O- and N-Alkylation of N-halosuccinimides in ionic reactions with 1-phenyltricyclo[4.1.0.02,7]heptane

Article abstract of DOI:10.1007/s11172-005-0279-6

N-Bromo and N-chlorosuccinimides add to 1-phenyltricyclo[4.1.0.0 ^2,7]heptane in CH₂Cl₂ with cleavage of the C(1)-C(7) bond to give isomeric 1:1 Markownikoff-type endo, anti-adducts of the norpinane structure in a ～3:7 rati

Full text of DOI:10.1007/s11172-005-0279-6

466
Russian Chemical Bulletin, International Edition, Vol. 54, No. 2, pp. 466—469, February, 2005
Oꢀ and NꢀAlkylation of Nꢀhalosuccinimides in ionic reactions
2
,7
with 1ꢀphenyltricyclo[4.1.0.0 ]heptane
V. A. Vasin,aꢀ A. V. Semenov, and V. V. Razin
a
bꢀ
aN. P. Ogarev Mordovian State University,
6
8 ul. Bol´shevistskaya, 430000 Saransk, Russian Federation.
Fax: +7 (834 2) 24 4796. Eꢀmail: vasin@mrsu.ru
Department of Chemistry, St. Petersburg State University,
b
2
6 Universitetskii prosp., Petrodvorets, 198904 St. Petersburg, Russian Federation.
Fax: +7 (812) 428 6939. Eꢀmail: vvrazin@hotmail.com
NꢀBromoꢀ and Nꢀchlorosuccinimides add to 1ꢀphenyltricyclo[4.1.0.02,7]heptane in CH Cl2
2
with cleavage of the C(1)—C(7) bond to give isomeric 1 : 1 Markownikoffꢀtype endo,antiꢀadducts
of the norpinane structure in a ~3 : 7 ratio corresponding to Nꢀ and Oꢀalkylation of succinimide.
Key words: bicyclo[3.1.1]heptane, Nꢀhalosuccinimides, competitive Nꢀ and Oꢀalkylaꢀ
tion reactions, succinimide anion, norpinane, electrophilic addition, 1ꢀphenyltriꢀ
cyclo[4.1.0.02 ]heptane.
,7
NꢀHalosuccinimides (NCS, NBS, and NIS) are
Scheme 1
1
known to act as electrophilic halogen carriers in ionic
addition to a multiple carbon—carbon bond. It is of note
that the overwhelming majority of cases involve conjuꢀ
gated halogenation of olefins, where an external or inꢀ
ternal nucleophile different from the succinimide anion
acts as a coreagent. Ionic addition of Nꢀhalosuccinꢀ
imides themselves to unsaturated compounds has been
discovered only recently; this occurs with electronꢀrich
R = H (2a), Me (3)
2
olefins like enamines and vinyl ethers. Particular emphaꢀ
The reactions of NBS and NCS with unsubstituted
sis should be placed on exclusive Nꢀalkylation of the inꢀ
termediate ambident succinimide anion in these reacꢀ
tions*.
2
,7
tricyclo[4.1.0.0 ]heptane (4) in an aprotic solvent afꢀ
forded, through cleavage of the C(1)—C(2) bond, the
corresponding adducts 5a,b in low (2—3%) yield, which
may be regarded as the ionic (electrophilic with respect to
Because the πꢀbond of olefins and the C—C bridge in
4
bicyclo[1.1.0]butanes are known to be similar in chemiꢀ
9
halogen) reaction products (Scheme 2).
cal behavior, Nꢀhalosuccinimides could be expected to
effect ionic cleavage of this formally saturated carbocyclic
system. Indeed, many examples of interꢀ and intramoꢀ
lecular conjugated halogenation of various derivatives of
Scheme 2
5
2,7
6—8
bicyclo[1.1.0]butane and tricyclo[4.1.0.0 ]heptane
has been reported to date. In particular, it was shown
6
,8
that in the reaction of 1ꢀphenyltricyclo[4.1.0.02,7]heptane
(
1) with NBS in aqueous acetone or MeOH, its
C(1)—C(7) bond undergoes strictly regioselective (acꢀ
cording to the Markownikoff rule) and highly stereoꢀ
selective cleavage to give norpinane adduct 2 or 3, respecꢀ
tively (Scheme 1).
