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dichloromethane for 12 h in a Soxhlet extractor. The blue solid brine (3 ꢁ 30 mL), saturated NH4Cl solution (3 ꢁ 30 mL), water
was dried under reduced pressure to afford the mixture of non- (30 mL) and dried with MgSO4. The solvent was evaporated and
substituted A4-ZnPc and mono-substituted A3B-ZnPc phthalo- the resulting oil was puried by column chromatography
cyanine (where A4 stands for four unsubstituted isoindoles of (hexane/AcOEt, 80 : 20) to obtain 4-(4-((trimethylsilyl)ethynyl)
the ZnPc and A3 for three unsubstituted isoindoles, B stands for phenoxy)phthalonitrile (3) as a white powder (420 mg, 81%).
the alkyne-containing isoindole; 400 mg of mixture, 25% cycli-
sation yield).
1H NMR (300 MHz, CDCl3, 300 K): d (ppm) ¼ 0.11 (s, 9H,
Si(CH3)3); 6.85 (d, 3J ¼ 8.7 Hz, 2H, H5); 7.07 (dd, 3J ¼ 8.5 Hz, 4J ¼
1H NMR (300 MHz, DMSO-d6, 298 K): d (ppm) ¼ 4.28 (s, 1H); 2.6 Hz, 1H, H2); 7.13 (d, 4J ¼ 2.6 Hz, 1H, H1); 7.39 (d, 3J ¼ 8.6 Hz,
7.55 (d, J ¼ 8.0 Hz, 2H); 7.67 (d, J ¼ 8.1 Hz, 1H); 7.81 (d, J ¼ 8.0 2H, H4); 7.57 (d, 3J ¼ 8.7 Hz, 1H, H3). 13C NMR (75 MHz, CDCl3,
Hz, 2H), 8.1 (m, 16H); 8.3 (s, 1H); 8.77 (d, J ¼ 8.1 Hz, 1H); 8.90 300 K): d (ppm) ¼ 5.1; 100.0; 110.0; 114.1; 120.6; 121.1; 122.1;
(m, 2H); 8.99 (m, 14H). MALDI-TOF MS: m/z ¼ 576.23 [ZnPc + 125.5; 124.7; 128; 128.5; 139.2; 141.6; 159.6; 165.4. MS ESI-Q: m/
H]+ (calcd for C32H17N8Zn+: 577.09), 692.5 [M + H]+ (calcd for z calc. ¼ 339.3 [M + Na]+ (calcd. for C18H9N4O2+: 339.09).
C
40H21N8OZn+: 693.11). UV-Vis (DMSO), lmax (nm) (0.1033): 344
4-(4-Bromophenoxy)phthalonitrile (4d). A mixture of 4-nitro-
(41.3), 603 (21.3), 640 (19.5), 667 (142.2).
phthalonitrile (1 g, 5.8 mmol), 3-bromophenol (1 g, 5.8 mmol)
4-(Carboxylato)phenoxy)phthalonitrile (4a). This compound and potassium carbonate (1.6 g, 11.6 mmol) was stirred in DMF
was synthesized by adapting the method described by Erdem (20 mL) at room temperature during 2 hours. Aer addition of
et al.29 and modied as follows (adapted for this regioisomer and 20 mL of water, the resulting precipitate was ltered off and
improvements are T conditions, solvent, and yields). A suspension washed with water (3 ꢁ 10 mL). The white-pink solid obtain was
of 4-nitro-phthalonitrile (3 g, 17.3 mmol), 3-hydroxybenzoic acid dry under reduce pressure to afford compound 4 (1.73 g, 95%).
(2.39 g, 17.3 mmol) and potassium carbonate (9.56 g, 75.2 mmol)
1H NMR (300 MHz, DMSO-d6, 298 K): d (ppm) ¼ 7.31 (d, 3J ¼
were stirred in DMF (30 mL) at room temperature during 15 hours. 8.8 Hz, 2H, H5); 7.58 (dd, 3J ¼ 8.6 Hz, 4J ¼ 2.6 Hz, 1H, H2); 7,63
Aer addition of 100 mL of 1 M hydrochloric acid, the resulting (d, 4J ¼ 2.6 Hz, 1H, H1); 7.92 (d, 3J ¼ 8.8 Hz, 2H, H4); 8,08 (d, 3J ¼
precipitate was ltered off and washed with water (3 ꢁ 50 mL). The 8.6 Hz, 1H, H3).
solid obtain was dry under reduce pressure (3.97 g, 98%).
1H NMR (300 MHz, DMSO-d6, 300 K): d (ppm) ¼ 7.45 (m, 2H);
Materials and methods
Chemicals
3
7.62 (m, 2H); 7.85 (m, 2H); 8.10 (d, J ¼ 8.7 Hz, 1H); 13.23 (s
broad, 1H). 13C NMR (75 MHz, DMSO-d6, 300 K): d (ppm) ¼
108.7; 115.3; 115.8; 116.8; 120.6; 122.4; 123.0; 124.7; 126.4;
Chemicals used in this study are from various providers: Acros
Organics [3-hydroxybenzoic acid (99%, ref. 120981000), 4-amino-
phenol (97%, ref. 104272500), 4-bromophenol (97%, ref.
