The synthesis of novel oxa-azamacrocycles

Article abstract of DOI:10.1055/s-1999-6066

Novel protected oxa-azamacrocycles 6a-f, 7a,c-f have been prepared by direct alkylation reaction between α,ω-bis[(2- mesitylsulfonyl)aminooxy]alkanes 2a-c and α,ω-bis(tosyl)alkanediols 3a,b in the presence of K₂CO₃ to give a mixture of the 1:1 (small macrocycles 6a- f) and 2:2 (large macrocycles 7a,c-f) adducts. Another method involved the reaction between bis (sulfonyl)amides 2a,b and ω-bromoalkanols 4a,b to give bis-alkanols 5a,b which were subsequently condensed with 2a,b under Mitsunobu conditions to give solely large macrocycles 7a,d in high yields. Macrocycle 7d was deprotected with HBr/HOAc to yield 8 as the tetrahydrobromide salt which was converted into its free base with methanolic KOH.

Full text of DOI:10.1055/s-1999-6066

1034
PAPER
The Synthesis of Novel Oxa-Azamacrocycles
Vladimir Kuksa, Colin Marshall, Solange Wardell, Paul Kong Thoo Lin*
School of Applied Sciences, The Robert Gordon University, St. Andrew Street, Aberdeen AB25 1HG, UK
E-mail: p.kong@rgu.ac.uk
Received 17 November 1998; revised 12 January 1999
Dedicated to the 75th birthday of Dr D.M. Brown, ScD, FRS
7a,c–f (2:2 adducts) [MH]+ with fragmentation ions at
[MH–Mts]+, [MH–2Mts]+, [MH–3Mts]+ and [MH–
4Mts]+. After evaporation of the filtrate the residue was
crystallised from a small volume of MeCN to give the
Abstract: Novel protected oxa-azamacrocycles 6a–f, 7a,c–f have
been prepared by direct alkylation reaction between a,w-bis[(2-
mesitylsulfonyl)aminooxy]alkanes 2a–c and a,w-bis(tosyl)al-
kanediols 3a,b in the presence of K2CO3 to give a mixture of the 1:1
(small macrocycles 6a–f) and 2:2 (large macrocycles 7a,c–f) ad- faster running spots as single products. The latter were de-
ducts. Another method involved the reaction between bis (sulf-
onyl)amides 2a,b and w-bromoalkanols 4a,b to give bis-alkanols
5a,b which were subsequently condensed with 2a,b under Mitsuno-
ducts [MH]+ with the fragmentation pattern [MH–Mts]+,
bu conditions to give solely large macrocycles 7a,d in high yields.
Macrocycle 7d was deprotected with HBr/HOAc to yield 8 as the
tetrahydrobromide salt which was converted into its free base with
methanolic KOH.
duced to be small macrocycles 6a–f since they gave in
their mass spectra base peaks corresponding to the 1:1 ad-
and [MH–2Mts]+. It is interesting to mention that the re-
action between 2a and 3b gave only small macrocycle 6b
in 83% yield.
Key words: synthesis, oxa-azamacrocycles, oxyamines, alkylation,
Mitsunobu reaction
The two macrocyclic systems 6 and 7 were also differen-
tiated by the examination of their NMR spectra. General-
ly, the chemical shifts of the hydrogen and carbon atoms
situated at a-positions of the oxygen and nitrogen in large
macrocyclic systems 7 were found to be in higher field
compared with the corresponding hydrogens and carbons
of 6. For example, in the 1H NMR spectrum of the small
macrocycle 6d, the a-hydrogens typically showed two
triplets at d = 3.66 and 3.47 while in the large macrocycle
7d those a-hydrogens exhibit two signals which partially
overlapped to appear as a multiplet at d 3.44–3.66 ppm.
Similarly, in the 13C NMR spectra of compounds 6d and
7d the chemical shifts of the a-carbons were found to be
d = 73.6 (C–O), 48.2 (C–N) and 72.9 (C–O), 47.4 (C–N)
respectively.
