A study of tautomerism in N,N-dialkyl-4(5)-bromoalkanecarboxamides

Article abstract of DOI:10.1007/s11172-010-0227-8

N,N-Dialkyl-4-bromobutanamides exist in solution in tautomeric equilibrium with N,N-dialkyl-N-(tetrahydrofuran-2-ylidene)ammonium bromides, while related 4,5-dibromopentanamides show no similar interconversions with the corresponding iminium salts. A simi

Full text of DOI:10.1007/s11172-010-0227-8

Russian Chemical Bulletin, International Edition, Vol. 59, No. 6, pp. 1237—1241, June, 2010
1237
A study of tautomerism in N,Nꢀdialkylꢀ4(5)ꢀbromoalkanecarboxamides*
A. V. Lozanova, A. V. Stepanov, and V. V. Veselovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
N,NꢀDialkylꢀ4ꢀbromobutanamides exist in solution in tautomeric equilibrium with
N,NꢀdialkylꢀNꢀ(tetrahydrofuranꢀ2ꢀylidene)ammonium bromides, while related 4,5ꢀdibroꢀ
mopentanamides show no similar interconversions with the corresponding iminium salts.
A similar difference is observed when comparing the chemical behavior of their homologs, viz.,
N,Nꢀdialkylꢀ5ꢀbromopentanamide and N,Nꢀdialkylꢀ5,6ꢀdibromohexanamide
Key words: N,Nꢀdialkylꢀ4(5)ꢀbromoalkanecarboxamides, N,NꢀdialkylꢀNꢀ(tetrahydrofuranꢀ
2ꢀylidene)ammonium bromides, N,NꢀdialkylꢀNꢀ(tetrahydropyranꢀ2ꢀylidene)ammonium bromꢀ
ides, ring—chain tautomerism.
Earlier,1 we have reported on ring—chain tautomerꢀ
ism of a novel type detected by 1H NMR spectroscopy in
solutions of N,Nꢀdialkylꢀ4ꢀhaloꢀ (1) and N,Nꢀdialkylꢀ5ꢀ
haloalkanecarboxamides (2) undergoing reversible inꢀ
terconversions into N,NꢀdialkylꢀNꢀ(tetrahydrofuranꢀ2ꢀ
ylidene)ꢀ (3) and N,NꢀdialkylꢀNꢀ(tetrahydropyranꢀ2ꢀ
ylidene)ammonium halides (4), respectively (Scheme 1).
These systems show predictable thermal effects and are
sensitive to the solvent polarity. The ratios of the tauꢀ
tomers in equilibrium mixtures (X = Br) under different
conditions are given under Scheme 1.
Later,2 we have found that N,NꢀdialkylꢀNꢀ(tetraꢀ
hydrofuranꢀ2ꢀylidene)ammonium bromides 5, which are
related to salts 3, can be obtained by bromination of
N,Nꢀdialkylpentꢀ4ꢀenamides and their derivatives (6)
(Scheme 2). Acyclic bromination products of the type 7,
whose formation is possible under these conditions, were
not detected. Moreover, a 1H NMR study of the behavior
of iminium salts 5 in solutions revealed no signs of their
possible transformations into the corresponding acyclic
isomers 7. Apparently, the observed pattern is due to (1)
a substantial rate difference between an intramolecular
interaction of the bromonium ion with the carbonyl group
and an attack of the bromide anion and (2) the higher
(than for unsubstituted salts 3) energy of activation of the
nucleophilic ring opening in compounds 5 at the secondꢀ
ary carbon atom.
Scheme 1
Scheme 2
Solvent
T/К
1 : 3
Solvent
CDCl
DMSOꢀd6
DMSOꢀd6
T/К
2 : 4
CDCl
CDCl
303
333
~2 : 3
~9 : 1
0 : 1
298 ~97 : 3
298
340
3
3
3
~1 : 1
~6 : 5
DMSOꢀd6 303
* Dedicated to Academician of the Russian Academy of Sciences
I. L. Eremenko on the occasion of his 60th birthday.
Y = H, SPh, SOPh, SO2Ph
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1211—1215, June, 2010.
1066ꢀ5285/10/5906ꢀ1237 © 2010 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
Lozanova et al.
Scheme 4
We found it interesting to attempt an independent synꢀ
thesis of dibromo amide of the type 7 and study its tendenꢀ
cy toward cyclization into the corresponding iminium salt.
