N-Perfluoroalkylsulfonylimido derivatives of arenecarboxylic acid amides and their oxidative aza Hofmann rearrangement

Article abstract of DOI:10.1016/j.jfluchem.2008.03.001

The analogues of carboxamides in which the sp²-hybridized oxygen atom is replaced by more electron-withdrawing groups, {double bond, long}NSO₂CF₃ and {double bond, long}NSO₂C₄F₉, have been

Full text of DOI:10.1016/j.jfluchem.2008.03.001

Journal of Fluorine Chemistry 129 (2008) 486–492
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
N-Perfluoroalkylsulfonylimido derivatives of arenecarboxylic acid amides
and their oxidative aza Hofmann rearrangement
1
1
*
Lev M. Yagupolskii , Irina I. Maletina, Liubov V. Sokolenko, Yurii G. Vlasenko , Sergey A. Buth
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 02094 Murmanskaya, Str. 5, Kiev, Ukraine
A R T I C L E I N F O
A B S T R A C T
The analogues of carboxamides in which the sp2-hybridized oxygen atom is replaced by more electron-
withdrawing groups, NSO2CF3 and NSO2C4F9, have been synthesized. The resulting N-perfluoroalk-
ylsulfonyl arenecarboxamidines ArC( NSO2Rf)NH2 (Rf = CF3, C4F9) undergo an oxidative Hofmann-type
Article history:
Received 26 December 2007
Received in revised form 4 March 2008
Accepted 5 March 2008
rearrangement to the corresponding carbodiimides ArN
C NSO2Rf under the action of (diacyloxy-
Available online 13 March 2008
iodo)arenes. Rearrangement of related compounds ArC( NSO2R)NH2 (R = CH3, Ph) containing fluorine-
free substituents at the sulfonyl group also occurs in similar conditions. It was found that the reactivity of
amidines rises with the increasing electron-withdrawing ability of the substituent R.
ß 2008 Elsevier B.V. All rights reserved.
Keywords:
Amidines
Rearrangements
X-ray structure
Carbodiimides
1. Introduction
These results encouraged us to explore the ability of
arenecarboxylic acid amidines (aza analogues of amides) to
Nucleophilic rearrangements of carboxylic acid derivatives via
migration of a substituent with its electron pair from carbon atom
to nitrogen atom (rearrangements of azides (Curtius), hydroxamic
acids (Lossen), amides (Hofmann)) are widely used in organic
chemistry for synthesis of isocyanates and amines [1].
As reported by us previously, substitution of a sp2-hybridized
oxygen atom in various compounds by the NSO2CF3 group (a
stronger electron acceptor) leads to significant changes in their
properties, in particular, increased reactivity [2] and acidity [3,4] as
well as a deepening of colour [5].
undergo the Hofmann rearrangement.
2. Results and discussion
2.1. Synthesis of N-substituted amidines
N-Trifluoromethylsulfonyl arenecarboximidoyl chlorides 1a–e
were converted to hitherto unknown N-trifluoromethylsulfonyl
arenecarboxamidines 2a–e by reaction with gaseous ammonia in
ether solution (Scheme 1).
We carried out systematic research on nucleophilic rearrange-
ments of carboxylic acid derivatives in which the carbonyl oxygen
atom is replaced by a trifluoromethylsulfonylimido group. Such
substitution in acid azides enables the Curtius rearrangement to
occur under very mild conditions affording carbodiimides [6]. Aza
analogues of hydroxamic acids containing the NSO2CF3 group
instead of the carbonyl oxygen atom undergo a Lossen-type
rearrangement to carbodiimides or N-trifluoromethylsulfonyl-N0-
arenechloroformamidines, depending on the reaction conditions
[7].
N-Methylsulfonylbenzamidine 3, N-phenylsulfonylbenzami-
dine 4, and N-nonafluorobutylsulfonyl-4-fluorobenzamidine 5
were prepared in the same manner (Scheme 2).
2.2. Structure of N-trifluoromethylsulfonyl arenecarboxamidines
Amidines 2a–e may exist in two tautomeric forms, A and B
(Scheme 3).
In the result of X-ray determination of amidine 2a we have
established that compounds 2a–e have the structure A in the solid
state. There is an interesting feature in the formation of the N(1)–
Hꢀ ꢀ ꢀO(2) intramolecular hydrogen bond (Nꢀ ꢀ ꢀO 2.806 (2), Oꢀ ꢀ ꢀH
˚
2.20 (2) (A), N(1)HO(2) 131.2 (19)8). The perspective view of
molecule 2a and selected geometrical parameters are given in
* Corresponding author. Tel.: +380 44 559 0349; fax: +380 44 573 2643.
Fig. 1. The analysis of 19F NMR spectra of the compounds with rigid
E-mail address: Yagupolskii@bpci.kiev.ua (L.M. Yagupolskii).
1
C
NSO2CF3 and C–NHSO2CF3 groups has confirmed that a signal of
Crystal structure analysis.
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.03.001

L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
487
Scheme 1.
Scheme 2.
the NSO2CF3 group is in the range ꢁ78 to ꢁ80 ppm, and that of
NHSO2CF3 group at ꢁ75 to ꢁ77 ppm [6,7]. In the 19F NMR spectra
of the compounds 2a–e signals at ꢁ79 to ꢁ80 ppm are observed,
which correspond to structure A in solution.
