Direct di- and triamination of polyfluoropyridines in anhydrous ammonia

Article abstract of DOI:10.1016/j.jfluchem.2009.02.005

Aminodefluorination of polyfluoropyridines (pentafluoro-, 3,5-dichlorotrifluoro-, 3- and 4-chlorotetrafluoro-, 2,3,5,6- and 2,3,4,6-tetrafluoro-, 3-chloro-2,4,6-trifluoro-, and 2,4,6-trifluoropyridine) in anhydrous ammonia has been investigated. Temperatu

Full text of DOI:10.1016/j.jfluchem.2009.02.005

Journal of Fluorine Chemistry 130 (2009) 461–465
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Direct di- and triamination of polyfluoropyridines in anhydrous ammonia
*
Soltan Z. Kusov, Vladimir I. Rodionov, Tamara A. Vaganova, Inna K. Shundrina, Evgenij V. Malykhin
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Avenue 9, 630090 Novosibirsk, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Aminodefluorination of polyfluoropyridines (pentafluoro-, 3,5-dichlorotrifluoro-, 3- and 4-chlorotetra-
fluoro-, 2,3,5,6- and 2,3,4,6-tetrafluoro-, 3-chloro-2,4,6-trifluoro-, and 2,4,6-trifluoropyridine) in
anhydrous ammonia has been investigated. Temperatures of the second and third amino group
introduction into pyridine ring were shown to increase significantly thus ensuring conditions for
selective preparation of mono-, di- and, in the case of perhalopyridines as starting compounds,
triaminoderivatives with high yield and purity.
Received 23 December 2008
Received in revised form 4 February 2009
Accepted 7 February 2009
Available online 13 February 2009
Keywords:
ß 2009 Elsevier B.V. All rights reserved.
Polyfluoropyridines
Diaminopyridines
Triaminopyridines
Anhydrous ammonia
Aminodefluorination
Nucleophilic substitution
1. Introduction
trifluoropyridine (8a) have been used as substrates under
investigation.
Aminodefluorination of electrophilic polyfluoroarenes includ-
ing polyfluoropyridines efficiently occurs in anhydrous ammonia
applied as a reagent and a solvent simultaneously [1,2]. The
advantages of this method are: (i) selectivity of synthesis of
arenes containing one and (or) two amino groups due to a
significant differences in the reaction conditions; (ii) a high
purity of products owing to the absence of hydrodeflurination
realized in aqueous-ammonia medium [2]; (iii) rationality and
universality of this processes as a route to practically important
compounds.
The purpose of this study is the development of aminode-
fluorination of polychlorofluoropyridines in anhydrous ammo-
nia as a selective method for preparation of novel halogenated
pyridines containing two and (or) three amino groups, which
are bioactive substance precursors [3,4] and building blocks
in synthesis of condensation type polymers, in particular,
hyperbranched polyimide membranes for gas separation
applications [5] and anion-exchange nanofiltration membranes
[6].
Monoamination of pyridines 1a–3a at the
g-position, and
pyridines 4a and 5a at the -position is known to proceed
a
selectively in aqueous NH3 or in its mixtures with organic solvents
(dioxane, THF) (1a [7], 2a [8], 3a [4], 4a [9], 5a [9,10]).
Monoamination of pyridines 6a and 8a results in a mixture of
isomers containing
about ammonolysis of pyridine 7a. However, the
a
- or
g
-amino group [11,12]; there are no data
-amino
g
derivatives of pyridines 6a–8a can be prepared selectively by
one-pot aminodefluorination/hydrodechlorination of 3a and 2a by
the action of Zn powder in aqueous ammonia [13]. As to the
multireplacement of fluorine atoms in pyridine framework with
amino groups, bis-aminodefluorination of pyridine 1a in aqueous
NH3 was an only known example [14] until the work [1], which has
demonstrated ability of anhydrous ammonia in carrying out of
selective mono- and bisaminodefluorination of pyridines 1a, 2a,
4a, 5a. Preparation of diaminoderivatives of pyridines 3a, 6a–8a
and triaminohalopyridines has not been reported.