It turned out that ( )ꢀNꢀ(4,5ꢀdibromopentanoyl)pyrrolꢀ
idine (7a) can be obtained in a conventional way from
known 4,5ꢀdibromopentanoic acid 8 and is a sufficiently
stable crystalline solid (Scheme 3). However, melting of
dibromide 7a (~50 °C) resulted in its complete transformaꢀ
tion into iminium salt 5a: the 1H NMR spectrum of the melt
is identical with that reported2b for compound 5a. The
~30% conversion of dibromide 7a into salt 5a was achieved
when its solution in CDCl3 was heated at 50 °C for 2 h.
Scheme 3
Scheme 5
In contrast to the aforesaid reaction of unsaturated
dialkylamides 6 with bromine, bromination of their hoꢀ
molog 9 (prepared from unsaturated acid 10) gives a ~3 : 1
mixture of cyclic iminium salt 11 and vicinal dibromide
12 (Scheme 4). This reaction outcome probably results
from an intramolecular attack (a) of the amide O atom on
bromonium cation 13 and a competitive reaction (b) inꢀ
volving the bromide ion. The structure of iminium salt 11
was confirmed by its hydrolysis to known lactone 14, as
well as by elemental analysis and spectroscopic studies.
Like its homologs 5 and in contrast to (tetrahydropyranꢀ
2ꢀylidene)ammonium salts 4, salt 11 in solutions underꢀ
goes no transformation into the corresponding acyclic tauꢀ
tomer 12 (1H NMR data). We also found that even proꢀ
longed heating of a solution of dibromide 12 (MeCN,
81—82 °C, 6 h) does not produce, in contrast to dibromo
amide 7a, appreciable amounts of the corresponding imiꢀ
nium bromide 11 (1H NMR data).
Compounds 17 were isolated in the individual state
using selective extraction and crystallization. The strucꢀ
tures of these products and a mixture of diastereomers 18
were confirmed by physicochemical and elemental analyꢀ
ses. In particular, the relative configurations of the subꢀ
stituents in stereoisomers 17 were determined by comparꢀ
ing the experimental coupling constants of the protons in
the 1H NMR spectrum with the calculated ones. The
calculations were performed with the MestrJ program
(www.mestrec.com); the thermodynamically preferable
conformations of stereoisomers 17 were found using the
Gaussian program.3 Characteristic were the coupling conꢀ
stants of the HC(3) and HC(6) protons, for which the
experimental and calculated J values are in satisfactory
Similar results were obtained in bromination of unsaturatꢀ
ed phenylsulfonyl derivative 15 prepared by alkylation of
known sulfonyl amide 16 with 4ꢀbromobutene (Scheme 5).
Workup of the reaction mixture gave isomeric iminium
salts 17a and 17b in a total yield of 60% (17a/17b = ~1.7 : 1)
and a ~1 : 1* mixture of diastereomeric dibromides 18.
* The plausible ratio of diastereomers 18 in the mixture, which
1
cannot be separated by chromatography. In the H NMR specꢀ
trum of the mixture, the signals for the identical protons of the
isomers overlap completely.

Tautomerism in 4(5)ꢀbromoalkanamides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1239
collisional activation). The interface capillary temperature was
213 °C, the main nitrogen flow was 19.4 conventional units, and
the auxiliary nitrogen flow was 0.4 conventional units. The obꢀ
servation time of activation in MS/MS spectra was 30 ms. The
activation energy was taken to be 40% of the relative maximum
collision energy. Column chromatography was carried out on
Silica gel 60 (0.04—0.06 mm, Fluka); Rf values were measured
on Silufol plates. Solvents, including light petroleum (b.p.
40—70 °C), were purified and dried according to standard
procedures. Pyrrolidine, N,Nꢀdiisopropylamine, hexꢀ5ꢀenoic
acid, and thionyl chloride were the Acros Organics chemicals.
agreement (Table 1). Based on the data obtained, we asꢀ
signed the 3R*,6S*ꢀ and 3R*,6R*ꢀconfigurations to isoꢀ
mers 17a and 17b, respectively. Interestingly, in contrast
to iminium salt 11 containing no phenylsulfonyl substituꢀ
ent, compounds 17 in solution undergo irreversible ring
opening leading to the corresponding linear dibromides
18. In this respect, major isomer 17a is much more stable
(halfꢀconversion time ~20 days, CDCl3, 20 °C, 1H NMR),
while minor isomer 17b is transformed into compound 18
virtually completely within ~12 h (CDCl3, 20 °C,
1H NMR). This difference in chemical behavior between
isomers 17 provides indirect evidence for their structural
features, namely, the pseudoꢀequatorial arrangement of
both substituents (at the C(3) and C(6) atoms) in the
thermodynamically preferable conformation of the more
stable isomer 17a. In the less stable isomer 17b, one subꢀ
stituent (SO2Ph) is in the pseudoaxial position.