The IR spectrum of compound 2a dissolved in methylene
chloride shows two medium-intensity bands at 3481 and
3344 cmꢁ1 arising from the vibrations nas (N–H) and ns (N–H),
respectively. Another weak band at 3253 cmꢁ1 is assigned to the
H-bonded N–H group. As the intensity of either free or H-bonded
N–H group vibrations is practically insensitive to dilution, one can
assume the intramolecular character of the H-bond in this
compound. Presumably, hydrogen atom of N–H group is bonded
with oxygen atom of the sulfonyl group.
proceed in the cold, whereas heating results in a mixture of
products among which N,N-dichloro-N0–trifluoromethylsulfonyl-
4-fluorobenzamidine predominates. Treatment of the amidine 2c
sodium salt with chlorine solution in glyme in the cold leads to
analogous results. Amidine 2c is unreactive both to sulfuryl
chloride and to tert-butyl hypochlorite even on heating.
The Hofmann rearrangement of carboxamides is known to
proceed under the action of oxidants as, for instance, lead
tetraacetate, (diacetoxyiodo)benzene, and [bis(trifluoroacetoxy)
iodo]benzene [9,10]. We carried out this reaction with compound
2c under anhydrous conditions in the presence of organic bases
(pyridine and di-iso-propylethylamine (DIEA), as in Ref. [9]) using
4-[bis(trifluoroacetoxy)iodo]toluene as an oxidant (Scheme 4). The
resulting carbodiimide 6c was isolated and characterized as its
morpholine derivative 7c.
2.3. The oxidative aza Hofmann rearrangement of N-substituted
amidines
Carbodiimides containing a trifluoromethylsulfonylimino group
are very sensitive to strong acids and bases. The rearrangement is
The classical Hofmann rearrangement of primary carboxamides
occurs under the action of alkaline solutions of sodium hypo-
chlorite or hypobromite [8]. The reaction of compounds 2a–e with
sodium hypobromite leads to nearly complete recovery of starting
amidines, whereas treatment with sodium hypochlorite results in
a mixture of unidentified products.
Attempts to obtain N-chloro or N-bromo-N0–trifluoromethyl-
sulfonyl-4-fluorobenzamidines under anhydrous conditions were
unsuccessful. The sodium or silver salts of N-trifluoromethylsul-
fonyl-4-fluorobenzamidine 2c in acetonitrile or glyme, if treated
with bromine, are converted into the N-bromo derivative which
decomposes to starting materials even in the dark at 20 8C.
Chlorination of the same salts with sulfuryl chloride in carbon
tetrachloride or with tert-butyl hypochlorite in glyme does not
˚
Fig. 1. Molecular structure of 2a. Selected bond lengths (A) and angles (8) for 2a:
C(8)–S(1) 1.829(2), O(1)–S(1) 1.4229(14), O(2)–S(1) 1.4279(14), N(2)–S(1)
1.5823(15), C(7)–N(2) 1.341(2), C(7)–N(1) 1.302(2), C(1)–C(7) 1.481(3);
O(2)S(1)C(8) 104.28(11), O(1)S(1)C(8) 104.83(10), N(2)S(1)C(8) 102.67(9),
O(2)S(1)N(2) 116.50(8), O(1)S(1)N(2) 108.82(8), C(7)N(2)S(1) 123.07(13),
N(1)C(7)N(2) 125.97(17), F(2)C(8)S(1) 110.39(16), F(1)C(8)S(1) 110.66(16),
F(3)C(8)S(1) 111.65(17), N(2)C(7)C(1) 115.53(16).
Scheme 3.

488
L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
Scheme 4.
Scheme 5.
conducted with excess of strong base, DIEA, and the reaction
products include trifluoroacetic acid. Both substances could lead to
polymerization of carbodiimide 6c, which may be the cause of a low
yield of product 7c.
When treated with 4-(diacetoxyiodo)toluene amidines 2a–e
rearrange in higher yields. Typically, a mixture of appropriate
amidine 2, triethylamine, and morpholine in glyme was added to
The data of Scheme 5 demonstrate that the Hofmann-type
rearrangement of compounds 2a–e occurs the more readily, the
stronger electron-donating ability of a substituent on the benzene
ring is. The reaction with amidines 2d,e bearing electron-with-
drawing groups on the ring provides very low yieldsof products 7d,e
mixed with the morpholinium salt of trifluoromethanesulfonamide.
Attempts to isolate the pure product from the mixture either
chromatographically or by crystallization were unsuccessful.
As assumed by analogy with carboxamides [10], formation of
carbodiimides 6a–e proceeds by the following mechanism
(Scheme 6).
a
suspension of 4-(diacetoxyiodo)toluene in glyme at 0 8C
(Scheme 5). The time and temperature required for the reaction
completion were varied according to the substituent on the
benzene ring.
Scheme 6.

L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
489
Scheme 7.
Scheme 8.
Scheme 9.
We propose the initial formation of an intermediate C, that loses
iodotoluene and undergoes aryl group migration from carbon atom
to nitrogen atom to give the carbodiimide 6.