X = Br (a), Cl (b)
*
Examples of antiꢀMarkownikoff radical addition of Nꢀhaloꢀ
succinimides to unsaturated compounds under special condiꢀ
tions were also documented.3
In the present work, we studied the reactions of NBS
and NCS with 1ꢀphenyltricycloheptane 1 in an aprotic
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 457—460, February, 2005.
066ꢀ5285/05/5402ꢀ0466 © 2005 Springer Science+Business Media, Inc.
1

Nꢀ and OꢀAlkylation of Nꢀhalosuccinimides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
467
1
solvent (CH Cl ) (Scheme 3). In each case, a mixture of
acterized by IR and H and 13C NMR spectra (Tables 1, 2).
Signals in the NMR spectra were assigned by comparing
them with relevant data for model compounds.6 The
configuration of the substituent at the C(7) atom in the
norpinanes is evident from the presence of a triplet signal
2
2
norpinaneꢀtype structural isomers 6a,7a and 6b,7b, reꢀ
spectively, was obtained. These are antiꢀaddition prodꢀ
ucts of Nꢀhalosuccinimide to the C(1)—C(7) bond
with an endoꢀattack of halogen at position 7, both the
Nꢀ and Oꢀnucleophilic centers of succinimide being inꢀ
volved. The ratio of the Oꢀ and Nꢀalkylation products
,8
1
10,11
for the H(7) proton in the H NMR spectrum.
configuration of the substituent at the C(6) atom is deterꢀ
The
(
(
7 : 6) in the reaction mixtures was 2.3 : 1 (a) and 1.8 : 1 (b)
H NMR data).
mined from a highꢀfield signal (δ ~0.6) for one of the
1
H(3) protons as a result of the effect of the endoꢀoriented
phenyl substituent.6
,8,12
The isomeric structures of the
Nꢀ and Oꢀalkylation products are unambiguously discrimiꢀ
Scheme 3
13
nated by the C chemical shifts of the carbon atoms of
the succinimide residue and the C(6) atom. The differꢀ
ence in the IR spectra of the isomers is also worth noting.
As in succinimide, the C=O stretching vibrations in comꢀ
–
1
pounds 6a,b are observed at ~1700 cm , while the reꢀ
spective absorption bands for compounds 7a,b appear at
–
1
1
747 cm
.
The structures of the Oꢀalkylation products 7a,b were
additionally confirmed by their easy hydrolysis in boiling
aqueous THF in the presence of Na CO to the correꢀ
2
3
sponding alcohols 2a,b (Scheme 4). Bromide 2a was idenꢀ
6
tified by comparing it with an authentic sample, while
chloride 2b was obtained by an independent synthesis
from hydrocarbon 1 and NCS in aqueous acetone in the
X = Br (a), Cl (b)
Individual components 6a,b and 7a,b were isolated
presence of Et N (cf. Ref. 8). The spectroscopic characꢀ
3
from the mixtures by fractional crystallization and charꢀ
teristics of compounds 2a,b are given in Tables 1 and 2.
