Efficient synthesis of some novel macrocyclic diamides using fast addition method

Article abstract of DOI:10.1055/s-2006-926357

Synthesis of some new macrocyclic diamides based on catechol scaffold by cyclization reactions between various diamines and 2-[2-(2-chloro-2-oxoethoxy) phenoxy]ethanoyl chloride using fast addition method has been described. The reactions were carried out in short reaction times and the expected macrocycles were obtained in good to high yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926357

PAPER
999
Efficient Synthesis of Some Novel Macrocyclic Diamides Using Fast Addition
Method
M
H
acrocyclic
D
iam
a
ides by
F
as
s
t
A
ddition
h
Method em Sharghi,* Abdolkarim Zare
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Fax +98(711)2280926; E-mail: shashem@chem.susc.ac.ir
Received 15 September 2005
ume of solvent, no side reactions and synthetic versatility
this method allows to provide various even or odd mem-
bered dilactams). In fact, because of high significance of
Abstract: Synthesis of some new macrocyclic diamides based on
catechol scaffold by cyclization reactions between various diamines
and 2-[2-(2-chloro-2-oxoethoxy)phenoxy]ethanoyl chloride using
(
fast addition method has been described. The reactions were carried these compounds and also in extension of the applicability
out in short reaction times and the expected macrocycles were ob- of fast addition method, herein, we would like to report an
tained in good to high yields.
efficient synthesis of some new macrocyclic diamides
Key words: macrocyclic diamide, fast addition, catechol, diamine, based on catechol structure using this method (Scheme 1).
dicarboxylic acid dichloride, cyclization
Catechol was reacted with 2-chloroacetic acid in water in
the presence of sodium hydroxide to give 2-[2-(2-hy-
droxy-2-oxoethoxy)phenoxy]acetic acid (1) as a white
Macrocyclic compounds with amide units in the macro
ring are of interest because they have important applica-
tions in selective noble metal complexing agents and met-
al ion-selective electrodes. For example, some of these
compounds were shown to be selective for the complex-
solid in 91% yield (Scheme 1). Treatment of 1 with thio-
nyl chloride gave 85% yield of 2-[2-(2-chloro-2-oxoeth-
oxy)phenoxy]ethanoyl chloride (2) (Scheme 1). The
cyclization reactions between dicarboxylic acid dichlo-
ride 2 and different diamines were performed by fast ad-
dition procedure without high dilution technique. This
step was carried out by fast addition of diamines in anhy-
drous solvent into a solution of dicarboxylic acid dichlo-
ride 2 in anhydrous solvent over a few seconds with
vigorous stirring at room temperature.
1
2
+ 1a
2+ 1b
2+ 1c
2+
1d
ation with Hg , Zn , Cu , and Sr ions. Further-
more, recently we have shown that these macrocycles can
efficiently catalyze the regioselective ring opening of ep-
2
a,b
oxides with elemental halogen or ammonium thiocyan-
ate. Interestingly, some macrocyclic amides are
receptors for anions such as OAc , H PO , F and Cl . In
2
c
–
–
–
– 3
2
4
Macrocycles 3a and 3b were synthesized to study the ef-
fect of alkyl chain length of aliphatic diamines on results
of cyclization reactions. As shown in Table 1, 1,6-diami-
nohexane gave higher yield than 1,3-diaminopropane
this case, the electronegative atom from anions (oxygen,
fluorine or chlorine) interact with NH groups of macrocy-
3
cles. Lactams also have been used as starting materials
for the preparation of polyaza-crowns and related com-
(
Table 1, entries 1 and 2). This aspect indicates the depen-
4
pounds such as cryptands. Although macrocyclic di-
dency of macrocyclization yield to the ring size of the
macrocycle. We have also extended the cyclization reac-
tion to aromatic diamines. As Table 1 indicates, when ar-
omatic diamines were used instead of aliphatic diamines,
the reaction yields were higher. Moreover, the presence of
amides have many applications, only a few methods have
been developed for their preparation. In these methods,
carboxylic acid derivatives such as dicarboxylic acid di-
5
6
esters, labile dicarboxylic acid dichlorides or bis(a-chlo-
4
a
roamide) compounds were allowed to react with
diamines under different conditions. The more common
methods involve high dilution, template effect, high
pressure approach, ESI-MS and ‘Crab-like’ tech-
niques. Most of these methods are associated with several
drawbacks such as long reaction times, low yields of prod-
ucts, harsh reaction conditions and difficulty in separation
and purification.
CO R as functional group on the ring of aromatic di-
2
amines afforded the macrocyclic diamides in higher
yields as well as shorter reaction times in comparison to
7
8
9
10
4d
the NO (Table 1, entries 5, 6, 8 and 10). In the synthesis
2
of compounds 3f–h, two-to-two cyclization products 4f–
h were also obtained in low yields, and were easily sepa-
rated from one-to-one adducts (Table 1, entries 7, 9 and
1
1).
Recently, we provided a synthetic route toward dilactam
We have also studied the effect of alkyl chain length of es-
1
1
derivatives. In this method, the cyclization reaction does
not require high dilution techniques or template effect.
