Synthesis of new lariat ethers containing polycyclic phenols and heterocyclic aromatic compound on graphite surface via mannich reaction

Article abstract of DOI:10.1007/BF03245889

Synthesis of novel lariat ethers containing polycyclic phenols and heterocyclic aromatic compound using graphite via Mannich reaction are herein described. For this purpose N-(methoxymethyl) azacrown ether 4 was synthesized in nearly quantitative yield. The reaction of N-(methoxymethyl) azacrown ether 4 with polycyclic phenols and heterocyclic aromatic compound was performed in 10-20 min in the presence of graphite. The graphite powder can be reused up to five times after simple washing with acetone.

Full text of DOI:10.1007/BF03245889

J. Iran. Chem. Soc., Vol. 7, No. 1, March 2010, pp. 275-288.
JOURNAL OF THE
Iranian
Chemical Society
Synthesis of New Lariat Ethers Containing Polycyclic Phenols and Heterocyclic
Aromatic Compound on Graphite Surface via Mannich Reaction
H. Sharghia,*, R. Khalifeha and A.R. Salimi Benib
aDepartment of Chemistry, Shiraz University, Shiraz 71454, I.R. Iran
bDepartment of Chemistry, Yasouj University, Yasouj, 75918-74831, I.R. Iran
(Received 13 March 2009, Accepted 21 May 2009)
Synthesis of novel lariat ethers containing polycyclic phenols and heterocyclic aromatic compound using graphite via
Mannich reaction are herein described. For this purpose N-(methoxymethyl) azacrown ether 4 was synthesized in nearly
quantitative yield. The reaction of N-(methoxymethyl) azacrown ether 4 with polycyclic phenols and heterocyclic aromatic
compound was performed in 10-20 min in the presence of graphite. The graphite powder can be reused up to five times after
simple washing with acetone.
Keywords: Azacrown ether, Mannich reaction, Graphite, Solvent less
INTRODUCTION
the ion selectivities of the macrocycle [3,4].
We have previously shown that new lariat ethers can be
prepared by the reaction of azacrown ether 3, phenols and
paraformaldehyde on solid supported (CaO and graphite)
[5,6]. In continuation of our interest in Mannich base
synthesis, in peculiar on solid supports, we now described new
method to the aminoalkylation of polycyclic and heterocyclic
aromatic compounds.
The Mannich reaction is one of the most useful synthetic
methods for functionalizing azacrown ethers with proton-
ionizable phenol groups [1].
Phenolic sidearms have been extensively used to enhance
the stability of the macrocyclic ligand for selected metal ions.
The sidearms are often composed of UV-active or
fluorophoric proton-ionizable materials that allow an
analytical
spectrophotometric methods [2].
determination
of
certain
cations
by
EXPERIMENTAL
The present study is a continuation of our efforts to
develop simple and general methods for the preparation of
new lariat ethers. A key element of this research is the
incorporation of additional proton-ionizable ligating units with
chromophoric and fluorophoric abilities onto ion-selective
macrocycles to provide changes in properties of the azacrown
ether upon metal ion binding while maintaining or improving
Instrumentation, Analyses and Starting Materials
NMR spectra were recorded on a Bruker Avance DPX-250
(1H NMR 250 MHz and 13C NMR 62.9 MHz) spectrometer in
pure deuterated solvents with tetramethylsilane as an internal
standard. IR spectra were obtained using a Shimadzu FT-IR
8300 spectrophotometer. Mass spectra were determined on a
Shimadzu GCMS-QP 1000 EX instruments at 70 or 20 ev.
Melting points were determined in open capillary tubes in a
Büchi-535 circulating oil melting point apparatus. The purity
*Corresponding author. E-mail: shashem@susc.ac.ir