Macrocycles with a heteroatom such as nitrogen and oxy-
gen have for the last decade demonstrated wide applica-
tion in many branches of science. For example aza-
macrocycles (cyclams) are important chelating agents for
metal and organic cations, anions and neutral mole-
cules.1,2 One of the many medical uses of heterocyclic
macrocycles is to sequester particle emitting radioiso-
topes for use with monoclonal antibody in radioimmuno-
diagnosis and radioimmunotherapy.3,4 More recently,
other workers have reported good anti-HIV activity for
many azamacrocycles and their metal complexes.5
For a number of years we have been interested in the
chemistry of oxyamino compounds6,7 and their corre-
sponding macrocyclic systems8 such as 8. We reason that
such heterocyclic system can exhibit ‘degenerate’ proper-
ties in their binding with metal ions. These systems can in
principle bind to alkali/alkali earth metals through the
oxygen atoms (as shown by crown ethers) or the transition
metals through the nitrogen atoms (as shown by cyclams).
In this paper, we report the synthesis and characterisation
of novel oxa-azamacrocyclic systems such as 6a-f,7a,c–f
containing N–O bonds. As far as we are aware it is the first
time such heteromacrocyclic system has been reported.
2 Mts-Cl, Py
r.t., 24h
H2NO
MtsHNO
.
( )n
1a-c
( )n
ONH2 2HCl
ONHMts
60-91%
2a-c
K2CO3, DMF
48h, r.t.
MtsHNO
TsO
( )n
( )m
3a,b
+
ONHMts
OTs
20-83%
2a-c
Mts ( )m
Mts
( )n
O
N
N
O
( )n
O
N
O
( )n
+
In the alkylation reactions between a,w-bis[(2-mesityl-
sulfonyl)aminooxy]alkanes 2a–c and bis(tosyl)alkanedi-
ols 3a,b in the presence of K2CO3 two products were
formed, showing distinct spots on TLC (acetone: petro-
leum ether (bp 80–100 oC), (1:3)) with an approximate Rf
values of 0.18 and 0.30. Recrystallisation of the mixture
from a large volume of MeCN gave the slower running
spot as a single product. Mass spectra of all these recrys-
tallised products showed base peaks for large macrocycles
N
( )m
Mts
Mts
O
N
N
O
Mts
( )m
Mts
6a-f
7a,c-f
1,2a n=1, b n=2, c n=4; 3a m=1, b m=2; 6,7a n=m=1,
b n=1 m=2, c n=2 m=1, d n=m=2, e n=4 m=1, f n=4
m=2
Scheme 1
Synthesis 1999, No. 6, 1034–1038 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Synthesis of Novel Oxa-Azamacrocycles
1035
X-ray crystallographic analysis of the compound with
larger Rf value obtained from the reaction between 2b and
3b, confirmed the structure of 1:1 adduct 6d (Figure 1).
Selected bond lengths and angles for compound 6d are
presented in Table 2. During the course of our studies on
the structure of oxa-azamacrocycle, we found that as the
size of the ring increases, it becomes more difficult to
grow single crystals since the degree of disorder increas-
es. Due to disorder, the molecular shape of the ten-mem-
bered macrocycle 6d in the crystalline state does not
exhibit the internal symmetry found in analogous eight-
membered ring system.8 Eight of the atoms from 6d are
displaced alternately above and below the best plane
through the ten atoms, with C8 and C11 on the plane.
K2CO3, DMF
24h, r.t.
MtsHNO
OH
+
( )k
4a,b
( )n
2a,b
ONHMts
Br
51-75%
( )k
OH
( )k
Mts
O
Mts
O
2a-c, Ph3P
DIAD, THF
2h, r.t.
Mts
N
N
N
N
O
N
N
( )n
( )n
( )n
57-81%
O
O
O
OH
( )k
5a,d
( )k
Mts
Mts
Mts
7a,d
1. HBr/CH3COOH
CH2Cl2, 24h, r.t.
2. KOH/MeOH
30min, r.t.
O
N
O
H
N
H
H
62%
N
O
N
H
O
8
2a n=1, b n=2; 4a k=1, b k=2; 5,7a n=k=1, d n=k=2
Scheme 2
alkanols 4a,b followed by ring closure under Mitsunobu
conditions. We are currently investigating the complexing
and chemical properties of the macrocycle 8.
