Electrophilic fluorination of N,N-dimethylaniline, N,N-dimethylnaphthalen- 1-amine and 1,8-bis(dimethylamino)naphthalene with N-F reagents

Article abstract of DOI:10.1016/j.jfluchem.2013.06.017

Reaction of N,N-dimethylaniline, N,N-dimethylnaphthalen-1-amine and 1,8-bis(dimethylamino)- naphthalene (proton sponge) with 1-chloromethyl-4- fluorodiazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) and N-fluorobenzenesulfonimide (NFSI) h

Full text of DOI:10.1016/j.jfluchem.2013.06.017

Journal of Fluorine Chemistry 154 (2013) 67–72
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Electrophilic fluorination of N,N-dimethylaniline,
N,N-dimethylnaphthalen-1-amine and
1,8-bis(dimethylamino)naphthalene with N–F reagents
*
Vladimir I. Sorokin, Alexander F. Pozharskii, Valery A. Ozeryanskii
Department of Organic Chemistry, Southern Federal University, Zorge 7, 344090 Rostov-on-Don, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Reaction of N,N-dimethylaniline, N,N-dimethylnaphthalen-1-amine and 1,8-bis(dimethylamino)-
naphthalene (proton sponge) with 1-chloromethyl-4-fluorodiazonia-bicyclo[2.2.2]octane bis(tetra-
fluoroborate) (Selectfluor) and N-fluorobenzenesulfonimide (NFSI) has been studied under various
conditions. Unlike the proton sponge, which is fluorinated rather selectively at the ortho-position to
NMe2 group, producing 2-fluoro derivatives in moderate yield, two other amines react with Selectfluor
and NFSI with strong tarring and the formation of complex mixtures of the corresponding biaryls,
biarylmethanes and N-demethylated products. 2-Fluoro and 4-fluoro derivatives are also formed in
minor quantities with the former isomer being predominant. Using the NFSI–ZrCl4 system results in
competitive chlorination of the aromatic ring.
Received 25 May 2013
Received in revised form 25 June 2013
Accepted 30 June 2013
Available online 10 July 2013
Keywords:
Arylamine
Proton sponge
Electrophilic substitution
Fluorination
ß 2013 Elsevier B.V. All rights reserved.
N–F reagents
1. Introduction
This is especially true for fluorination of strongly activated
aromatic compounds such as arylamines. In the present paper,
Direct fluorination of aromatic compounds has been of interest
to organic chemists for several decades. This is caused by wide
application of fluoroorganics in such important areas as polymers,
drugs, pesticides, functional dyes, liquid crystals, etc. [1]. Until late
1980s, a typical set of reagents for electrophilic fluorination of
aromatic C–H bonds included F2 [2,3], CsSO4F, CF3OF, RCO2F, ArIF,
XeF2 and some others [2]. They, however, suffer from such
drawbacks as bad handling and rather strong oxidative ability.
A significant contribution into this field had been done by
Umemoto who introduced in 1986 N-fluoropyridinium salts as the
first N–F fluorinating agents [4]. Now this class of compounds
encounters about 100 representatives; many of them are
commercially available. Unlike the above fluorinating agents of
the first generation, the N–F reagents are less aggressive, easily
stored and generally more selective [5]. Along with N-fluoropyr-
idinium salts, the most used among them are 1-chloromethyl-4-
fluorodiazonia-bicyclo[2.2.2]octane bis(tetrafluoroborate) (trade-
mark Selectfluor, 1) and N-fluorosulfonimides, e.g. N-fluorobenze-
nesulfonimide (NFSI, 2) (Fig. 1).
we describe results of electrophilic fluorination of three typical
dimethylaminoarenes: N,N-dimethylaniline (3), N,N-dimethyl-
naphthalen-1-amine (4) and 1,8-bis(dimethylamino)naphthalene
(known as ‘‘proton sponge’’, 5). These amines differ from one
another by the number of conjugated rings and NMe2 groups
allowing investigation of influence of these factors on ease and
regioselectivity of fluorination. In most experiments, compounds 1
and 2 were used as fluorinating reagents. Additionally, an NFSI–
ZrCl4 system suggested by Yamamoto [6] has been tested in some
instances.
