50 ?100); and
intractable material.
3.1.5. Reaction with 3-methylcatechol
Sodium ?0.11 g, 5 mmol), 3-methylcatechol ?0.29 g, 2.3
mmol) and 2,4,6-tribromo-3,5-di¯uoro-pyridine ?0.75 g,
4.3 mmol) in THF ?50 ml) gave a white solid ?0.93 g) which,
after puri®cation by column chromatography on silica
gel using dichloromethane/hexane ?1:1) as eluant, gave a
mixture consisting of 2,4-dibromo-3-¯uoro-6-methyl-benzo-
[e]pyridino[3,2-b]1,4-dioxin 7a, 2,4-dibromo-3-¯uoro-9-
methyl-benzo[e]pyridino[3,2-b]1,4-dioxin 7b, 1,3-dibromo-
4-¯uoro-6-methyl-benzo[e]pyridino[4.3-b]1,4-dioxane 7c
and 1,3-dibromo-4-¯uoro-9-methyl-benzo[e]pyridino-
[4.3-b]1,4-dioxane 7d ?0.29 g, 36%) in a ratio 8:8:5:5
?measured by 19F NMR integration of the crude reaction
mixture) as a white crystalline solid; ?found: C, 38.3; H, 1.5;
N, 3.6. C12H6Br2FNO2 requires: C, 38.6; H, 1.6; N, 3.7%);
dH 2.27, 2.28, 2.29 and 2.30 ?3H, all s, CH3), 6.8±7.0 ?5H, m,
Ar±H); dF À111.43 and À111.78 ?both s, 7a and 7b),
3.1.2. Reaction with phenol *two equivalents)
Sodium ?0.28 g, 12 mmol), phenol ?0.95 g, 10 mmol) and
2,4,6-tribromo-3,5-di¯uoro-pyridine ?1.5 g, 4.3 mmol) in
THF ?50 ml) gave a white solid ?2.26 g) which, after pur-
i®cation by column chromatography on silica gel using
dichloromethane/hexane ?1:4) as eluant, gave 2,4,6-tri-
bromo-3,5-diphenoxy-pyridine 3 ?0.87 g, 41%) as a white
crystalline solid; mp 172.2±173.9 8C; ?found: C, 41.7; H,
2.1; N, 2.8. C17H10Br3NO2 requires: C, 40.8; H, 2.0; N,
2.8%); dH 6.7±7.3 ?m, ArH); dC 115.4 ?s, Arortho), 123.7
?s, Arpara), 127.2 ?s, C-4), 130.2 ?s, Armeta), 132.6
‡
À133.66 and À133.69 ?both s, 7c and 7d); m/z ?EI ) 377

354
H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
‡
‡
‡
?M , 49%), 375 ?M , 100%), 373 ?M , 53%); and intract-
able material.
3.2.3. 2-2,6-Dibromo-3,5-difluoro-4-
trimethylsilyl-pyridine 11
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?1.0 g, 2.84 mmol),
n-butyllithium ?1.9 ml, 3.55 mmol), diethyl ether ?15 ml)
and chlorotrimethylsilane ?0.38 g, 3.5 mmol) gave, after
column chromatography on silica gel using diethyl acet-
ate/hexane ?1:1) as eluant, 2-2,6-dibromo-3,5-di¯uoro-4-
trimethylsilyl-pyridine 11 ?0.82 g, 85%); mp 86±88 8C;
?found: C, 27.8; H, 2.6; N, 3.4. C8H9Br2F2NSi requires:
C, 27.8; H, 2.60; N, 4.05%); dC 0.66 ?s, CH3), 122.4 ?X part
3.1.6. Reaction with 4-methylcatechol
Sodium ?0.12 g, 5 mmol), 4-methylcatechol ?0.29 g,
2.3 mmol)
and
2,4,6-tribromo-3,5-di¯uoro-pyridine
?0.75 g, 4.3 mmol) in THF ?50 ml) gave a white solid
?0.84 g) which, after puri®cation by column chromatogra-
phy on silica gel using dichloromethane/hexane ?1:1) as
eluant, gave a mixture consisting of 2,4-dibromo-3-¯uoro-
7-methyl-benzo[e]pyridino[3,2-b]1,4-dioxin 8a, 2,4-dib-
romo-3-¯uoro-8-methyl-benzo[e]pyridino[3,2-b]1,4-dioxin
8b, 1,3-dibromo-4-¯uoro-7-methyl-benzo[e]pyridino[4.3-
b]1,4-dioxane 8c and 1,3-dibromo-4-¯uoro-8-methyl-ben-
zo[e]pyridino[4.3-b]1,4-dioxane 8d ?0.22 g, 27%) in a ratio
3:3:2:2 ?measured by 19F NMR integration of the crude
reaction mixture) as a white crystalline solid; ?found: C,
38.6; H, 1.7; N, 3.7. C12H6Br2FNO2 requires: C, 38.6; H,
1.6; N, 3.7%); dH 2.27±2.3 ?3H, overlapping s, CH3); dF
À111.45 and À111.59 ?both s, 8a and 8b), À133.60 and
2
of ABX system, C-2), 127.4 ?t, JCF 33.6, C-4), 158.5 ?dd,
‡
1JCF 257, 3JCF 8.4, C-3); dH 0.36 ?s); dF À99.7 ?s); m/z ?EI )
‡
‡
347 ?M , 24), 345 ?M , 47), 343 ?25), 77 ?100%).