2. Results and discussion
Perhalogenated pyridines
– pentafluoropyridine (1a), 3,5-
dichlorotrifluoropyridine (2a), 3-chlorotetrafluoropyridine (3a),
4-chlorotetrafluoropyridine (4a), as well as tetra- or tri-haloge-
nated ones – 2,3,5,6-tetrafluoropyridine (5a), 2,3,4,6-tetrafluor-
opyridine (6a), 3-chloro-2,4,6-trifluoropyridine (7a), 2,4,6-
To develop the investigation of activity of ammonia as a
nucleophile and a medium for aromatic nucleophilic substitution,
we established that bis-aminodefluorination of the all set of
substrates (pyridines 1a–8a) proceeds successfully in anhydrous
NH3 (Schemes 1–5). In the reactions of pyridines 1a–3a containing
fluorine atoms at the
g- and both a-positions, their triaminoder-
* Corresponding author. Fax: +7 383 3309752.
E-mail address: malykhin@nioch.nsc.ru (E.V. Malykhin).
ivatives are formed (Schemes 1 and 2). The processes were carried
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.02.005

462
S.Z. Kusov et al. / Journal of Fluorine Chemistry 130 (2009) 461–465
Scheme 1.
Scheme 3.
Scheme 2.
out in a steel autoclave under pressure so that molar volume of the
reagents and temperature allowed liquid or liquid-like state of
ammonia.1 Reaction conditions, reactant amounts, and product
yields are given in Table 1.
mino-4-chloro-3,5-difluoropyridine (4b) and 2,6-diamino-3,5-
difluoropyridine (5b) are formed selectively upon the action of
anhydrous NH3 (Entries 7 and 8, Table 1, correspondingly, Scheme
3), and can be obtained with purity 99% by crystallization of the
crude products.
Mono-aminodefluorination of tetra- and trihalogenated pyr-
idines 6a, 7a, and 8a with liquid ammonia realizes at 20–50 8C.
Comparison of 19F NMR data of the reaction mixtures obtained
with spectral characteristics of the known monoaminoderivatives
Bis-aminodefluorination of symmetrical pyridines 1a and 2a
selectively realizes at 60–100 8C and leads to the formation of 2,4-
diamino-3,5,6-trifluoropyridine (1b) and 2,4-diamino-3,5-
dichloro-6-fluoropyridine (2b) correspondingly (Entries 1 and 3,
Table 1; Scheme 1). Purification of the crude products to more than
99% purity has been easily performed by a single crystallization.
Introduction of third amino group into pyridines 1b and 2b
requires a higher temperature and a longer reaction time (Entries 2
and 4, Table 1; Scheme 1). Crude products contain more impurities,
but individual 2,4,6-triamino-3,5-difluoropyridine (1c) and 2,4,6-
triamino-3,5-dichloropyridine (2c) (purity 99%) have been isolated
by using simple experimental procedures.
of pyridines 6a–8a [11–13] evidences that mixtures of g- and a-
monoaminoderivatives in 2–4:1 ratio, respectively, are formed in
these reactions. Bis-aminodefluorination of pyridines 6a and 7a at
120 8C results in the selective formation of
a,g-diamines–2,4-
diamino-3,6-difluoropyridine (6b) and 2,4-diamino-3-chloro-6-
fluoropyridine (7b) (Entries 9 and 10, Table 1, correspondingly,
Scheme 4). It is necessary to note that 19F NMR data of diamine 7b
do not ensure undoubted ascertainment of its structure by using
the substituents shielding parameters [16]. However, taking into
account the known effects of F, Cl, and H atoms on the orientation
of nucleophilic substitution in polyhalogenated pyridines
[12,17,18], replacement of fluorine atoms at C-2 should be realized
upon aminodefluorination of both tetrahalogenated pyridines 6a
and 7a. This regioselectivity is favored by the ortho-halogen
activating effect and by the absence of para-fluorine deactivating
effect. The opposite combination of these factors – the presence of
para-deactivating fluorine and the absence of ortho-activating
halogen – prevents the replacement of fluorine atom at the
position 6. It provides the high selectivity of bis-aminodefluorina-
tion of 6a and 7a, as compared with reaction of 3a (see above). The
Selective mono-aminodefluorination of pyridine 3a containing
chlorine atom at a
b-position, by anhydrous NH3 occurs at 10 8C
and results in known [4] 4-amino-3-chloro-2,5,6-trifluoropyridine
according to 19F NMR data of the reaction mixture. Upon bis-
aminodefluorination of 3a the mixture of 2,4-diamino-5-chloro-
3,6-difluoropyridine (3b) and 2,4-diamino-3-chloro-5,6-difluoro-
pyridine (3c) in 3:1 ratio is formed (Entry 5, Table 1; Scheme 2).