2. Results
Table 1 summarizes experimental results that allow comparing
the chosen arylamines in fluorination reaction. The reactions were
conducted in CHCl3 for NFSI and in MeCN for Selectfluor and the
temperature varied from ambient to 60–61 8C.
2.1. N,N-Dimethylaniline
Although quite some time has passed since introducing the N–F
reagents, many aspects of their application remain unexplored.
In all experiments, a significant tarring and low selectivity were
observed with this substrate.
The formation of fluorodimethylanilines was observed only
with NFSI (entries 1–3), and the ortho-isomer was predominant
(entry 3). The main reaction products were diphenylmethane 6 and
* Corresponding author. Tel.: +7 863 2975146; fax: +7 863 2975146.
E-mail address: vv_ozer2@sfedu.ru (V.A. Ozeryanskii).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.06.017

68
V.I. Sorokin et al. / Journal of Fluorine Chemistry 154 (2013) 67–72
Fig. 3. Side products when using NFSI and NFSI–ZrCl4 mixtures.
On lowering the temperature to 0 or ꢁ15 8C, a significant drop
in the yield of 2- and 4-fluorodimethylanilines (from 10–13% down
to 1–2% total) was observed. Regardless on the conditions used,
diphenylmethanes and biphenyls were the only reaction products
in the experiments with Selectfluor (entries 4, 5).
Fig. 1. Structures of Selectfluor (1) and NFSI (2).
2.2. N,N-Dimethylnaphthalen-1-amine
As in the case of 3, a considerable tarring occurs at fluorination
of 4. At the same time, there are two notable differences between
these substrates. First, amine 4 is less reactive towards both
fluorinating agents. Thus, about 60 and 50% of unchanged 4 were
detected in volatile fractions when using NFSI and Selectfluor at
room temperature, respectively (entries 6 and 9). The second
notable difference is a higher selectivity of 4. This conclusion
results from the larger total yield of ring-fluorinated compounds
for 4 if compared with that for 3 (cf. entries 1 and 2 with 6 and 7,
respectively). A lesser number of side-products in the case of 4 also
agrees with this point. Indeed, unlike 3, no N-demethylated or ring-
methylated compounds were noticed in the reaction mixtures,
although the formation of coupling products 12 and 13 (11% and
4%, respectively, almost independent on temperature), was
observed (Fig. 4). As for 3, the benzenesulfonic acid derivatives
8 and 9 have been also detected after NFSI fluorination.
Fig. 2. Main reaction products on fluorination of amine 3.
biphenyl 7 (Fig. 2) along with their numerous N-demethylated and
ring-fluorinated derivatives. The total amount of diphenylmethane
and biphenyl derivatives in volatile fractions, independently on
the temperature, was about 20% and 12%, respectively. Among
other reaction products identified in experiments with NFSI were
the starting 3 (4% at 25 8C), N-methylaniline (1.3%), N,N,4-
trimethylaniline (1.9%), N,4-dimethylaniline (1.3%), N-formyl-N-
methylaniline (1.4%), 4-methylaminobenzaldehyde (7%) and
4-dimethylaminobenzaldehyde (8%). Additionally, the sulfur
derivatives 8 and 9 were detected in ꢀ2% yields each (Fig. 3).
Surprisingly, but in the case of NFSI–ZrCl4 system, along with
the above-mentioned products, 2-chlorodimethylaniline (10%)
together with phenylsulfonyl halides 10 (3%) and 11 (6%) were also
produced.
We were unable to isolate the ring-fluorinated products of 4 in
pure state to estimate the regioselectivity of the process.
However, from indirect arguments one can suggest that the
2-fluoro-N,N-dimethylnaphthalen-1-amine is the isomer that
prevails. Thus, the 19F NMR spectrum of a crude reaction mixture
in CDCl3 contained the doublet-of-doublets signal of the fluorine
Table 1
Selected results of fluorination of dimethylaminoarenes (amine/N–F reagent ratio is 1:1).
.