(
)ꢀ4,5ꢀDibromopentanoic acid (8),4 N,Nꢀdiisopropylꢀ2ꢀpheꢀ
nylsulfonylacetamide (16),2b and 4ꢀbromobutene5 were prepared
according to known procedures.
(
)ꢀNꢀ(4,5ꢀDibromopentanoyl)pyrrolidine (7a). A stirred
mixture of acid 8 (2.07 g, 8 mmol), SOCl2 (9.1 g, 76.5 mmol),
and DMF (0.3 mL) was heated at 50 °C (Ar) for 3 h and concenꢀ
trated in vacuo to give 4,5ꢀdibromopentanoyl chloride with the
following 1H NMR spectrum (200.13 MHz), δ: 2.08 (dddd, 1 H,
HC(3), J = 5.6 Hz, J = 8.1 Hz, J = 10.0 Hz, J = 15.2 Hz); 2.66
(dddd, 1 H, H´C(3), J = 2.9 Hz, J= 6.9 Hz, J = 9.9 Hz, J = 15.2 Hz);
3.19 (m, 2 H, HC(2)); 3.61 (dd, 1 H, HC(5), J = 10.0 Hz,
J = 10.1 Hz); 3.89 (dd, 1 H, H´C(5), J = 4.1 Hz, J = 10.1 Hz);
4.20 (dddd, 1 H, HC(4), J = 2.9 Hz, J = 4.1 Hz, J = 10.0 Hz,
J = 10.0 Hz). This crude acid chloride was dissolved in CH2Cl2
(15 mL); a solution of pyrrolidine (1.14 g, 16 mmol) in CH2Cl2
(7 mL) was added with stirring at –10 °C (Ar) for 10 min. The
reaction mixture was stirred at –10 °C for 1 h and concentrated
in vacuo. The product was extracted with MeOBut and the exꢀ
tract was concentrated in vacuo. The resulting crude amide 7a
(1.9 g, 76%) was subjected to lowꢀtemperature (–20 °C) crystalꢀ
lization from light petroleum to give amide 7a as colorless
crystals, m.p. 45—49 °C*. Found (%): C, 34.38; H, 4.82;
Br, 51.16; N, 4.41. C9H15Br2NO. Calculated (%): C, 34.53;
H, 4.83; Br, 51.05; N, 4.47. IR (KBr, ν/cm–1): 644, 784, 872,
916, 988, 1036, 1164, 1192, 1224, 1256, 1340, 1364, 1444,
1632, 2868—3028. 1H NMR (200.13 MHz), δ: 1.80—2.14
(m, 5 H, HC(3), 2 CH2); 2.42—2.74 (m, 3 H, H´C(3), 2 HC(2));
3.47 (m, 4 H, HCN); 3.65 (dd, 1 H, HC(5), J = 9.0 Hz, J =
= 10.4 Hz); 3.86 (dd, 1 H, H´C(5), J = 4.5 Hz, J = 10.4 Hz);
4.33 (dddd, 1 H, HC(4), J = 2.5 Hz, J = 4.5 Hz, J = 9.9 Hz,
J = 9.9 Hz).
N,NꢀDimethylhexꢀ5ꢀenamide (9). Thionyl chloride (11.9 g,
100 mmol) was added with stirring at 60 °C for 40 min to acid 10
(6.84 g, 60 mmol) and DMF (60 mg). The reaction mixture was
stirred at 80—100 °C (Ar) for 5 h and concentrated in vacuo. The
residue was distilled to give the corresponding acid chloride
(6.92 g) with b.p. 53—55 °C (30 Torr), which was dissolved in
THF (15 mL). The resulting solution was added at –10 °C (Ar)
to a stirred solution of dimethylamine (6.75 g, 150.0 mmol) in
THF (70 mL). The reaction mixture was stirred at 0 °C for 1 h,
kept at 20 °C for an additional 15 h, and treated with water
(30 mL). The organic layer was separated, washed with water
and brine, dried over Na2SO4, and concentrated in vacuo. The
residue was distilled to give amide 9 (6.77 g, 92%) with b.p.