If morpholine is added to the reaction mixture not at the same
time as the amidine but 1–2 h later, the urea 8c is obtained
(Scheme 7):
It is likely that acetic acid released in the reaction is added to the
carbodiimide and the resulting adduct is hydrolyzed giving urea 8c
(conversions of this kind were described previously [11]).
To compare the reactivity of fluorine-containing arenecarbox-
amidines 2 to that of analogous fluorine-free amides and amidines,
we carried out the rearrangement with benzamide 9, N-methyl-
Compound 5 contains the somewhat stronger electron-with-
drawing NSO2C4F9 group (in comparison with the NSO2CF3
group in compound 2c). As a result, amidine 5 undergoes the
Hofmann-type rearrangement (Scheme 9) much more readily;
the reaction is complete within 24 h at room temperature (cf. to
72 h necessary for amidine 2c to rearrange under the same
conditions).
3. Conclusions
The aza analogues of arenecarboxamides containing the
NSO2CF3 and NSO2C4F9 groups instead of the carbonyl oxygen
atom have been synthesized. The conditions which allow
compounds of this kind to undergo an oxidative Hofmann-type
rearrangement have been found. It has been shown that the
reaction substantially depends on the nature of the substituents on
the benzene ring. It is facilitated by electron-donating and
hindered by electron-withdrawing groups. To compare the
reactivity of arenecarboxamides and their various aza analogues,
sulfonylbenzamidine 3, and N-phenylsulfonylbenzamidine
4
under the same conditions (Scheme 8).
It is evident (Scheme 8) that in going from benzamide to its aza
analogues containing the NSO2CH3, NSO2Ph, and NSO2CF3
groups, the reaction time decreases as the electron-withdrawing
ability of the group rises, i.e., the reactivity of the compounds under
study increases in the order 9 < 3 < 4 < 2c.

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L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
the same rearrangement under similar conditions with benza-
mide and benzamidines containing the NSO2CH3 and NSO2Ph
groups have also been realized. As found, the Hofmann-type
rearrangement of compounds PhC( X)NH2 proceeds the more
readily, the stronger the electron-withdrawing ability of the
substituent X is.
4.2.2.2.N-Trifluoromethylsulfonyl-3-trifluoromethylbenzcarboximi-
doyl chloride. b.p. 135 8C/0.03 Torr. m.p. 62–64 8C. 19F NMR
(CHCl3):
d
ꢁ61.7 (s, 3F, CF3), ꢁ78.9 (s, 3F, SO2CF3). Anal. calcd
for C9H4ClF6NO2S: Cl 10.4. Found Cl 10.5.
4.3. General procedure for the synthesis of amidines (2–5)
Through
a solution of the corresponding carboximidoyl
4. Experimental
chloride (13 mmol) in anhydrous ether (50 mL), a slow stream
of anhydrous gaseous ammonia was bubbled at ꢁ15 8C over
20 min. The precipitated ammonium chloride was filtered off, the
filtrate was concentrated to dryness, and the residue was purified
by crystallization (from ether/hexane or ethylacetate/hexane)
affording pure amidines 2–5.
4.1. General
Moisture-sensitive reactions were carried out under dry
argon using flame-dried glassware. All chemicals were of
reagent grade or were purified by standard methods before
use. Solvents were distilled from appropriate drying agents
immediately prior to use. Some reactions were monitored by
thin-layer chromatography (TLC) on precoated silica gel
Kieselgel 60 F/UV254 plates (Merck); spots were visualized with
UV light. Purification of most products was performed by
column chromatography (CC) on Silica gel, 70–230 mesh 60A
(Aldrich). 13C NMR spectra were recorded on a Bruker DRX 500
instrument at 125 MHz, 1H and 19F NMR spectra were recorded
at 299.5 and 282.2 MHz, respectively, with a Varian VXR-300
spectrometer, and chemical shifts are given in ppm relative to
Me4Si and CCl3F, respectively, as internal standards. IR spectra
were recorded with a Vertex 70 (Bruker) instrument (KBr tablets
or solutions in CH2Cl2). Melting points were determined in open
capillaries and are uncorrected. Elemental analysis was per-
formed in the Analytical Laboratory of the Institute of Organic
Chemistry, NAS of Ukraine, Kiev.
The preparations of N-methylsulfonyl benzcarboximidoyl
chloride [12] N-phenylsulfonyl benzcarboximidoyl chloride [13],
N-trifluoromethylsulfonyl arenecarboximidoyl chlorides 1a–c
[6,14], and N-nonafluorobutylsulfonyl-4-fluorobenzcarboximidoyl
chloride [6] were described previously. Compounds 1d,e were
synthesized from the corresponding N-trifluoromethylsulfonyl
benzamides according to the literature procedure [6]. Character-
ization data of these compounds and starting N-trifluoromethyl-
sulfonyl benzamides are listed below.
4.3.1. N-Trifluoromethylsulfonylbenzamidine (2a)
m.p. 125–127 8C (ether/hexane). 1H NMR ([D6]acetone):
d 7.58–
7.77 (3H, m, ArH), 8.07–8.09 (2H, m, ArH), 8.60–9.20 (2H, w s,
NH2); 19F NMR ([D6]acetone):
(125 MHz, [D6]DMSO):
1JCF = 320 Hz); IR (KBr):
d
ꢁ79.1 (s, 3F, SO2CF3); 13C {1H} NMR
d
166.1, 133.4, 131.8, 128.7, 128.3, 119.6 (q,
3444, 3326, 3259 (N–H), 1631 (C N).
n
Anal. calcd for C8H7F3N2O2S: C 38.1, H 2.8, N 11.1. Found C 37.9, H
2.8, N 11.0.