304411000), copper iodide (99.9%, ref. 201500050), 1,8-diazabicyclo
[5.4.0]undec-7-ene (98%, ref. 160615000), 1,2-dicyanobenzene
(98%, ref. 174012500), dimethylsulfoxide (>99.7%, ref. 34844),
octanol (99%, ref. 150630020), tetrakis(triphenylphosphine) palla-
131.0; 133.4; 136.3; 154.0; 160.6; 166.3. MS ESI-Q: m/z ¼ 262.83
[M ꢀ H]ꢀ (calcd for C18H9N4O2 : 263.03).
+
4-(Amino)phenoxy)phthalonitrile (4b). This compound was
synthesized according to a method described by D'Souza et al.30
and modied as follows (improvements are RT conditions,
solvent, and yields). A mixture of 4-nitro-phthalonitrile (3 g, 17.3
mmol), 4-aminophenol (1.89 g, 17.8 mmol) and potassium
dium (99%, ref. 202380010), triethylamine (99%, ref. 157910010),
carbonate (4.78 g, 34.6 mmol) was stirred in DMF (30 mL) at
room temperature during 15 hours. Aer addition of 60 mL of
water, the resulting precipitate was ltered off and washed with
water (3 ꢁ 20 mL). The pale yellow solid obtain was dry under
reduce pressure to afford compound 4 (3.8 g, 94%).
zinc acetate dihydrate (98%, ref. 207640010)], Carlo Erba [potas-
sium carbonate (pure, 359809)], Fisher Chemicals [THF (BHT-
stabilized, ref. T/0701/21), Copper sulfate (II) CuSO4$5H2O (98%,
ref. C/8520/60)], Fluka [N-(3-dimethylaminopropyl)-N0-ethyl-
carbodiimide hydrochloride ($98%, ref. 03450)], IRIS Biotech [32-
azido-5-oxo-3,9,12,15,18,21,24,27,30-nonaoxa-6-azadotriacontan-1-
oic acid (554.59 g molꢀ1, ref. PEG2015)], Sigma-Aldrich [3-
aminopropyltriethoxysilane ($98%, ref. A3648), dimethylforma-
mide (>99%, ref. 15440), ethynyltrimethyl-silane (98%, ref.
101061688), 6-phosphohexanoic acid (97%, 693839) N,N0-dicyclo-
hexylcarbodiimide (99%, D80002), sodium L-ascorbate (98%, ref.
A7631), N-hydroxysuccinimide (98%, ref. 130672), sodium
hydroxide pellets ($98%, ref. S5881) and TCI [4-nitro-1,2-
dicyanobenzene (TCI, >98%, ref. N0524)] and Tioxide® [titanium
dioxide rutile powder]. Chemicals were used as received without
any further purication when no otherwise stated.
1H NMR (300 MHz, DMSO-d6, 300 K): d (ppm) ¼ 5.18 (s, 2H);
6.64 (d, 3J ¼ 8.9 Hz, 2H); 6.85 (d, 3J ¼ 8.9 Hz, 2H); 7.25 (dd, 3J ¼
8.8 Hz, 4J ¼ 2.6 Hz, 1H); 7,6 (d, 4J ¼ 2.6 Hz, 1H); 8.02 (d, 3J ¼ 8.8
Hz, 1H). 13C NMR (75 MHz, DMSO-d6, 300 K): d (ppm) ¼ 106.9;
114.9; 115.4; 116.0; 116.4; 120.7; 121.3; 121.4; 136.1; 143.0;
146.9; 162.2. MS ESI-Q: m/z ¼ 233.87 [M ꢀ H]ꢀ (calcd for
C
14H8N3O: 234.07).
4-(4-((Trimethylsilyl)ethynyl)phenoxy)phthalonitrile (4c). It
was synthesized upon modication of the original procedure
described by us15 that led to a signicant improvement in yields.
A solution of trimethylsilylacetylene (328 mg, 3.34 mmol) in
triethylamine (20 mL) was added to a mixture of de 4-(4-bro-
mophenoxy)phthalonitrile (4) (0.5 g, 1.67 mmol), palladium
(tetrakis-triphenyl)phosphine (193 mg, 0.167 mmol) and copper
Characterizations
iodide (159 mg, 0.835 mmol) under argon atmosphere. The
mixture was heated at 60 C during 2 hours. Aer addition of column chromatography using silica gel (60A, SDS) and a
dichloromethane (30 mL), the organic layer was washed with specic mixture of solvents as described in Section 2.
Chromatography. Compounds 4a–4d were puried on
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6320 | RSC Adv., 2015, 5, 6315–6322
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