PREPARATION OF A CARBAZOLE-BASED MACROCYCLE VIA PRECIPITATION-DRIVEN ALKYNE METATHESIS
Checked by Scott E. Denmark and Christopher R. Butler.
1. Procedure
2. Notes
1.
All glassware was oven-dried at 140 °C overnight.
2.
Carbazole (96%) was purchased from Acros and used as received.
3.
1-Bromotetradecane (97%),
sodium hydride (60% dispersion in mineral oil),
CuI (99.999%),
Pd(PPh3)2Cl2 (98%),
piperidine (redistilled, 99.5+%),
triethylamine (99.5%),
p-nitrophenol (≥ 99%) and grade 62 silica gel with pore size of 150 Å were purchased from the Aldrich Chemical Company, Inc. and used as received unless further purification is indicated.
4.
THF and DMF were dried by standing over 4 Å molecular sieves over night before use. Carbon tetrachloride was distilled over P
2O
5 and stored over 3 Å molecular sieves.
5.
A small portion of compound
1 was further purified by recrystallization from ethanol to afford analytically pure material. The analytical data from compound
1 were as follows: mp 42–44 °C; TLC: R
f = 0.22 (hexanes);
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.87 (t,
J = 7.4 Hz, 3 H), 1.23–1.40 (m, 22 H), 1.87 (tt,
J = 7.3 and 7.3 Hz, 2 H), 4.30 (t,
J = 7.3 Hz, 2 H), 7.22 (dt,
J = 7.8 and 0.9 Hz, 2 H), 7.40–7.48 (m, 4 H), 8.10 (d,
J = 7.8 Hz, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 14.1, 22.7, 27.3, 28.9, 29.3, 29.4, 29.47, 29.54, 29.57, 29.62, 29.64, 31.9, 43.0, 108.6, 118.6, 120.3, 122.8, 125.5, 140.4. IR (KBr): 3048, 2947, 2919, 2869, 2848, 2341, 2360, 1628, 1600, 1485, 1465, 1453, 1371, 1351, 1328, 1235, 1153, 1122 cm
−1; LRMS (EI):
m/
z 363.3, 180.1. Anal. Calcd for C
26H
37NO: C, 85.89; H, 10.26; N, 3.85. Found: C, 86.12; H, 10.66; N, 4.03. The spectroscopic data were in agreement with those previously reported.
2
6.
N-Iodosuccinimide (95%) was purchased from the Aldrich Chemical Company, Inc. and used as received.
7.
The analytical data from compound
2 were as follows: mp 79–80 °C;
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.88 (t,
J = 7.1 Hz, 3 H), 1.22–1.30 (m, 22 H), 1.81 (tt,
J = 7.1 and 7.1 Hz, 2 H), 4.21 (t,
J = 7.4 Hz, 2 H), 7.16 (d,
J = 8.6 Hz, 2 H), 7.70 (dd,
J = 8.6 and 1.7 Hz, 2 H), 8.32 (d,
J = 1.5 Hz, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 14.1, 22.7, 27.2, 28.8, 29.31, 29.35, 29.35, 29.42, 29.51, 29.56, 29.61, 29.63, 29.65, 31.9, 43.2, 81.6, 110.9, 124.0, 129.3, 134.5, 139.5; IR (KBr): 3062, 2921, 2847 1585, 1466, 1428, 1374, 1348, 1312, 1290, 1236, 1216, 1152, 1047, 1014 cm
−1; LRMS (EI):
m/
z 615.1, 431.9, 208.1. These spectroscopic data were in agreement with those previously reported.
2
8.
1-Trimethylsilylacetylene (98+%) was purchased from GFS Chemicals and used as received.
9.
Upon addition of 1-trimethylsilylacetylene, a significant exotherm (15 °C) was observed, and stirring became difficult as the piperidine hydroiodide was formed.
10.
