Sodium sulfide on coal fly ash (Na2S/CFA) as a reagent for the synthesis of dithia[3.3]cyclophanes

Article abstract of DOI:10.1139/cjc-2020-0041

The use of coal fly ash as a new support for a reagent for organic synthesis was investigated. Coal fly ash supported sodium sulfide was found to be an effective reagent for the synthesis of dithiacyclophanes, notably giving better results than alumina-supported sodium sulfide.

Full text of DOI:10.1139/cjc-2020-0041

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Sodium Sulfide on Coal Fly Ash (Na2S/CFA) as a Reagent for
the Synthesis of Dithia[3.3]cyclophanes
Marc R. MacKinnon,a Ryan N. Warren,a Simon Brake,a Baozhong Zhang,a Li Wang,b
Graham J. Bodwella,*
a)
Chemistry Department, Memorial University of Newfoundland, St. John’s, NL,
Canada, A1B 3X7.
b)
Institute of Environmental Science, Shanxi University, Taiyuan, Shanxi
030006, China.
Abstract: The use of coal fly ash as a new support for a reagent for organic
synthesis was investigated. Coal fly ash-supported sodium sulfide was found to be
an effective reagent for the synthesis of dithiacyclophanes, notably giving better
results than alumina-supported sodium sulfide.
Key words: solid supports, coal fly ash, cyclophanes, thioethers
Introduction
A
mainstay of cyclophane chemistry is the synthesis of
dithia[3.3]cyclophanes and their subsequent conversion to more strained
[2.2]cyclophanes via a variety of ring contraction reactions.1 Dithia[3.3]cyclophanes
II are typically synthesized from bis(bromomethyl)arenes I (Scheme 1). This can be
3
done directly using Na2S·9H2O2 or Na2S/Al2O3 (Scheme 1A) or indirectly by
conversion of a dibromide I to the corresponding dithiol III followed by either thiol-
bromide coupling, or oxidative homocoupling (disulphide formation) and
subsequent desulfurization (Scheme 1B).4

Page 2 of 17
Direct methods have the advantage of requiring just a single synthetic step,
but their applicability is limited to the synthesis of cyclophanes with two equivalent
aromatic units. The same is true for the indirect method of oxidative homocoupling
of dithiols, but this approach is advantageous when the benzylic bromides are
especially hindered.3b It has also been shown to be applicable within the context of
dynamic covalent chemistry as a means to access higher cyclic oligomers and cage-
type cyclophanes.3a
Scheme 1. Existing methods for the synthesis of dithia[3.3]cyclophanes.
To gain access to cyclophanes with non-equivalent aromatic units, thiol-
bromide coupling is the longstanding method of choice. Of course, it can also be
employed for the synthesis of cyclophanes with equivalent aromatic units and, in
such cases, it usually proceeds more effectively than any of the direct methods. A
drawback of this method is the need for high dilution conditions and long addition
times.
Na2S/Al2O3 was first introduced by Regen5 in 1980 as a reagent for the
synthesis of dialkyl sulfides and was subsequently employed by others for the
synthesis of various cyclic thioethers.6 Its use for the synthesis of dithiacyclophanes