Sharghi et al.
determination of the substrates and reaction monitoring were
the residue was dissolved in CHCl3 (100 ml). The organic
layer was washed with saturated sodium bicarbonate solution
(2 × 100 ml), and water (2 × 100 ml), dried (anhydrous
calcium chloride) and CHCl3 was removed under reduced
pressure to give 2 as a yellow oil (90% yield). IR (CH2Cl2):
750.3(m), 1068.5(m), 1186.1(s), 1595(s), 1759(s), 2981.7(w),
3066.6(m) cm-1. 1H NMR (CDCl3, 250 MHz): ꢀ = 1.28 (t, 6H),
4.27 (q, 4H), 4.72 (s, 4H), 6.92 (s, 4H). 13C NMR (CDCl3,
62.9 MHz): ꢀ = 14.5, 61.6, 67.1, 115.4, 122.9, 148.4, 169.4.
5,6,7,8,9,10-Hexahydro-2H-1,13,4,7,10-benzodioxa-
accomplished by TLC on silica gel PolyGram SILG/UV 254
plates. Column chromatography was carried out on columns of
silica gel 60 (70-230 mesh) in glass columns (2-3 cm
diameter) using 15-30 gram of silica gel per one gram of crude
mixture. Chemicals Material were either prepared in our
laboratories or were purchased from Fluka, Aldrich and Merck
Chemical Companies
Synthesis of 1,2-Phenylenedioxy Diacetic Acid (1)
To the mixture of catechol (11 g, 0.1 mol), and
chloroacetic acid (28.4 g, 0.3 mol) at 90 °C on a water-bath, a
solution of NaOH 33% (W/V) (48 g, in 97.5 ml water) was
added dropwise. The mixture was stirred at 90 °C for 2 h, and
after cooling to room temperature, the solution was kept in ice
bath. Then concentrated HCl was added dropwise to the
solution with stirring. The mixture was allowed to warm to
room temperature and the solution was filtered and the white
precipitates were washed with cold water. Crystallization of
the residue from hot water afforded white solid of 1, (20.5 g,
91% yield). m.p.: 178-179 ꢀC, (Lit. [19]: 177-178 ºC). IR
(KBr): 662(w), 753(m), 781(w), 822(w), 858(w), 1062(m),
1193(s), 1209(s), 1232(s), 1402(w), 1433(m), 1508(s),
triaza cyclo pentadecine-3,11 (4H,12H)-dione (3).
A
solution of 1,2-phenylenedioxy dicarboxylicacid diester 2 (2 g,
7.1 mmol) and diethylentriamine (0.73 g, 7.1 mmol) in ethanol
(100 ml) was left at room temperature for overnight. Then
white needles precipitate which were filtered as aza-crown
ether 3 in 80% yield. Decomposed in 233 °C. IR (KBr):
750(s), 1040(s), 1120(s), 1210(s), 1250(vs), 1320(s), 1420(s),
1450(s), 1500(s), 1540(s), 1590(w), 1640(vs), 2850(s),
1
2950(s), 3030(w), 3380(s), 3430(br) cm-1. H NMR (CDCl3,
250 MHz): ꢁ = 1.75 (s, 1H), 2.94 (t, 4H), 3.50 (t, 4H), 4.48 (s,
4H), 6.84-7.00 (m, 4H), 7.81 (s, 2H). 13C NMR (CDCl3, 62.9
MHz): ꢀ = 38.5, 47.8, 67.2, 112.6, 122.4, 146.4, 167.6. Mass
m/z (%): 295(M++2, 0.9), 294 (M++1, 2.9), 293 (M+, 5.4),
225(50.6), 180(10.5), 167(17.3), 150(14.9), 121(17.7),
85(33.6), 69(78.7), 56(78.4), 43(100).
1
1598(w), 740(s), 2535(w), 2631(w), 2850(m) cm-1. H NMR
(DMSO-d6, 250 MHz): ꢁ = 4.68 (s, 4H), 6.88-6.90 (m, 4H).
13C NMR (DMSO-d6, 62.9 MHz): ꢁ = 65.5, 114.4, 121.8,
147.7, 170.7. Mass m/z (%): 228 (M+ +2, 1.7), 227(M++1,
10.1), 226(M+, 87.0), 181(8.9), 168(14.3), 151(27.9),
135(15.2), 123(100), 107(38.7), 81(52.7), 64(43.4), 43(25.7).
[2-(2-Chloro-2-oxoethoxy)phenoxy]acetyl chloride (2a).
[2-(Carboxymethoxy)phenoxy]acetic acid (5.65 g, 0.025 mol)
was heated in thionyl chloride (50 ml) for 4 h at 50-60 ꢀC. The
thionyl chloride was evaporated at low temperature and
residue was recrystallized from petroleum ether to give 2a as a
white cream solid in 85% (5.4 g) yield. m.p.: 48-49 ꢀC, (Lit.
[19]: 48-49 ºC). 1H NMR (CDCl3): ꢀ = 4.99 (s, 4H), 6.78-6.95
(m, 4H); 13C NMR (CDCl3): ꢀ = 73.6, 116.3, 123.5, 146.8,
170.6. Anal. Calcd. for C10H8Cl2O4 (263.074): C, 45.66; H,
3.07. Found: C, 45.75; H, 2.95.
7-(Methoxymethyl)-5,6,7,8,9,10-hexahydro-2H-1,13,4,7,
10-benzodioxatriazacyclopentadecine-3,11(4H,12H)-dione
(4). Azacrown ether 3 (5 mmol) was added to solution of
paraformaldehyde (6 mmol) in 75 ml of dry CH3OH. The
mixture was stirred at room temperature for 24 h. CH3OH was
evaporated under vacuum at 40 ꢀC. N-(Methoxymethyl)
azacrown ether 4 was obtained in quantitive yield. m.p.: 161-
162 ꢀC. IR (KBr): 575(m), 756(s), 822(m), 1053(s), 1130(s),
1223(m), 1265(s), 1427(w), 1512(s), 1543(m), 1593(w),
1686(vs), 2843(m), 3414(s) cm-1. 1H NMR (CDCl3, 250
MHz): ꢁ = 2.96 (t, 4H, J = 5.3 Hz), 3.30 (s, 2H), 3.56 (t, 4H, J
= 5.3 Hz), 4.11 (s, 2H), 6.83-7.03 (m, 4H), 7.42 (s, 2H). 13C
NMR (CDCl3, 62.9 MHz): ꢁ = 35.2, 49.9, 56.0, 67.0, 81.5,
112.7, 121.9, 146.2, 167.4. Mass m/z (%): 307(-OMe, 0.3),
306(16.8), 305(7.0), 194(12.0), 293(2.6), 225(18.1),
155(11.7), 139(39.2), 121(18.3), 85(34.8), 65(8.1), 42(100).
Anal. Calcd. for C16H23N3O6 (337.371): C, 56.96; H, 6.87.
Found: C, 56.82; H, 6.65.
Ethyl 2[2-(2-ethoxy-2-oxoethoxy) phenoxy] acetate (2b).
1,2-Phenylenedioxy diacetic acid (2.26 g, 0.01 mol), ethanol
(75 ml) and concentrated sulfuric acid (0.1 ml) were refluxed
with stirring for 12 h. The ethanol was removed in vaccum and
276