Entry
Amine
N–F reagent
Conditions
ortho: para Selectivity by GC (%)
Number of products by GC
1
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
NFSI
CHCl3, 25 8C, 10 h
CHCl3, reflux, 5 h
CHCl3, reflux, 5 h
MeCN, 25 8C, 10 h
MeCN, 60 8C, 5 h
CHCl3, 25 8C, 10 h
CHCl3, reflux, 5 h
CHCl3, reflux, 5 h
MeCN, 25 8C, 10 h
MeCN, 60 8C, 5 h
CHCl3, 25 8C, 10 h
CHCl3, reflux, 5 h
CHCl3, reflux, 5 h
MeCN, 25 8C, 10 h
MeCN, 60 8C, 5 h
4:2
16
17
17
15
18
21
17
19
17
20
10
16
18
11
16
2
NFSI
10:3
a
a
a
3
NFSI
7:1
b
4
Selectfluor
Selectfluor
NFSI
b
5
6
11:1
14:1
7
NFSI
c
8
NFSI
6
9
Selectfluor
Selectfluor
NFSI
9:2
10
11
12
13
14
15
23:3
59(26)c,d
49(16)d:2
NFSI
c
NFSI
8
Selectfluor
Selectfluor
47(15)d:9
52(17)d:10
a
20 mol% of ZrCl4 as catalyst.
b
c
Neither starting nor fluorinated amines were detected.
Only ortho-isomer was detected.
d
Isolated yield in parenthesis.

V.I. Sorokin et al. / Journal of Fluorine Chemistry 154 (2013) 67–72
69
Fig. 6. Structure of N-methylimide 19.
ortho-fluorine atom induces essential polarization of the hydrogen
bridge, which therefore is highly asymmetrical and the NH proton
preferably (over 70%) belongs to the nitrogen atom attached to the
non-fluorinated benzene ring (cf. 4-nitro derivative of the proton
sponge [7]).
Another minor product that had been unexpectedly isolated
almost in all experiments was 2-fluoro-8-dimethylamino-1-
naphthol (18). The 1H NMR spectrum contained a broaden peak
Fig. 4. Structures of coupling products on fluorination of naphthylamines 4 and 5.
atom at
d
= –99.0 ppm. This is very close to the 19F signal in the
spectrum of 2-fluoro-1,8-bis(dimethylamino)naphthalene whose
structure was established unambiguously (see below). Besides,
there is a close similarity between the doublet resonances of 1-
NMe2 groups induced by coupling with the ortho-fluorine atom in
the 1H NMR spectra of both 2-fluoronaphthalene derivatives
of the chelated hydroxyl group at d 14.86 ppm which is typical for
8-dimethylamino-1-naphthols [8]. The appearance of the 8-NMe2
group as a singlet at 2.83 ppm indicates the absence of the fluorine
substituent in the neighbourhood. The NOESY spectrum of 18
revealed n.o.e. between 4-H and 5-H as well as between the 7-H
and 8-NMe2 fragments. Although nucleophilic substitution of the
dimethylamino by OH group in the proton sponge series has been
recently reported [9], we find it rather difficult to explain the
formation of naphthol 18 in view of absence of any special OH-
nucleophile in the reaction mixture. Even so, one can suggested
that protons arising in the process of electrophilic substitution
convert the primarily formed 2-fluoro-1,8-bis(dimethylamino)-
naphthalene (15) into cation 15H+, which then undergoes
nucleophilic displacement of the HN+Me2 group under action of
water traces. Such kind of acid catalysis is rather wide spread in
proton sponges [9].
It is known, that reactions of diamine 5 with strong oxidants
[10a,10b] or reducing agents [10c] are sometimes accompanied by
mono-demethylation of the NMe2 groups. We have also registered
signs of this phenomenon by GC/MS and NMR techniques both
with NFSI and Selectfluor. However, the exact assignment of the
demethylated structure to 16 or 17 (Fig. 5) was not possible due to
minority of the process. Another distinct observation is the
presence in the reaction mixtures of two compounds with masses
and fragmentation corresponding to isomeric difluorinated deri-
vatives. Their total content did not exceed 1% and 7% for reagents 2
and 1, respectively.
(
d
= 3.0 ppm, J = 2.6 Hz).