4.3.2. N-Trifluoromethylsulfonyl-4-methoxybenzamidine (2b)
m.p. 125–126 8C (ether/hexane). 1H NMR ([D6]acetone):
d 3.94
(3H, s, OCH3), 7.10–8.11 (4H, dd, ArH), 8.50–8.70 (1H, w s, NH),
9.00–9.20 (1H, w s, NH); 19F NMR ([D6]acetone):
SO2CF3); 13C {1H} NMR (125 MHz, [D6]DMSO):
d
d
ꢁ79.2 (s, 3F,
165.1, 163.6,
130.6, 123.3, 119.7 (q, 1JCF = 325 Hz), 114.1, 55.5; IR (KBr):
n 3429,
3342, 3254 (N–H), 1636 (C N). Anal. calcd for C9H9F3N2O3S: C
38.3, H 3.2, N 9.9. Found C 38.2, H 3.3, N 9.8.
4.3.3. N-Trifluoromethylsulfonyl-4-fluorobenzamidine (2c)
m.p. 103–106 8C (ether/hexane). 1H NMR ([D6]acetone):
d
7.36–
7.42 (2H, m, ArH), 8.15–8.20 (2H, m, ArH), 8.40–9.40 (2H, w s,
NH2); 19F NMR ([D6]acetone):
d
ꢁ79.9 (s, 3F, SO2CF3), ꢁ105.4 (s, 1F,
ArF); 13C {1H} NMR (125 MHz, [D6]DMSO):
d 165.2 (d,
1JCF = 250 Hz), 164.9, 131.2 (d, JCF = 9 Hz), 128.2, 119.6 (q,
3
2
1JCF = 316 Hz), 115.8 (d, JCF = 22 Hz); IR (KBr):
n 3412, 3342,
3272 (N–H), 1663, 1524 (C N). Anal. calcd for C8H6F4N2O2S: C
35.6, H 2.2, N 10.4. Found C 35.5, H 2.3, N 10.3.
4.2. N-Trifluoromethylsulfonyl arenecarboximidoyl chlorides (1d,e)
and the corresponding N-trifluoromethylsulfonyl benzamides
4.3.4. N-Trifluoromethylsulfonyl-4-trifluoromethylbenzamidine (2d)
m.p. 114–115 8C (ether/hexane). 1H NMR ([D6]acetone):
d
7.95–
4.2.1. N-Trifluoromethylsulfonyl-4-
s, NH2); 19F NMR
trifluoromethylbenzcarboximidoyl chloride (1d)
8.29 (4H, dd, ArH), 8.80–9.60 (2H,
w
([D6]acetone):
d
ꢁ62.7 (s, 3F, CF3), ꢁ79.2 (s, 3F, SO2CF3); 13C
4.2.1.1.N-Trifluoromethylsulfonyl-4-trifluoromethylbenzamide. m.p.
{1H} NMR (125 MHz, [D6]DMSO):
d 164.9, 136.3, 132.6 (q,
175–176 8C (from benzene). 1H NMR ([D6]acetone):
d
4.41–5.31
2JCF = 32 Hz), 129.1, 125.5 (q, JCF = 4 Hz), 123.6 (q, JCF = 263 Hz),
119.6 (q, 1JCF = 313 Hz); IR (KBr):
3
1
(1H, w s, NH), 7.96–8.28 (4H, dd, ArH); 19F NMR ([D6]acetone):
d
n 3400, 3337, 3263 (N–H), 1655,
ꢁ63.3 (s, 3F, CF3), ꢁ76.2 (s, 3F, SO2CF3). Anal. calcd for C9H5F6NO3S:
1529 (C N). Anal. calcd for C9H6F6N2O2S: C 33.8, H 1.9, N 8.8.
Found C 33.7, H 1.9, N 8.7.
C 33.7, H 1.6, N 4.4. Found C 33.8, H 1.5, N 4.5.
4.2.1.2.N-Trifluoromethylsulfonyl-4-trifluoromethylbenzcarboximi-
doyl chloride. b.p. 110 8C/0.05 Torr. m.p. 74–75 8C. 19F NMR
4.3.5. N-Trifluoromethylsulfonyl-3-trifluoromethylbenzamidine (2e)
m.p. 93–94 8C (ether/hexane). 1H NMR ([D6]acetone):
d 7.82–
(CHCl3):
d
ꢁ63.9 (s, 3F, CF3), ꢁ78.7 (s, 3F, SO2CF3). Anal. calcd
7.91 (1H, m, ArH), 8.08–8.10 (1H, m, ArH), 8.36–8.39 (2H, m, ArH),
8.80–9.09 (1H, w s, NH), 9.41–9.71 (1H, w s, NH); 19F NMR
for C9H4ClF6NO2S: Cl 10.4. Found Cl 10.5.