All reagents were purchased from Aldrich and Lancaster and used
without further purification. Mps were determined on a Gallenkamp
melting point apparatus in open capillaries and are uncorrected.
TLC was performed on Kieselgel plates (Merck) 60 F254 in
CHCl3:MeOH (97:3 or 99:1) or acetone:petroleum ether (bp. 80–
Figure 1. Crystal Structure of N2,N6-di(2-mesitylsulfonyl)-2,6-diaza-
1,7-dioxacyclodecane 6d. Hydrogen atoms are omitted for clarity.
o
100 C) (1:3) and visualised using UV-light or an iodine vapour
bath. Silica gel Kieselgel 60 (230–400 mesh ASTM) was used for
column chromatography. IR spectra were recorded on a Perkin-
Elmer 781 IR spectrophotometer. 1H and 13C NMR spectra were re-
corded on a JEOL JNM-EX90 FT NMR spectrometer in CDCl3 un-
less otherwise stated. FAB-MS were obtained on a VG Analytical
AutoSpec (25kV) spectrometer (low resolution) or VG Analytical
Large oxa-azamacrocycle 7 is the system in which we are
most interested. It was obtained as the sole product by the
synthetic route outlined in Scheme 2. This involved first
an alkylation reaction between a,w-bis[(2-mesitylsulf-
onyl)aminooxy]alkanes 2a–c and w-bromoalkanols 4a,b ZAB-E instrument (accurate mass). DMF was distilled prior to use.
CH2Cl2 and THF were distilled over P2O5. a,w-bis(aminooxy)al-
kane dihydrochlorides 1a–c were prepared according to the de-
scribed procedure.7
to give bis-alkanols 5a,d which were subsequently con-
densed with another molecule of bis(sulfonyl)amides 2a,b
under Mitsunobu conditions. The products obtained
showed identical spectral properties to the large macro-
cyles 7a,d prepared via the alkylation reaction described
above. Deprotection of the large macrocycle 7d was per-
formed with 30% HBr/HOAc to give the macroheterocy-
cle 8 as the tetrahydrobromide salt. Hydrobromide salt of
8 was converted into its free base with methanolic KOH.
Crystal Structure Analysis of N2,N6-Bis(2-mesitylsulfonyl)-1,7-
dioxa-2,6-diazacyclodecane (6d)
Crystal data: C24H34N2O6S2, colourless, M=510.67, T=150 oK,
monoclinic, space group P21/n, a=6.4161(12), b=26.751(6),
c=14.5990(5) Å, b=92.95(3)o, V=2502.5(8) Å3, Z=4,
Dx=1.355gcm–3; graphite monochromated Mo-Ka radiation,
l=0.71073 Å, m=0.255mm–1.
In this paper we report the synthesis and characterisation
of novel oxa-azamacrocycles. Two synthetic routes lead-
ing to macrocycles 7 were applied. Alkylation reaction
between bis(sulfonyl)amides 2a–c and bis(tosyl)al-
kanediols 3a,b gave mixtures of small (1:1 adduct) and
large (2:2 adduct) macrocycles in approximately 1:1 ratio.
To obtain the large macrocyclic systems such as 7, we
have introduced a new synthetic strategy which involved
an alkylation of bis(sulfonyl)amides 2a,b with w-brom-
Data collection: The unit cell and intensity data were collected on a
Delft Instruments Fast diffractometer. 8725 reflections were col-
lected, of which 3574 were independent reflections,with 2θ range
for data collection of 2.07 to 25.09o.
Structure Solution and Refinement: Structure solution and refine-
ment were achieved using SHELXS869 and SHELX93.10 Full-matrix
least squares on F2 of all data converged to R=0.1238 and
wR=0.2742. Atomic coordinates, bond lengths, angles and thermal
parameters have been deposited at the Cambridge Crystallographic
Data Centre, deposition number 102823.