53—55 °C (1.0 Torr). 1H NMR (200.13 MHz), δ: 1.71 (m, 2 H,
H2C(3)); 2.08 (m, 2 H, H2C(4)); 2.26 (m, 2 H, H2C(2)); 2.91
and 2.97 (both s, 3 H each, 2 Me); 4.89—5.06 (m, 2 H, H2C(6));
Thus, our study revealed a dramatic influence of
the position of the halogen atom in N,Nꢀdialkylbromoꢀ
alkanamides on their tendency toward ring—chain tautoꢀ
merism.
Experimental
Melting points were measured on a Kofler hot stage. IR
spectra were recorded on a Specord Mꢀ80 instrument. 1H and
13C NMR spectra were recorded on Bruker ACꢀ200, Bruker
AMꢀ300, and Bruker Avance 600 spectrometers at 298 K with
reference to the solvent signals (δ 7.27 and 77.0 (CDCl3) and
δ 1.94 and 1.24 (CD3CN), respectively). Mass spectra (EI, 70 eV)
were measured on a Finnigan MAT ITDꢀ700 instrument; an
ESI mass spectrum was recorded on a Finnigan MAT LCQ specꢀ
trometer (capillary potential 4530 V). A solution of a sample in
methanol was infused through a syringe into the ionization chamꢀ
ber at a rate of 10 μL min–1; mass spectra (MS) (scan range from
m/z 100 to m/z 2000) and tandem mass spectra (MS/MS) were
recorded in the positive ion mode (helium was used as a gas for
Table 1. Experimental and calculated coupling constants
of selected protons in stereoisomers 17
Comꢀ
pound
Assignment
δ
Jexp
Jcalc
Hz
17a
17b
HС(3)
HС(6)
HС(3)
HС(6)
5.33
5.10
5.8
2.4, 9.6
3.0, 11.3
5.0, 7.0
2.5, 12.0
2.2, 7.8
2.2, 10.3
3.8, 5.2
2.7, 11.6
1
* The H NMR spectrum of the melt is virtually identical with
5.00
that of iminium salt 5a.2b

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
Lozanova et al.
5.77 (dddd, 1 H, HC(5), J = 6.9 Hz, J = 6.9 Hz, J = 10.1 Hz,
J = 16.8 Hz) (cf. Ref. 6).
was added in portions at 10 °C (Ar) for 5 min to a stirred solution
of N,Nꢀdiisopropylꢀ2ꢀphenylsulfonylacetamide (16) (849 mg,
3.0 mmol) in DMF (4 mL). After 30 min, 4ꢀbromobutene
(446 mg, 3.3 mmol) was added. The reaction mixture was warmed
to 20 °C, kept at this temperature for 15 h, and decomposed with
water (15 mL). The organic material was extracted with ButOMe.
The organic layer was separated, washed with water and brine,
dried with Na2SO4, and concentrated in vacuo. The residue was
chromatographed on SiO2. Gradient elution with light petroꢀ
leum—ButOMe from 2 : 1 to 1 : 1 gave amide 15 (0.8 g, 80%)
as colorless crystals, m.p. 66—68 °C (from light petroleum).
Found (%): C, 64.43; H, 7.97; N, 4.20; S, 9.53. C18H27NO3S.
Calculated (%): C, 64.06; H, 8.06; N, 4.15; S, 9.50. IR (KBr,
ν/cm–1): 528, 568, 688, 712, 760, 848, 920, 1040, 1080, 1136,
1184, 1208, 1300, 1368, 1448, 1480, 1584, 1640, 2960—3032.