Table 1. Yields, melting points, elemental analysis data, and IR spectra of bicycloheptanes 2a,b, 6a,b, and 7a,b
Compound
Yield
%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
IR,
ν/cm
(
%)
—
1
(
С
H
N
synꢀ7ꢀBromoꢀendoꢀ6ꢀphenylbiꢀ 35а
cyclo[3.1.1]heptanꢀ6ꢀol (2a)
70—71
(ether)b
58.53 5.55
58.44 5.66
—
C H BrO
3211 m.br, 3025 w, 2941 m,
2938 m, 1702 m, 1448 m,
1
3
15
1
037 m, 767 m, 700 s
synꢀ7ꢀChloroꢀendoꢀ6ꢀphenylbiꢀ 31a
cyclo[3.1.1]heptanꢀ6ꢀol (2b)
64—65
(ether)
70.38 6.44
70.11 6.79
—
C13H ClO
3363 m.br, 3025 w, 2954 m,
2939 m, 1450 m, 1072 m,
15
1
024 s, 891 s, 765 s, 702 vs
58.75 5.05 3.97 C H18BrNO2 2948 m, 2865 w, 1708 vs,
Nꢀ(synꢀ7ꢀBromoꢀendoꢀ6ꢀphenylꢀ
bicyclo[3.1.1]heptꢀ6ꢀyl)ꢀ
succinimide (6a)
Nꢀ(synꢀ7ꢀChloroꢀendoꢀ6ꢀphenylꢀ 10
bicyclo[3.1.1]heptꢀ6ꢀyl)ꢀ
succinimide (6b)
8
170—171
(ether—
hexane)
160—161
(ether)
1
7
58.63 5.21 4.02
1689 vs, 1450 m, 1351 s,
1197 s, 1107 m, 746 m, 703 m
67.32 5.72 4.44 C H18ClNO2 2953 m, 2934 w, 1694 vs,
17
67.21 5.97 4.61
1453 w, 1352 m, 1200 m,
1109 w, 909 w, 748 m, 706 m
5
5
ꢀ[(synꢀ7ꢀBromoꢀendoꢀ6ꢀphenylꢀ 43
bicyclo[3.1.1]heptꢀ6ꢀyl)oxy]ꢀ
127—128
58.83 5.12 4.11 C H18BrNO2 2956 w, 2916 w, 2868 w,
17
(CH Cl —
58.63 5.21 4.02
1747 vs, 1560 s, 1554 vs,
1375 s, 1263 s, 1178 m,
775 w, 709 w
2
2
3
2
,4ꢀdihydroꢀ2Hꢀpyrrolꢀ
ꢀone (7a)
pentane)
ꢀ[(synꢀ7ꢀChloroꢀendoꢀ6ꢀphenylꢀ 47
114—115
67.37 5.86 4.56 C H18ClNO2 2958 w, 2939 w, 2869 w,
17
bicyclo[3.1.1]heptꢀ6ꢀyl)oxy]ꢀ
(CH Cl —
67.21 5.97 4.61
1747 vs, 1560 s,
2
2
3
2
,4ꢀdihydroꢀ2Hꢀpyrrolꢀ
ꢀone (7b)
pentane)
1554 vs, 1375 s, 1265 s,
1182 m, 771 w, 709 w
a
b
In the halohydroxylation.
cf. Ref. 8: m.p. 78 °C (hexane).

468
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Vasin et al.
Table 2. H and 13C NMR spectra of bicycloheptanes 2b, 6a,b, and 7a,b
1
Comꢀ
pound
δH (J/Hz)
δC
C H NO C(6) C(7) C(1), C(2), C(3) C arom. C H NO
2
H(7) H(1),
t) H(5)
br.d)
H(2),
H(4)
H(3)
(1 H all)
H arom.
4
4
2
.