The advantages of this method (fast addition) are high
yield, short reaction time, ease of purification, low vol-
ter moiety (CO R) present on aromatic diamines on the
2
yields and the solubility of products in organic solvents.
The results have illustrated that increment of the length of
alkyl chain decreased the yields of diamides and increased
the yields of tetraamides (Table 1, entries 6–11). This as-
pect enhanced the solubility of dilactams and tetralactams
in organic solvents. The useful solvents for synthesis of
macrocycles 3a–h and 4f–h were ethyl acetate, dichlo-
SYNTHESIS 2006, No. 6, pp 0999–1004
x
x
.
x
x
.2
0
0
6
Advanced online publication: 27.02.2006
DOI: 10.1055/s-2006-926357; Art ID: Z17305SS
Georg Thieme Verlag Stuttgart · New York
©

1
000
H. Sharghi, A. Zare
PAPER
O
TLC using silica gel SILG/UV 254 plates. Chromatography was
carried out on a column over silica gel 60, 0.063–0.200 mm (70–
OH
OH
2
30 mesh ASTM). IR spectra were run on a Shimadzu FTIR-8300
OH
OH
O
O
1
13
spectrophotometer. The H (250 MHz) and C NMR (62.5 MHz)
were run on a Bruker Avance DPX-250, FT-NMR spectrometer (d
in ppm, J in Hz). Mass spectra were recorded on a Shimadzu GC
MS-QP 1000 EX apparatus. Microanalyses were performed on a
Perkin-Elmer 240-B microanalyzer. Melting points were recorded
on a Büchi B-545 apparatus in open capillary tubes and are uncor-
rected.
NaOH, H2O
0 °C
+
3 Cl
CO2H
9
O
1
O
Cl
Cl
2
-[2-(2-Hydroxy-2-oxoethoxy)phenoxy]acetic Acid (1)
O
SOCl2
To a mixture of catechol (11.01 g, 100 mmol) and 2-chloroacetic
acid (28.35 g, 300 mmol) at 90 °C on a water-bath, was added drop-
wise a solution of aq 33% (w/v) NaOH solution (48.02 g in 97.5 mL
H2N-X-NH2
fast addition
50–60 °C
O
H O). The mixture was stirred at 90 °C for 2 h and after cooling to
2
r.t., the solution was kept in ice bath. Then, concentrated HCl was
added dropwise to the solution with stirring. The mixture was al-
lowed to warm to r.t. and the solution was filtered and the white pre-
O
2
O
O
O
cipitate was washed with cold H O. Crystallization of the residue
2
X
X
from hot water afforded 1 as white crystals; yield: 20.58 g (91%);
NH
N
H
N
H
O
1
3
mp 176–177 °C (Lit. mp 177–178 °C).
O
O
O
O
X
+
2
-[2-(2-Chloro-2-oxoethoxy)phenoxy]ethanoyl Chloride (2)
O
The acid 1 (5.65 g, 25 mmol) was heated in SOCl (50 mL) for 4 h
2
H
N
H
N
NH
at 50–60 °C. The SOCl was evaporated under vacuo at low temper-
2
ature (40 °C) and the residue was crystallized from petroleum ether
O
O
O
(
bp 60–80 °C) to give 2 as white crystals; yield: 5.58 g (85%);
3
a–h
4f–h
mp 48–49 °C.
–
1
IR (KBr): 3075, 2977, 1805 (s), 1501 cm .
3
X
3
e
X
1
H NMR (CDCl , 250 MHz): d = 4.96 (s, 4 H), 6.78–6.88 (complex,
3
NO2
O
4 H).
13
a
C NMR (CDCl , 62.5 MHz): d = 73.3, 116.7, 123.5, 146.5, 170.6.
3
Ethyl, Pentyl and Octyl 3,4-Diaminobenzoate; General Proce-
dure
The appropriate alcohol (2.0 mmol) and carboxylic acid (2.0 mmol)
O
b
( )4
f
O
O
were added to a stirred mixture of Al O (acidic type 540 C, 0.31 g,
2
3
O
O
( )3
( )6
3.0 mmol) and MeSO H (1 mL). The mixture was allowed to stir in
3
c
d
g
N
an oil bath at 80 °C for 2–3 h, then poured into H O (20 mL), and
H
2
extracted with CHCl (50 mL). The organic layer was washed with
3
sat. aq solution of NaHCO (2 × 20 mL), dried (CaCl ), and evapo-
3
2
1
4
h
rated to give the corresponding ester.
Ethyl 3,4-Diaminobenzoate
Pale yellow solid; yield: 0.32 g (89%); mp 79–80 °C.
Scheme 1
IR (KBr): 3327, 3188, 3048, 2959, 1686 cm–1 (s).
romethane, acetone, acetonitrile, THF, diethyl ether and 1H NMR (CDCl
, 250 MHz): d = 1.25 (t, 3 H, J = 6.9 Hz), 3.52 (s,
H), 4.24 (q, 2 H, J = 6.9 Hz), 6.60 (d, 1 H, J = 8.1 Hz), 7.33–7.41
3
4
ethyl acetate–dichloromethane (1:1). In all reactions,
chloroform, DMSO and DMF were found to be unsuitable
as solvents.