([D6]acetone):
NMR (125 MHz, [D6]DMSO):
124.8, 123.6 (q, JCF = 250 Hz), 119.6 (q, JCF = 321 Hz). Anal. calcd
d
ꢁ61.7 (s, 3F, CF3), ꢁ78.5 (s, 3F, SO2CF3); 13C {1H}
4.2.2. N-Trifluoromethylsulfonyl-3-
d 164.4, 133.4, 132.2, 129.9, 129.5,
trifluoromethylbenzcarboximidoyl chloride (1e)
1
1
4.2.2.1.N-Trifluoromethylsulfonyl-3-trifluoromethylbenzamide. m.p.
148–149 8C (from benzene); Ref. [15] 148–149.5 8C. 1H NMR
for C9H6F6N2O2S: C 33.8, H 1.9, N 8.8. Found C 33.7, H 2.0, N 8.8.
([D6]acetone):
8.15–8.18 (1H, m, ArH), 9.17–9.31 (1H, w s, NH); 19F NMR
([D6]acetone):
ꢁ61.4 (s, 3F, CF3), ꢁ77.9 (s, 3F, SO2CF3). Anal. calcd
for C9H5F6NO3S: C 33.7, H 1.6, N 4.4. Found C 33.9, H 1.5, N 4.3.
d 7.63–7.68 (1H, m, ArH), 7.82–8.00 (2H, m, ArH),
4.3.6. N-Methylsulfonylbenzamidine (3)
m.p. 118–120 8C (ethylacetate/hexane); Ref. [16] 122–123 8C.
1H NMR ([D6]acetone):
d
3.02 (3H, s, SO2CH3), 7.51–7.67 (3H, m,
d
ArH), 7.98–8.00 (2H, m, ArH), 8.12–8.36 (2H, w s, NH2); 13C {1H}

L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
491
NMR (125 MHz, [D6]DMSO):
41.4.
d
162.3, 133.4, 132.2, 128.4, 127.8,
4-(diacetoxyiodo)toluene [18] (3 mmol) in glyme at 0 8C over
15 min. The reaction mixture was stirred at the appropriate
temperature during the time necessary for the rearrangement
(Schemes 5 and 8). Column chromatography (eluent hexane/
ethylacetate 2:1 for compounds 7a, 7c–e, 12, 13 and hexane/
ethylacetate 1:1 for compounds 7b, 11, 10) and following
crystallization (from ether/hexane) gave pure products 7a–e,
10–13. For compound 10, repeated column chromatography
(eluent chloroform) before crystallization was applied.
4.3.7. N-Phenylsulfonylbenzamidine (4)
m.p. 148–150 8C (ethylacetate/hexane); Ref. [13] 149–151 8C.
1H NMR ([D6]acetone):
ArH), 8.20–8.60 (2H,
d
w
7.48–7.64 (6H, m, ArH), 7.96–8.04 (4H, m,
s, NH2); 13C {1H} NMR (125 MHz,
[D6]DMSO):
127.8, 126.0.
d 162.7, 142.4, 133.1, 132.4, 132.1, 128.9, 128.4,
4.6.1. 4-[N-Phenyl-N0-trifluoromethylsulfonylamidino]morpholine
4.3.8. N-Nonafluorobutylsulfonyl-4-fluorobenzamidine (5)
m.p. 86–87 8C (ether/hexane). 1H NMR ([D6]acetone):
d
7.37–
(7a)
m.p. 115–116 8C; Ref. [6] 112–114 8C. 1H NMR ([D6]acetone):
d
7.43 (2H, m, ArH), 8.18–8.22 (2H, m, ArH), 8.77–9.02 (1H, w s, NH),
9.22–9.50 (1H, w s, NH); 19F NMR ([D6]acetone):
d
ꢁ80.0 (s, 3F,
3.59 (4H, t, 2CH2), 3.72 (4H, t, 2CH2), 7.21–7.25 (3H, m, ArH), 7.40–
7.45 (2H, m, ArH), 8.87 (1H, s, NH); 19F NMR ([D6]acetone):
d
ꢁ79.1
SO2(CF2)3CF3), ꢁ104.6 (s, 1F, ArF), ꢁ113.1 (s, 2F, SO2(CF2)3CF3),
ꢁ120.0 (s, 2F, SO2(CF2)3CF3), ꢁ125.0 (s, 2F, SO2(CF2)3CF3); 13C {1H}
(s, 3F, SO2CF3); 13C {1H} NMR (125 MHz, [D6]DMSO):
d 154.5, 138.6,
NMR (125 MHz, [D6]DMSO):
d
165.3 (d, 1JCF = 250 Hz), 164.8, 131.3
1
128.9, 124.7, 122.3, 119.6 (q, JCF = 320 Hz), 65.4, 47.3.
3
2
(d, JCF = 9 Hz), 128.1, 115.8 (d, JCF = 22.5 Hz), 120.3–107.8 (m,
C4F9); IR (KBr):
n
3401, 3338, 3261 (N–H), 1659, 1519 (C N). Anal.