MS, m/z (Irel (%)): 337 [M]+ (4), 322 (9), 280 (2), 273 (3),
254 (2), 241 (2), 232 (17), 230 (8), 219 (2), 213 (2), 197 (16),
196 (69), 169 (5), 154 (17), 144 (44), 143 (66), 142 (70), 141 (34),
128 (15), 125 (46), 118 (12), 111 (21), 100 (54), 95 (58), 85 (100),
76 (50), 69 (74), 55 (55). 1H NMR (200.13 MHz), δ: 1.17, 1.33
and 1.42 (all d, 3 H each, 3 Me, J = 6.8 Hz); 1.42 (d, 3 H, Me,
J = 6.5 Hz); 1.83—2.16 (m, 4 H, 2 CH2); 3.46 (quint, 1 H,
HC(Me)2, J = 6.8 Hz); 4.25—4.40 (m, 2 H, HC(Me)2, HCS);
4.98 and 5.03 (both m, 1 H each, H2C=); 5.70 (m, 1 H, HC=);
7.47—7.85 (m, 5 H, Harom).
(3R*,6S*)ꢀ and (3R*,6R*)ꢀNꢀ(6ꢀBromomethylꢀ3ꢀphenylsulꢀ
fonyltetrahydropyranꢀ2ꢀylidene)ꢀN,Nꢀdiisopropylammonium broꢀ
mides (17a,b) and N,Nꢀdiisopropylꢀ5,6ꢀdibromoꢀ2ꢀphenylsulfoꢀ
nylhexanamides (18). A solution of Br2 (0.48 g, 3.0 mmol) in
CHCl3 (60 mL) was added at –10 °C (Ar) for 30 min to a stirred
solution of amide 15 (1.01 g, 3.0 mmol) in CHCl3 (50 mL). The
reaction mixture was kept at this temperature for 30 min and
concentrated in vacuo at 20 °C. The organic material was exꢀ
tracted from the residue (1.49 g) with Et2O (3×15 mL) and dried
in vacuo (2 Torr) to give a ~1.7 : 1 mixture of isomers 17a/17b
(0.9 g, 60%) (1H NMR) as a yellow powder. Isomer 17a was
isolated by extraction with chloroform followed by precipitation
with Et2O (20 → –20 °C). The purity of compound 17a was
~90% (1H NMR). Crystallization of this product and the chloroꢀ
formꢀinsoluble residue containing the minor component gave
analytically pure isomers 17a and 17b.
(
)ꢀNꢀ(6ꢀBromomethyltetrahydropyranꢀ2ꢀylidene)ꢀN,Nꢀ
dimethylammonium bromide (11) and ( )ꢀN,Nꢀdimethylꢀ5,6ꢀdiꢀ
bromohexanamide (12). A solution of Br2 (1.39 g, 8.7 mmol) in
CHCl3 (25 mL) was added at 0 °C (Ar) for 1 h to a stirred
solution of amide 9 (1.23 g, 8.7 mmol) in CHCl3 (25 mL). The
reaction mixture was kept at this temperature for 20 min and
concentrated in vacuo. The residue was triturated with Et2O
(4×10 mL) until a homogeneous powdery product was formed,
while decanting the ethereal solution. The product was crystalꢀ
lized from MeCN—Et2O to give light yellow salt 11 (2.02 g,
77%), m.p. 85—89 °C (in a sealed capillary). Found (%): C, 31.31;
H, 5.05; Br, 52.81; N, 4.70. C8H15Br2NO. Calculated (%):
C, 31.92; H, 5.02; Br, 53.09; N, 4.65. IR (CHCl3, ν/cm–1): 656,
824, 924, 960, 1032, 1080, 1242, 1304, 1336, 1400, 1416, 1424,
1432, 1460, 1656, 2448, 2752, 2936, 3368. MS, m/z (Irel (%);
scan range from m/z 60 to m/z 500): 303.9 (20), 302.0 (30),
299.9 (15), 223.1 (10), 222.1 (100), 221.1 (10), 220.1 (90),
140.0 (15). MS/MS (m/z 302; the activation energy was 50% of
the relative maximum collision energy): 222.0 (25), 221.0 (5),
220.0 (85), 219.3 (5), 141.0 (10), 140.1 (100), 138.2.9 (5). MS/MS
(m/z 221; the activation energy was 30% of the relative maxiꢀ
mum collision energy): 222.1 (15), 220.1 (20), 140.1 (100).