(
1
complex, 2 H).
3
C NMR (CDCl , 62.5 MHz): d = 14.8, 60.8, 115.2, 118.6, 121.7,
3
1
23.5, 133.5, 140.7, 167.3.
In conclusion, we have prepared some novel macrocyclic
dilactams and tetralactams by cyclization reactions be-
tween dicarboxylic acid dichloride and different diamines
+
+
MS: m/z (%) = 181 (M + 1, 18.6), 180 (M , 97.1), 152 (57.0), 151
6.4), 135 (100), 107 (45.5), 75 (1.4), 73 (1.7), 45 (5.6), 43 (51.2).
(
(
aliphatic and aromatic) using fast addition technique.
Pentyl 3,4-Diaminobenzoate
Furthermore, these macrocycles with different ring sizes Pale yellow solid; yield: 0.38 (85%); mp 65–67 °C.
were obtained in high yields and short reaction times. The
applications of these compounds in organic and analytical
chemistry are currently under investigation.
IR (KBr): 3331, 3190, 3050, 2950, 1685 cm–1 (s).
1
H NMR (CDCl , 250 MHz): d = 0.94–1.02 (complex, 5 H), 1.54–
3
1
1
.72 (complex, 4 H), 3.63 (s, 4 H), 4.28 (t, 2 H, J = 7.0 Hz), 6.66 (d,
H, J = 8.2 Hz), 7.40–7.47 (complex, 2 H).
1
3
All chemicals were obtained from Merck or Fluka. Solvents were
purified and dried according to reported methods and stored over
molecular sieves.12 The progress of reactions was followed with
C NMR (CDCl , 62.5 MHz): d = 16.9, 26.6, 30.1, 37.9, 63.5,
3
115.3, 118.7, 121.7, 123.6, 133.3, 140.8, 167.4.
Synthesis 2006, No. 6, 999–1004 © Thieme Stuttgart · New York

PAPER
Macrocyclic Diamides by Fast Addition Method
1001
Table 1 Macrocyclization Reactions between Dicarboxylic Acid Dichloride 2 and Various Diamines Using Fast Addition Method
Entry
Diamine
Product
3a
Reaction time (min)
Solvent
acetone
acetone
EtOAc
Yield (%)a
1
2
3
10
5
31
70
45
H2N
NH2
NH2
3b
H2N
2
( )4
H N
NH2
3c
5
N
H
4
NH2 NH2
3d
3
EtOAc
75
5
6
H N
NO2
3e
3f
5
3
CH Cl
69
89
2
2
2
2
H2N
O
CH Cl
2
H2N
H2N
O
7
8
9
O
O
O
O
O
4f
3
3
3
3
3
CH Cl
7
82
11
74
16
2
2
2
2
2
2
H2N
H2N
O
O
O
O
O
3g
4g
3h
4h
CH Cl
2
H2N
H2N
( )3
CH Cl
2
H2N
H2N
( )3
( )6
( )6
1
1
0
1
CH Cl
2
H2N
H2N
CH Cl
2
H2N
H2N
a
Isolated yields.
+
+
MS: m/z (%) = 223 (M + 1, 15.2), 222 (M , 41.5), 194 (28.3), 166
Dilactams 3a–h and 4f–h; General Procedure
(
(
14.1), 151 (2.5), 135 (100), 107 (25.6), 71 (4.9), 57 (38.5), 43
46.1).
A solution of diamine (2.0 mmol) in anhyd solvent (50 mL) was
added quickly to a vigorous stirring solution of dicarboxylic acid
dichloride (2.0 mmol) in anhyd solvent (50 mL) at r.t. The mixture
was stirred for a further 3–10 min (see Table 1 for solvent used and
time of reaction). The organic layer was washed first with aq
Octyl 3,4-Diaminobenzoate
Pale yellow solid; yield: 0.44 g (83%); mp 56–58 °C.
IR (KBr): 3329, 3191, 3054, 2955, 1685 cm–1 (s).
NaHCO
3
solution (2 × 50 mL), then with H O (2 × 50 mL), and
2
dried (MgSO ). The crude product obtained by evaporation of the
solvent was purified by column chromatography over silica gel us-
ing n-hexane–EtOAc as eluent (15:1 to 10:1).
4
1
H NMR (CDCl , 250 MHz): d = 0.88 (t, 3 H, J = 6.8 Hz), 1.25–
3
1
.34 (complex, 10 H), 1.70 (m, 2 H), 3.59 (s, 4 H), 4.24 (t, 2 H,
J = 7.0 Hz), 6.68 (d, 1 H, J = 8.3 Hz), 7.44–7.51 (complex, 2 H).
1
3
5,6,7,8-Tetrahydro-2H-1,11,4,8-benzodioxadiazacyclotri-
decine-3,9(4H,10H)-dione (3a)
Colorless crystals; mp 178–179 °C.