4
4
(
[OH]
C(5) C(4)
(
2
6
6
7
7
b
a
b
a
b
5.21 3.00 1.88—2.05 0.57—0.77, 7.25—7.45
[1.76 (s)] 79.4 59.4 49.2 23.1 12.2 125.3 (2 C),
—
(
5.8) (5.8)
(2 Н),
1.15—1.32
(5 Н)
127.8,
128.2 (2 C),
141.9
2
.12—2.27
(
2 Н)
4.76 4.15 2.12—2.31 0.45—0.62, 7.30—7.43 2.42—2.60, 66.9 53.0 44.8 24.6 11.3 127.0 (2 C), 28.3,
(
5.9) (5.9)
(4 Н)
1.19—1.35
(3 Н),
2.60—2.78
127.7,
128.1 (2 C),
139.2
177.0
7
.58—7.63
(
2 Н)
4.58 4.16 2.02—2.32 0.43—0.63, 7.25—7.40 2.42—2.59, 66.4 57.6 44.6 22.6 11.5 127.1 (2 C), 28.3,
(
6.0) (6.0)
(4 Н)
1.17—1.35
(3 H),
2.59—2.77
127.6,
128.1 (2 C),
138.8
177.0
7
.53—7.65
(
2 H)
5.06 3.65 2.07—2.35 0.51—0.72, 7.31—7.44 2.48—2.57, 93.7 52.8 48.0 25.3 11.6 127.7 (2 C), 30.2,
(
5.8) (5.8)
(4 Н)
1.19—1.35
(3 H),
.57—7.68
2.60—2.70
127.8,
128.7 (2 C), 192.6,
135.4 193.6
4.89 3.65 2.00—2.14 0.55—0.74, 7.30—7.43 2.48—2.57, 93.6 57.6 48.0 23.4 11.9 127.1 (2 C), 30.3,
31.1,
7
(
2 H)
(
5.8) (5.8)
(2 Н),
.19—2.36
1.19—1.35
(3 H),
7.59—7.66
(2 H)
2.61—2.69
127.8,
128.6 (2 C), 192.7,
135.1 193.7
31.2,
2
(
2 Н)
Scheme 4
the sake of correctness, it should be noted that several
examples of competitive Nꢀ/Oꢀalkylation in ionic addiꢀ
1
3
14
tion of Nꢀhaloamides of carboxylic and sulfonic acids
to alkenes have been documented. However, for Nꢀ
haloimides of dicarboxylic acids, such a competition was
discovered by us for the first time.
Experimental
X = Br (a), Cl (b)
1H and 13C NMR spectra were recorded on a Bruker ACꢀ300
spectrometer (300.130 and 75.468 MHz, respectively) in CDCl3.
IR spectra were recorded on an InfraLUM FTꢀ02 Fourier specꢀ
As expected, the chemiꢀ, regioꢀ, and stereoselectivity
of the addition of NBS and NCS to hydrocarbon 1 proved
to be similar to those for bromomethoxylation (ꢀhydroxyꢀ
lation) of the same substrate. For this reason, the addition
studied can well be treated in terms of the ionic (electroꢀ
philic with respect to halogen) mechanism adopted for
the above addition reactions and other conjugated haloꢀ
trometer (KBr pellets).
Tricycloheptane 1 6 and NCS 15 were prepared according to
known procedures; NBS ("pure" grade) was crystallized from
dioxane before use.
Reactions of hydrocarbon 1 with NBS and NCS (general
procedure). The corresponding Nꢀhalosuccinimide (10 mmol)
was added in small portions under nitrogen at –10 °C for 15 min
to a stirred solution of hydrocarbon 1 (1.70 g, 10 mmol) in
4
genation reactions of bicyclobutane compounds. Openꢀ
ing of the bicyclobutane system is initiated by an attack of
the halogen atom at position 7 according to the orientatꢀ
ing effect of the phenyl substituent and occurs with inverꢀ
4
0 mL of dry CH Cl . The reaction mixture was stirred at –10 °C
2 2
4
for 30 min and then at 20 °C for 4 h and concentrated. The
sion of the configuration at the site under attack. The
1
13
residue was analyzed by H and C NMR spectroscopy. Indiꢀ
vidual products 6a,b and 7a,b were isolated by fractional crystalꢀ
lization. Their yields, physicochemical constants, elemental
nucleophilic attack of the succinimide anion on the interꢀ
mediate norpinanyl cation is antiꢀstereoselective, which
is characteristic of other external nucleophiles.6 Our case
is interesting since the succinimide anion as an ambident
nucleophile undergoes both Nꢀ and Oꢀalkylation, the latꢀ
ter being dominant approximately in the 1 : 2 ratio. For
,8
1
analysis data, and IR spectra are given in Table 1; their H and
13
C NMR data are presented in Table 2.