Diamines 3b and 3c have been prepared for the first time and
isolated from the mixture by TLC; more convenient technique for
isomers separation has not been found. Substituents location in
these diamines and in derivatives of pyridines 6a and 7a (see
below) has been established by 19F NMR data with use of the
substituents shielding parameters [16]. Regioselectivity of 3a bis-
aminodefluorination is determined by the known electronic effects
of ring halogens [12,17,18]. Replacement of fluorine atom at the
position 6 is activated by ortho-chlorine effect, but deactivated by
para-fluorine effect. On the other hand, both ortho-fluorine and
para-chlorine effects promote nucleophilic substitution at the
position 2. By these reasons diamine 3b prevails among the
reaction products. Subsequent replacement of the remaining
a-
fluorine atom in both pyridines 3b and 3c results in the formation
of 2,4,6-triamino-3-chloro-5-fluoropyridine (3d) (Entry 6, Table 1;
Scheme 2). Thus, the one-pot tri-aminodefluorination of pyridine
3a with anhydrous ammonia allows triamine 3d to be prepared
with good yield.
Scheme 4.
Replacement of fluorine atom at the most reactive
polyfluoropyridine with chlorine or hydrogen (in going to 4a and
5a) leads to the change of the reaction centre from - to -position.
-diamines–2,6-dia-
g-position of
g
a
a
-Monoaminoderivatives (see [1]), and a,a
1
Critical parameters for NH3: rc 0.24 g/cm3, Tc 132.6 8C, and Pc 112.5 atm [15].
Scheme 5.

S.Z. Kusov et al. / Journal of Fluorine Chemistry 130 (2009) 461–465
463
Table 1
Experimental conditions and product yields for reactions of polyfluoropyridines (1–8) with NH3.
Entry
Polyfluoropyridines
Reactant amountsa
Substrate (g)
Reaction conditions
Reaction products
Di(tri)amines
Liquid
Temperature
Time (h)
Crude productb
yields (g)
Isolated product
yields (g/%)
NH3 (mL)
(8C, Æ5)
1c
2
1a
1a
2a
2a
3a
3a
4ae
5a
6a
7a
8a
8.0
3.0
10
50
20
50
40
30
20
25
40
25
30
35
100
150
60
15
50
10
24
7
1b
7.1
2.8
9.0
4.2
2.7d
2.8
0.7
3.8
2.8
1.9
2.7f
6.5/81
1.8/60
6.5/65
3.5/70
1c
3c
4
2b
5.0
3.0
3.0
1.0
5.0
3.0
2.0
3.0
140
100
160
115
150
120
120
120
2c
5
3b,3c
3d
6
20
10
67
10
14
35
1.9/66
0.6/60
3.5/70
1.5/50
1.8/90
1.1g/40
7c
8
4b
5b
9
6b
10
11
7b
8b,8c
a
An autoclave volume is 100 mL in Entries 1, 3, 4, 8, and 50 mL in Entries 2, 5, 6, 7, 9–11.
b
c
d
e
f
Purity of the crude products in Entries 1, 3, 5, 7–11 is >95%, in Entries 2, 4, 6 is >90% (19F NMR data).
Preparation of compounds 1b, 2b and 4b has been reported in [1].
Composition of the crude product: diamine 3b:diamine 3c = 3:1 (19F NMR data).
Replacement of
g-chlorine in diamine 4b with formation of triamine 1c (ꢀ5%) occurs for 100 h at 180 8C.