IR (KBr): 3334, 3078, 2956, 1647 cm–1 (s).
C NMR (CDCl , 62.5 MHz): d = 14.5, 23.0, 26.5, 29.2, 29.6, 29.7,
3
3
2.2, 65.1, 115.3, 118.8, 121.8, 123.7, 133.3, 140.7, 167.3.
+
+
MS: m/z (%) = 265 (M + 1, 6.7), 264 (M , 31.6), 165 (1.3), 151
(
(
3.3), 135 (40.6), 107 (19.0), 84 (19.7), 70 (31.8), 56 (60.0), 43
78.3), 41 (100).
Synthesis 2006, No. 6, 999–1004 © Thieme Stuttgart · New York

1
002
H. Sharghi, A. Zare
PAPER
10-Nitro-8,13-dihydrodibenzo[b,h][1,4,7,10]dioxadiazacy-
1
H NMR (CDCl , 250 MHz): d = 1.92 (t, 2 H, J = 5.9 Hz), 3.63 (t,
3
4
H, J = 5.9 Hz), 4.47 (s, 4 H), 6.98–7.09 (complex, 4 H), 7.41 (s, 2
clododecine-7,14(6H,15H)-dione (3e)
H).
Colorless crystals; mp 252–253 °C (dec.).
1
3
IR (KBr): 3348, 3122, 3063, 2960, 1697 (s), 1676 cm–1 (s).
C NMR (CDCl , 62.5 MHz): d = 28.1, 40.1, 71.4, 115.4, 124.5,
3
1
49.2, 168.5.
1
H NMR (DMSO-d , 250 MHz): d = 4.82 (s, 2 H), 4.88 (s, 2 H),
6
+
+
MS: m/z (%) = 265 (M + 1, 11.7), 264 (M , 11.9), 150 (9.9), 142
7.04 (d, 2 H, J = 7.7 Hz), 7.32 (dd, 2 H, J = 6.1, 7.7 Hz), 8.10–8.18
(
(
3.9), 122 (12.5), 114 (4.6), 100 (3.7), 99 (8.9), 92 (8.4), 76 (7.2), 70
9.1), 57 (17.3), 52 (45.5), 42 (100).
(complex, 2 H), 8.35 (s, 1 H), 9.92 (s, 1 H), 10.17 (s, 1 H).
13
C NMR (CDCl , 62.5 MHz): d = 70.9, 71.9, 117.3, 118.0, 120.4,
3
Anal. Calcd for C H N O (264.28): C, 59.08; H, 6.10; N, 10.60.
Found: C, 59.01; H, 6.19; N, 10.51.
121.0, 122.1, 122.4, 123.3, 129.0, 137.2, 143.7, 148.4, 148.6, 167.3,
167.6.
13
16
2
4
+
+
MS: m/z (%) = 344 (M + 1, 11.8), 343 (M , 25.8), 193 (5.3), 192
4
,5,6,7,8,9,10,11-Octahydro-1,14,4,11-benzodioxadiazacyclo-
(
(
14.0), 179 (8.0), 164 (100), 149 (8.4), 122 (26.4), 121 (55.8), 108
7.0), 92 (11.4), 76 (14.1), 52 (55.2.
hexadecine-3,12(2H,13H)-dione (3b)
Colorless crystals; mp 199–201 °C.
IR (KBr): 3342, 3069, 2948, 1649 cm–1 (s).
Anal. Calcd for C H N O (343.29): C, 55.98; H, 3.82; N, 12.24.
Found: C, 56.11; H, 3.76; N, 12.33.
16
13
3
6
1
H NMR (CDCl , 250 MHz): d = 1.52–1.69 (complex, 8 H), 3.49 (t,
3
4
H, J = 5.7 Hz), 4.52 (s, 4 H), 6.86–7.04 (complex, 4 H), 7.54 (s, 2
Ethyl 7,14-Dioxo-6,7,8,13,14,15-hexahydrodiben-
zo[b,h][1,4,7,10]dioxadiazacyclododecine-10-carboxylate (3f)
Colorless crystals; mp 186–187 °C.
IR (KBr): 3364, 3242, 3050, 2980, 1721 (s), 1699 (s), 1653 cm–1 (s).
H).
1
3
C NMR (CDCl , 62.5 MHz): d = 24.5, 30.1, 41.0, 70.7, 118.2,
3
1
24.6, 149.3, 168.8.
+
+
1
MS: m/z (%) = 307 (M + 1, 7.0), 306 (M , 30.3), 248 (5.5), 236
(
(
H NMR (CDCl , 250 MHz): d = 1.35 (t, 3 H, J = 7.0 Hz), 4.36 (q,
3
4.3), 184 (4.2), 150 (9.3), 137(44.8), 121 (45.7), 114 (15.8), 107
15.9), 97 (38.6), 43 (100).
2 H, J = 7.0 Hz), 4.60 (s, 2 H), 4.65 (s, 2 H), 6.90–7.00 (complex, 4
H), 7.79–7.99 (complex, 3 H), 8.26 (s, 1 H), 9.18 (s, 1 H).