Fluorination of 4 with NFSI–ZrCl4 system, as in the case of 3, was
also accompanied by the formation of ring-chlorinated products
(15% of total content) together with sulfur derivatives 8–11.
2.3. 1,8-Bis(dimethylamino)naphthalene
Reactivity of proton sponge 5 towards fluorinating agents 1 and
2 strongly differs from that of amines 3 and 4. Despite some tarring,
in none of our experiments even traces of coupling compounds of
type 6, 7, 12 and 13 were noticed. Negligible amounts (0.3%) of
binaphthyl proton sponge 14 and its non-identified monofluoro
derivative were registered only at use of NFSI–ZrCl4 system. The
most remarkable result, obtained both with NFSI and Selectfluor, is
the formation of considerable amount (47–59% by GC) of 2-fluoro-
1,8-bis(dimethylamino)naphthalene (15) (Fig. 5) isolated as a pale
yellow oil in a pure state (15–26%, entries 11, 12, 14 and 15). Its
structure has been proved by multinuclear NMR spectroscopy.
Thus, in the 1H NMR spectrum of 15 in CDCl3, two signals of
unequal NMe2 groups are observed with that of 1-NMe2 group
being a doublet (J = 3.2 Hz) due to the through space coupling with
fluorine. Besides, NOESY experiment revealed interactions be-
tween 4-H and 5-H atoms as well as between 7-H and 8-NMe2
group. Addition structural evidence was extracted from the NMR
spectral data of salt 15ꢂHClO4. The proton NMR spectrum of this
salt in a CD3CN solution unambiguously shows the existence of
intramolecular H-bonding between two dimethylamino groups in
the protonated cation. Thus, the NH proton is considerably
deshielded and appears as a broad peak at 18.24 ppm. The peaks
No benzenesulfonic acid derivatives of type 8–11 were
registered among the fluorination products of 5 with NFSI. Instead,
the formation of methylbenzenesulfonimide 19 was observed
(Fig. 6), which was absent in case of amines 3 and 4. In contrast, no
essential difference in behaviour of amines 3–5 with regard of
formation of benezenesulfonyl derivatives, as well as ring
chlorination products, occurs at use of NFSI–ZrCl4 system. Some
amount of unchanged 5 (ꢀ7% with NFSI and ꢀ30% with Selectfluor)
was recovered in most experiments.
of the 1-NMe2 and 8-NMe2 groups at d 3.14 and 3.26 ppm are split
into triplet and doublet signals with the coupling constants 3JNH,1-
3
NMe = 1.4 Hz and JNH,8-NMe = 4.0 Hz, correspondingly. Clearly, the
3. Discussion
It is well established that aromatic fluorination with N–F
reagents can proceed by one of the two mechanisms: common
SE2Ar and the single electron transfer (SET) mechanism. The exact
pathway is mostly determined by the substrate and reagent
nature, as well as the reaction conditions [11]. In 1972, Knunyants
et al. [12] studying fluorination of 3 with perfluoropiperidine
found, similar to us that the reaction occurs mainly at the ortho-
positions. Besides, the formation of some amount of diphenyl-
methane 6 was observed. Using EPR spectroscopy they also
detected free radicals in the reaction mixture and on the basis of
Fig. 5. Fluorination products of proton sponge 5.

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V.I. Sorokin et al. / Journal of Fluorine Chemistry 154 (2013) 67–72
Scheme 1. Proposed oxidative mechanism of formation of 6.
these observations and Fayadh’s assumption on the mechanism of
benzoyl peroxide oxidation of N,N-dialkylanilines [13] had
suggested the SET mechanism for these processes (Scheme 1).
In our case, we also believe that the fluorination proceeds
predominately via the SET mechanism, especially for 3 and 5.