Composition of the crude product: diamine 8b:diamine 8c = 9:1 (19F NMR data).
Diamine 8b.
g
absence in pyridine 8a of the both
chlorine) activating the nucleophilic substitution in polyfluor-
opyridines leads to the reaction deceleration and closing in the
b
-halogen atoms (fluorine or
(5a) were prepared by published procedures [1]; 3-chlorotetra-
fluoropyridine (3a), 2,3,4,6-tetrafluoropyridine (6a), 3-chloro-
2,4,6-trifluoropyridine (7a), and 2,4,6-trifluoropyridine (8a) were
prepared with use of original methods, their physical parameters
were identical to those reported in the literature ((3a) and (6a)
[19], (7a) [20], (8a) [10]).
rates of
a- and g-fluorine replacement, so that complete bis-
aminodefluorination of this substrate takes a three times greater
process duration and results in the mixture of 2,4-diamino-6-
fluoropyridine (8b) and 2,6-diamino-4-fluoropyridine (8c) in 9:1
ratio (Entry 11, Table 1; Scheme 5). Considerably predominant
a
,g
-
4.2. General
diamine 8b has been isolated in a preparative scale with purity
>99% using the technique based on the different capacity of
diamines to form complexes with 18-crown-6 [1,2]. Replacement
of the remaining fluorine atom by amino group in diamines 6b–8b
is not realized up to 160 8C that can be caused by reduced
electrophilicity of these partially halogenated compounds in
comparison with diaminotrihalopyridines 1b, 2b, 3b, and 3c.
1H and 19F NMR spectra were recorded on NMR spectrometers
Bruker AV-300 (300.13 and 282.36 MHz for 1H and 19F corre-
spondingly) using residual proton signals of the deuterated solvent
and C6F6 (
d
= À163.0 ppm from CCl3F) as internal standards;
d are
given in ppm relative to TMS and CCl3F, J are given in Hz. IR spectra
were recorded on Bruker Vector-22 instrument. UV spectra were
recorded on Fourier spectrometer HP 8453. The precise molecular
weights of ions were determined by high resolution mass
spectrometry on Thermo Scientific DFS instrument, ionizing
energy 70 eV. GC–MS identification of mixture components was
performed using Hewlett Packard G1081A equipment comprising
an HP 5890 Series II gas chromatograph and an HP5971 mass
selective detector; electron ionization energy of 70 eV; HP5
column (5% of biphenyl and 95% of dimethylsiloxane),
3. Conclusion
Thus, the polyhalogenated pyridines undergo aminodefluor-
ination by the action of anhydrous ammonia at À33 to 160 8C with
formation of mono- (see also [1]), di- and even triaminopyridines
(the last ones have been obtained from perhalopyridines). The
revealed relative reactivity of polyfluoropyridines and their
aminoderivatives, as well orientation of fluorine replacement
are in agreement with the known set of total electronic effects of
substituents. Considerable temperature differences provide high
selectivity of the first, second and third amino group introduction
into pyridine framework independently of starting compound
(one-pot synthesis); isolated product yields (purity 99%) are 50–
80%. These results together with data of [1,2] characterize the
direct amination of electrophilic arenes with anhydrous ammonia
as universal route to aromatic compounds containing one, two, and
three amino groups, which are demanded for modern materials
and fine organic synthesis.
30 m  0.25 mm  0.25
mm; with helium as carrier gas, flow rate
column temperature programming from 50 8C
1 mL minÀ1
;
(2 min) at an increment of 10 8C minÀ1 to 280 8C (5 min); injector
temperature 280 8C; ion source temperature 173 8C; data acquisi-
tion rate 1.2 scan sÀ1 in the mass range 30–650 amu. Analyses of
product mixtures and purity of products were performed on HP
5890 Series II gas chromatograph (thermo conductivity detector);
HP5 column (5% of biphenyl and 95% of dimethylsiloxane),
30 m  0.22 mm  2.6
mm; with helium as carrier gas, flow rate
column temperature programming from 90 8C
1 mL minÀ1
;
(2 min) at an increment of 10 8C minÀ1 to 330 8C (5 min); injector
temperature 300 8C; detector temperature 320 8C.