1
3
Anal. Calcd for C H N O (306.36): C, 62.73; H, 7.24; N, 9.14.
Found: C, 62.66; H, 7.19; N, 9.02.
C NMR (CDCl , 62.5 MHz): d = 14.7, 61.6, 71.9, 73.6, 117.5,
3
16
22
2
4
118.3, 122.1, 124.3, 124.5, 127.2, 127.4, 127.8, 128.4, 129.9, 149.3,
1
49.6, 165.8, 167.5, 168.6.
5
,6,7,8,9,10-Hexahydro-2H-1,13,4,7,10-benzodioxatriazacyclo-
+
+
MS: m/z (%) = 371 (M + 1, 20.3), 370 (M , 22.7), 325 (17.2), 248
(
(
pentadecine-3,11(4H,12H)-dione (3c)
Colorless crystals; mp 230 °C (dec.).
IR (KBr): 3360, 3244, 3080, 2979, 1676 cm–1 (s).
8.4), 207 (19.7), 206 (100), 192 (12.4), 178 (39.8), 163 (39.8), 136
10.3), 122 (10.5), 108 (6.3), 92 (10.2), 52 (24.8).
Anal. Calcd for C H N O (370.36): C, 61.62; H, 4.90; N, 7.56.
1
9
18
2
6
1
H NMR (CDCl , 250 MHz): d = 1.75 (s, 1 H), 2.94 (t, 4 H, J = 5.3
Found: C, 61.52; H, 4.77; N, 7.39.
3
Hz), 3.48 (t, 4 H, J = 5.3 Hz), 4.48 (s, 4 H), 6.87–6.98 (complex, 4
H), 7.81 (s, 2 H).
Diethyl 7,14,23,30-Tetraoxo-6,7,8,13,14,15,22,23,24,29,30,31-
dodecahydrotetrabenzo[b,h,n,t][1,4,13,16,7,10,19,22]tetra-
oxatetraazacyclotetracosine-10,27-dicarboxylate (4f)
Colorless crystals; mp 242–244 °C.
1
3
C NMR (CDCl , 62.5 MHz): d = 38.5, 47.8, 67.2, 112.6, 122.4,
3
1
46.5, 167.5.
+
+
MS: m/z (%) = 294 (M + 1, 73.3), 293 (M , 12.0), 278 (1.1), 250
IR (KBr): 3356, 3269, 3070, 2953, 1720 (s), 1693 (s), 1657 cm–1 (s).
(
(
3.7), 192 (1.3), 150 (4.1), 121 (19.8), 108 (1.2), 100 (8.2), 99
14.1), 92 (5.1), 86 (8.9), 85 (32.0), 71 (20.3), 57 (29.5), 52 (19.9),
1
H NMR (DMSO-d , 250 MHz): d = 1.34 (t, 6 H, J = 6.9 Hz), 4.38
6
4
4 (85.5), 43 (100), 42 (84.4).
(q, 4 H, J = 6.9 Hz), 4.68–4.79 (complex, 8 H), 7.03–7.11 (complex,
8
H), 7.78–7.88 (complex, 6 H), 8.15 (s, 2 H), 9.31 (s, 2 H).
Anal. Calcd for C H N O (293.32): C, 57.33; H, 6.53; N, 14.33.
Found: C, 57.42, H, 6.69; N, 14.41.
14
19
3
4
1
3
C NMR (DMSO-d , 62.5 MHz): d = 14.5, 61.3, 71.8, 73.2, 117.9,
6
1
18.6, 122.5, 124.1, 124.9, 127.7, 127.9, 128.1, 128.5, 129.8, 149.8,
7H,16H-Naphtho[1,8-ef][1,11,4,8]benzodioxadiazacyclotri-
150.5, 167.0, 167.15, 168.4.
decine-8,17(9H,18H)-dione (3d)
Colorless crystals; mp 276 °C (dec.).
IR (KBr): 3294, 3053, 2922, 1661 cm–1 (s).
MS: m/z (%) = 576 (3.3), 476 (2.6), 434 (1.8), 373 (1.1), 389 (4.3),
3
70 (7.3), 354 (11.4), 326 (15.4), 312 (20.1), 297 (4.8), 267 (8.2),
239 (3.7), 222 (2.5), 206 (23.7), 178 (6.9), 150 (41.8), 134 (3.4), 121
(100), 106 (4.2), 92 (7.6), 76 (12.1), 52 (44.3).
1
H NMR (250 MHz, DMSO-d ): d = 4.68 (s, 4 H), 7.12 (d, 2 H,
6
J = 7.5 Hz), 7.21 (dd, 2 H, J = 5.7, 7.5 Hz), 7.58 (dd, 2 H,
J = 6.8, 7.9 Hz), 7.86 (d, 2 H, J = 6.8 Hz), 7.98 (d, 2 H, J = 7.9 Hz),
Anal. Calcd for C H N O (740.71): C, 61.62; H, 4.90; N, 7.56.
3
8
36
4
12
Found: C, 61.75; H, 4.82; N, 7.67.
1
1.06 (s, 2 H).