1H NMR (200.13 MHz), δ: 1.82—2.21 (m, 4 H, H2C(4),
H2C(5)); 2.94 (m, 2 H, H2C(3)); 3.29 and 3.41 (both s, 3 H each,
2 Me); 3.69 (m, 2 H, H2CBr); 5.06 (m, 1 H, HC(6)).
The combined ethereal supernatants were concentrated
in vacuo and the residue was chromatographed on SiO2 with
light petroleum—MeOBut (1 : 3) as an eluent. The yield of diꢀ
bromo amide 12 was 0.60 g (23%), colorless oil, Rf 0.32 (light
petroleum—MeOBut, 1 : 4). Found (%): C, 31.70; H, 5.10;
Br, 52.99; N, 4.95. C8H15Br2NO. Calculated (%): C, 31.92; H,
5.02; Br, 53.09; N, 4.65. IR (thin film, ν/cm–1): 568, 612, 648,
752, 804, 872, 936, 1056, 1148, 1232, 1264, 1336, 1400, 1480,
1496, 1552, 1644, 1692, 1728, 2936, 3176. MS, m/z (Irel (%)):
300 [M – 1]+ (2), 223 (11), 222 (74), 221 (5), 220 (75), 175 (5),
164 (2), 149 (19), 147 (18), 141 (26), 140 (89), 133 (4), 121 (13),
114 (24), 107 (8), 100 (21), 98 (20), 94 (19), 86 (69), 73 (22),
1
72 (100), 69 (28), 67 (47), 55 (73). H NMR (200.13 MHz), δ:
1.65—2.41 (m, 6 H, 3 H2C); 2.91 and 2.98 (both s, 3 H each,
2 Me); 3.62 (dd, 1 H, HC(6), J = 9.4 Hz, J = 10.3 Hz); 3.82 (dd,
1 H, H´C(6), J = 4.5 Hz, J = 10.3 Hz); 4.16 (dddd, 1 H, HC(5),
J = 3.4 Hz, J = 4.5 Hz, J = 8.2 Hz, J = 9.3 Hz). 13C NMR
(50.03 MHz), δ: 22.4, 32.3, 35.7 and 36.3 (4 CH2); 35.4 and 37.2
(2 Me); 52.6 (HCBr); 172.1 (C=O).
Bromide 17a: colorless crystals, m.p. 145—151 °C (decomp.).
Found (%): C, 43.73; H, 5.29; Br, 32.35; N, 2.75; S, 6.49.
C18H27Br2NO3S. Calculated (%): C, 43.47; H, 5.47; Br, 32.14;
N, 2.82; S, 6.45. IR (KBr, ν/cm–1): 648, 688, 720, 760, 800, 856,
896, 940, 1040, 1068, 1088, 1104, 1120, 1152, 1224, 1288, 1296,
1312, 1328, 1340, 1376, 1392, 1412, 1448, 1520, 1568, 1616,
2936—3800. MS, m/z (Irel (%); scan range from m/z 100 to
m/z 510): 498.9 (10), 497.9 (50), 495.9 (100), 495.1 (20), 493.9
(50), 456.0 (15), 454.0 (30), 452.0 (15), 418.2 (40), 416.0 (35),
374.2 (5), 313.1 (15), 276.3 (25), 274.0 (20); MS/MS (m/z 496;
the activation energy was 30% of the relative maximum collision
energy): 455.8 (55), 453.8 (100), 451.8 (50), 373.9 (5), 355.9 (5),
353.9 (15), 314.8 (10), 312.8 (20), 290.0 (15), 276.0 (35),
(
)ꢀ6ꢀBromomethyltetrahydropyranꢀ2ꢀone (14). A solution
of salt 11 (0.9 g, 3 mmol) and NaOAc•3H2O (0.45 g, 3.3 mmol)
in a mixture of MeCN (8 mL) and water (0.7 mL) was stirred at
20 °C for 5 h and concentrated in vacuo. The product was extracꢀ
ted from the residue with MeOBut. The extract was washed with
water and brine, dried with Na2SO4, and concentrated in vacuo.
The residue was chromatographed on SiO2 with light petroꢀ
leum—MeOBut (1 : 3) as an eluent. The yield of lactone 14 was
0.49 g (85%), colorless oil, Rf 0.43 (light petroleum—MeOBut,
1 : 4). 1H NMR (200.13 MHz), δ: 1.90 (m, 4 H, 2 H2C); 2.53
(m, 2 H, H2C); 3.58 (dd, 1 H, HCBr, J = 4.9 Hz, J = 9.8 Hz); 3.58
(dd, 1 H, H´CBr, J = 3.7 Hz, J = 9.8 Hz); 4.51 (dddd, 1 H,
HC(6), J = 3.5 Hz, J = 4.7 Hz, J = 5.8 Hz, J = 10.3 Hz) (cf. Ref. 7).