4. Experimental
4.3. Synthetic procedures
4.1. Materials
4.3.1. Typical procedure for the reaction of polyhalopyridines with
liquid NH3
The following commercial products were used: 18-crown-6,
tert-butyl methyl ether (t-BuMeO), acetone, liquid NH3, plates
Kieselgel 60 F254 (Merck), silica gel 60 0.063–0.100 mm (Merck).
Pentafluoropyridine (1a), 3,5-dichlorotrifluoropyridine (2a), 4-
chlorotetrafluoropyridine (4a), and 2,3,5,6-tetrafluoropyridine
Polyhalopyridine was placed into a steel autoclave, the required
amount of liquid NH3 was added through a measuring funnel with
back pressure and the autoclave was sealed. The reaction mixture
was heated up to the given temperature upon stirring by rotation

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S.Z. Kusov et al. / Journal of Fluorine Chemistry 130 (2009) 461–465
of the autoclave and kept under these conditions for the necessary
time. On completion, the autoclave was cooled, NH3 was slowly
vented through a pressure release valve, and products were
extracted with acetone (3 Â 40 mL). Solvent was evaporated to
give crude product, which was then purified. Reactant amounts,
reaction conditions, and product yields are listed in Table 1.
Methods of isolation of compounds obtained for the first time and
their characteristics are given below.
0.4 (by TLC, eluent CHCl3:CH3OH, 5:6, v/v) was collected, solvent
was evaporated and the product obtained was crystallized from
CHCl3 to give triamine 3d, purity 99%, mp 202–203 8C. UV (EtOH):
lmax (log
(NH2) cmÀ1
C(6)NH2), 5.17 (br.s, 2H, C(4)NH2). 19F NMR (acetone-d6):
e
) 213 (2.2), 294 (0.5) nm. IR (KBr):
n 3437, 3324, 3188
.
1H NMR (acetone-d6):
d
4.89 (br.s, 4H, C(2)NH2,
d
À173.7
(s, 1F, F-5). EIMS, m/z (rel. int): 178 [M]+ (30), 176 [M]+ (100), 149
[MÀHCN]+ (12), 114 [MÀHCNÀCl]+ (12). HRMS calcd. for
C5H6ClFN4: 176.0259, found: 176.0256.
4.3.2. 2,4-Diamino-3,5,6-trifluoropyridine (1b)
The crude product (Entry 1, Table 1) was purified by crystal-
lization from a benzene–hexane mixture (1:1, v/v), purity 99%, mp
114–116 8C [1].
4.3.8. 2,6-Diamino-4-chloro-3,5-difluoropyridine (4b) (Entry 7,
Table 1)
The crude product was purified by crystallization from CCl4,
purity 99%, mp 145–146 8C, for spectral characteristics see [1].
4.3.3. 2,4,6-Triamino-3,5-difluoropyridine (1c)
The crude product (Entry 2, Table 1) was sublimed, dissolved in
t-BuMeO, and filtered through a SiO2 layer (50 g). Fraction with Rf
0.3 (by TLC, eluent CHCl3:CH3OH, 5:6, v/v) was collected, solvent
was evaporated and the product obtained was crystallized from
CHCl3 to give triamine 1c, purity 99%, mp 210–210.5 8C. UV (EtOH):
4.3.9. 2,6-Diamino-3,5-difluoropyridine (5b) (Entry 8, Table 1)
The crude product was purified by sublimation, purity 99%, mp
156.5–158 8C, for spectral characteristics see [1].