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
General Procedure for Synthesis of Compounds 5-21
N-(Methoxymethyl) azacrown ether (1 mmol),
7-[(8-Hydroxy-7-quinolinyl)methyl]-5,6,7,8,9,10-hexa-
4
hydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-decine-
3,11(4H,12H)-dione (7). Rrecrystallization from EtOAc gave
compound 7 as white powder in 89% yield. m.p.: 222 ꢀC. IR
(KBr): 752(s), 818(m), 1053(s), 1130(s), 1215(s), 1257(s),
1439(m), 1504(s), 1682(vs), 2851(w), 3302(m), 3410(s) cm-1.
1H NMR (CDCl3, 250 MHz): ꢁ = 2.78(t, 4H, J = 5.3 Hz), 3.54
(t, 4H, J = 5.3 Hz), 3.89 (s, 2H), 4.32 (s, 4H), 6.82-7.04 (m,
4H), 7.22 (d, 1H, J = 8.4 Hz), 7.35-7.40 (m, 2H), 7.89 (s, 2H),
8.09 (dd, 1H, J1 = 8.3, J2 = 1.4 Hz), 8.62 (dd, 1H, J1 = 4.2, J2 =
1.5 Hz). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 35.6, 51.1, 52.7,
67.5, 113.2, 117.4, 118.9, 121.7, 122.2, 127.7, 129.8, 135.9,
137.9, 146.8, 148.0, 150.3, 167.3. Anal. Calcd. for C24H26N4O5
(450.487): C, 63.99; H, 5.82. Found: C, 64.14; H, 5.95.
polycyclic phenol or heterocyclic aromatic compound (1.2
mmol), and graphite (1 g) were thoroughly mixed. The
resulting fine powder was transferred to a round-bottom flask
and stirred in an oil bath at 100 ºC for the 10-20 min. After
cooling, acetone was added to the mixture and graphite was
removed by filtration. Evaporation of the solvent under
reduced pressure gave the crude products, which were purified
by flash column chromathography (eluent:n-hexane/EtOAc
1/1) or recrystallized from EtOAc.
7-[(1-Hydroxy-2-naphthyl)methyl]-5,6,7,8,9,10-hexa-
hydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-decine-
3,11(4H,12H)-dione (5). Rrecrystallization from EtOAc gave
compound 5 as white powder in 81% yield. m.p.: 177 ꢀC. IR
(KBr): 752(m), 810(m), 1045(s), 1126(s), 1261(s), 1439(m),
1504(s), 1543(s), 1666(vs), 2851(w), 2924(w), 3290(br) cm-1.
1H NMR (CDCl3, 250 MHz): ꢁ = 2.76 (t, 4H, J = 5.3 Hz), 3.52
(t, 4H, J = 5.3 Hz), 3.91 (s, 2H), 4.50 (s, 4H), 6.93-7.10 (m,
5H), 7.24-7.41 (m, 3H), 7.45 (s, 2H), 7.70 (d, 1H, J = 8.1 Hz),
7.79 (d, 1H, J = 8.3 Hz), 10.24 (s, 1H). 13C NMR (CDCl3, 62.9
MHz): ꢁ = 35.7, 52.7, 58.1, 68.7, 114.2, 115.2, 119.2, 121.4,
123.0, 125.0, 126.1, 126.5, 127.4, 134.1, 147.5, 152.2, 168.3.
Mass m/z (%): 450(M++1, 0.5), 435(0.5), 381(0.4), 367(1.0),
311(0.9), 294(3.4), 293(5.2), 292(3.9), 225(41.0), 162(1.8),
156(63.7), 128(100), 102(26.5), 85(37.5), 69(82.6), 56(63.1).
Anal. Calcd. for C24H26N4O5 (449.499): C, 66.80; H, 6.05.
Found: C, 66.95; H, 6.23.
7-[(5-Chloro-8-hydroxy-7-quinolinyl)methyl]-5,6,7,8,9,
10-hexahydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-
decine-3,11(4H,12H)-dione (8). Rrecrystallization from
EtOAc gave compound 8 as white powder in 92% yield. m.p.:
238 ꢀC. IR (KBr): 751(w), 818(w), 1049(m), 1261(m),
1
1439(m), 1527(m), 1682(s), 2808(m), 3321(m), 3418(m). H
NMR (CDCl3, 250 MHz): ꢁ = 2.79 (t, 4H, J = 5.3 Hz), 3.54 (q,
4H J = 5.3 Hz), 3.87 (s, 2H), 4.40 (s, 4H), 6.80-7.05 (m, 4H),
7.51 (dd, 1H, J1 = 9.1, J2 = 8.5 Hz), 7.52 (s, 1H), 7.82 (s, 2H),
8.42 (dd, 1H, J1 = 8.5, J2 = 1.5 Hz), 8.71 (dd, 1H, J1 = 4.3, J2 =
1.5 Hz). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 35.4, 50.4, 52.6,
67.4, 113.1, 119.5, 122.2, 122.5, 125.5, 128.9, 132.8, 146.7,
148.6, 149.3, 167.4. Mass m/z (%): 484(M+, 0.3), 412(0.2),
372(0.8), 370(1.4), 306(0.5), 305(0.2), 294(10.7), 293(8.2),
292(25.8), 274(0.9), 249(4.1), 225(44.6), 192(47.1),
163(26.7), 128(48.5), 85(58.9), 69(84.7), 56(100). Anal.
Calcd. for C24H25ClN4O5 (484.932): C, 55.44; H, 5.20. Found:
C, 55.29; H, 5.02.
7-[(2-Hydroxy-1-naphthyl)methyl]-5,6,7,8,9,10-hexa-
hydro-2H-1,13,4,7,10-benzodioxatriazacyclopentadecine-
3,11(4H,12H)-dione (6). Rrecrystallization from EtOAc gave
compound 6 as white powder in 83% yield. m.p.: 185-186 ꢀC.
IR (KBr): 748(s), 810(w), 1045(s), 1122(m), 1207(w),
1257(s), 1315(m), 1439(s), 1500(s), 1543(m), 1593(m),
7-[(1-Chloro-4-hydroxy-9-oxo-9H-thioxanthen-3-yl)
methyl]-5,6,7,8,9,10-hexahydro-2H-1,13,4,7,10-benzodioxa-
1
1678(vs), 2847(w), 2916(w), 3406(br) cm-1. H NMR (CDCl3,
triazacyclopentadecine-3,11(4H,12H)-dione
(9).
250 MHz): ꢁ = 2.80 (t, 4H, J = 5.3 Hz), 3.49 (t, 4H, J = 5.3
Hz), 4.17 (s, 2H), 4.44 (s, 4H), 6.80-7.06 (m, 5H), 7.18-7.35
(m, 2H), 7.49 (s, 2H), 7.59 (d, 1H, J = 8.9 Hz), 7.70 (d, 1H, J =
7.2 Hz), 7.87 (d, 1H, J = 8.5 Hz), 9.84 (s, 1H). 13C NMR
(CDCl3, 62.9 MHz): ꢁ = 35.9, 51.3, 53.1, 68.3, 112.5, 114.7,
118.3, 121.4, 122.8, 126.5, 128.7, 129.7, 133.0, 147.2, 154.7,
168.1. Anal. Calcd. for C24H26N4O5 (449.499): C, 66.80; H,
6.05. Found: C, 66.67; H, 5.86.
Rrecrystallization from EtOAc gave compound 9 as white
powder in 71% yield. Decomposed = 220 ꢀC. IR (KBr):
748(s), 806(m), 1045(s), 1122(m), 1261(s), 1299(s), 1435(s),
1500(s), 1543(s), 1593(m), 1678(vs), 2847(w), 3306(br) cm-1.
1H NMR (DMSO-d6, 250 MHz): ꢁ = 2.46 (t, 4H, J = 5.3 Hz),
3.37 (t, 4H, J = 5.3 Hz), 3.74 (s, 2H), 4.43 (s, 4H), 7.00-7.12
(m, 4H), 7.31 (s, 1H), 7.42 (d, 2H, J = 7.2 Hz), 7.58 (t, 2H, J =
7.1 Hz), 8.14 (s, 2H). 13C NMR (DMSO-d6, 62.9 MHz): ꢁ =
277