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was first reported by our group3 in 1995 and has since been employed for this
purpose often by us7 and by others.8 The advantages of this reagent over Na2S·H2O
are its ease of handling, lack of odour, shorter reaction times and the need for only
moderate dilution. The yields, however, do not come up to those obtained using
thiol-bromide coupling, so this prompted us to explore ways of addressing this
issue. Initial work in this area was aimed at the investigation of coal fly ash (CFA) as
a solid support for Na2S instead of alumina.
CFA is the air-mobile fine particulate matter expelled along with the flue
gasses from coal-fired boilers in thermal power plants. It constitutes 85-95% of the
residue from the burning of coal and annual production was estimated to exceed
750 million tonnes in 2015.9 The principal constituents of fly ash are SiO2, Al2O3,
Fe2O3 and CaO. The particles are typically spherical and lie in a size range of 0.5–
300, much of which is <75 m.10 Many other minor inorganic constituents are
present and the distribution of the components is variable depending upon the
source of the coal. CFA has been described as “one of the most abundant and
complex anthropogenic materials”.9 Beyond its chemical complexity, the relatively
small particle size represents a clear physical difference between it and the basic
alumina (cf. ≈90 m) used to prepare Na2S/Al2O3.
Although a substantial proportion of the CFA that is produced globally is
being used for purposes such as soil amelioration,9 the production of materials for
use in the construction and ceramics industries,9 depth separation,9 zeolite
synthesis,9 gas absorption11 and wastewater treatment.12 CFA is also finding
increasing use in the field of catalysis.9 This includes numerous examples of CFA-
supported metal catalysts for use in organic synthesis. A very recent example is the
use of Bi2O3-ZnO/CFA as a catalyst for the synthesis of tetrasubstituted imidazoles.13
In contrast, to the best of our knowledge, there do not appear to be any examples of
CFA-supported reagents for application in organic synthesis. We report here the
preparation of Na2S/CFA as a reagent for the synthesis of dithiacyclophanes.
Experimental

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General. All solvents and commercial chemicals were used as received. Fly ash used
for this study came from the Datang International Tuoketuo Power Plant in
Tuoketuo, Inner Mongolia, PRC. Solvents were removed under reduced pressure
using a rotary evaporator. Chromatographic separations were achieved using
Silicycle silica gel 60, particle size 40–63  . Thin-layer chromatography was
performed using precoated plastic-backed POLYGRAM® SIL G/UV254 silca gel
plates, layer thickness 200  . Compounds were visualized using a UV lamp (254
and 365 nm). Melting points were measured using an Opti-Melt apparatus and are
uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a
Bruker Avance III 300 MHz spectrometer using CDCl3 solutions. Chemical shifts are
relative to internal standards: Me4Si (H=0.00 ppm), CHCl3 (H=7.26 ppm) and CDCl3
(C=77.23 ppm). Low-resolution and high-resolution mass spectra were obtained
using an Agilent 1260 Infinity LC-6230 TOF LC/MS instrument.
Preparation of Na2S/CFA. Na2S·9H2O (3.16 g, 13.2 mmol) was dissolved in deionized
H2O (100 mL) and poured onto fly ash (3.02 g) in a 250 mL round-bottomed flask.
The resulting slurry was evaporated to dryness under reduced pressure and then
dried to constant weight under high vacuum to give Na2S/CFA as a brittle, chunky
grey solid (5.15 g, 2.55 mmol/g of Na2S). Prior to use, the reagent was ground using
a mortar and pestle to afford a grey powder. Note: Na2S·9H2O is deliquescent, so it
is important that this compound be in the solid state when used to prepare
Na2S/CFA. Liquefied, or partially liquefied, material will tend to give a reagent with
fewer mmol/g Na2S than expected. For this work, a recently purchased bottle of
Na2S·9H2O with no signs of liquefaction of the contents was employed.
General experimental procedure for the synthesis of dithiacyclophanes.
Bis(bromomethyl)arene (1 eq) was dissolved in 10% EtOH/CH2Cl2 in an Erlenmeyer
flask. Na2S/CFA (3 eq of Na2S) was added in four roughly equal portions over 1 h.
The reaction mixture was stirred at rt until the starting material had been fully
consumed (tlc analysis). The reaction mixture was gravity filtered and the filtrate