The analytical data from compound
3 were as follows: TLC R
f = 0.32 (
n-hexane/EtOAc, 20/1);
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.28 (s, 18 H), 0.87 (t,
J = 7.1 Hz, 3 H), 1.22–1.31 (m, 22 H), 1.83 (p,
J = 7.1 Hz, 2 H), 4.25 (t,
J = 7.2 Hz, 2 H), 7.29 (d,
J = 8.1 Hz, 2 H), 7.56 (dd,
J = 8.5 and 1.6 Hz, 2 H), 8.19 (d,
J = 1.0 Hz, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 0.15, 14.1, 22.7, 27.2, 28.9, 29.32, 29.34, 29.45, 29.51, 29.57, 29.61, 29.63, 29.65, 31.9, 43.3, 92.0, 106.3, 108.8, 113.7, 122.3, 124.7, 130.0, 140.5; IR (film): 2926, 2854, 2153, 1869, 1629, 1598, 1483, 1406, 1382, 1350, 1318, 1287, 1248, 1202, 1149, 1133, 1059 cm
−1; MS (EI):
m/
z 555.4, 372.1, 73.1. These spectroscopic data were in agreement with those previously reported.
2
11.
A small portion of compound
4 was further purified by column chromatography (
n-hexanes/EtOAc, 100/1 to 20/1) to afford analytically pure material. The analytical data from compound
4 were as follows: TLC R
f = 0.29 (
n-hexanes/EtOAc, 20/1);
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.88 (t,
J = 7.3 Hz, 3 H), 1.22–1.35 (m, 22 H), 1.84 (tt,
J = 7.1 and 7.1 Hz, 2 H), 3.00 (s, 2 H), 4.25 (t,
J = 7.3 Hz, 2 H), 7.32 (d,
J = 8.6 Hz, 2 H), 7.60 (dd,
J = 8.3, 1.5 Hz, 2 H), 8.21 (d,
J = 1.1 Hz, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 14.1, 22.7, 27.2, 28.9, 29.30, 29.33, 29.43, 29.50, 29.56, 29.60, 29.62, 29.64, 31.9, 43.3, 75.4, 84.7, 108.9, 112.7, 122.2, 124.7, 130.1, 140.6; IR (film): 3279 (s), 2924 (s), 2849 (s), 2103 (s), 1630 (m), 1598 (s), 1483 (s), 1381 (m), 1349 (s), 1321 (w), 1290 (s), 1234 (m), 1153 (s), 1134 (m), 882 (s), 812 (s), 728 (w), 681 (m), 653 (s), 614 (s) cm
−1; LRMS (EI):
m/
z 411.3, 228.1, 75.0. Anal. Calcd for C
30H
37N: C, 87.54; H, 9.06; N, 3.40. Found: C, 87.38; H, 8.78; N, 3.63. These spectroscopic data were in agreement with those previously reported.
2
12.
The appearance of more than one
1H NMR singlet around d 3.1 ppm (terminal acetylene) indicated the presence of mono-desilylation side product. In this case,
4 was further purified by column chromatography [
n-hexanes/EtOAc, 100/1 to 20/1, TLC R
f = 0.29 (
n-hexanes/EtOAc, 20/1].
13.
Pd2(dba)3 and PPh3 (99%) were purchased from Strem Chemicals, Inc. and used as received.
14.
4-Benzoyl-4'-bromobiphenyl (99%) was purchased from Lancaster and used as received.
15.
The submitters reported the use of a Kugelrohr short-path distillation apparatus (Cat. No. Z401137-1SET), which was purchased from Aldrich Chemical Company, Inc.
16.