Indeed, both these amines differ by close and very low first
ionization potentials, IP1, equal to 7.10 [14a] and 7.05 eV [14b],
respectively. Next, the formation of diphenylmethane 6 and
biphenyl 7 derivatives in fluorination of 3 and dinaphthyl 14
with 5 (only in experiments with NFSI–ZrCl4 system) indicates the
involvement of free radical species as intermediates. Similar
formation of 7 and 14 was previously observed on nitration of 3
[15] and 5 [16]. Another indirect evidence for substrate oxidation
during fluorination is the detection of S-phenyl benzenesulfo-
nothioate 8 on treatment of 3 and 5 with NFSI. Previously, it has
been found that compounds of such a kind are formed on reduction
of arenesulfonyl chlorides with potassium iodide [17]. As
suggested, the reaction first leads to the formation of thiophenol
intermediate, which then couples with yet unreacted ArSO2Cl.
Interestingly, in several instances we have also found thiophenol in
the crude reaction mixtures, for example, at fluorination of 5 with
NFSI in chloroform under reflux (2%). However, the nature of
reducing agent in such cases is unclear.
charged halogen atom of NBS or reagents 1 and 2. Such interaction
(structure 22) should favour the formation of the ortho- -complex
relatively to its para-counterpart thus providing ortho-selectivity.
In molecule 3, the NMe2 group rotates around the Car–N bond
relatively free [23] that makes the Me2N ! Hal coordination not so
profitable. As a result, aniline 3 is brominated with NBS at para-
s
position [20] due to generally higher stability of para-s-complex
[24]. The predominance of ortho-fluoro derivative of 3 at use of
reagents 1, 2 or perfluoropiperidine [12] can be explained by
considerably higher positive charge at the N-halogen atom of these
reagents in comparison with that of NBS. What about 1-
dimethylaminonaphthalene (4), its NMe2 group under wide range
of conditions exists in conformation 23, which is unfavourable for
ortho-substitution [25]. This explains the predominant para-
bromination of 4 with NBS. On the other hand, the prevalence
of ortho-fluorinated product at using reagents 1 and 2 with 4
(Table 1, entries 6–10) can be attributed to their higher
coordinating ability promoting the formation of ortho-s-complex.
Such a view is supported by Shreeve’s group work, in which they
isolated N-fluoroamines by action of Selectfluor on primary and
secondary aliphatic amines [26]. Futhermore, Borodkin have
observed by means of 19F NMR spectroscopy the formation of
dimer 24 arising in reaction mixtures during fluorination of
aromatic compounds with Selectfluor in ionic liquids (Fig. 8) [27].
See also recent work on the same topic [28] (Fig. 7).
To get deeper inside into the problem, we have conducted PM6
[29] simulation in MOPAC package [30] of NFSI attack on ortho-
and para-positions of amine 3 (Table 2).
In contrast, the formation of radical species at fluorination of 1-
dimethylaminonaphthalene (4) is questionable due to the relative
inertness of this amine to fluorinating agents and its rather high IP1
value (7.50 eV) [14b].
One of the striking peculiarities of proton sponge 5 is an
unprecedented ortho-selectivity of its halogenation in reactions
with electrophiles containing electropositive halogen atom such as
NCS [18], NBS [19] or NFSI and Selectfluor as in our case. Thus, 5 is
ortho-brominated with NBS in THF at ꢁ70 8C in 90% yield [19a]
while, at using Br2 in CCl4 at room temperature, 4-bromoderivative
becomes the only isolable product in 52% yield [19b]. Unlike 5, the
bromination of 3 with NBS proceeds quantitatively at para-
position [20]. Till now, there has been no information in the
literature on NBS bromination of 1-dimethylaminonaphthalene
(4), but in our hands (THF, 1 mol of NBS, 20. . .ꢁ78 8C) the reaction
led mostly to its 4-bromo derivative.
In our opinion, the distinctions in positional selectivity of
amines 3–5 towards NBS and fluorinating agents 1 and 2 stems
from the conformational behaviour of their NMe2 groups. Thus, the
peri-NMe2 groups in molecule 5 do not rotate freely and adopt one
of the two conformations, 20 or 21. Though the latter is less stable
(by 4.7 kcal molꢁ1 [21]) it can be fixed via intramolecular hydrogen
bonding with an appropriate ortho-substituent, e.g. OH group, or
via n ! d interaction with a heavy atom (Si, Fe etc.) [22]. One can
assume that similar fixation of the out-inverted NMe2 group is
possible at interaction of its free electron pair with positively
Fig. 7. Conformations of NMe2 groups in naphthalene derivatives and its influence
on selectivity of halogenation.