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was concentrated under reduced pressure. The residue was subjected to column
chromatography to afford thiacyclophanes.
2,11-Dithia[3.3]metacyclophane (2a). Dibromide 1a (132 mg, 0.500 mmol) and
Na2S/CFA (610 mg, 1.50 mmol Na2S) reacted for 24 h following completion of the
addition of the reagent to afford 2a (51 mg, 0.19 mmol, 75%). Rf (40%
1
dichloromethane/hexanes) = 0.45; mp = 120–121 °C (lit.2b 120–121 °C); H NMR
(300 MHz, CDCl3)  = 6.86 (s, 8H), 3.81 (s, 8H); 13C NMR (75 MHz, CDCl3)  = 135.50,
129.56, 129.15, 129.11, 38.30; HRMS (APPI(+)) calcd for C16H16S2: 272.0693, found:
272.0725.
6,15-Diiodo-2,11-dithia[3.3]metacyclophane (2b). A) Using Na2S/Al2O3: To a well-
stirred solution of 1,3-bis(bromomethyl)-5-iodobenzene (1b)20 (1.00 g, 2.57 mmol)
in 10% ethanol/dichloromethane (167 mL) was added Na2S/Al2O3 (1.89 g, 5.13
mmol Na2S) in two portions at 15 min intervals. The reaction was stirred at room
temperature for 45 min and then filtered through a short plug of Celite®. The
filtrate was concentrated under reduced pressure and the residue was subjected to
column chromatography (19  3.3 cm, 50% dichloromethane/hexanes) to yield 2b
(0.350 mg, 0.668 mmol, 52%) as a white solid. B) Using Na2S/CFA: Dibromide 1b
(195 mg, 0.500 mmol) and Na2S/CFA (0.666 g, 1.50 mmol Na2S) reacted for 24 h
following completion of the addition of the reagent to afford 2b (72 mg, 0.14 mmol,
1
55%). Rf (50% dichloromethane/hexanes) = 0.54; mp = 165–170 °C; H NMR (300
MHz, C6D6)  = 7.01 (d, J= 1.4 Hz, 4H), 6.58 (s, 2H), 3.10 (s, 8H); 13C NMR (75 MHz,
CDCl3)  = 138.99, 136.12, 130.72, 94.16, 37.45; HRMS (APPI(+)) calcd for
C16H14I2S2: 523.8626, found: 523.8609.
6,15-Dimethoxy-2,11-dithia[3.3]metacyclophane (2c). Dibromide 1c (172 mg, 0.585
mmol) and Na2S/CFA (713 mg, 1.76 mmol Na2S) reacted for 24 h following
completion of the addition of the reagent to afford 2c (85 mg, 0.26 mmol, 89%). Rf
14
1
(dichloromethane) = 0.40; mp = 123–125 °C (lit. 121 °C); H NMR (300 MHz,

Page 6 of 17
CDCl3)  = 6.49 (s, 2H), 6.47 (s, 4H), 3.72 (s, 6H); 13C NMR (75 MHz, CDCl3)  =
159.52, 138.42, 124.71, 112.96, 55.29, 37.92; HRMS (APPI(+)) calcd for C18H20O2S2:
332.0905, found: 332.0939.
2,11,20-Trithia[33](1,3,5)cyclophane (4). Tribromide 3 (178 mg, 0.500 mmol) and
Na2S/CFA (0.915 g, 2.25 mmol Na2S) reacted for 24 h following completion of the
addition of the reagent to afford 4 (24 mg, 0.073 mmol, 29%). Rf (50%
15
1
dichloromethane/hexanes) = 0.36; mp = 250–252 °C (lit. 254–255 °C); H NMR
(300 MHz, CDCl3)  = 6.89 (s, 6H) 3.84 (s, 12H); 13C NMR (75 MHz, CDCl3)  = 137.05,
130.25, 38.52; HRMS (APPI(+)) calcd for C18H18S3: 330.0571, found: 330.0578.
2,11-Dithia[3.3]paracyclophane (6). Dibromide 5 (132 mg, 0.500 mmol) and
Na2S/CFA (685 mg, 1.50 mmol Na2S) reacted for 18 h following completion of the
addition of the reagent to afford 6 (32 mg, 0.12 mmol, 49%). Rf (20%
1
dichloromethane/hexanes) = 0.35; mp = 222–225 °C (lit.16 224 °C); H NMR (300
MHz, CDCl3)  = 6.86 (s, 8H), 3.81 (s, 8H); 13C NMR (75 MHz, CDCl3)  = 135.51,
129.58, 38.31; HRMS (APPI(+)) calcd for C16H16S2: 272.0693, found: 272.0692.
8,21-Di-t-butyl-2,15-dithia[3.3](1,3)pyrenophane (8). Dibromide 7 (222 mg, 0.500
mmol) and Na2S/CFA (609 mg, 1.50 mmol Na2S) reacted for 0.5 h following
completion of the addition of the reagent to afford 8 (68 mg, 0.11 mmol, 44%). Rf
(40% dichloromethane/hexanes) = 0.27; mp = 248.2–250.1 °C (lit.8a 246–249 °C); 1H
NMR (300 MHz, CDCl3)  = 8.30 (d, J = 9.2 Hz, 4H), 8.12 (s, 4H), 7.99 (d, J = 9.2 Hz,
4H), 7.03 (s, 2H), 4.40 (s, 8H), 1.54 (s, 18H); 13C NMR (75 MHz, CDCl3)  = 148.97,
132.53, 130.73, 129.23, 128.19, 127.27, 125.50, 123.07, 122.53, 35.66, 35.11, 31.87,
29.71 (one aromatic signal fewer than expected); HRMS (APPI(+)) calcd for
C44H40S2: 632.2571, found: 632.2545.
1,7-Dioxa-15,24-dithia[7.3.3](1,3,5)cyclophane (10a). Dibromide 9a (2.12 g, 3.39
mmol) and Na2S/CFA (2.59 g, 8.49 mmol Na2S) reacted for 23 h following