4.6.2. 4-[N-(4-Methoxyphenyl)-N0-
calcd for C11H6F10N2O2S: C 31.4, H 1.4, N 6.7. Found C 31.6, H 1.3, N
6.5.
trifluoromethylsulfonylamidino]morpholine (7b)
m.p. 140–142 8C; Ref. [7] 142–144 8C. 1H NMR ([D6]acetone):
d
3.56 (4H, t, 2CH2), 3.68 (4H, t, 2CH2), 3.83 (3H, s, OCH3), 6.96–7.20
(4H, dd, ArH), 8.73 (1H, s, NH); 19F NMR ([D6]acetone):
d
ꢁ79.1 (s,
4.4. Salts of N-trifluoromethylsulfonyl-4-fluorobenzamidine (2c)
3F, SO2CF3); 13C {1H} NMR (125 MHz, [D6]DMSO):
d 156.8, 154.8,
1
4.4.1. Sodium salt of N-trifluoromethylsulfonyl-4-fluorobenzamidine
A solution of amidine 2c (4 mmol) in ether (20 mL) was added
dropwise to a stirred suspension of sodium hydride (4 mmol) in
ether. The reaction mixture was heated under reflux until the
evolution of hydrogen ceased. The ether was evaporated in vacuo
(0.03 Torr) to give 1.28 g (a quantitative yield) of N-trifluoro-
methylsulfonyl-4-fluorobenzamidine sodium salt. 1H NMR
131.1, 124.8, 119.6 (q, JCF = 320 Hz), 114.0, 65.5, 55.1, 47.2.
4.6.3. 4-[N-(4-Trifluoromethylphenyl)-N0-
trifluoromethylsulfonylamidino]morpholine (7d)
It was obtained as a 2:1 mixture with the morpholinium salt of
trifluoromethanesulfonamide.
1H NMR ([D6]acetone):
d 3.69–3.86 (8H, m, 4CH2), 7.42–7.75
([D6]DMSO):
d
7.11–7.17 (2H, m, ArH), 8.01–8.06 (2H, m, ArH);
ꢁ77.6 (s, 3F, SO2CF3), ꢁ112.7 (s, 1F, ArF).
(4H, dd, ArH), 9.10 (1H, s, NH); 19F NMR ([D6]acetone):
d
ꢁ61.6 (s,
19F NMR ([D6]DMSO):
d
3F, CF3), ꢁ79.2 (s, 3F, SO2CF3).
4.4.2. Silver salt of N-trifluoromethylsulfonyl-4-fluorobenzamidine
Amidime 2c (4 mmol), dry silver oxide (2 mmol), and anhy-
drous acetonitrile (50 mL) were heated under reflux for 48 h.
Unchanged silver oxide was filtered off and acetonitrile was
evaporated in vacuo (0.05 Torr) to give 1.48 g (98%) of a grey solid.
4.6.4. 4-[N-(3-Trifluoromethylphenyl)-N0-
trifluoromethylsulfonylamidino]morpholine (7e)
It was obtained as a 1:1 mixture with the morpholinium salt of
trifluoromethanesulfonamide.
1H NMR ([D6]acetone):
d 3.72–3.83 (8H, m, 4CH2), 7.54–7.68
19F NMR (CH3CN):
d
ꢁ78.6 (s, 3F, SO2CF3), ꢁ103.6 (s, 1F, ArF).
(4H, m, ArH), 9.00–9.14 (1H, w s, NH); 19F NMR ([D6]acetone):
d
ꢁ61.5 (s, 3F, CF3), ꢁ78.5 (s, 3F, SO2CF3).
4.5. The aza Hofmann rearrangement of compound (2c) with 4-
4.6.5. Morpholino-4-carbanilide (10)
[bis(trifluoroacetoxy)iodo]toluene
m.p. 156–158 8C; Ref. [19] 161.5–162 8C. 1H NMR ([D6]DMSO):
d
3.43 (4H, t, 2CH2), 3.61 (4H, t, 2CH2), 6.92–6.94 (1H, m, ArH),
A solution of freshly prepared 4-[bis(trifluoroacetoxy)iodo]to-
luene [17] (3 mmol) in anhydrous glyme (10 mL) was added
dropwise to a stirred solution of amidine 2c (2 mmol) and pyridine
(4 mmol) in glyme (10 mL) at 0 8C in 15 min. After 5 min, DIEA
(8 mmol) and morpholine (6 mmol) were added to the reaction
mixture at 0 8C. After stirring for 24 h at room temperature, the
solution was concentrated to dryness in vacuo (10 Torr). Column
chromatography (eluent hexane/ethylacetate 2:1) and following
crystallization (from ether/hexane) gave 0.18 g (27%) of pure 7c.
7.21–7.26 (2H, m, ArH), 7.46 (2H, d, ArH), 8.54 (1H, s, NH).
4.6.6. 4-[N-Phenyl-N0-methylsulfonylamidino]morpholine (11)
m.p. 123–125 8C. 1H NMR ([D6]acetone):
d 2.90 (3H, s, SO2CH3),
3.40 (4H, t, 2CH2), 3.61 (4H, t, 2CH2), 7.14–7.24 (3H, m, ArH), 7.39–
7.44 (2H, m, ArH), 8.52–8.62 (1H, w s, NH); 13C {1H} NMR
(125 MHz, [D6]DMSO):
46.9, 42.4. Anal. calcd for C12H17N3O3S: C 50.9, H 6.1, N 14.8. Found
C 50.9, H 6.0, N 14.9.