Sharghi et al.
34.5, 50.7, 53.3, 69.1, 115.8, 122.4, 124.1, 126.2, 126.7,
4.33 (s, 4H), 6.82 (d, 1H, J = 8.3 Hz), 6.88-7.05 (m, 4H), 7.52
(dd, 1H, J1 = 8.4, J2 = 1.9 Hz), 7.68 (d, 1H, J = 1.9 Hz), 7.71
(s, 2H), 9.46 (s, 1H), 10.73 (s, 1H). 13C NMR (DMSO-d6, 62.9
MHz): ꢁ = 35.1, 49.9, 51.9, 67.3, 114.1, 115.6, 121.9, 124.7,
128.1, 129.6, 133.2, 146.7, 161.7, 166.8, 190.7. Mass m/z (%):
429(M++2, 0.3), 428(M++1, 3.0), 427(M+, 5.8), 425(0.4),
356(3.0), 306(1.4), 294(2.0), 293(5.8), 292(12.0), 247(14.7),
225(23.0), 176(12.2), 139(24.9), 121(33.9), 85(62.6),
56(100.0). Anal. Calcd. for C22H25N3O6 (427.451): C, 61.88;
H, 5.90. Found: C, 62.01; H, 6.06.
128.0, 128.7, 129.2, 129.8, 132.4, 134.8, 147.8, 150.2, 167.7,
178.9. Anal. Calcd. for C28H26ClN3O6S (568.041): C, 59.20;
H, 4.61. Found: C, 59.35; H, 4.43.
7-[(4-Hydroxy-1-methyl-9-oxo-9H-thioxanthen-3-yl)
methyl]-5,6,7,8,9,10-hexahydro-2H-1,13,4,7,10-benzodioxa-
triazacyclopentadecine-3,11(4H,12H)-dione
(10).
Rrecrystallization from EtOAc gave compound 10 as white
powder in 75% yield. Decomposed = 226 ꢀC. IR (KBr):
748(s), 810(w), 1045(s), 1122(m), 1211(m), 1257(s), 1304(m),
1439(s), 1500(s), 1543(s), 1593(m), 1678(vs), 2847(w),
N-[(3,11-Dioxo-3,4,5,6,9,10,11,12-octahydro-2H-1,13,4,
7,10-benzodioxatriazacyclopentadecin-7(8H)-yl)methyl]-2-
hydroxybenzamide (13). Rrecrystallization from EtOAc gave
compound 13 as white powder in 77% yield. m.p.: 187-188
ꢀC. IR (KBr): 748(s), 818(w), 1057(s), 1126(m), 1223(s),
1257(s), 1443(m), 1508(s), 1539(s), 1678(vs), 2854(m),
1
2924(w), 3306(br) cm-1. H NMR (DMSO-d6, 250 MHz): ꢁ =
2.54(s, 3H), 2.66 (t, 4H, J = 5.3 Hz), 3.41 (t, 4H, J = 5.3 Hz),
3.74 (s, 2H), 4.47 (s, 4H), 7.04-7.16 (m, 6H), 7.47 (d, 1H, J =
7.7 Hz), 7.63 (t, 1H, J = 7.7 Hz), 8.15 (s, 2H), 8.25 (d, 2H, J =
8.1 Hz), 11.08 (s, 1H). 13C NMR (DMSO-d6, 62.9 MHz): ꢁ =
32.4, 34.5, 50.8, 53.7, 69.1, 115.7, 121.5, 122.4, 125.5, 126.1,
128.7, 129.7, 130.1, 132.0, 132.5, 135.5, 147.7, 149.1, 167.6,
181.5, 183.4. Anal. Calcd. for C29H29N3O6S (547.623): C,
63.60; H, 5.34. Found: C, 63.49; H, 5.45.
1
3286(s), 3418(s) cm-1. H NMR (CDCl3, 250 MHz): ꢁ = 2.67
(t, 4H, J = 5.3 Hz), 3.40 (t, 4H, J = 5.3 Hz), 4.23 (d, 2H, J =
5.4 Hz), 4.38 (s, 4H), 6.80-6.99 (m, 6H), 7.34 (t, 1H, J = 7.4
Hz), 7.54 (s, 2H), 7.81 (d, 1H, J = 7.4 Hz), 8.95 (t, 1H, J = 5.2
Hz), 12.25 (s, 1H). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 35.0,
49.6, 51.5, 67.2, 113.3, 115.1, 117.3, 118.5, 121.7, 127.9,
133.8, 146.2, 159.9, 166.8, 170.3. Anal. Calcd. for C22H26N4O6
(442.465): C, 59.72; H, 5.92. Found: C, 59.90; H, 6.10.
7-(3-Ethyl-2-hydroxybenzyl)-5,6,7,8,9,10-hexahydro-
2H-1,13,4,7,10-benzodioxatriazacyclopentadecine-3,11(4H,
12H)-dione (14). Rrecrystallization from EtOAc gave
compound 14 as white powder in 83% yield. m.p.: 160 ꢀC. IR
(KBr): 748(s), 814(m), 1045(s), 1122(s), 1211(s), 1257(s),
1439(m), 1458(s), 1504(s), 1659(vs), 2827(m), 3329(s) cm-1.
1H NMR (CDCl3, 250 MHz): ꢁ = 0.89 (t, 3H, J = 7.5 Hz), 2.27
(q, 2H, J = 7.5 Hz), 2.65 (t, 4H, J = 5.3 Hz), 3.45 (t, 4H, J =
5.3 Hz), 3.67 (s, 2H), 4.40 (s, 4H), 6.62 (t, 1H, J = 7.4 Hz),
6.75 (d, 1H, J = 6.5 Hz), 6.81-6.96 (m, 5H), 7.38 (s, 2H), 9.03
(s, 1H). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 13.3, 22.1, 35.1,
52.1, 57.1, 68.0, 114.4, 119.0, 120.6, 122.4, 126.3, 128.2,
130.2, 146.8, 153.6, 167.6. Mass m/z (%): 429(M++2, 0.1),
428(M++1, 2.2), 427(M+, 3.0), 425(0.7), 355(3.8), 305(5.2),
294(0.7), 293(3.0), 292(12.0), 247(1.7), 225(16.4), 155(10.5),
139(39.9), 121(40.3), 85(71.1), 56(100.0). Anal. Calcd. for
C23H29N3O5 (427.494): C, 64.62; H, 6.84. Found: C, 64.48; H,
6.98.
7-[(1-Fluoro-4-hydroxy-9-oxo-9H-thioxanthen-3-yl)
methyl]-5,6,7,8,9,10-hexahydro-2H-1,13,4,7,10-benzodioxa-
triazacyclopentadecine-3,11(4H,12H)-dione
(11).
Rrecrystallization from EtOAc gave compound 11 as white
powder in 73% yield. Decomposed = 227 ꢀC. IR (KBr):
748(s), 810(w), 1045(s), 1122(m), 1207(w), 1257(s), 1315(m),
1439(s), 1500(s), 1543(m), 1593(m), 1678(vs), 2847(w),
1
2916(w), 3406(br) cm-1. H NMR (DMSO-d6, 250 MHz): ꢁ =
2.63 (t, 4H, J = 5.3 Hz), 3.37 (t, 4H, J = 5.3 Hz), 3.72 (s, 2H),
4.42 (s, 4H), 6.98-7.14 (m, 4H), 7.43-7.61, 8.11 (s, 2H), 7.21
(d, 1H, J = 7.1 Hz). 13C NMR (DMSO-d6, 62.9 MHz): ꢁ =
34.6, 50.9, 53.1, 68.9, 113.1, 113.5, 115.5, 116.5, 122.3,
126.6, 128.5, 129.3, 132.6, 135.4, 146.8, 147.6, 153.8, 157.9,
167.5, 178.0. Anal. Calcd. for C28H26FN3O6S (551.587): C,
60.97; H, 4.75. Found: C, 61.14; H, 4.58.
3-[(3,11-Dioxo-3,4,5,6,9,10,11,12-octahydro-2H-1,13,4,7,
10-benzodioxatriazacyclopentadecin-7(8H)-yl)methyl]-4-
hydroxybenzaldehyde (12). Rrecrystallization from EtOH
gave compound 12 as white powder in 81% yield. m.p.: 221-
222 ꢀC. IR (KBr): 760(s), 838(m), 1053(s), 1126(s), 1219(s),
1257(s), 1439(m), 1504(s), 1597(s), 1659(vs), 1686(vs),
1
3086(m), 3398(s) cm-1. H NMR (DMSO-d6, 250 MHz): ꢁ =
2.43 (t, 4H, J = 5.3 Hz), 3.31 (t, 4H, J = 5.3 Hz), 3.57 (s, 2H),
278