1
274.0 (40). H NMR (600.13 MHz, CD3CN), δ: 1.39 and 1.48
(both d, 3 H each, 2 Me, J = 6.5 Hz); 1.53 and 1.58 (both d, 3 H
each, 2 Me, J = 6.8 Hz); 1.87 (dddd, 1 H, HaxC(5), J = 8.0 Hz,
J = 10.4 Hz, J = 11.25 Hz, J = 14.4 Hz); 2.26 (dddd, 1 H,
HeqC(5), J = 2.5 Hz, J = 3.0 Hz, J = 10.3 Hz, J = 14.4 Hz); 2.29
(dddd, 1 H, HaxC(4), J = 2.5 Hz, J = 9.6 Hz, J = 11.3 Hz,
J = 15.2 Hz); 2.40 (dddd, 1 H, HeqC(4), J = 2.4 Hz, J = 8.0 Hz,
(
)ꢀN,NꢀDiisopropylꢀ2ꢀphenylsulfonylhexꢀ5ꢀenamide (15).
A ~55% suspension (142 mg) of NaH (~3.3 mmol) in mineral oil

Tautomerism in 4(5)ꢀbromoalkanamides
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 6, June, 2010
1241
J = 10.3 Hz, J = 15.2 Hz); 3.70 (dd, 1 H, HCBr, J = 7.2 Hz,
J = 12.2 Hz); 3.85 (dd, 1 H, H´CBr, J = 3.0 Hz, J = 12.2 Hz);
4.22 (sept, 1 H, HCN, J = 6.8 Hz); 4.61 (sept, 1 H, HC´N,
J = 6.5 Hz); 5.10 (dddd, 1 H, HC(6), J = 3.0 Hz, J = 3.0 Hz,
J = 7.2 Hz, J = 11.3 Hz); 5.36 (dd, 1 H, HC(3), J = 2.4 Hz,
3 H each, 2 Me, J = 6.8 Hz); 1.29 and 1.30 (both d, 3 H each,
2 Me, J = 6.4 Hz); 1.41 (d, 3 H, Me, J = 6.7 Hz); 1.56—2.41
(m, 4 H, 2 CH2); 3.50 (m, 2 H, HC(Me)2, HC(6)); 3.81 (m, 1 H,
H´C(6)); 4.04 (m, 1 H, HC(5)); 4.33 (m, 2 H, H´C(Me)2, HCS);
7.51—7.85 (m, 5 H, Harom). 13C NMR (50.03 MHz, CDCl3), δ:
20.0, 20.1, 20.3, and 21.2 (4 Me); 26.1, 26.9, 32.8, 33.4, 35.5,
and 35.9 (3 CH2); 46.9, 50.0, 50.5, and 51.4 (3 CH); 65.9, 66.4
(HCS); 172.1 (C=O).
J = 9.6 Hz); 7.51 (t, 1 H, J = 7.5 Hz); 7.78 (dd, 2 H, HCarom
,
J = 7.5 Hz, J = 7.8 Hz); 8.04 (d, 1 H, HCarom, J = 7.8 Hz).
13C NMR (150.03 MHz, CD3CN), δ: 19.6, 20.3 20.2, 20.8
(4 Me); 20.9 (C(4)), 25.0 (C(5)), 33.3 (C—Br); 54.7 (HCN) 58.6
(HC´N); 60.0 (HCS); 86.3 (C(6)); 130.5, 131.4, 132.1, 137.2
(C—Ar); 166.3 (C=N).
References
Bromide 17b: light yellow crystals, m.p. 95—107 °C (deꢀ
comp.). Found (%): C, 43.69; H, 5.13; Br, 32.51; N, 2.75; S, 6.55.