d 154.4, 139.5, 129.3, 123.8, 120.4, 65.3,
m.p. 144–146 8C; Ref. [6] 142–144 8C. 1H NMR ([D6]acetone):
3.60 (4H, t, 2CH2), 3.73 (4H, t, 2CH2), 7.14–7.32 (4H, m, ArH), 8.80–
d
4.6.7. 4-[N-Phenyl-N0-phenylsulfonylamidino]morpholine (12)
9.00 (1H, w s, NH); 19F NMR ([D6]acetone):
d
ꢁ79.2 (s, 3F, SO2CF3),
m.p. 109–110 8C. 1H NMR ([D6]acetone):
d
3.37 (4H, t, 2CH2),
3.58 (4H, t, 2CH2), 6.97–7.85 (10H, m, ArH), 8.68 (1H, s, NH); 13C
{1H} NMR (125 MHz, [D6]DMSO):
154.3, 143.7, 139.0, 131.4,
129.1, 128.7, 125.6, 123.8, 120.3, 65.3, 47.0. Anal. calcd for
17H19N3O3S: C 59.1, H 5.5, N 12.2. Found C 59.2, H 5.5, N 12.1.
ꢁ117.2 (s, 1F, ArF); 13C {1H} NMR (125 MHz, [D6]DMSO):
d 159.4
1
3
(d, JCF = 241 Hz), 154.7, 134.8, 125.2 (d, JCF = 7.5 Hz), 119.5 (q,
2
1JCF = 321 Hz), 115.4 (d, JCF = 22.5 Hz), 65.5, 47.3.
d
C
4.6. The aza Hofmann rearrangement of compounds (2–5, 9) with 4-
(diacetoxyiodo)toluene
4.6.8. 4-[N-(4-Fluorophenyl)-N0-
nonafluorobutylsulfonylamidino]morpholine (13)
Light-yellow oil; Ref. [6] m.p. 127–129 8C. 1H NMR ([D6]acet-
A mixture of corresponding amidine 2–5 (2 mmol) or benza-
mide 9 (2 mmol) with triethylamine (6 mmol) and morpholine
(4 mmol) in glyme was added dropwise to a stirred suspension of
one):
d 3.62 (4H, m, 2CH2), 3.73 (4H, m, 2CH2), 7.17–7.33 (4H, m,

492
L.M. Yagupolskii et al. / Journal of Fluorine Chemistry 129 (2008) 486–492
ArH), 8.90 (1H, s, NH); 19F NMR ([D6]acetone):
d
ꢁ80.5 (s, 3F,
(173 parameters; observed/variable ratio 9.61; the largest and
3
˚
SO2(CF2)3CF3), ꢁ112.9 (s, 2F, SO2(CF2)3CF3), ꢁ117.0 (s, 1F, ArF),
minimal peaks in the final difference map 0.25 and ꢁ0.28 e/A ,
ꢁ120.4 (s, 2F, SO2(CF2)3CF3), ꢁ125.4 (s, 2F, SO2(CF2)3CF3); 13C {1H}
weighting scheme is as follows: v
= 1/[s2(Fo2) + (0.0358P)2 +
1
NMR (125 MHz, [D6]DMSO):
d
159.3 (d, JCF = 240 Hz), 154.5,
0.2173P], where P = (Fo2 + 2Fc2)/3). Full crystallographic details
have been deposited at Cambridge Crystallographic Data Centre
(CCDC). Any request to the CCDC for these materials should quote
the full literature citation and reference number CCDC 669739.
3
2
134.8, 125.0 (d, JCF = 9 Hz), 115.5 (d, JCF = 22.5 Hz), 118.0–108.0
(m, C4F9), 65.4, 47.2. Anal. calcd for C15H13F10N3O3S: C 35.7, H 2.6,
N 8.3, S 6.4. Found C 35.9, H 2.5, N 8.2, S 6.4.
4.7. The aza Hofmann rearrangement leading to N-(4-fluorophenyl)-
N0-trifluoromethylsulfonylurea (8c)
4.8.2. Crystal data for 2a
C8H7F3N2O2S, M = 252.22, triclinic, space group P i (N 2),
˚
a = 5.5343(9), b = 9.4529(16), c = 10.3516(17) A,
a = 84.387(2),
3
˚
A mixture of amidine 2c (2 mmol) with triethylamine (6 mmol)
in glyme (10 mL) was added dropwise to a stirred suspension of 4-
(diacetoxyiodo)toluene (3 mmol) in glyme (15 mL) at 0 8C over
15 min. After stirring for 1–2 h at room temperature, morpholine
(4 mmol) was added to the reaction mixture in one portion. The
reaction mixture was stirred for 24 h at room temperature. Column
chromatography (eluent ethylacetate) and following crystalliza-
tion (from ether/hexane) gave pure product 8c. m.p. 136–140; Ref.
b
= 76.624(2)8
g
= 75.366(2),
V = 509.32(15) A ,
= 0.348 mmꢁ1, F(0 0 0) = 256, crystal size ca.
Z = 2,
dc = 1.645 g cmꢁ3
,
m
0.42 mm ꢄ 0.37 mm ꢄ 0.3 mm.
References
[1] M.B. Smith, J. March, March’s Advanced Organic Chemistry: Reactions, Mechan-
isms and Structure, 5th Edition, Wiley-Interscience Publishers, 2001, pp. 1410–
1417.
[2] V.N. Boiko, N.V. Kirii, L.M. Yagupolskii, J. Fluorine Chem. 67 (1994) 119–123.