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
7-(2-Hydroxy-3-isopropyl-6-methylbenzyl)-5,6,7,8,9,10-
hexahydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-
decine-3,11(4H,12H)-dione (15). Rrecrystallization from
EtOAc gave compound 15 as white powder in 85% yield.
m.p.: 202-203 ꢀC. IR (KBr): 752(s), 814(m), 1049(s), 1122(s),
1211(s), 1261(s), 1439(m), 1458(s), 1504(s), 1547(s),
1335(vs), 1295(s), 1257(s), 1218(s), 1128(s), 1085(m),
1
1056(s), 830(m), 817(m), 750(s) cm-1. H NMR (DMSO-d6,
250 MHz): ꢁ = 2.51 (t, 4H, J = 5.3 Hz), 3.37 (t, 4H, J = 5.3
Hz), 3.65 (s, 2H), 4.40 (s, 4H), 6.89 (d, 1H, J = 8.9 Hz), 6.96-
7.11 (m, 4H), 7.80 (s, 2H), 7.95 (dd, 1H, J = 8.9, 2.3 Hz), 8.11
(d, 1H, J = 2.2 Hz). 13C NMR (DMSO-d6): ꢁ = 35.5, 50.6,
52.4, 68.3, 114.7, 115.6, 122.4, 124.7, 126.0, 126.3, 126.6,
139.7, 147.4, 162.6, 167.4. MS m/z (%): 445(M++1, 0.3),
444(M+, 1.3), 427(14.3), 414(0.5), 356(0.4), 340(0.4),
292(4.9), 225(39.2), 207(10.6), 193(5.3), 180(9.7), 167(20.5),
150(19.3), 121(22.3), 113(18.0), 85(48.7), 69(80.7), 56(92.4),
43(100.0). Anal. Calcd. for C21H24N4O7 (444.438): C, 56.75;
H, 5.44; N, 12.61. Found: C, 56.68; H, 5.39; N, 12.43.
7-(1H-Indol-3-ylmethyl)-5,6,7,8,9,10-hexahydro-2H-1,
13,4,7,10-benzodioxatriazacyclopentadecine-3,11(4H,12H)-
dione (18). Rrecrystallization from EtOAc gave compound 18
as white powder in 70% yield. m.p.: 190-191 ꢀC. IR (KBr):
748(s), 818(m), 1049(s), 1126(s), 1219(s), 1257(s), 1439(m),
1504(s), 1535(s), 1597(m), 1686(vs), 2804(w), 2928(w),
3271(m), 3414(s) cm-1. 1H NMR (CDCl3, 250 MHz): ꢁ = 2.75
(t, 4H, J = 5.3 Hz), 3.54 (t, 4H, J = 5.3 Hz), 3.85 (s, 2H), 4.41
(s, 4H), 6.70 (t, 2H, J = 7.4 Hz), 6.85-7.04 (m, 4H), 7.08 (s,
2H), 7.30 (d, 1H, J = 8.1 Hz), 7.61 (s, 2H), 7.63 (d, 1H, J = 7.3
Hz), 8.60 (s, 1H). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 35.6,
46.6, 51.9, 67.6, 110.7, 111.3, 118.9, 119.5, 122.2, 122.5,
124.1, 127.3, 136.4, 146.5, 167.5. Mass m/z (%): 423(M++1,
0.2), 422(M+, 0.5), 421(0.1), 420(0.3), 349(0.8), 306(0.4),
293(0.6), 292(1.5), 280(1.5), 245(1.1), 225(20.2), 167(10.3),
130(100.0), 102(27.7), 85(48.4), 69(82.9). Anal. Calcd. for
C23H26N4O4 (422.477): C, 65.39; H, 6.20. Found: C, 65.54; H,
6.36.
1
1666(vs), 2820(m), 2947(m), 3340(s) cm-1. H NMR (CDCl3,
250 MHz): ꢁ = 0.88(s, 3H), 0.91(s, 3H), 2.13(s, 3H), 2.78 (t,
4H, J = 5.3 Hz), 2.83-290 (m, 1H), 3.48 (t, 4H, J = 5.3 Hz),
3.72 (s, 2H), 4.41 (s, 4H), 6.52 (d, 2H, J = 7.6 Hz), 6.82-6.96
(m, 5H), 7.34 (s, 2H), 9.90 (s, 1H). 13C NMR (CDCl3, 62.9
MHz): ꢁ = 19.7, 22.2, 26.6, 35.5, 53.7, 54.4, 68.5, 113.2,
114.9, 119.1, 121.5, 122.9, 125.2, 133.6, 147.3, 154.2, 168.2.
Mass m/z (%): 457(M++2, 0.3), 456(M++1, 1.8), 455(M+, 2.3),
382(2.0), 294(1.3), 293(7.1), 292(8.6), 249(0.5), 225(33.8),
204(12.1), 167(15.4), 147(28.8), 119(39.1), 85(59.8),
69(100.0). Anal. Calcd. for C22H26N4O6 (442.465): C, 65.91;
H, 7.30. Found: C, 65.79; H, 7.43.
7-(2-Hydroxy-5-methylbenzyl)-5,6,7,8,9,10-hexahydro-
2H-benzo[b][1,4,7,10,13]dioxatriazacyclopentadecine-
3,11(4H,12H)-dione (16). Purification by flash column
chromatography, eluted with n-hexane/ ethyl acetate (1/1),
gave compound 16 as white powder in 87% yield. m.p.: 206
ꢀC. IR (KBr): 3400(s), 3200(br), 2900(m), 2860(m), 2680(vs),
1662(vs), 1598(m), 1540(s), 1506(s), 1438(m), 1259(s),
1215(s), 1128(s), 1047(s), 815(s), 740(s) cm-1. 1H NMR
(CDCl3, 250 MHz): ꢁ = 2.22 (s, 3H), 2.75 (t, 4H, J = 5.3 Hz),
3.54 (t, 4H, J = 5.3 Hz), 3.73 (s, 2H), 4.51 (s, 4H), 6.64 (d, 1H,
J = 8.0 Hz), 6.87-7.07 (m, 6H), 7.56 (s, 2H), 8.14 (s, 1H). 13
C
NMR (CDCl3, 62.9 MHz): ꢁ = 20.8, 36.2, 53.3, 56.0, 68.7,
114.9, 116.1, 122.4, 123.2, 129.5, 130.0, 131.0, 147.6, 154.0,
168.3. MS m/z (%): 415(M++2, 1.2), 414(M++1, 4.2), 413(M+,
10.0), 396(2.4), 341(16.5), 292(37.7), 225(41.9), 206(15.5),
180(12.3), 176(23.2), 162(27.5), 121(93.3), 91(85.4),
85(60.8), 69(60.0), 56(86.6), 43(100.0). Anal. Calcd. for
C22H27N3O5 (413.467): C, 63.91; H, 6.58; N, 10.16. Found: C,
63.75; H, 6.43; N, 9.87.
7-(2-Hydroxy-5-nitrobenzyl)-5,6,7,8,9,10-hexahydro-
2H-benzo[b][1,4,7,10,13]dioxatriazacyclopentadecine-3,11
(4H,12H)-dione (17). Rrecrystallization from EtOH gave
compound 17 as yellow powder in 50% yield. Decomposed =
239.5 °C (decomp.). IR (KBr): 3390(s), 3200(br), 2850(m),
1667(vs), 1600(s), 1550(vs), 1530(vs), 1500(s), 1440(s),
7-[(2-Methyl-1H-indol-3-yl)methyl]-5,6,7,8,9,10-hexa-
hydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-decine-
3,11(4H,12H)-dione (19). Rrecrystallization from EtOAc
gave compound 19 as white powder in 73% yield. m.p.: 192-
193 ꢀC. IR (KBr): 741(s), 818(m), 1049(s), 1122(s), 1223(s),
1257(s), 1439(m), 1508(s), 1535(s), 1597(m), 1678(vs),
1
2804(w), 2893(w), 3329(m), 3406(s) cm-1. H NMR (CDCl3,
250 MHz): ꢁ = 2.37 (s, 3H), 2.74 (t, 4H, J = 5.3 Hz), 3.48 (t,
4H, J = 5.3 Hz), 3.73 (s, 2H), 4.35 (s, 4H), 6.50 (t, 1H, J = 7.5
Hz), 6.83-7.06 (m, 5H), 7.18 (d, 1H, J = 8.1 Hz), 7.52 (d, 1H, J
= 7.5 Hz), 7.54 (s, 2H), 8.03 (s, 1H). 13C NMR (CDCl3, 62.9
MHz): ꢁ = 11.7, 35.7, 47.5, 52.3, 67.2, 107.3, 110.3, 113.0,
279