Synthesis 1999, No. 6, 1034–1038 ISSN 0039-7881 © Thieme Stuttgart · New York

1036
V. Kuksa et al.
PAPER
a,w-bis[(2-Mesitylsulfonyl)aminooxy]alkanes 2a–c
1H NMR: d = 7.32(s, 2H,NH), 7.04 (s, 4H), 4.00 (s, 4H); 2.65 (s,
a,w-bis(Aminooxy)alkane dihydrochloride 1 (20 mmol) was stirred
in pyridine at r.t for 30 min and 2-mesitylsulfonyl chloride (40
mmol) was added portionwise to the mixture which was stirred at
r.t. for 24h. Pyridine was removed under reduced pressure and res-
idue was dissolved in CHCl3 (50 mL), washed with 2M HCl (2x50
mL), H2O (50 mL), sat. NaHCO3 (50 mL) and dried (Na2SO4).
Evaporation of solvent followed by crystallisation from toluene or
EtOH afforded the title compound.
12H), 2.49 (s, 6H).
13C NMR: d = 143.6, 140.8, 132.1, 130.8 (arom. C), 73.8, 22.9, 21.0.
IR (Nujol): n = 3250, 1600 (N–H), 1350, 1160 (SO2) cm–1.
1,3-bis[(2-Mesitylsulfonyl)aminooxy]propane (2b)
Yield 79%; mp. 157–158 oC (EtOH).
1H NMR: d = 7.05 (s, 2H, NH), 6.95 (s, 4H), 3.75 (t, 4H), 2.58 (s,
12H), 2.29 (s, 6H), 1.73 (p, 2H).
13C NMR: d = 143.6, 140.7, 132.0, 130.8, 73.5, 26.8, 23.0, 21.0.
1,2-bis[(2-Mesitylsulfonyl)aminooxy]ethane (2a)7
Yield 91%; mp 116–117 oC (dec., toluene).
Table 1 N,N’ -Bis(2-mesitylsulphonyl)dioxadiazacycloalkanes 6a-f and N,N’,N’’,N’’’-Tetra(2-mesitylsulfonyl)- tetra-
oxatetraazacycloalkanes 7a, c–f
Comp-
ound
Yield
%
mp.
oC
1H NMR
d, ppm
13C NMR
d, ppm
MS-FAB
m/z
6a
6b
6c
6d
30
83
26
45
179–180
161–162
165–166
154–155
6.95 (s, 4H), 3.74 (s, 4H),
3.29 (s, 4H), 2.64 (s, 12H),
2.28 (s, 6H)
143.8, 141.5, 131.7, 129.2,
74.4, 48.3, 22.6, 20.7
Calcd for C22H30N2O6S2
482.6180 Found 482.1545,
[MH]+
6.93 (s, 4H), 3.55 (s, 4H),
3.38 (t, 4H), 2.62 (s, 12H),
2.26 (s, 6H), 2.07 (p, 2H)
143.8, 141.9, 132.1, 129.2,
74.1, 48.7, 24.2, 23.2, 21.0
Calcd for C23H32N2O6S2
496.6449 Found 497.1542
[MH]+
6.97 (s, 4H), 3.66 (t, 4H), 3.49
(t, 4H), 2.65 (s, 12H), 2.29 (s,
6H), 1.56 (p, 2H)
143.9, 141.8, 131.9, 129.5,
73.5, 49.4, 27.7, 22.9, 20.9
Calcd for C23H32N2O6S2
496.6449 Found 497.1958
[MH]+
6.94 (s, 4H), 3.66 (t, 4H), 3.47
(t, 4H), 2.62 (s, 12H), 2.27 (s,
6H), 2.00 (p, 2H), 1.43 (p,
2H)
143.6, 141.5, 131.9, 129.9,
73.6, 48.2, 28.7, 27.7, 22.9,
20.9
Calcd for C24H34N2O6S2
510.6718 Found 511.1973
[MH]+
6e
27
45
163–164
178–179
6.94 (s, 4H), 3.67 (s, 4H),
3.52 (t, 4H), 2.62 (s, 12H),
2.27 (s, 6H), 1.39-1.60 (m,
6H)
143.5, 141.4, 131.6, 129.2,
75.0, 47.9, 26.0, 22.6, 22.0,
20.5
Calcd for C25H36N2O6S2
524.6987 Found 525.2093
[MH]+
6f
6.90 (s, 4H), 3.48 (t, 4H), 3.28
(2, 4H), 2.60 (s, 12H), 2.24 (s,
6H), 1.28-1.64 (m, 8H)
143.6, 141.6, 131.9, 129.7,
77.2, 47.6, 27.1, 22.9, 22.6,
21.4, 20.9
Calcd for C26H38N2O6S2
538.7255 Found 539.2250
[MH]+
7a
7c
7d
28a
57b
245–246
(dec.)