3.2.4. 2,6-Dibromo-3,5-difluoro-pyridine-
4-carboxylic acid 12
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?0.4 g, 1.14 mmol),
diethyl ether ?15 ml), n-butyllithium ?0.76 ml, 1.42 mmol)
and carbon dioxide gas ?passed through the solution for 2 h)
gave after the aqueous layer was acidi®ed and extracted with
ether, 2,6-dibromo-3,5-di¯uoro-pyridine-4-carboxylic acid
12 ?0.12 g, 35%) as white crystals; mp 154±156 8C; ?found:
C, 22.8; N, 4.1; H, 0.3. C6HBr2F2NO2 requires: C, 22.7; N,
4.4; H, 0.3%); dC 106.4 ?t, 2JCF 24.2, C-4), 123.4 ?X part of
‡
‡
À133.65 ?both s, 8c and 8d); m/z ?EI ) 377 ?M , 27%), 375
‡
‡
?M , 60%), 373 ?M , 28%), 39 ?100); and intractable
material.
1
3
3.2. Generation and reactions of 4-lithio-
2,6-dibromo-3,5-difluoro-pyridine 9
ABX system, C-2), 152.6 ?dd, JCF 270.4, JCF 3.9, C-3),
159.1 ?s, COOH); dH 6.26 ?bs, COOH); dF À110.56 ?s); m/z
‡
‡
‡
?EI ) 316 ?M , 100), 272 ?M ±COOH, 100%).
3.2.1. General procedure
A three necked ¯ask, equipped with a low temperature
thermometer, a drying tube and ¯ushed with dry nitrogen,
was charged with 1 and diethyl ether. The mixture was
cooled to À78 8C before n-butyllithium ?1.6 M solution in
hexanes) was added. The resulting solution, which gradually
turned yellow in colour, was stirred at À78 8C for 90 min.
19F NMR analysis of the crude mixture indicated complete
conversion of the starting material to 4-lithio-2,6-dibromo-
3,5-di¯uoro-pyridine 9; dF À89.7 ?s). The electrophile was
added to the cool solution and the mixture was allowed to
warm to room temperature overnight. Addition of water,
followed by extraction by dichloromethane ?3 Â 20 ml),
drying ?MgSO4) and evaporation gave the crude product.
Puri®cation of the functional pyridine derivative was accom-
plished by column chromatography on silica gel, recrystal-
lisation or vacuum sublimation, as indicated.