Sharghi et al.
O
117.9, 119.3, 121.2, 122.2, 128.5, 133.3, 135.1, 146.6, 167.5.
OH
OH 1) 3ClCH2COOH/ NaOH(33%)
90°C, 2 h
O
O
Mass m/z (%): 436(M+, 0.7), 364(1.3), 363(0.5), 294(1.5),
293(1.6), 292(1.8), 280(2.5), 249(0.8), 225(11.9), 157(28.4),
144(100.0), 102(10.2), 85(19.1), 69(34.3). Anal. Calcd. for
C24H28N4O4 (436.504): C, 66.04; H, 6.47. Found: C, 66.18; H,
6.33.
2) HCl(37%)
OH
OH
1
O
O
O
R
O
N
O
O
H
NH2CH2CH2NHCH2CH2NH2
7-(1H-Imidazol-1-ylmethyl)-5,6,7,8,9,10-hexahydro-2H-
1,13,4,7,10-benzodioxatriazacyclopentadecine-3,11(4H,
12H)-dione (20). Rrecrystallization from EtOAc gave
compound 20 as white powder in 82% yield. m.p.: 172-173
ꢀC. IR (KBr): 756(s), 814(m), 1061(s), 1126(s), 1215(s),
1261(s), 1439(m), 1504(s), 1539(s), 1593(w), 1678(vs),
HN
H
N
O
R
3
O
O
2a
2b
R= Cl
R= OCH2CH3
1
2851(w), 3402(s) cm-1. H NMR (CDCl3, 250 MHz): ꢁ = 2.79
Scheme 1
(t, 4H, J = 5.3 Hz), 3.62 (t, 4H, J = 5.3 Hz), 4.49 (s, 4H), 4.90
(s, 2H), 6.86-7.03 (m, 5H), 7.08 (s, 1H), 7.43(s, 2H), 7.53(s,
1H). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 34.8, 49.5, 60.4, 67.3,
113.2, 119.7, 122.4, 129.6, 137.7, 146.3, 167.5. Anal. Calcd.
for C18H23N5O4 (373.406): C, 57.90; H, 6.21. Found: C, 57.78;
H, 6.08.
presence of 33% (w/v) sodium hydroxide solution at 90 °C,
for 2 h to give sodium 1,2-phenylenedioxydiacetate, which
was acidified with concentrated HCl to yield 1,2-phenylene
dioxydiacetic acid 1 in 91% yield. Treatment of diacid 1 with
thionyl chloride give 85% yield of white cream solid of 1,2-
phenylene dioxydiacetyl dichloride 2a. The cyclization
reaction between dicarboxylic acid dichloride 2a and
diethylenetriamine was performed by the preceding procedure
without high dilution technique. This step was carried out with
fast addition of diethylenetriamine in dry ethyl acetate into a
solution of dicarboxylic acid dichloride in dry ethyl acetate
over a few seconds with vigorously stirring at room
temperature. The mixture was stirred for further 20 min to
give compound 3 in 45% yield. We also decided to use a
different pathway to prepare compound 3, as follows.
Treatment of diacid 1 with ethanol in the presence of sulfuric
acid as catalyst under reflux condition for 12 h, gave 90%
yield of dicarboxylic acid diester 2b as a yellow oil. The
cyclization reaction was then performed by mixing of
dicarboxylic acid diester 2b and diethylenetriamine in ethanol
at room temperature and keeping over night without stirring.
After that, azacrown ether 3 was precipitated out as white
needle crystals and filtered in 80% yield. The successful
cyclization at the terminal amine position seems to be due to
the difference in the reactivities between the terminal
(primary) and the secondary amine nitrogens in the starting
diethylenetriamine materials and it appeared to be dependent
on the macrocycle’s ring size.
7-(1H-Benzimidazol-1-ylmethyl)-5,6,7,8,9,10-
hexahydro-2H-1,13,4,7,10-benzodioxatriazacyclopenta-
decine-3,11(4H,12H)-dione (21). Rrecrystallization from
EtOAc gave compound 21 as white powder in 84% yield.
m.p.: 180 ꢀC. IR (KBr): 741(s), 818(m), 1049(s), 1126(s),
1215(m), 1261(s), 1450(m), 1504(s), 1535(s), 1597(w),
1678(vs), 2858(w), 3421(s) cm-1. 1H NMR (CDCl3, 250
MHz): ꢁ = 2.84 (t, 4H, J = 5.1 Hz), 3.61 (t, 4H, J = 5.3 Hz),
4.46 (s, 4H), 5.07 (s, 2H), 6.86-7.05 (m, 4H), 7.13-7.26 (m,
2H), 7.37 (s, 2H), 7.46 (d, 1H, J = 7.9 Hz), 7.77 (d, 1H, J = 7.7
Hz), 7.93 (s, 1H). 13C NMR (CDCl3, 62.9 MHz): ꢁ = 35.2,
50.3, 60.3, 67.5, 109.6, 113.5, 120.5, 122.6, 123.6, 134.3,
143.3, 146.5, 167.6. Anal. Calcd. for C22H25N5O4 (423.465):
C, 62.40; H, 5.95. Found: C, 62.26; H, 6.13.
RESULTS AND DISCUSSION
Aza-crown ethers have been prepared by template effect,
[7] high dilution technique, [8] reaction of diester with
diamine or polyamine [9] or fast addition technique [10].
The reaction sequence leading to the formation of the aza-
crown ether 3 is shown in Scheme 1. Each of the starting
materials for the three step processes is readily available.
Catecol was allowed to react with chloroacetic acid in the
280