6.95 (s, 4H), 3.57 (s, 4H),
3.37 (s, 4H), 2.58 (s, 12H),
2.29 (s, 6H)
144.1, 141.8, 132.2, 129.3,
74.1, 48.0, 23.1, 21.0
Calcd for C44H60N4O12S4
965.2360 Found 965.3169
[MH]+
27
229–230
(dec.)
6.97 (s, 8H), 3.50 (s, 8H),
3.34 (t, 8H), 2.61 (s, 12H),
2.31 (s, 6H), 1.38 (p, 4H)
144.1, 141.8, 132.0, 129.5,
72.5, 48.2, 27.0, 23.0, 21.0
Calcd for C46H64N4O12S4
993.2898 Found 993.3482
[MH]+
37a
82b
192–195
(dec.)
6.96 (s, 8H), 3.44-3.66 (m,
16H), 2.88 (s, 24H), 2.60 (s,
12H), 1.87 (p, 4H), 1.38 (p,
4H)
144.0, 141.8, 132.0, 129.6,
72.9, 47.4, 27.3, 24.0, 23.1,
21.0
Calcd for C48H68N4O12S4
1021.3435 Found 1021.2
[MH]+
7e
7f
20
37
238–239
(dec.)
6.95 (s, 8H), 3.55 (s, 8H),
3.36 (t, 8H), 2.63 (s, 24H),
2.29 (s, 12H), 1.05-1.32 (m,
12H)
143.9, 141.9, 132.0, 129.6,
75.6, 48.1, 28.0, 23.0, 22.5,
21.0
Calcd for C50H72N4O12S4
1049.3973 Found 1049.4108
[MH]+
188–191
(dec.)
6.93 (s, 8H), 3.11-3.40 (m,
16H), 2.59 (s, 24H), 2.26 (s,
12H), 2.10 (p, 4H), 0.95-1.40
(m, 12H)
143.7, 141.6, 131.8, 129.6,
75.6, 47.2, 27.9, 23.9, 22.9,
21.8, 20.9
Calcd for C52H76N4O12S4
1077.4510 Found 1077.4421
[MH]+
a Alkylation reaction
b Mitsunobu reaction
Synthesis 1999, No. 6, 1034–1038 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Synthesis of Novel Oxa-Azamacrocycles
1037
IR (Nujol): n = 3200, 1600 (N–H), 1330, 1155 (SO2) cm–1.
nooxy]propane (5b)
Obtained as yellow oil in 75% yield.
1H NMR: d = 6.93 (s, 4H), 3.68 (t, 4H), 3.21–3.40 (m, 8H), 2.60 (s,
12H), 2.28 (s, 6H), 1.85 (p, 4H), 1.35 (p, 2H).
13C NMR: d = 143.6, 141.3, 131.7, 129.4, 77.2, 72.2, 46.6, 29.6,
26.8, 22.7, 20.6.
1,5-Bis[(2-mesitylsulfonyl)aminooxy]pentane (2c)
Yield 60%; mp. 110.5–111.5 oC (toluene).
1H NMR: d = 6.96 (s, 4H), 3.74 (t, 4H, J = 6.15 Hz)), 2.61 (s, 12H),
2.29 (s, 6H), 1.36 (m, 6H).
13C NMR: d = 143.3, 140.5, 131.8, 130.8, 76.4, 27.5, 22.8, 21.8,
20.8.
IR (neat): n = 3450 (OH), 2820, 2720, 1600, 1560, 1330, 1170
(SO2), 850 cm–1.