1
3
Pentyl 7,14-Dioxo-6,7,8,13,14,15-hexahydrodiben-
zo[b,h][1,4,7,10]dioxadiazacyclododecine-10-carboxylate (3g)
Colorless crystals; mp 148–151 °C.
IR (KBr): 3360, 3250, 3080, 2959, 1719 (s), 1695 (s), 1651 cm–1 (s).
C NMR (CDCl , 62.5 MHz): d = 70.5, 118.2, 122.1, 123.0, 123.5,
3
1
25.7, 126.8, 132.4, 135.5, 148.4, 167.9.
+
+
MS: m/z (%) = 349 (M + 1, 25.3), 348 (M , 100), 272 (2.6), 198
(
(
13.7), 184 (60.5), 169 (58.2), 154 (8.9), 141 (4.5), 122 (8.9), 108
1.9), 92 (6.9), 76 (15.4), 52 (54.9).
1
H NMR (CDCl , 250 MHz): d = 0.86–0.94 (complex, 5 H), 1.53–
3
1
2
1
.70 (complex, 4 H), 4.24 (t, 2 H, J = 6.8 Hz), 4.50 (s, 2 H), 4.55 (s,
H), 6.82–6.91 (complex, 4 H), 7.79–7.92 (complex, 3 H), 8.29 (s,
H), 9.11 (s, 1 H).
Anal. Calcd for C H N O (348.35): C, 68.96; H, 4.63; N, 8.04
Found: C, 68.82; H, 4.50; N, 7.93.
20
16
2
4
Synthesis 2006, No. 6, 999–1004 © Thieme Stuttgart · New York

PAPER
Macrocyclic Diamides by Fast Addition Method
1003
1
3
C NMR (CDCl , 62.5 MHz): d = 16.9, 22.9, 26.5, 34.6, 64.3, 70.2,
(3.2), 290 (18.7), 275 (9.7), 192 (78.0), 178 (100), 164 (11.6), 150
(40.7), 129 (4.0), 122 (33.5), 108 (2.7), 92 (11.4), 52 (26.6).
3
7
1
1.9, 117.5, 118.4, 122.1, 124.3, 124.5, 127.3, 128.3, 129.8, 132.8,
36.2, 149.3, 149.6, 165.9, 167.5, 168.6.
Anal. Calcd for C H N O (909.03): C, 66.06; H, 6.65; N, 6.16.
5
0
60
4
12
+
+
MS: m/z (%) = 413 (M + 1, 11.1), 412 (M , 14.9), 354 (1.1), 290
Found: C, 65.94; H, 6.54; N, 5.98.
(
(
11.8), 262 (12.7), 248 (35.4), 233 (24.7), 192 (8.4), 178 (100), 164
18.8), 136 (10.6), 122 (9.0), 108 (5.5), 92 (9.0), 42 (11.4).
Acknowledgment
Anal. Calcd for C H N O (412.44): C, 64.07; H, 5.87; N, 6.79.
22
24
2
6
Found: C, 63.95; H, 5.96; N, 6.71.
We thank the Shiraz University council for partial support of this
work. We are also grateful to Dr. A. Khalafi-Nezhad for helpful dis-
cussion and to Mr. H. Sajedian Fard for recording the NMR spectra.
Dipentyl 7,14,23,30-Tetraoxo-6,7,8,13,14,15,22,23,24,29,30,31-
dodecahydrotetrabenzo[b,h,n,t][1,4,13,16,7,10,19,22]tetraoxo-
tetraazacyclotetracosine-10,27-dicarboxylate (4g)
Colorless crystals; mp 218–220 °C.
References
IR (KBr): 3360, 3240, 2935, 3055, 2961, 1719 (s), 1680 (s), 1655
cm (s).
(1) (a) Shamsipur, M.; Fakhari, A. R.; Sharghi, H.; Eshghi, H.;
Ganjali, M. R. Polish J. Chem. 2002, 76, 1665; Chem. Abstr.
2003, 138, 244761. (b) Shamsipur, M.; Rouhani, S.; Ganjali,
M. R.; Sharghi, H.; Eshghi, H. Sensors and Actuators B
–
1
1
H NMR (CDCl , 250 MHz): d = 0.89–1.03 (complex, 10 H), 1.59–
3
1
4
2
.69 (complex, 8 H), 4.31 (t, 4 H, J = 7.0 Hz), 4.72 (s, 4 H), 4.77 (s,
H), 7.02–7.07 (complex, 8 H), 7.91–8.02 (complex, 6 H), 8.14 (s,
H), 9.21 (s, 2 H).
1
999, 59, 30. (c) Shamsipur, M.; Rouhani, S.; Ganjali, M.
R.; Eshghi, H.; Sharghi, H. Microchem. J. 1999, 63, 202.
d) Shamsipur, M.; Rouhani, S.; Sharghi, H.; Ganjali, M. R.;
(
1
3
C NMR (CDCl , 62.5 MHz): d = 16.7, 22.2, 27.1, 34.2, 63.4, 70.9,
3
Eshghi, H. Anal. Chem. 1999, 71, 4938. (e) Ostaszewski,
R.; Stevens, T. W.; Verboom, W.; Reinhoudt, D. N. Recl.