4.3.10. 2,4-Diamino-3,6-difluoropyridine (6b) (Entry 9, Table 1)
The crude product was purified by crystallization from a
benzene–hexane mixture (1:1, v/v), purity 99%, mp 91.5–92.5 8C.
lmax (log
3190 (NH2) cmÀ1. 1H NMR (acetone-d6):
C(6)NH2), 5.03 (br.s, 2H, C(4)NH2). 19F NMR (acetone-d6):
(s, 2F, F-3, F-5). EIMS, m/z (rel. int): 160 [M]+ (100), 133 [MÀHCN]+
(11), 132 [MÀCNH2]+ (12). HRMS calcd. for C5H6F2N4: 160.0555,
found: 160.0541.
e
) 209 (2.5), 293 (0.6) nm. IR (KBr):
n 3465, 3436, 3360,
d
4.64 (br.s, 4H, C(2)NH2,
d
À172.1
UV (EtOH): lmax (log
3484, 3304, 3192 (NH2); 2965 (Cap–H) cmÀ1. 1H NMR (acetone-d6):
5.30 (br.s, 2H, C(2)NH2), 5.52 (br.s, 2H, C(4)NH2), 5.65 (d, 1H,
JH,F = 4, H-5). 19F NMR (acetone-d6):
e) 210 (2.3), 273 (0.4) nm. IR (KBr): n 3499,
d
d
À173.1 (dd, 1F,
JH,F = 4, JF,F = 24, F-3), À76.6 (d, 1F, JF,F = 24, F-6). EIMS, m/z (rel.
int): 145 [M]+ (100), 125 [MÀHF]+ (19), 118 [MÀHCN]+ (17), 117
[MÀCNH2]+ (16). HRMS calcd. for C5H5F2N3: 145.0452, found:
145.0451.
4.3.4. 2,4-Diamino-3,5-dichloro-6-fluoropyridine (2b)
The crude product (Entry 3, Table 1) was purified by crystal-
lization from CH2Cl2, purity 99%, mp 137–139 8C, for spectral
characteristics see [1].
4.3.11. 2,4-Diamino-3-chloro-6-fluoropyridine (7b)
4.3.5. 2,4,6-Triamino-3,5-dichloropyridine (2c)
The crude product (Entry 4, Table 1) was purified by crystal-
lization from CHCl3, purity 99%, mp 193–194 8C. UV (EtOH): lmax
The crude product (Entry 10, Table 1) was purified by
sublimation, purity 99%, mp 104.5–106 8C (from CCl4). UV (EtOH):
l
max (log
e
) 217 (2.2), 275 (0.2) nm. IR (KBr):
n
3479, 3457, 3361,
5.55 (br.s,
(log
e
) 221 (1.8), 294 (0.3) nm. IR (KBr):
n
d
3451, 3432, 3349, 3299,
5.15 (br.s, 4H, C(2)NH2,
3300 (NH2); 2920 (Cap–H) cmÀ1. 1H NMR (acetone-d6):
d
3164 (NH2) cmÀ1. 1H NMR (acetone-d6):
2H, C(2)NH2), 5.71 (s, 1H, H-5), 5.77 (br.s, 2H, C(4)NH2). 19F NMR
C(6)NH2), 5.32 (br.s, 2H, C(4)NH2). EIMS, m/z (rel. int): 196 [M]+
(10), 194 [M]+ (65), 192 [M]+ (100), 165 [MÀHCN]+ (15), 156
[MÀHCl]+ (14), 130 [MÀHCNÀCl]+ (14). HRMS calcd. for
C5H6Cl2N4: 191.9969, found: 191.9970.
(acetone-d6):
d
À74.7 (s, 1F, F-6). EIMS, m/z (rel. int): 163 [M]+ (38),
161 [M]+ (100), 143 [MÀHF]+ (17), 141 [MÀHF]+ (52), 134
[MÀHCN]+ (13), 133 [MÀCNH2]+ (11). HRMS calcd. for C5H5ClFN3:
161.0156, found: 161.0161.
4.3.6. 2,4-Diamino-5-chloro-3,6-difluoropyridine (3b) and 2,4-
diamino-3-chloro-5,6-difluoropyridine (3c)
4.3.12. 2,4-Diamino-6-fluoropyridine (8b) and 2,6-diamino-4-
fluoropyridine (8c)
Thecrudeproduct(Entry5,Table1)beingthemixtureofdiamines
3b and 3c (3:1, 19F NMR data) was separated by thin-layer
chromatography, eluent CHCl3:CH3OH (10:1, v/v). 2,4-Diamino-5-
chloro-3,6-difluoropyridine (3b) (Rf 0.3), mp127–129 8C. UV (EtOH):
The crude product (Entry 11, Table 1) contains diamines 8b and
8c in 9:1 ratio (19F NMR data). 2,6-Diamino-4-fluoropyridine (8c)
being the minor component has the signal at À106.0 ppm in 19F
NMR spectrum of the mixture and M 127 (GC–MS data). The major
component diamine 8b was isolated by the followed procedure.