V.I. Sorokin et al. / Journal of Fluorine Chemistry 154 (2013) 67–72
71
4. Conclusions
In summary, we have shown that N,N-dimethylaniline,
N,N-dimethylnaphthalen-1-amine and 1,8-bis(dimethylamino)-
naphthalene react with electrophilic N–F reagents (Selectfluor
and NFSI) producing complex mixtures of substances, in which the
ring fluorinated and coupling products prevail. The fluorination
mostly proceeds at ortho- rather than para-position that was
ascribed to the SET mechanism and especially to the stabilization
of transition state for the ortho-attack via Me2N ! F and CH. . .O
bonding. The proton sponge has been shown to demonstrate much
higher selectivity in comparison with two other arylamines that
allowed us to isolate and fully characterize its first fluorinated
derivative. For the first time, chlorination under the action of NFSI–
ZrCl4 system has been observed.
Fig. 8. Dimeric structure of intermediate 24.
5. Experimental
5.1. General indications and spectroscopic measurements
N,N-Dimethylaniline and N,N-dimethylnaphthalen-1-amine
were purified by vacuum distillation before use. 1,8-Bis(dimethy-
lamino)naphthalene and Selectfluor were purchased from Aldrich,
NFSI from Alfa-Aesar. 1H NMR and 13C{H} NMR spectra were
recorded with Bruker DPX-250 using TMS as the external standard.
19F NMR spectra were performed with Buker DRX 500 with CFCl3 as
the external standard. GC/MS were performed on Varian 3400
equipped with Finnigan MAT ITD-700 mass detector and known
compounds in the reaction probes were identified using NIST’07
mass-spectra database.
Fig. 9. Transition states corresponding to the NFSI ortho- (a) and para-attack (b) on
molecule 3.
As expected, the calculations predict the para-s-complex to be
about 62 kJ more favourable than the ortho-complex. On the other
hand, the transition state corresponding to NFSI attack on the
ortho-position lies on ꢀ22 kJ below than that for the para-attack.
The structure of a transition state is known to reveal factors which
determine the reaction pathway. In our case, this is the formation
of C–H. . .O hydrogen bonds between N–CH3 and SO2 groups
(Fig. 9a). A transition state corresponding to the para-attack of
5.2. General procedure for NFSI fluorination
fluorinating reagent on
3 (Fig. 9b) does not provide such
stabilization. Evidently, this sort of C–H. . .O hydrogen bonding
may operate for NCS and NBS. It can be especially important for
ortho-halogenation of amine 5 as the proton sponge NMe2 groups
are considerably planarized and hence their hydrogen atoms are
more available for this sort of coordination [22]. Such ortho-
directed fluorination is instructive to compare with the action of
the F2/TfOH system, suggested some time ago for the electrophilic
meta-fluorination of anilines via conversion of its amino groups
To a solution of amine (0.1 mmol) in 3 mL of CHCl3 the
corresponding amount of NFSI in 2 mL of the same solvent was
added. The reaction mass was stirred at selected temperature
during the time indicated in Table 1. The resulting solution was
washed with water (2 ꢃ 15 mL), dried over Na2SO4 and evaporated
to dryness. The residue was analyzed either by GC/MS or separated
by column chromatography.
+
into the –NH3 functionality [3a].
5.3. General procedure for Selectfluor fluorination
Another interesting aspect of the studied reactions is the ring
chlorination at using the NFSI–ZrCl4 system. In the parent article
[6] and in later literature, we have not found any examples of
similar processes. We have established that no reaction occurs on
reflux of dimethylaminoarenes with one equivalent of ZrCl4 in
CHCl3 solution even for 24 h, indicating a key role of NFSI during
chlorination. The detection of binaphthyl 14 when diamine 5 was
subjected to the NFSI–ZrCl4 treatment gave some clue about
radical mechanism of the reaction. One can imagine that the
preliminary oxidation of arylamine by NFSI is accompanied by the
ZrIV ! ZrIII reduction. This initiates the release of a chlorine atom
competing with the fluorine electrophile in the aromatic ring
attack. Obviously, further studies of this mechanism are required
to elucidate also the pathways leading to the formation of
benzenesulfonyl halides 10 and 11.