Page 7 of 17
completion of the addition of the reagent to afford 10a (940 mg, 2.54 mmol, 75%).
Rf (50% dichloromethane/hexanes) = 0.30; mp = 126–128 °C (lit.17 126–128 °C); 1H
NMR (300 MHz, CDCl3)  = 6.75 (s, 2H), 6.40 (s, 4H), 4.11–4.07 (m, 4H), 3.78 (d, J =
14.7 Hz, 4H), 3.74 (d, J = 14.8 Hz, 4H), 1.76 (m, 4H), 1.64–1.55 (m, 2H); 13C NMR (75
MHz, CDCl3)  = 158.03, 138.56, 124.21, 113.50, 65.74, 38.88, 27.38, 21.89; HRMS
(APPI(+)) calcd for C21H24O2S2: 372.1218, found: 372.1289.
1,8-Dioxa-16,25-dithia[8.3.3](1,3,5)cyclophane (10b). Dibromide 9b (220 mg, 0.343
mmol) and Na2S/CFA (343 mg, 0.880 mmol Na2S) reacted for 24 h following
completion of the addition of the reagent to afford 10b (105 mg, 0.272 mmol, 79%).
Rf (50% dichloromethane/hexanes) = 0.30; mp = 163–167 °C (lit.17 165–167 °C); 1H
NMR (300 MHz, CDCl3)  = 6.70 (s, 2H), 6.38 (s, 4H), 3.88–3.84 (m, 4H), 3.79 (d, J =
14.7 Hz, 2H), 3.74 (d, J = 14.7 Hz, 2H), 1.75–1.69 (m, 4H), 1.58–1.55 (m, 4H); 13C
NMR (75 MHz, CDCl3)  = 159.04, 138.51, 124.44, 113.32, 64.60, 38.88, 28.03. 20.71;
HRMS (APPI(+)) calcd for C22H26O2S2: 386.1372, found: 386.1384.
1,9-Dioxa-17,26-dithia[9.3.3](1,3,5)cyclophane (10c). Dibromide 9c (200 mg, 0.305
mmol) and Na2S/CFA (345 mg, 0.91 mmol Na2S) reacted for 24 h following
completion of the addition of the reagent to afford 10c (120 mg, 0.199 mmol, 65%).
Rf (50% dichloromethane/hexanes) = 0.40; mp = 157–160 °C (lit.18 158–159 °C); 1H
NMR (300 MHz, CDCl3)  = 6.78 (s, 2H), 6.38 (s, 4H), 3.85–3.70 (m, 12H), 1.80–1.73
(m, 4H), 1.58–1.52 (m, 4H), 1.40–1.32 (m, 2H); 13C NMR (75 MHz, CDCl3)  = 158.83,
128.42, 124.20, 112.83, 65.48, 33.88, 27.11, 24.69, 24.10; HRMS (APPI(+)) calcd for
C23H28O2S2: 400.1529, found: 400.1591.
1,10-Dioxa-18,27-dithia[10.3.3](1,3,5)cyclophane (10d). Dibromide 9d (203 mg,
0.303 mmol) and Na2S/CFA (357 mg, 0.910 mmol Na2S) reacted for 24 h following
completion of the addition of the reagent to afford 10d (100 mg, 0.241 mmol, 80%).
1
Rf (50% dichloromethane/hexanes) = 0.40; mp = 138-141 °C (lit.18 139–140 °C); H
NMR (300 MHz, CDCl3)  = 6.81 (s, 2H), 6.37 (s, 4H), 3.82–3.75 (m, 12H), 1.76–1.68