IR (Nujol): n = 3210, 1600 (N–H), 1322, 1165 (SO2) cm–1.
LRMS-FAB: Calcd for C27H42N2O8S2 586.7671 Found 587.2
[MH]+.
N,N’-Bis(2-mesitylsulfonyl)dioxadiazacycloalkanes 6a–f and
N,N’,N’’,N’’’-Tetra(2-mesitylsulfonyl)- tetraoxatetraazacycloal-
kanes 7a,c–f; General Procedure (Alkylation Reaction)
N,N’,N’’,N’’’-Tetra(2-mesitylsulfonyl) tetraoxatetraazacyclo-
alkanes 7a,d; General Procedure (Mitsunobu reaction)
To a stirred solution of 5 (3.30 mmol), 2 (3.30 mmol), and Ph3P
(1,79 g, 6.82 mmol) in anhyd THF (30 mL) DIAD (1.38 g, 6.82
mmol) was added dropwise at r.t. The mixture was allowed to stir
for 2h at r.t. and THF was evaporated to dryness. The residue was
dissolved in boiling EtOH (30 mL) and cooled to r.t. The precipitate
formed was filtered off, washed with cold EtOH and dried to give
macrocycle 7 as white solid, which was recrystallised from MeCN
to give pure product with same spectral characteristics as those ob-
tained via the alkylation reaction (Table 1).
A mixture of 3 (2.13 mmol), 4 (2.13 mmol), and K2CO3 (6.40
mmol) in anhyd DMF (60 mL) was stirred for 48 h at r.t. Solvent
was removed in vacuo and the residue was dissolved in CHCl3 (50
mL), washed with 2M HCl (2x50mL), H2O (2x50 mL), brine (50
mL), and dried with Na2SO4. Solvent was then evaporated to dry-
ness to give an oil which was dissolved in anhyd MeCN (3 mL) and
cooled to –18 oC to give a mixture of macrocycles 6 and 7. This sol-
id was dissolved in boiling MeCN (150 mL), and left at 0 oC for 3
days. The precipitate formed was filtered off, washed with cold
MeCN, and dried to give large macrocycle 7 as a white solid. The
filtrate was reduced in volume and residue was recrystallised from
MeCN to give small macrocycle 6 as a white solid (Table 1).
1,7,11,17-Tetraoxa-2,6,12,16-tetraazacycloicosane (8)
1,7,11,17-Tetraoxa-2,6,12,16-tetraazacycloicosane Tetrahydro-
bromide
A mixture of protected macrocycle 7d (1.44g, 1.41 mmol), 30%
HBr/HOAc (6.20 g) in anhyd CH2Cl2 (30 mL) was stirred at r.t. for
24 h. The orange precipitate formed was filtered off, washed with
CH2Cl2 (4x10 mL), EtOAc (2 x 10 mL), EtOH (2 x 10 mL), and
dried in vacuo over P2O5 to afford the tetrahydrobromide salt of the
macrocycle 8 as a white powder in 77% yield, mp 200–202oC (dec).
N,N’-Bis(w’-hydroxyalkyl)-a,w-bis[(2-mesitylsulfonyl)]ami-
nooxy]alkanes 5a,d; General Procedure
A mixture of 2 (4.72 mmol), w-bromoalkanol 4 (9.44 mmol) and an-
hyd K2CO3 (11.72 mmol) in anhyd DMF (35 mL) was stirred at r.t.
for 24 h. DMF was removed in vacuo, residue was dissolved in
CHCl3 (50 mL), washed with 1M HCl (2x50 mL), H2O (50 mL), sat.
NaHCO3 (50 mL), and dried (Na2SO4). Solvent was removed in
vacuo to give 5.
+
1H NMR (DMSO-d6): d = 7.70 (br s, 8H, ONH2 ), 4.05 (t, 8H), 3.35
N,N’-Bis(2-hydroxyethyl)-1,2-bis[(2-mesitylsulfonyl)]ami-
nooxy]ethane (5a)
(t, 8H), 1.80–2.30 (m, 8H).
Obtained as white solid in 51% yield, mp 90–93 oC (EtOH).