A small portion (500 mg) of compound
5 was further purified by recrystallization from hot
isopropyl acetate (ca. 20 mL) to provide analytically pure material. The analytical data from compound
5 were as follows: mp 162–167 °C; TLC R
f = 0.26 (CH
2Cl
2/
n-hexanes, 1/1);
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.88 (t,
J = 7.1 Hz, 3 H, C
H3), 1.19–1.41 (m, 22 H, C
H2), 1.89 (tt,
J = 7.1, 7.1 Hz, 2 H), 4.31 (t,
J = 7.3 Hz, 2 H), 7.40 (d,
J = 8.4 Hz, 2 H), 7.52 (m, 4 H), 7.61 (tt,
J = 7.5, 1.4 Hz, 2 H), 7.66–7.71 (m, 10H), 7.74 (d,
J = 8.6 Hz, 4 H), 7.85 (m, 4 H), 7.92 (d,
J = 8.4 Hz, 4 H), 8.32 (d,
J = 1.4 Hz, 2 H);
13C NMR (CDCl
3, 125 MHz) δ: 14.1, 22.7, 27.2, 28.9, 29.3, 29.46, 29.51, 29.57, 29.61, 29.62, 29.64, 31.9, 43.4, 87.6, 92.0, 109.1, 113.7, 122.5, 123.8, 124.2, 126.8, 127.2, 128.3, 129.8, 130.0, 130.8, 132.1, 132.4, 136.4, 137.7, 139.2, 140.6, 144.4, 196.3; IR (KBr): 2924, 2851, 2201, 1648, 1600, 1522, 1481, 1384, 1317, 1277, 1150 cm
−1. LRMS (MALDI):
m/
z 923.94, 825.5, 809.5, 755.9, 740.8, 567.4, 551.4, 545.4. Anal. Calcd for C
68H
61NO
2: C, 88.38; H, 6.65; N, 1.52. Found: C, 88.06; H, 6.41; N, 1.70. These spectroscopic data were in agreement with those previously reported.
2
17.
The submitters found that the appearance of more than one
1H NMR triplet around d 4.3 ppm (α-methylene protons on the tetradecyl side chain) indicated the presence of unreacted starting material and/or mono-alkynylated product. In this case,
5 could be further purified by column chromatography [
n-hexanes/CH
2Cl
2, 1/1 v/v, TLC R
f = 0.26 (CH
2Cl
2/
n-hexane, 1/1)].
18.
Gram-scale preparation of trisamidomolybdenum(VI) propylidyne is reported in the preceding
Organic Syntheses report.
19.
A red precipitate was observed during mixing, and was presumably due to the low solubility of the species generated in CCl
4. In the case of chloroform, ethyl acetate or THF as solvent, no precipitate was observed.
20.
Only a portion of monomer
5 dissolved in CCl
4 at the start of the reaction. However, the poor solubility of
5 did not affect the macrocycle synthesis. As the metathesis reaction proceeded, monomer
5 dissolved and was transformed into soluble macrocycles.
21.
In addition to CCl
4, 1,2,4-trichlorobenzene and toluene are alternative solvents for the macrocycle synthesis. The amount of aromatic impurities observed in the reaction (based on
1H NMR analysis) conducted in CCl
4 was less than that observed in toluene.
22.
In a previous report on the small-scale synthesis of macrocycle
6 via precipitation-driven alkyne metathesis,
2 the reaction was conducted at 30 °C. However, for gram-scale preparation, the low solubility of oligomeric intermediates dramatically increased the solution viscosity and made stirring difficult. Raising the reaction temperature from 30 °C to 50 °C greatly improved the intermediate solubility and allowed efficient stirring.
23.