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(m, 4H), 1.58–1.48 (m, 4H), 1.42–1.36 (m, 4H); 13C NMR (75 MHz, CDCl3)  = 158.82,
138.43, 124.11, 112.88, 66.35, 38.78, 28.43, 27.10, 23.70; HRMS (APPI(+)) calcd for
C24H30O2S2: 414.1686, found: 414.1742.
15,24-Dithia[7.3.3](1,3,5)cyclophane (12a). Dibromide 11a (250 mg, 0.401 mmol)
and Na2S/CFA (453 mg, 1.23 mmol Na2S) reacted for 18 h following completion of
the addition of the reagent to afford 12a (103 mg, 0.279 mmol, 70%). Rf (20%
dichloromethane/hexanes) = 0.30; mp = 144–147 °C (lit.19 145.5–146.5 °C); 1H NMR
(300 MHz, CDCl3)  = 7.10 (s, 2H), 6.65 (s, 4H), 3.83 (d, J = 15.3 Hz, 4H), 3.77 (d, J =
15.3 Hz, 4H), 2.37–2.33 (m, 4H), 1.56–1.52 (m, 4H), 1.16–1.08 (m, 6H); 13C NMR (75
MHz, CDCl3)  = 142.88, 137.03, 128.71, 127.10, 39.22, 34.10, 28.83, 26.49, 26.28;
HRMS (APPI(+)) calcd for C23H28S2: 368.1632, found: 368.1641.
16,25-Dithia[8.3.3](1,3,5)cyclophane (12b). Dibromide 11b (230 mg, 0.360 mmol)
and Na2S/CFA (424 mg, 1.08 mmol Na2S) reacted for 19 h following completion of
the addition of the reagent to afford 12b (119 mg, 0.311 mmol, 87%). Rf (20%
1
dichloromethane/hexanes) = 0.30; mp = 118–120 °C (lit.19 119–121 °C); H NMR
(300 MHz, CDCl3)  = 7.19 (s, 2H), 6.65 (s, 4H), 3.83 (s, 8H), 2.39–2.37 (m, 4H), 1.41–
1.38 (m, 4H), 1.31–1.26 (m, 4H), 1.01–0.97 (m, 4H); 13C NMR (75 MHz, CDCl3)  =
137.19, 126.63, 127.40, 120.33, 39.66, 35.45, 29.40, 26.01, 24.54; HRMS (APPI(+))
calcd for C24H30S2: 382.1789, found: 382.1793.
17,26-Dithia[9.3.3](1,3,5)cyclophane (12c). Dibromide 11c (230 mg, 0.352 mmol)
and Na2S/CFA (399 mg, 1.05 mmol Na2S) reacted for 18 h following completion of
the addition of the reagent to afford 12c (99 mg, 0.250 mmol, 71%). Rf (20%
1
dichloromethane/hexanes) = 0.30; mp = 156–159 °C (lit.19 158–159 °C); H NMR
(300 MHz, CDCl3)  = 7.12 (s, 2H), 6.63 (s, 4H), 3.86 (d, J = 14.9 Hz, 4H), 3.76 (d, J =
14.9 Hz, 4H), 2.36 (t, J = 7.7 Hz, 4H), 1.58–1.49 (m, 4H), 1.33–1.28 (m, 10H); 13C NMR
(75 MHz, CDCl3)  = 142.54, 137.09, 128.66, 126.44, 39.11, 33.92, 27.39, 26.40,
25.41, 24.88; HRMS (APPI(+)) calcd for C25H32S2: 396.1945, found: 396.1948.