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
For synthesis of new lariat ethers, the reaction of the
25% and graphite is better than CaO (entries 2, 3, 5, 6, 8, 9). In
another study to increase the yield, experiments were done
under solven-free condition in the presence of CaO and
graphite. But with these methods yield was very low (27-37
%) (Table 1 entries 13 and 14). Increases of time and
temperature have no effect on the yield (Table 1, entries 15
and 16).
Bogatsky and co-worker reported that secondary amines
can be converted to methoxymethyl amines, which are active
electrophilic reagents in the Mannich reaction and react
azacrown ether 3 with ꢀ-naphtol and paraformaldehyde via
Mannich reaction was chosen as a model and its behavior was
studied under a variety of conditions via TLC and NMR
spectroscopy (Table 1).
Mannich reaction of azacrown ether 3 and ꢀ-naphtol with
appropriate solvent was carried out under reflux conditions
(entries 1, 4, 7). We next screened CaO and graphite for
Mannich reaction of azacrown ether
3 under similar
conditions. We found the yields were further improved to 12-
Table 1. Mannich Reaction of Azacrown Ether 3 (1 mmol) with ꢀ-Naphtol (1 mmol)
and Paraformaldehyde (1.1 mmol) under Various Conditions
Entry
Conditions
T (ºC)
t (min)
Yield (%)a
Ref.
[11]
1
2
Benzene
Reflux
Reflux
120
120
12
16
Benzene/CaO
3
4
5
Benzene/graphite
CCl4
Reflux
Reflux
Reflux
120
120
120
21
10
12
[12]
[11]
CCl4/CaO
6
7
8
9
10
11
12
13
14
15
16
CCl4/graphite
Toluene
Reflux
Reflux
Reflux
Reflux
120
120
120
120
1.5
120
120
20
16
19
22
Toluene/CaO
Toluene/graphite
Al2O3/MW
(GMA)b
25
N.R.
N.R.
N.R.
27
32
35
[13]
[14]
[15]
[5]
100
100
100
100
100
130
(AMA)c
CaO
Graphite
Graphite
20
60
10
[6]
Graphite
37
a Isolated yield. bGraphite/CH3SO3H. cAl2O3/CH3SO3H.
O
O
OH
N
H
OH
N
H
O
O
O
(CH2O)n
N
HN
+
H
N
O
H
N
O
O
Scheme 2
281

Sharghi et al.
readily with electron rich aromatics such as phenols [12].
reflux conditions (entries 1, 3, 5) [11,12]. The final product 5
was obtained in 2 h of heating with low yields (10-19%). We
next screened graphite for Mannich reaction of N-
(methoxymethyl) azacrown ether 4 under similar conditions.
We found the yields were further improved to 16-25% (entries
2, 4, 6). In another study, the effect of microwave was
investigated and it was found that compound 5 was not
prepared under this condition (entry 7) [13]. In an attempt to
“greenfiy” the synthetic procedure and increase its rate and
yield experiments were done under solven-free condition [14].
During the course of our studies aimed at developing solvent-
free procedures, [15-17] we have now discovered that graphite
alone promotes a very efficient Mannich reaction of activated
In view of this subject, the reaction of azacrown ether 3
with paraformaldehyde and methanol at room temperature for
24 h afforded N-(methoxymethyl) azacrown ether 4 in nearly
quantitative yield. N-(Methoxymethyl) azacrown ether 4 was
used in the next step without any purification (Scheme 3).
To exploit a method for preparation of new lariat ethers 5-
21, the reaction of the N-(methoxymethyl) azacrown ether 4 (1
mmol) with ꢁ-naphtol (1 mmol) via Mannich reaction was
chosen as a model and its behavior was studied under a variety
of conditions via TLC and NMR spectroscopy (Table 2).
Condensation of the N-(methoxymethyl) azacrown ether 4
and ꢀ-naphtol with appropriate solvent was carried out under
O
N
O
N
H
O
H
O
CH3OH
(CH2O)n
HN
+
N
rt / 24 h
OCH3
O
O
H
H
N
N
O
O
3
4
Scheme 3
Table 2. Mannich reaction of N-(methoxymethyl) Azacrown Ether 4 (1 mmol) with
ꢀ-Naphtol (1 mmol) under Various Conditions
Entry
1
Conditions
Benzene
T (ºC)
Reflux
t (min)
120
Yield (%)a
12
Ref.
[11]
2
3
4
5
6
7
8
9
10
11
12
13
Benzene/graphite
CCl4
CCl4/graphite
Toluene
Reflux
Reflux
Reflux
Reflux
Reflux
120
120
120
120
120
1.5
120
120
20
21
10
16
19
25
N.R.
N.R.
N.R.
70
75
81
[12]
[11]
Toluene/graphite
Al2O3/MW
(GMA)b
[13]
[14]
[15]
100
100
100
70
100
130
(AMA)c
CaO
Graphite
Graphite
3600
10
Graphite
6
82
a Isolated yield. bGraphite/CH3SO3H. cAl2O3/CH3SO3H.
282