3.2.5. 2,6-Dibromo-3,5-difluoro*4-pyridyl)
phenyl ketone 13
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?1.0 g, 2.84 mmol),
n-butyllithium ?1.9 ml, 3.55 mmol), diethyl ether ?15 ml)
and benzoyl chloride ?0.61 g, 4.32 mmol) gave, after pur-
i®cation by column chromatography using dichloro-
methane/hexane ?1:4) as eluant and recrystallisation from
hexane, 2,6-dibromo-3,5-di¯uoro?4-pyridyl) phenyl ketone
13 ?0.61 g, 57%) as a white solid; ?found: C, 38.2; N, 3.6; H,
1.4. C12H5Br2F2NO requires: C, 38.2; N, 3.7; H, 1.3%); dC
123.3 ?X part of an ABX system, C-2), 126.24 ?m, C-4),
129.5 ?s, C-ortho), 130.3 ?s, C-meta), 134.9 ?s, C-ipso),
1
3
135.9 ?s, C-para), 152.1 ?dd, JCF 266.3, JCF 3.9, C-3),
184.5 ?s, C=O); dH 7.5±7.7 ?m, Ar±H); dF À112.24 ?s); m/z
‡
‡
‡
‡
?EI ) 375 ?M , 7%), 377 ?M , 14), 379 ?M , 7).
3.2.6. 2,6-Dibromo-3,5-difluoro*4-pyridyl)
4-methylphenyl ketone 14
3.2.2. 2,6-Dibromo-3,5-difluoro-pyridine 10
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?1.0 g, 2.84 mmol),
n-butyllithium ?1.9 ml, 3.55 mmol), diethyl ether ?15 ml)
and water ?10 ml) gave, after sublimation, 2,6-dibromo-3,5-
di¯uoro-pyridine 10 ?0.55 g, 71%) as a white solid; mp 110±
111 8C; ?found: C, 22.2; N, 5.0; H, 0.4; Br, 58.3; F, 13.7.
C5HBr2F2N requires: C, 22.2; N, 5.1; H, 0.3; Br, 58.6; F,
13.9%); dC 113.7 ?t, 2JCF 23.9, C-4), 122.6 ?X part of ABX,
C-2), 155.4 ?dd, 1JCF 270.5, 3JCF 4.9, C-3); dH 7.31 ?t, 3JHF
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?1.0 g, 2.84 mmol),
n-butyllithium ?1.9 ml, 3.55 mmol), diethyl ether ?15 ml)
and p-toluoyl chloride ?0.66 g, 4.26 mmol) gave, after
recrystallisation, 2,6-dibromo-3,5-di¯uoro?4-pyridyl) 4-
methylphenyl ketone 14 ?0.85 g, 77%); mp 145±146 8C;
?found: C, 39.9; H, 1.8; N, 3.6. C13H7Br2F2NO requires: C,
39.9; H, 1.7; H, 4.0%); dC 26.9 ?s, CH3), 123.3 ?X part of an
2
ABX system, C-2), 126.5 ?t, JCF 21.4, C-4), 130.1 ?s, C-
ortho), 130.3 ?s, C-meta), 132.3 ?s, C±Cz.dbnd6;O), 147.2
‡
‡
6.3); dF À109.53 ?d, 3JFH 7.1); m/z ?EI ) 271 ?M , 56%),
‡
1
3
273 ?M , 100), 275 ?56), 274 ?5%).
?s, C±CH3), 152.0 ?dd, JCF 258, JCF 1.9, C-3), 184

H. Benmansour et al. / Journal of Fluorine Chemistry 112 *2001) 349±355
355
?s, C=O); dH 1.36 ?3H, s, CH3), 7.28 and 7.60 ?4H, AB, JAB
RꢀF† ˆ 0:0302 for 3082 re¯ections with I ꢂ 2s, GOF ˆ
‡
‡
Ê 3
8.4, Ar±H); dF À112.28 ?s); m/z ?EI ) 389 ?M , 4%), 391
1:047. The largest peak on the residual map is 0.49 a/A .
‡
?M , 8), 393 ?4), 119 ?100), 91 ?55), 65.?52).