Page 9 of 17
18,27-Dithia[10.3.3](1,3,5)cyclophane (12d). Dibromide 11d (202 mg, 0.303 mmol)
and Na2S/CFA (347 mg, 0.910 mmol Na2S) reacted for 18 h following completion of
the addition of the reagent to afford 12d (105 mg, 0.256 mmol, 84%). Rf (20%
1
dichloromethane/hexanes) = 0.30; mp = 173–177 °C (lit.20 175–177 °C); H NMR
(300 MHz, CDCl3)  = 7.10 (s, 2H), 6.63 (s, 4H), 3.83 (d, J = 14.9 Hz, 4H), 3.76 (d, J =
14.9 Hz, 4H), 2.34–2.29 (m, 4H), 1.48–1.25 (m, 14H); 13C NMR (75 MHz, CDCl3)  =
142.71, 137.20, 128.75, 126.48, 38.99, 35.55, 29.56, 28.49, 26.67, 26.33; HRMS
(APPI(+)) calcd for C26H34S2: 410.2102, found: 410.2088.
Results and Discussion
Na2S/CFA was prepared in a fashion analogous to that of Na2S/Al2O3.3
Whereas Na2S/Al2O3 is normally obtained as a free-flowing pale pink solid,
Na2S/CFA was obtained as a brittle, chunky grey solid. When used in this form, poor
results were obtained, but when the reagent was ground with a mortar and pestle
prior to use, the results were much better. The reagent gradually loses its
effectiveness over the course of a few weeks as it changes from a free-flowing grey
powder to a brick-like grey solid, likely due to the hygroscopic nature of CFA. The
shelf-life of Na2S/CFA appears to be significantly shorter than that for Na2S/Al2O3
and it is best to use freshly prepared and to store it under an inert atmosphere.
The reaction of 1,3-bis(bromomethyl)benzene (1) with Na2S/CFA under the
conditions used for reactions Na2S/Al2O3 led to the formation of 2,11-
dithia[3.3]metacyclophane in 75% yield (Table 1, Entry 1). This is not only much
better than the best reported yield using Na2S·9H2O (48%),2 but also significantly
better than that obtained using Na2S/Al2O3 (65%).3 It even comes close to the best
reported yield using thiol-bromide coupling (80%).21
Diiodocyclophane 2b was not previously known, but the iodide substituents
offers interesting opportunities for cross-coupling reactions,22 possibly leading to
interesting macrocyclic cyclophanes. Accordingly, reactions of 1b with both
Na2S/Al2O3 and Na2S/CFA were performed (Table 1, Entry 2), giving yields of 52%

Page 10 of 17
and 55%, respectively. In this case, the benefit of using Na2S/CFA was slight. In
contrast, the reaction of 1c with Na2S/CFA (89%) proved to be superior even to the
thiol-bromide coupling, which afforded dimethoxycyclophane 2c in just 49% yield
(Table 1, Entry 3).14
Chart 1. Dibromides used in this study and the corresponding dithiacyclophanes
obtained using Na2S/CFA.

Page 11 of 17
Table 1. Yields of dithiacyclophanes using Na2S/CFA and other methods.
Entry
Substrate Product
Isolated Yield (%)
Aa (lit.)
Bb (lit.)
Cc (lit.)
Dd,e
75
55
89
29
49
44
75
79
65
80
70
86
71
84
1
1a
1b
1c
2a
48 (2)
65 (3)
52e
80 (21)
2
2b
–
–
3
2c
–
–
49 (14)
4
3
4
24 (15)
–
5 (23)
5
5
6
–
–
–
–
–
–
–
–
–
–
–
52 (24)
6
7
8
14 (8a)
71 (17)
68 (17)
49 (18)
58 (18)
39 (19)
59 (19)
45 (19)
49 (20)
–
–
–
–
–
–
–
–
–
7
9a
9b
9c
10a
10b
10c
10d
12a
12b
12c
12d
8
9
10
11
12
13
14
9d
11a
11b
11c
11d
a Using Na2S·9H2O.
b Using Na2S/Al2O3.
c Using thiol-bromide coupling.
d Using Na2S/CFA.
e This work.
Trithiacyclophane 4 has only ever been obtained in low yield using either
Na2S·9H2O (24%)15 or thiol-bromide coupling (5%).23 Indeed, this is a rare case
where thiol-bromide coupling is inferior to direct methods. The use of Na2S/CFA
resulted in a small improvement in the yield of 4 (29%) (Table 1, Entry 4), but still
well behind the >65% yield reported by Johnson using SbCl3-mediated oxidative