To a solution of amine (0.1 mmol) in 3 mL of MeCN the
corresponding amount of Selectfluor in 2 mL of MeCN was added.
The reaction mass was stirred at selected temperature during the
time indicated in Table 1. The resulting solution was diluted with
15 mL of water and the products were extracted with toluene
(3 ꢃ 5 mL). The extract was then dried over Na2SO4 and evaporated
to dryness and the residue was analyzed either by GC/MS or
separated by column chromatography.
5.4. 1,8-Bis(dimethylamino)-2-fluoronaphthalene (15)
The solution of NFSI (0.32 g, 1 mmol) in 5 mL of chloroform was
added to 0.2 g (0.93 mmol) of 1,8-bis(dimethylamino)naphthalene
in 10 mL of CHCl3. The orange-red reaction mass was stirred at
room temperature for 10 h. Then, it was washed with water
(2 ꢃ 30 mL), dried over Na2SO4 and evaporated to a minimum
volume. The products were separated by column chromatography
on silica gel, using diethyl ether as eluent. 1,8-Bis(dimethylamino)-
Table 2
PM6 calculated energy of selected states corresponding to NFSI attack on DMA 3.
Position of
attack
s
(kJ)
-Complex
Transition
state (kJ)
Barrier
2-fluoronaphthalene (Rf 0.45) was obtained as pale-yellow oil,
a
height (kJ)
20
0.057 g (26%). nD ¼ 1:6004. UV/Vis (hexane): lmax (log
e
) = 317
= 3058, 2883, 1578, 1450,
1378, 1338, 1232, 1030, 944, 822, 786, 753, 687, 637 cmꢁ1. 1H NMR
(250 MHz, CDCl3): = 7.44 (dd, J = 8.9 and 5.3 Hz, 1 H, H-4), 7.39
ortho
para
ꢁ411.80
ꢁ474.16
ꢁ278.57
ꢁ255.81
65.77
87.96
(3.57), 239 (4.24) nm. IR (liquid film):
n
a
Energy difference between transition state and substrate molecule.
d

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V.I. Sorokin et al. / Journal of Fluorine Chemistry 154 (2013) 67–72
(b) K. Uneyama, Organofluorine Chemistry, Blackwell Publishing Ltd., Oxford,
2006 p. 339;
(c) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004 p.
308;
(dd, J = 8.0 and 1.3 Hz, 1 H, H-5), 7.29 (dd, J = 8.0 and 7.6 Hz, 1 H, H-
6), 7.20 (dd, J = 12.1 and 8.9 Hz, 1 H, H-3), 7.04 (d, J = 7.6 Hz, 1 H, H-
7), 3.00 (d, J = 3.2 Hz, 6 H, 1-NMe2), 2.84 (s, 6 H, 8-NMe2) ppm. 19
F
(d) C. Deleuze-Masquefa, G. Moarbess, S. Khier, N. David, S. Gayraud-Paniagua,
F. Bressolle, F. Pinguet, P.A. Bonnet, Eur. J. Med. Chem 44 (2009) 3406–3411;
(e) G.A. Kraus, I. Jeon, M. Nilsen-Hamilton, A.M. Awad, J. Banerjee, B. Parvin,
Molecules 13 (2008) 986–994;
NMR (470 MHz, CDCl3):
d
= –109.8 (br dd, J = 10.9 and 3.7 Hz) ppm.
= 158.04 (d, J = 242.3 Hz, Car), 151.42
13C NMR (72 MHz, CDCl3):
d
(d, J = 5.9 Hz, Car), 134.73 (d, J = 10.5 Hz, Car), 134.46 (br s, Car),
124.98 (d, J = 4.7 Hz, Car), 124.69 (s, Car), 124.6 (d, J = 7.5 Hz, Car),
122.49 (s, Car), 116.61 (d, J = 25.8 Hz, Car), 114.55 (s, Car), 45.18 (s, 8-
NMe2), 44.55 (d, J = 3.4 Hz, 1-NMe2) ppm. EI–MS: m/z (%) = 232
(68) [M+], 217 (25), 201 (74), 186 (100), 172 (20), 145 (27), 125
(10), 107 (6), 42 (8). C14H17FN2 (232.30): calcd. C 72.39, H 7.38, N
12.06; found C 72.25, H 7.35, N 12.11.