[3] I. Leito, I. Kaljurand, I.A. Koppel, L.M. Yagupolskii, V.M. Vlasov, J. Org. Chem. 63
(1998) 7868–7874.
[4] P. Burk, I.A. Koppel, I. Koppel, L.M. Yagupolskii, R.W. Taft, J. Comput. Chem. 17
(1996) 30–41.
[5] L.M. Yagupolskii, V.N. Petrik, Yu.L. Slominskii, Tetrahedron Lett. 43 (2002) 3957–
3959.
[7] 136–140 8C. 1H NMR ([D6]DMSO):
d 6.90–7.10 (2H, m, ArH),
7.40–7.60 (2H, m, ArH), 8.92 (1H, s, NH); 19F NMR ([D6]DMSO):
d
ꢁ76.0 (s, 3F, SO2CF3), ꢁ122.7 (s, 1F, ArF); 13C {1H} NMR (125 MHz,
1
[D6]DMSO):
d
157.4, 156.9 (d, JCF = 271 Hz), 137.6, 121.0 (q,
1JCF = 329 Hz), 119.4 (d, JCF = 3.5 Hz), 114.6 (d, JCF = 24 Hz).
3
2
4.8. X-ray crystallography
[6] L.M. Yagupolskii, S.V. Shelyazhenko, I.I. Maletina, V.N. Petrik, E.B. Rusanov, A.N.
Chernega, Eur. J. Org. Chem. (2001) 1225–1233.
[7] L.M. Yagupolskii, S.V. Shelyazhenko, I.I. Maletina, L.V. Sokolenko, A.N. Chernega,
E.B. Rusanov, I.F. Tsymbal, J. Fluorine Chem. 128 (2007) 515–523.
[8] E.S. Wallis, J.F. Lane, in: R. Adams (Ed.), Organic Reactions, vol. 3, J. Wiley and
Sons, New York, 1949, pp. 267–306.
[9] A.C. Myers, J.A. Kowalski, M.A. Lipton, Bioorg. Med. Chem. Lett. 14 (2004) 5219–
5222.
[10] K. Swaminathan, N. Venkatasubramanian, J. Chem. Soc. Perkin Trans. II (1975)
1161–1166.
[11] Ch.A. Ramsden, H.L. Rose, J. Chem. Soc. Perkin Trans. I 16 (1997) 2319–2327.
[12] A. Lawson, R.B. Tinkler, J. Chem. Soc. (C) (1969) 652–655.
[13] G.I. Derkach, G.F. Dregval, A.V. Kirsanov, Zh. Obshch. Khim. 30 (1960) 3402–3407.
Chem. Abstr. 55 (1961) 21029 b.
All crystallographic measurements were performed at room
temperature on a Bruker Smart Apex II diffractometer operating in
the
the least-squares treatment of 2150 reflections in the
2.95–26.748. The intensity data were collected within the range of
v
and
w
scans mode. The cell parameters were obtained from
u
range of
2.95 ꢂ
u
ꢂ 26.008 (ꢁ6 < h < 6, ꢁ11 < k < 11, ꢁ11 < l < 12) using
˚
Mo K
a
radiation (
l
= 0.71078 A). The intensities of 5568 reflec-
tions were collected (1980 unique reflections, Rint = 0.02). Data
were corrected for Lorentz and polarization effects. The SADABS
procedure [20] absorption correction (the ratio of minimum to
maximum apparent transmission is 0.713887) was applied.
[14] L.M. Yagupolskii, V.N. Petrik, N.V. Kondratenko, L. Soova¨li, I. Kaljurand, I. Leito, I.A.
Koppel, J. Chem. Soc. Perkin Trans. 2 11 (2002) 1950–1955.
[15] G.G.I. Moore, A.C. Conway, US Patent 3,705,185 (1972).
[16] R.B. Tinkler, J. Chem. Soc. (B) (1970) 1052.
4.8.1. Structure solution and refinement
[17] I.I. Maletina, V.V. Orda, L.M. Yagupolskii, Zh. Org. Khim. 10(2) (1974) 294–296.
Chem. Abstr. 80 (1974) 120418 r.
[18] K.H. Pausacker, J. Chem. Soc. (1953) 107–109.
[19] R.A. Henry, W.M. Dehn, J. Am. Chem. Soc. 71 (1949) 2297–2300.
[20] G.M. Sheldrick, SADABS: Program for Scaling and Correction of Area Detector
Data, University of Gottingen, Germany, 1996.
[21] G.M. Sheldrick, SHELXS97: Program for the Solution of Crystal Structure, Uni-
versity of Gottingen, Germany, 1997.
The structure was solved by direct methods and refined by the
full-matrix least-squares technique in the anisotropic approxima-
tion for non-hydrogen atoms using the SHELXS97 and SHELXL97
programs [21,22]. Hydrogen atoms were located in the difference
Fourier maps and refined isotropically. In the refinement 1980
reflections (1662 reflections with I ꢃ 2
s(I)) were used. Conver-
gence was obtained at R1 = 0.0347 and wR2 = 0.0815, GOF = 1.047
[22] G.M. Sheldrick, SHELXL97: Program for the Refinement of Crystal Structures,
University of Gottingen, Germany, 1997.