Trav. Chim. Pays-Bas 1991, 110, 198. (f) Bartsch, R. A.;
Chapoteau, E.; Czech, B. P.; Krzykawski, J.; Kumar, A.;
Robinson, T. W. J. Org. Chem. 1994, 59, 616.
7
1
2.4, 117.2, 119.1, 122.2, 124.8, 125.2, 127.7, 128.5, 130.1, 132.2,
35.6, 149.1, 149.8, 164.4, 167.9, 168.7.
MS: m/z (%) = 577 (2.1), 466 (1.4), 452 (2.3), 428 (5.9), 412 (7.1),
82 (2.1), 354 (3.4), 341 (5.4), 339 (3.9), 297 (2.4), 296 (4.9), 220
3.3), 203 (100), 150 (2.5), 122 (6.9), 108 (2.5), 92 (2.9), 76 (7.2),
2 (17.1).
3
(
5
(2) (a) Sharghi, H.; Massah, A. R.; Eshghi, H.; Niknam, K. J.
Org. Chem. 1998, 63, 1455. (b) Sharghi, H.; Niknam, K.;
Pooyan, M. Tetrahedron 2001, 57, 6057. (c) Sharghi, H.;
Nasseri, M. A.; Niknam, K. J. Org. Chem. 2001, 66, 7287.
Anal. Calcd for C H N O (824.87): C, 64.07; H, 5.87; N, 6.79.
44
48
4
12
Found: C, 64.15; H, 5.98; N, 6.65.
(
3) (a) Bondy, C. R.; Loeb, S. J. Coord. Chem. Rev. 2003, 240,
7. (b) Wisner, J. A.; Beer, P. D.; Drew, M. G. B.;
7
Octyl 7,14-Dioxo-6,7,8,13,14,15-hexahydrodiben-
zo[b,h][1,4,7,10]dioxadiazacyclododecine-10-carboxylate (3h)
Colorless crystals; mp 135–136 °C.
IR (KBr): 3355, 3240, 3060, 2924, 1721 (s), 1693 (s), 1657 cm–1 (s).
Sambrook, M. R. J. Am. Chem. Soc. 2002, 124, 12469.
4) (a) Krakowiak, K. E.; Bradshaw, J. S.; Izatt, R. M. J. Org.
Chem. 1990, 55, 3364. (b) Kimura, E.; Lin, Y.; Machida, R.;
Zenda, H. J. Chem. Soc., Chem. Commun. 1986, 1021.
(c) Singh, H.; Kumar, S.; Hundal, M. S.; Hundal, G.;
Kaurand, N. Tetrahedron 1997, 53, 1084. (d) Krakowiak,
K. E.; Bradshaw, J. S.; Izatt, R. M. J. Heterocycl. Chem.
(
1
H NMR (CDCl , 250 MHz): d = 0.92 (t, 3 H, J = 6.8 Hz), 1.26–
3
1
.37 (complex, 10 H), 1.76 (m, 2 H), 4.30 (t, 2 H, J = 7.1 Hz), 4.69
(
s, 2 H), 4.74 (s, 2 H), 7.01–7.09 (complex, 4 H), 7.97 (d, 1 H,
1
1
990, 27, 1585. (e) Zeng, F.; Zimmerman, S. C. Chem. Rev.
997, 97, 1681. (f) Izatt, R. M.; Christensen, J. J. Synthetic
J = 7.8 Hz), 8.01–8.12 (complex, 3 H), 9.23 (s, 1 H).
1
3
C NMR (CDCl , 62.5 MHz): d = 14.5, 23.1, 26.4, 29.1, 29.58,
3
Multidentate Macrocyclic Compounds; Academic Press:
New York, 1978. (g) Grayson, S. M.; Frechet, J. M. J. Chem.
Rev. 2001, 101, 3819. (h) Lindoy, L. F. J. Iranian Chem.
Soc. 2004, 1, 1; http://www.ics-ir.org/jics.
2
1
9.6, 32.2, 65.8, 72.0, 73.6, 117.5, 118.4, 121.9, 124.5, 124.6,
27.9, 128.6, 130.1, 132.4, 137.2, 149.3, 149.6, 167.4, 168.6.
+
+
MS: m/z (%) = 455 (M + 1, 13.7), 454 (M , 16.7), 332 (9.9), 325
(
(
14.0), 290 (47.1), 275 (15.0), 192 (6.3), 179 (18.7), 178 (100), 164
15.9), 136 (9.9), 122 (7.4), 108 (4.4), 92 (6.7), 52 (9.0).
(5) (a) Gryko, D. T.; Piqtek, P.; Jurzak, J. Tetrahedron 1997, 53,
7957. (b) Jurczak, J.; Stankiewicz, T.; Kasprzyk, S.;
Lipkowski, P. Tetrahedron 1993, 49, 1478.
Anal. Calcd for C H N O (454.52): C, 66.06; H, 6.65; N, 6.16.
Found: C, 66.21; H, 6.51; N, 6.03.