The crude product
6 (after methanol wash, before column separation) was obtained in 98% yield (6.13 g) and contained a small amount of aromatic impurities (mainly 4-benzoyl-4'-bromobiphenyl). Macrocycles of high purity were obtained after column chromatography. The analytical data from compound
6 were as follows: mp 222–224 °C; TLC; R
f = 0.89 (CHCl
3/CH
2Cl
2, 3/1);
1H NMR
pdf (CDCl
3, 500 MHz) δ: 0.88 (t,
J = 7.1 Hz, 12 H), 1.20–1.45 (m, 88 H), 1.90 (tt,
J = 7.1, 7.1, 8 H), 4.31 (t,
J = 7.1 Hz, 8 H), 7.39 (d,
J = 8.5 Hz, 8 H), 7.71 (dd,
J = 8.3, 1.3 Hz, 8 H), 8.42 (d,
J = 0.7 Hz, 8 H);
13C NMR (CDCl
3, 125 MHz) δ: 14.1, 22.7, 27.3, 29.0, 29.35, 29.50, 29.55, 29.60, 29.64, 29.67, 31.9, 43.3, 89.0, 108.9, 114.4, 122.6, 123.9, 129.3, 140.1; IR (KBr): 2922, 2848, 1628, 1599, 1570, 1490, 1382, 1352, 1307, 1283, 1214, 1148, 1131 cm
−1; MS (MALDI):
m/
z 1542.7, 1370.1. Anal. Calcd for C
112H
140N
4: C, 87.22; H, 9.15; N, 3.63; Found: C, 86.84; H, 9.19; N, 3.26. These spectroscopic data were in agreement with those previously reported.
2
24.
The checkers found that accurate analytical data could be obtained from
6 only after thorough drying at 0.3 mm Hg in an Abderhalden apparatus heated with refluxing xylenes.
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
This finding has important practical significance in that it demonstrates that the solubility of longer arylene ethynylene oligomers, especially those overshooting the target macrocycle length, must be taken into consideration to accomplish high-yield macrocycle syntheses. All the intermediate compounds should be sufficiently soluble along the reaction pathway to allow the thermodynamically stable product to be obtained through reversible alkyne metathesis.
It is envisioned that the successful preparation of macrocycles using the precipitation-driven, reversible alkyne-metathesis may open the way to other two-dimensional or three-dimensional arylene ethynylene structures, as well as alkyne-bridged oligomers and polymers.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
Carbazole:
9H-Carbazole; (86-74-8)
1-Bromotetradecane; (112-71-0)
Sodium hydride; (7646-69-7)
N-Iodosuccinimide:
1-Iodo-2,5-Pyrrolidinedione; (516-12-1)
Copper(I) iodide; (7681-65-4)
Dichlorobis(triphenylphosphine)palladium(II); (13965-03-2)
Piperidine; (110-89-4)
1-Trimethylsilylacetylene:
Silane, ethynyltrimethyl-; (1066-54-2)
Tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3]; (52409-22-0)
Triphenylphosphine; (603-35-0)
4-Benzoyl-4'-bromobiphenyl:
ethanone, (4'-bromo[1,1'-biphenyl]-4-yl)phenyl-; (63242-14-8)
Trisamidomolybdenum(VI) propylidyne:
Molybdenum, tris[N-(1,1-dimethylethyl)-3,5-dimethylbenzenaminato]propylidyne-, (T-4)-; (616886-28-3)
p-Nitrophenol:
4-Nitrophenol; (100-02-7)
9-Tetradecylcarbazole:
9-Tetradecyl-9H-carbazole; (20863-25-6)
3,6-Diiodo-9-tetradecylcarbazole:
3,6-Diiodo-9-tetradecyl-9H-carbazole; (197860-64-3)
3,6-Bis[(trimethylsilyl)ethynyl]-9-tetradecylcarbazole:
9H-Carbazole, 9-tetradecyl-3,6-bis[(trimethylsilyl)ethynyl]- ; (197860-65-4)
3,6-Diethynyl-9-tetradecylcarbazole; (188740-71-8)
3,6-Bis(benzoylbiphenyl)ethynyl-9-tetradecylcarbazole:
Methanone, [(9-tetradecyl-9H-carbazole-3,6-diyl)bis(2,1-ethynediyl[1,1'-biphenyl]-4',4-diyl)]bis[phenyl-; (791090-33-0)
Carbazole-based tetrakismacrocycle; (245648-36-6)
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