The crude product was solved in t-BuMeO (50 mL) under reflux and
insoluble admixture was filtered off. To the solution obtained 18-
crown-6 (5.3 g, 20 mmol) was added and the mixture was kept for
1 h at ꢀ20 8C upon stirring. The precipitate was filtered off and
washed with a small amount of t-BuMeO. Complex of diamine 8b
with 18-crown-6 (6.1 g) was obtained. The complex was decom-
posed with water (50 mL) and diamine 8b was extracted with t-
BuMeO (8 mL Â 20 mL). The combined extract was dried over
MgSO4, and solvent was distilled off to give diamine 8b.
2,4-Diamino-6-fluoropyridine (8b), mp 100.5–101.5 8C. UV
l
max (log
3190 (NH2) cmÀ1
C(4)NH2). 19F NMR (DMSO-d6):
e
)212(2.7),278(0.4)nm.IR(KBr):
n
3491,3437,3387,3303,
.
1H NMR (DMSO-d6):
d 5.2 (br.s, 4H, C(2)NH2,
d
À165.2 (d, 1F, JF,F = 25, F-3), À80.0
(d, 1F, JF,F = 25, F-6). EIMS, m/z (rel. int):181 [M]+ (32), 179[M]+ (100),
159 [MÀHF]+ (15), 152 [MÀHCN]+ (22), 151 [MÀCNH2]+ (13). HRMS
calcd. for C5H4ClF2N3: 179.0062, found: 179.0063.
2,4-Diamino-3-chloro-5,6-difluoropyridine (3c) (Rf 0.5), mp
105–106 8C. UV (EtOH): lmax (log
(KBr):
3473, 3447, 3361, 3312, 3193 (NH2) cmÀ1
(acetone-d6): 5.48 (br.s, 2H, C(2)NH2), 5.94 (br.s, 2H, C(4)NH2).
19F NMR (acetone-d6):
e
) 211 (2.4), 281 (0.3) nm. IR
n
.
1H NMR
d
d
À176.6 (d, 1F, JF,F = 26, F-5), À95.6 (d, 1F,
JF,F = 26, F-6). EIMS, m/z (rel. int): 181 [M]+ (31), 179 [M]+ (100), 159
[MÀHF]+ (17), 152 [MÀHCN]+ (13), 151 [MÀCNH2]+ (10). HRMS
calcd. for C5H4ClF2N3: 179.0062, found: 179.0060.
(EtOH): lmax (log
3367, 3189 (NH2); 2925 (Cap–H) cmÀ1. 1H NMR (acetone-d6):
(br.s, 2H, C(2)NH2), 5.39 (br.s, 2H, C(4)NH2), 5.47 (d, 1H, JH,H = 1.5,
H-3), 5.62 (dd, 1H, JH,H = 1.5, JH,F = 2, H-5). 19F NMR (acetone-d6):
e
) 218 (2.2), 271 (0.2) nm. IR (KBr):
n
3454,
d
5.12
d
4.3.7. 2,4,6-Triamino-3-chloro-5-fluoropyridine (3d)
The crude product (Entry 6, Table 1) was sublimed, dissolved in
t-BuMeO, and filtered through a SiO2 layer (50 g). Fraction with Rf
À76.0 (br.s, 1F, F-6). EIMS, m/z (rel. int): 127 [M]+ (100), 107
[MÀHF]+ (15), 100 [MÀHCN]+ (24). HRMS calcd. for C5H6FN3:
127.0546, found: 127.0539.

S.Z. Kusov et al. / Journal of Fluorine Chemistry 130 (2009) 461–465
465
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