Page 12 of 17
homocoupling followed by desulfurization.4a Paracyclophane 6 was obtained in
49% yield from dibromide 5 (Table 1, Entry 5), which is just shy of the 52% yield
reported for a thiol-bromide coupling.24 Dibromide 7 reacted to afford
(1,3)pyrenophane 8 in 44% yield (Table 1, Entry 6), which greatly exceeds the 14%
yield reported using Na2S/Al2O3.8a
Two series of dibromides, 9a-d and 11a-d, reacted with Na2S/CFA to afford
the corresponding series of tethered dithiacyclophanes 10a-d and 12a-d (Table 1,
Entries 7–14), which serve as key intermediates in the synthesis of
[n](2,7)pyrenophanes.15,16,17,18 and other (2,7)pyrenophanes7,8b,25 In every case, the
yields were found to exceed those using Na2S/Al2O3. For the systems with oxygen-
containing long bridges 10a-d, the average increase in yield was 13.3%, and for
those with purely aliphatic long bridges 12a-d, the average increase in yield
(29.8%) was much more pronounced. Several of the reactions leading to 10a-d and
12a-d have been performed several times and only small variations in yield have
been obtained.
Na2S/CFA was found to give better results than Na2S·9H2O (2 examples),
which was already known to be a less-effective method. More importantly, it was
found to show consistent and significant improvement over Na2S/Al2O3. For the 11
examples that were investigated, the average increase in yield was 19.5%. Even
more encouraging was the performance of Na2S/CFA compared to thiol-bromide
coupling, which has long been regarded as the method of choice for
dithiacyclophane synthesis. For the 4 cases that were examined, Na2S/CFA gave
only slightly reduced yields for 2 of them and significantly improved yield in the
other 2.
While Na2S/CFA clearly outperforms Na2S/Al2O3, the reasons for its
superiority are not so clearly identifiable. As stated earlier, the main differences
between the alumina used to prepare Na2S/Al2O3 and CFA are particle size and
chemical composition. If the chemical composition of the support plays no role,
then it may simply be related to the relatively small particle size of CFA. On the
other hand, the highly complex nature of CFA9 raises the possibility that one or more
of its components, even very minor ones, are involved in the chemistry. The results

Page 13 of 17
of this preliminary study do not provide any evidence to support or refute either of
these notions and far more detailed studies will be required to provide meaningful
answers. Whatever the reasons, there is no doubt that the change in supporting
Na2S with alumina to CFA was beneficial in the synthesis of dithiacyclophanes. CFA
may then also be beneficial when used as a support for other reagents.
Conclusions
CFA-supported sodium sulfide (Na2S/CFA) has been found to be superior to
both Na2S·9H2O and alumina-supported sodium sulfide (Na2S/Al2O3) for the
synthesis dithiacyclophanes from bis(bromomethyl)arenes. It even outperformed
thiol-bromide coupling in some cases and was only slightly less effective when it did
not. Although the reasons for the improved yield have not been firmly established,
the results suggest that CFA deserves to be investigated further as a solid support
for other reagents in organic synthesis.
Acknowledgements
The Natural Science and Engineering Research Council (NSERC) of Canada
and the Hundreds of Talents program of Shanxi Province (Grant No.
205653901018) are gratefully acknowledged for financial support of this work
(G.J.B.).
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Scheme 1. Existing methods for the synthesis of dithia[3.3]cyclophanes.
Chart 1. Dibromides used in this study and the corresponding dithiacyclophanes
obtained using Na2S/CFA.
Table 1. Yields of dithiacyclophanes using Na2S/CFA and other methods.