25
30
2
6
(6) (a) Petranek, J.; Ryba, O. Collect. Czech. Chem. Commun.
1980, 45, 1567. (b) Petranek, J.; Ryba, O. Collect. Czech.
Chem. Commun. 1983, 48, 1945.
7) (a) Overman, L. E. J. Org. Chem. 1972, 37, 4214.
Dioctyl 7,14,23,30-Tetraoxo-6,7,8,13,14,15,22,23,24,29,30,31-
dodecahydrotetrabenzo[b,h,n,t][1,4,13,16,7,10,19,22]tetra-
oxotetraazacyclotetracosine-10,27-dicarboxylate (4h)
Colorless crystals; mp 201–204 °C.
(
(
b) Knops, P.; Sendhoff, N.; Mekelburger, H. B.; Vogtle, F.
Top. Curr. Chem. 1992, 161, 1. (c) Bradshaw, J. S.;
Krakowiak, K. E.; Izatt, R. M. Chemistry of Heterocyclic
Compounds, Vol. 51; Wiley: New York, 1993.
(d) Gunnlaugsson, T.; Gunaratne, H. Q. N.; Nieuwenhuyzen,
M.; Leonard, J. P. J. Chem. Soc., Perkin Trans. 1 2002,
IR (KBr): 3362, 3244, 3070, 2926, 1715 (s), 1678 (s), 1661 cm–1 (s).
1
H NMR (CDCl , 250 MHz): d = 0.89 (t, 6 H, J = 6.7 Hz), 1.24–
3
1
.35 (complex, 20 H), 1.72 (m, 4 H), 4.26 (t, 4 H, J = 7.1 Hz), 4.54
1954. (e) Kleefisch, G.; Kreutz, C.; Bargon, J.; Silva, G.;
(
s, 4 H), 4.65 (s, 4 H), 6.98–7.07 (complex, 8 H), 7.55 (d, 2 H,
Schalley, C. A. Sensors 2004, 4, 136.
J = 7.9 Hz), 7.68–7.79 (complex, 4 H), 8.04 (s, 2 H), 9.05 (s, 2 H).
(
8) (a) Alexander, V. Chem. Rev. 1995, 95, 275. (b)Thompson,
M. C.; Busch, D. H. J. Am. Chem. Soc. 1964, 86, 3651.
9) (a) Jurczak, J.; Pietraszkiewiez, M. Top. Curr. Chem. 1985,
1
3
C NMR (CDCl , 62.5 MHz): d = 14.2, 22.8, 26.1, 29.3, 29.9, 30.2,
3
3
1
2.4, 66.2, 71.4, 73.2, 117.1, 118.3, 122.2, 124.8, 125.1, 127.6,
29.2, 129.9, 133.1, 137.5, 149.8, 150.3, 166.5, 167.7, 168.3.
(
130, 183. (b) Jurczak, J.; Gryko, D. T.; Lipkowski, P.;
MS: m/z (%) = 576 (1.5), 454 (2.9), 439 (3.7), 438 (2.5), 424 (2.1),
11 (2.1), 397 (12.8), 396 (21.4), 381 (2.4), 378 (1.7), 348 (2.0), 332
Saíański, P. Rev. High Pressure Technol. 1998, 7, 1236.
4
Synthesis 2006, No. 6, 999–1004 © Thieme Stuttgart · New York

1
004
H. Sharghi, A. Zare
PAPER
(11) (a) Sharghi, H.; Eshghi, H. Tetrahedron 1995, 51, 913.
(
10) (a) Tabushi, I.; Okino, H.; Kuroda, Y. Tetrahedron Lett.
976, 17, 4339. (b) Tabushi, I.; Taniguchi, Y.; Kato, H.
1
(b) Sharghi, H.; Niknam, K.; Massah, A. H. J. Heterocycl.
Chem. 1999, 36, 601. (c) Sharghi, H.; Paziraee, Z. Synthesis
2004, 600.
Tetrahedron Lett. 1977, 18, 1049. (c) Gryko, D. T.; Piatek,
P.; Saíański, P.; Jurczak, J. Tetrahedron: Asymmetry 1998,
9
, 1771. (d) Gryko, D. T.; Piatek, P.; Jurczak, J. Synthesis
(12) Vogel, A. I. Practical Organic Chemistry; Longman, Green
and Co.: London, 1954, 161.
1999, 336. (e) Szczepańska, A.; Saíański, P.; Jurczak, J.
Heterocycles 2000, 52, 537. (f) Achmatowicz, M.;
Szczepańska, A.; Gryko, D. T.; Saíański, P.; Jurczak, J.
Supramol. Chem. 2000, 12, 93. (g) Szczepańska, A.;
Saíański, P.; Jurczak, J. Tetrahedron 2003, 59, 4775.
(13) Wang, X.; Wei, T.; Chen, J.; Li, J. Synth. Commun. 1996, 26,
2765.
(14) Sharghi, H.; Hosseini, S. M. Synthesis 2003, 879.
Synthesis 2006, No. 6, 999–1004 © Thieme Stuttgart · New York