Reaction of hydrocarbon 1 with NCS in aqueous acetone.
NꢀChlorosuccinimide (1.34 g, 10 mmol) was added in small

Nꢀ and OꢀAlkylation of Nꢀhalosuccinimides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
469
portions at –10 °C for 10 min to a stirred mixture of hydrocarꢀ
5. V. V. Razin and N. Yu. Zadonskaya, Zh. Org. Khim., 1990,
26, 2342 [J. Org. Chem. USSR, 1990, 26, 2021 (Engl.
Transl.)]; V. V. Razin, N. Yu. Zadonskaya, A. G. Alekseev,
and Yu. A. Makarychev, Zh. Org. Khim., 1992, 28, 972 [Russ.
J. Org. Chem., 1992, 28, 750 (Engl. Transl.)].
6. V. V. Razin, N. Yu. Zadonskaya, and Kh. T. Shamurzaev,
Zh. Org. Khim., 1991, 27, 1253 [J. Org. Chem. USSR, 1991,
27, 1093 (Engl. Transl.)].
7. V. V. Razin, N. Yu. Zadonskaya, and Yu. A. Makarychev,
Zh. Org. Khim., 1990, 26, 674 [J. Org. Chem. USSR, 1990, 26,
578 (Engl. Transl.)]; V. V. Razin and Yu. A. Makarychev,
Zh. Org. Khim., 1992, 28, 2490 [Russ. J. Org. Chem., 1992,
28, 2009 (Engl. Transl.)]; V. V. Razin, R. N. Zolotarev, and
M. E. Yakovlev, Zh. Org. Khim., 1998, 34, 859 [Russ. J. Org.
Chem., 1998, 34, 809 (Engl. Transl.)]; V. A. Vasin, A. V.
Semenov, and V. V. Razin, Zh. Org. Khim., 2002, 38, 845
[Russ. J. Org. Chem., 2002, 38, 803 (Engl. Transl.)].
8. E. Gerstner, R. Kemmer, and M. Christl, Chem. Ber., 1994,
127, 381.
bon 1 (1.70 g, 10 mmol) and Et N (1.04 g, 10 mmol) in water
3
(
20 mL) and acetone (70 mL). The reaction mixture was stirred
at this temperature for 0.5 h and at 20 °C for 3.5 h. Then the
product was extracted with ether (3×50 mL) and the organic
layer was washed with water (3×20 mL) and dried with MgSO4.
The solvent was evaporated and the residue was crystallized to
give chlorohydrin 2b (0.69 g). Its physicochemical constants,
elemental analysis data, and IR spectrum are given in Table 1;
1
13
its H and C NMR data are presented in Table 2.
Hydrolysis of adducts 7a,b (general procedure). Sodium carꢀ
bonate (0.5 g) was added to a solution of compound 7a or 7b
(
1.3 mmol) in 15 mL of aqueous THF (1 : 1). The reaction
mixture was refluxed for 1 h and cooled. The products were
extracted with ether (3×5 mL). The extracts were dried with
MgSO . The solvent was removed and the solid residue was
4
purified by crystallization to give compounds 2a and 2b in 70
and 67% yields, respectively. The physicochemical constants of
6
compound 2a are identical with the literature data.
9
. V. A. Vasin, I. Yu. Bolusheva, S. G. Kostryukov, E. P.
Sanaeva, A. A. Ramzevich, and V. V. Razin, Zh. Org. Khim.,
1996, 32, 698 [Russ. J. Org. Chem., 1996, 32, 668 (Engl.
Transl.)].
This work was financially supported by the Ministry
of Education of the Russian Federation (Grant
E 02ꢀ5.0ꢀ361).
1
1
0. K. B. Wiberg and B. A. Hess, J. Org. Chem., 1966, 31, 2250.
1. V. V. Razin, V. A. Vasin, and I. E. Blinkov, Zh. Org. Khim.,
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Received February 3, 2004;
in revised form October 11, 2004