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5.5. 1,8-Bis(dimethylamino)-2-fluoronaphthalene perchlorate
(15ꢂHClO4)
To a solution of 15 (0.03 g, 0.13 mmol) in 5 mL of dry diethyl
ether, 0.016 mL (0.13 mmol) of 55% HClO4 was added under
vigorous shaking. The precipitated salt was separated by decanta-
tion and washed twice with 5 mL of ether to obtain after drying
0.038 g (88% yield) of perchlorate 15 HClO4. Crystallization from
methanol gave colourless crystals: mp 268–270 8C. 1H NMR
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4221–4232.
(250 MHz, CD3CN):
d
= 18.24 (br s, 1 H, N–H+–N), 8.09 (dd,
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J = 9.2 and 5.3 Hz, 1 H, H-4), 8.08 (dd, J = 8.3 and 1.0 Hz, 1 H, H-5),
7.98 (br dd, J = 7.8 and 1.0 Hz, 1 H, H-7), 7.71 (dd, J = 8.3 and 7.8 Hz,
1 H, H-6), 7.57 (dd, J = 11.9 and 9.2 Hz, 1 H, H-3), 3.26 (d, J = 4.0 Hz,
6 H, 8-NMe2), 3.14 (t, J = 1.4 Hz, 6 H, 1-NMe2) ppm.
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5.6. 8-Dimethylamino-2-fluoronaphthalen-1-ol (18)
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251–256.
The compound was obtained as light-brown fraction with Rf
0.80 during the separation of base 15 on silica gel (see above). Its
amount varied from experiment to experiment (2–6%). Light-
brown oil slowly crystallized upon cooling in refrigerator: mp 55–
57 8C. UV/Vis (hexane):
(CCl4): = 3059, 2955, 2870, 2292, 1551, 1463, 1416, 1359, 1334,
1271, 1029, 945 cmꢁ1. 1H NMR (250 MHz, CDCl3):
= 14.68 (s, 1 H,
lmax (loge) = 304 (3.37), 229 (4.14) nm. IR
n
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4579;
d
OH), 7.62 (dd, J = 7.2 and 1.7 Hz, 1 H, H-5), 7.37 (dd, J = 7.2 and
6.8 Hz, 1 H, H-6), 7.33 (dd, J = 6.8 and 1.7 Hz, 1 H, H-7), 7.27 (dd,
J = 10.9 and 8.9 Hz, 1 H, H-3), 7.19 (dd, J = 8.9 and 4.7 Hz, 1 H, H-4),
(b) N.J. Farrer, K.L. Vikse, R. McDonald, J.S. McIndoe, Eur. J. Inorg. Chem. (2012)
733–740.
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[22] (a) A.F. Pozharskii, A.V. Degtyarev, O.V. Ryabtsova, V.A. Ozeryanskii, M.E.
Kletskii, Z.A. Starikova, L. Sobczyk, A. Filarowski, J. Org. Chem. 72 (2007)
3006–3019;
2.83 (s, NMe2) ppm. 19F NMR (470 MHz, CDCl3):
d = –137.1 (dd,
J = 10.5 and 4.6 Hz) ppm. EI–MS: m/z (%) = 205 (100) [M+], 204 (28),
190 (37), 170 (33), 142 (29), 133 (57), 115 (69). C12H12FNO
(205.23): calcd. C 70.23, H 5.89, N 6.82; found C 70.20, H 5.87, N
6.86.
(b) A.F. Pozharskii, O.V. Ryabtsova, V.A. Ozeryanskii, A.V. Degtyarev, O.N.
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10122.
Acknowledgements
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1704–1707.
We thank the Russian Foundation for Basic Research (projects
08-03-00028 and 11-03-00073) for financial support of this study.
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