C18H27Br2NO3S. Calculated (%): C, 43.47; H, 5.47; Br, 32.14;
N, 2.82; S, 6.45. IR (KBr, ν/cm–1): 456, 512, 584, 648, 696,
720, 768, 792, 856, 896, 952, 1048, 1080, 1104, 1128, 1152,
1256, 1284, 1300, 1312, 1380, 1400, 1420, 1448, 1544, 1612,
2864—3800. MS, m/z (Irel (%); scan range from m/z 100 to
m/z 2000): 498.1 (15), 496.1 (30), 494.1 (20), 454.1 (10), 419.3
(20), 418.2 (100), 417.0 (20), 416.2 (90), 376.2 (15), 336.3 (20),
313.1 (10), 277.2 (10), 276.0 (20); MS/MS (m/z 496; the activaꢀ
tion energy was 30% of the relative maximum collision energy):
377.6 (5), 371.9 (10), 356.0 (15), 353.9 (35), 352.0 (15), 314.9
(15), 312.8 (40), 289.9 (25), 276.0 (90), 275.0 (20), 274.0 (100),
250.0 (15), 232.1 (10), 223.7 (5), 178.9 (5), 142.9 (5); MS/MS
(m/z 418; the activation energy was 30% of the relative maxiꢀ
mum collision energy): 419.1 (5), 417.9 (15), 416.0 (10), 377.9 (5),
376.9 (15), 375.9 (95), 373.9 (100), 333.9 (5), 295.0 (5), 294.0 (25),
292.0 (35), 291.0 (30), 276.9 (70), 275.9 (40), 274.9 (70),
274.2 (40), 249.8 (8), 234.0 (45), 232.0 (45), 197.1 (5), 196.1
(40), 152.0 (5). 1H NMR (600.13 MHz, CDCl3), δ: 1.57 and
1.58 (both d, 3 H each, 2 Me, J = 6.5 Hz); 1.75 and 1.77 (both d,
3 H each, 2 Me, J = 6.8 Hz); 2.10—2.20 (m, 3 H, HC(4),
H2C(5)); 2.70—2.80 (m, 1 H, H´C(4)); 3.57 (dd, 1 H, HCBr,
J = 7.3 Hz, J = 12.1 Hz); 3.82 (td, 1 H, H´CBr, J = 2.5 Hz,
J = 12.1 Hz); 4.15 (m, 1 H, HCN); 5.2 (m, 1 H, HC´N); 5.3
(m, 1 H, HC(6), J = 2.5 Hz, J = 12.0 Hz); 6.9 (dd, 1 H, HC(3),
J = 5.0 Hz, J = 7.0 Hz); 7.7 (t, 1 H, HCarom, J = 7.7 Hz); 7.8
(t, 1 H, HCarom, J = 7.5 Hz); 8.1 (d, 1 H, HCarom, J = 7.9 Hz).
13C NMR (150.03 MHz, CDCl3), δ: 19.8, 20.0, 20.1 and 21.5
(4 Me); 21.8 (C(4)), 26.0 (C(5)), 35.8 (C—Br); 53.4 (HCN) 58.2
(HCN); 59.3 (HCS); 84.2 (C(6)); 128.6 (C—Ar); 129.8(C—Ar);
134.2(C—Ar); 136.1(C—Ar); 166.9 (C=N).
Concentration of the above ethereal supernatant in vacuo
gave a mixture of diastereomers 18 (0.59 g, 40%) as colorꢀ
less crystals, m.p. 108—110 °C (light petroleum—MeOBut).
Found (%): C, 43.67; H, 5.52; Br, 31.77; N, 2.81; S, 6.38.
C18H27Br2NO3S. Calculated (%): C, 43.47; H, 5.47; Br, 32.14;
N, 2.82; S, 6.45. IR (KBr, ν/cm–1): 480, 536, 568, 688, 720, 756,
800, 824, 872, 920, 1044, 1088, 1132, 1212, 1272, 1280, 1300,
1336, 1368, 1448, 1512, 1644, 2968—3800. MS, m/z (Irel (%)):
497 [M]+ (2), 484 (7), 483 (5), 482 (18), 481 (11), 454 (2),
440 (5), 433 (11), 418 (22), 415 (12), 390 (4), 377 (5), 376 (26),
374 (19), 358 (67), 356 (89), 354 (44), 338 (9), 323 (13), 316 (14),
294 (5), 276 (12), 274 (16), 254 (6), 241 (13), 234 (15), 232 (39),
197 (37), 196 (75), 185 (20), 175 (23), 167 (18), 154 (23), 153 (61),
151 (25), 143 (89), 142 (91), 141 (62), 128 (54), 125 (62), 119 (58),
110 (46), 100 (82), 94 (74), 85 (100), 76 (75), 70 (60), 67 (75),
57 (61). 1H NMR (600.13 MHz, CDCl3), δ: 1.20 and 1.41 (both d,
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Received October 15, 2009;
in revised form March 1, 2010