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
and unactivated phenol compounds with N-(methoxymethyl)
azacrown ether 4 (1 mmol) and ꢀ-naphtol (1 mmol) were
mixed thoroughly. The mixture was heated in an oil bath at
100 °C with stirring for 10 min until the reaction was
completed (Scheme 4). The product was isolated by simple
extraction of the solid mass by acetone followed by the usual
workup.
azacrown ether 4 at 100 °C in high yield, without any of the
environmental disadvantages of using toxic solvents.
Moreover the effect of different amount of graphite on the
model compound was studied in another experiment. The
result showed that the best yield was obtained when 1 g of
graphite was used. The increase in amount of graphite had
negligible effects on the efficiency of the reaction.
Furthermore the use of smaller amounts of graphite led to a
pasty reaction mixture which makes the stirring difficult and
so had not good effects on the efficiency of the model
reaction.
A
variety of structurally divergent proton-ionizable
ligating units possessing a wide range of functional groups
was chosen to investigate the scope and the generality of the
graphite promoted Mannich reaction (Table 3).
In a similar manner to the reaction of ꢀ-naphtol, ꢁ-naphtol,
was reacted with N-(methoxymethyl) azacrown ether 4 in the
presence of graphite to produce the corresponding product 2 in
In a typical experiment, graphite, N-(methoxymethyl)
O
O
OH
N
N
H
OH
H
O
O
O
Graphite
+
N
N
OCH3
100ꢀC / 10 min
O
H
N
H
N
O
O
4
5
Scheme 4
Table 3. Mannich Reaction of N-(Methoxymethyl) Azacrown Ether 4 (1 mmol) with Polycyclic Phenols and Heterocyclic
Aromatic Compound (1 mmol)
Poly nuclear phenols or
heterocycles aromatic
Time
(min)
Yield
(%)a
Entry
Amine
Product
O
O
N
H
N
H
OH
OH
O
O
O
O
N
N
1
10
81
OCH3
H
N
H
N
O
O
5
4
O
N
H
O
HO
N
2
10
83
4
O
H
N
HO
O
6
283

Sharghi et al.
Table 3. Continued
O
N
H
OH
O
O
OH
N
N
N
3
4
4
12
12
89
92
H
N
O
O
7
N
H
OH
Cl
OH
Cl
O
O
N
N
N
4
H
N
O
8
O
OH
N
OH
Cl
H
O
O
S
S
N
5
6
7
4
4
4
15
14
16
71
75
73
H
N
O
Cl
O
O
9
O
OH
N
OH
H
O
S
S
N
O
H
N
CH3
O
O
CH3
OH
O
10
O
N
OH
F
H
O
S
S
N
O
H
N
O
F
O
O
11
O
N
H
OH
OH
O
N
8
4
16
81
O
H
N
CHO
CHO
O
12
284

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
Table 3. Continued
O
N
H
O
O
OH
O
OH
N
N
H
9
4
4
4
12
10
10
77
83
85
NH2
O
H
N
O
13
O
N
H
OH
O
O
OH
CH3
N
10
11
CH3
H
N
O
14
O
H3C
HO
N
H
CH3
OH
CH3
CH3
O
N
O
H
N
H3C
H3C
O
15
O
OH
N
H
OH
O
N
12
4
10
87
O
H
N
CH3
O
Me
16
O
N
H
OH
OH
NO2
O
O
N
13
14
4
4
20
12
50
70
H
N
NO2
O
17
O
H
N
N
H
O
H
N
N
O
H
N
O
18
285

Sharghi et al.
Table 3. Continued
O
H
N
N
H
O
O
H
N
N
15
4
4
11
10
73
82
H
N
O
19
O
N
N
H
O
O
N
N
N
16
H
N
HN
O
20
O
N
N
H
O
O
N
N
N
17
4
4
10
14
84
75
H
N
HN
O
21
O
N
H
OH
O
OH
N
18b
O
H
N
O
5
aIsolated yields. bIsolated yields is after 5 time reused graphite.
83% yields (Table 3, entry 2).
ether 4 and thioxantone building blocks allowed the
As expected, various polycyclic phenols were found to
react with N-(methoxymethyl) azacrown ether 4 in the
presence of graphite to give the corresponding lariat ethers in
good to excellent yields. As shown in Table 3, the presented
method is suitable for aminoalkylation of 5-chloro-8-
hydroxyquinoline and 8-hydroxyquinoline.
We decided herein to synthesis some of new lariat ethers
containing thioxanthone derivatives as side arms. The
Mannich reaction between N-(methoxymethyl) azacrown
preparation of three-dimensional new lariat ethers 9-11 (Table
3, entries 5-7).
In the next step, we tried to attach the p-hydroxy benzaldehyde
side arm to the azacrown ether ring by derivatization of N-
(methoxymethyl) azacrown ether 4. The carbonyl group at
para position on the benzo unit of the final lariat ether is
attractive site for functionalization such as imines that lead to
synthesis of new chromogenic lariat ethers.
N-H acids (amides) are appropriate for the functionalization
286

Synthesis of New Lariat Ethers Containing Polycyclic Phenols
Shiraz University. We are also grateful to Mr. H. Sajedian
Fard and Mr. M. S. Darvish Tafvizi for helpful cooperation.
of azacrown ethers using Mannich reaction. Heating N-
(methoxymethyl) azacrown ether 4 with salicylamide at 100
°C for 12 min gave products of aminomethylation in good
yield.
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Aminomethylation of phenols with N-(methoxymethyl)
azacrown ether 4 usually occurs in the positon ortho to the
phenolic OH group even if the para position is unsubstituted.
Possibly preferential attack on the ortho positions is caused by
formation of a six membered transition state where the
phenolic proton activates the aminomethylating reagent [18].
Formation of benzylamine bonds occurred very rapidly within
10-20 min when the phenols had either electron-donating or
electron-withdrawing substituents.
In another study, we used thymol as a phenolic fragment
for the prepration of new lariat ether. For comparison we also
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polycyclic phenols and heterocyclic aromatic compounds
using nontoxic and inexpensive graphite powder. The
advantages of this environmentally benign and safe protocol,
mild reaction conditions, high product yields, short reaction
times, reusability of graphite, and the elimination of solvents.
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