The plane of the carbonyl group in molecule 14 is almost
parallel to the plane of heterocycle ?corresponding dihedral
angle is À10.08), whilst the dihedral angle between the plane
of C=O group and the plane of Ph-ring is À67.28. The
molecules in the stacks are connected by their centres of
symmetry and the heterocycles of adjacent molecules over-
3.2.7. 1,1-Bis*2,6-dibromo-3,5-difluoro-4-pyridyl)ethyl
acetate 16
2,4,6-Tribromo-3,5-di¯uoro-pyridine ?1.0 g, 2.84 mmol),
n-butyllithium ?1.9 ml, 3.55 mmol), diethyl ether ?15 ml)
and acetyl chloride ?0.33 g, 4.26 mmol) gave, after column
chromatography using dichloromethane/hexane ?1:3 v/v) as
eluant, 1,1-bis?2,6-dibromo-3,5-di¯uoro-4-pyridyl)ethyl
acetate 16 ?0.41 g, 23%); mp 158±160 8C; ?found: C,
27.0; H, 1.2; N, 4.2. C14H6Br4F4N2O2 requires: C, 26.6;
H, 0.95; N, 4.4%); dC 21.4 ?s, COCH3), 26.9 ?s, CH3), 78.14
?s, C±O), 124.3 ?X part ABX system, C-2), 128.5 ?m, C-4),
Ê
lap with interplanar distances of 3.68 and 3.45 A. Also there
Ê
are short intermolecular contacts Br±O 3.054 A connecting
the stacks in c-direction.
Acknowledgements
1
153.1 ?d, JCF 267, C-3), 168.5 ?s, C=O); dH 2.16 ?3H, s,
We thank the European Union TMR Scheme for funding
?studentship to H.B.), the University of Durham ?Under-
graduate Research Project to G.M.) and the Royal Society
?University Research Fellowship to G.S.).
‡
OCOCH3), 2.34 ?3H, s, C±CH3); dF À108.05 ?s); m/z ?EI )
‡
629 ?M ±H, 0.4), 627 ?0.3), 632 ?0.2), 587 ?5.2), 43 ?100%);
‡
CIÀ 569 ?M ±OCOCH3, 100%).
3.3. X-ray crystallography
References
Crystal data for 2,6-dibromo-3,5-di¯uoro?4-pyridyl)
methylphenylketone14:C13H7Br2F2NO,M ˆ391:02,mono-
clinic, space group P21/c, a ˆ 7:4899?15), b ˆ 22:206?4),
[1] R.D. Chambers, P.R. Hoskin, A. Kenwright, P. Richmond, G.
Sandford, J. Fluorine Chem. 2001, in press.
[2] I.J. Collins, Chem. Soc., Perkin Trans. 1 ?2000) 2845.
[3] B. Iddon, H. Suschitzky, Polychloroheteroaromatic compounds, in:
H. Suschitzky ?Ed.), Polychloroaromatic Compounds, Plenum Press,
New York, 1974, p. 197.
Ê
Ê 3
c ˆ 8:6648?17) A, b ˆ 113:35?3)8, U ˆ 1323:1?5) A ,
Fꢀ0 0 0† ˆ 752, Z ˆ 4, Dc ˆ 1:963 mg mÀ3
,
m ˆ 6:14
mmÀ1 ?Mo Ka, l ˆ 0:71073 A), T ˆ 120:0?1) K. A 19375
re¯ections ?1:83 ꢁ y ꢁ 30:368) were collected on a Bruker
SMART-CCDdiffractometer ? o-scan, 0.38/frame) yielding
3736 unique data ?Rmerg ˆ 0:071). The structure was solved
by direct method and re®ned by full-matrix least squares
on F2 for all data using SHELXL software [10]. All non-
hydrogen atoms were re®ned with anisotropic displacement
parameters, H-atoms were placed at calculated positions
and re®ned using the `riding'-mode. Final wR2ꢀF2† ˆ
0:0758 for all data ?172 re®ned parameters), conventional
Ê
[4] R.D. Chambers, C.R. Sargent, Adv. Heterocycl. Chem. 28 ?1981) 1.
[5] M.J. Silvester, Adv. Heterocycl. Chem. 59 ?1994) 1.
[6] G.M. Brooke, J. Fluorine Chem. 86 ?1997) 1.
[7] R.D. Chambers, C.W. Hall, J. Hutchinson, R.W.J. Millar, Chem. Soc.,
Perkin Trans. 1 ?1998) 1705.
[8] P.L. Coe, A.J.J. Rees, J. Fluorine Chem. 101 ?2000) 45.
[9] R. Filler, in: J.F. Liebman, A. Greenberg, W.R. Dolbier ?Eds.),
Fluorine Containing Molecules, Structure, Reactivity, Synthesis and
Applications, VCH Publishers, New York, 1988.
[10] G.M. Sheldrick, SHELXTL, Version 5/VMS Bruker Analytical X-ray
Instruments, Madison, WI, USA, 1995.