IR (KBr disk): n = 2890, 2710, 2640, 2460, 2400, 1570, 1525, 1460,
1335, 1170, 1040, 1010, 990 cm–1.
1H NMR: d = 6.94 (s, 4H), 3.82 (t, 4H), 3.44 (s, 4H), 3.40 (t, 4H),
2.58 (s, 12H), 2.29 (s, 6H), 2.09 (s, 2H, OH).
13C NMR: d = 143.9, 141.7, 131.9, 129.3, 73.0, 58.8, 52.0, 22.9,
20.9.
HRMS-FAB: Calcd for [MH]+ C12H32Br4N4O4 616.0465 Found
293.2197 [MH–4HBr]+.
1,7,11,17-Tetraoxa-2,6,12,16-tetraazacycloicosane (8)
To a suspension of the tetrahydrobromide salt of 8 (0.67g, 1.09
mmol) in MeOH (5 mL) a solution of KOH (0.36g, 6.06 mmol) in
MeOH (5 mL) was added. The mixture was stirred at r.t. for 30 min,
and filtered off. The filtrate was evaporated in vacuo and the residue
was resuspended in CHCl3 (2 x 10 mL), resulting solution was fil-
tered and evaporation of the solvent gave macrocycle 8 (0.30 g,
80%) as viscous yellow oil.
IR (Nujol): n = 3330 (OH), 1610, 1570, 1340, 1180 (SO2), 1090,
1060, 1040, 915, 860, 740 cm–1.
LRMS-FAB: Calcd for C24H36N2O8S2 544.6864 Found 545.1
[MH]+.
N,N’-Bis(3-hydroxypropyl)]-1,3-bis[(2-mesitylsulfonyl)]ami-
1H NMR: d = 5.64 (br s, 4H, 4xONH), 3.73 (t, 16H, 4xCH2O), 2.96
Table 2 Selected bond lengths (Å) and angles (o) of N2,N6-Bis(2-mes-
itylsulfonyl)-1,7-dioxa-2,6-diazacyclodecane 6d
(t, 8H, 4xCH2N), 1.56–1.94 (m, 8H, 4xCH2).
13C NMR: d = 71.0 (C–O), 50.5 (C–N), 28.4, 25.4.
Bond lengths, (Å)
O(3)-N(1)
Angles, (o)
IR (neat): n = 3250 (N–H), 2920, 2860 (C–H), 1480, 1435, 1370,
1060, 900 cm–1.
1.443(5)
1.446(6)
1.438(6)
1.444(5)
1.508(6)
1.500(6)
1.501(8)
1.507(8)
1.533(7)
1.509(7)
N(1)-O(3)-C(7)
111.0(4)
110.4(4)
109.7(4)
108.8(3)
112.2(4)
116.9(4)
111.5(4)
108.0(4)
111.5(4)
107.8(4)
O(3)-C(7)
O(4)-C(9)
O(4)-N(2)
N(2)-C(10)
N(1)-C(12)
C(12)-C(11)
C(11)-C(10)
C(9)-C(8)
C(8)-C(7)
C(9)-O(4)-N(2)
O(4)-N(2)-C(10)
O(3)-N(1)-C(12)
N(1)-C(12)-C(11)
C(12)-C(11)-C(10)
C(11)-C(10)-N(2)
O(4)-C(9)-C(8)
C(7)-C(8)-C(9)
O(3)-C(7)-C(8)
Acknowledgement
We would like to thank the Robert Gordon University and CVCP
Award for financial support, the Centre of Mass Spectrometry at the
University of Wales, Swansea, for mass spectroscopic analysis and
the EPSRC X-ray data collection service based at the University of
Cardiff. Thanks to Dr. M. Fraser for his comments on this paper and
Mr. Yann Emzivat for his technical support.
Synthesis 1999, No. 6, 1034–1038 ISSN 0039-7881 © Thieme Stuttgart · New York

1038
V. Kuksa et al.
PAPER
(6) Kong Thoo Lin, P., Maguire, N. M., Brown, D. M.,
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Article Identifier:
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Synthesis 1999, No. 6, 1034–1038 ISSN 0039-7881 © Thieme Stuttgart · New York