The synthesis of metal-free phthalocyanines from phthalonitriles with hexamethyldisilazane

Article abstract of DOI:10.1246/bcsj.77.1401

Metal-free phthalocyanines were prepared in good yields by heating phthalonitriles with hexamethyldisilazane, (NH₄)₂SO ₄, and DMF. Good yields of metal-free phthalocyanines involving peripherally substituted phthalocyanines were attained with a catalytic amount of hexamethyldisilazane. Naphthalocyanine was also prepared. Additional additives were examined to accelerate the formation of the phthalocyanine framework.

Full text of DOI:10.1246/bcsj.77.1401

Ó 2004 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 77, 1401–1404 (2004) 1401
The Synthesis of Metal-Free Phthalocyanines from Phthalonitriles
with Hexamethyldisilazane
ꢀ
Hitoshi Uchida, Hideyuki Yoshiyama, Paidi Yella Reddy, Shuichi Nakamura, and Takeshi Toru
Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology,
Gokiso, Showa-ku, Nagoya 466-8555
Received January 23, 2004; E-mail: toru@nitech.ac.jp
Metal-free phthalocyanines were prepared in good yields by heating phthalonitriles with hexamethyldisilazane,
(NH4)2SO4, and DMF. Good yields of metal-free phthalocyanines involving peripherally substituted phthalocyanines
were attained with a catalytic amount of hexamethyldisilazane. Naphthalocyanine was also prepared. Additional additives
were examined to accelerate the formation of the phthalocyanine framework.
Metal-free phthalocyanines (H2-Pcs) 2 are an important class
of phthalocyanines. They often serve as precursors not only for
normal metal–Pcs, but also for those not easily obtainable by
direct synthesis from phthalic anhydrides, phthalimides, or
phthalonitriles with metal salts.1 H2-Pcs are usually prepared
from phthalonitriles in alcohols such as 1-pentanol or 2-dimeth-
ylaminoethanol.2 The formation of H2-Pcs is promoted by
the addition of a basic catalyst such as DBN,3 DBU,3 tertiary
amines,3c ammonia,4 benzene tellurolate,5 selenolate5 or thio-
late.5 Recently, the cerium-promoted formation of H2-Pcs in
Scheme 1.
pentanol was reported.6 When alkali metal7 or alkali earth met-
al alkoxides8 are used, H2-Pcs are obtained after acidic treat-
ment of the initial alkali (or alkali earth) metal–phthalocya-
nines. Heating phthalonitriles without a solvent in the presence
of hydroquinone is another effective method.9 In addition to
these phthalonitrile-based syntheses, H2-Pcs are also obtainable
from diiminoisoindolines.10 Recently, we found that hexameth-
yldisilazane (HMDS) is an excellent regent for use in the for-
mation of metal–Pcs from phthalonitriles11 or phthalimides.12
Furthermore, we also reported the first synthesis of H2-Pcs from
phthalimides or phthalic anhydrides upon treatment with
HMDS.13 In continuation of our study to develop new methods
for the preparation of phthalocyanines, we now report a new
convenient route for the synthesis of H2-Pcs from phthaloni-
triles with HMDS.
Results and Discussion
Phthalonitrile 1 was heated with HMDS and DMF14 in a
sealed tube to avoid the evaporation of volatile substances in-
cluding HMDS (Scheme 1). The results obtained under various
conditions are shown in Table 1. The reaction with 1 and
Scheme 2.
ꢁ
HMDS in a molar ratio of 1.0:2.0 for 10 h at 100 C gave no
H2-Pc 2 (entry 1), but heating for 24 h afforded 2 in a 59% yield
mote the formation of the phthalocyanine skeleton.
Since such an effect is not present in the formation of H2-Pc,
an additive such as (NH4)2SO4 is necessary for the acceleration
of the cyclization. HMDS, possibly coordinated with
(NH4)2SO4, activates the cyano group of phthalonitrile for in-
tramolecular cyclization to give the diiminoisoindoline deriva-
tive. This activated HMDS also promotes further intermolecu-
lar reactions. HMDS is requisite for the formation of 2 (entry
ꢁ
(entry 2). Heating at 150 C for 10 and 24 h gave 2 in 23% and
56% yields, respectively (entries 5 and 7). (NH4)2SO4 was
found to accelerate the formation of the phthalocyanine skele-
ꢁ
ton, giving 2 in 68% and 72% yields for 24 h at 100 C and
ꢁ
150 C, respectively (entries 4 and 8). In the preparation of
metal–Pcs, a metal template effect would be expected to pro-
Published on the web July 9, 2004; DOI 10.1246/bcsj.77.1401

1402 Bull. Chem. Soc. Jpn., 77, No. 7 (2004)
Table 1. Preparation of H2-Pc 2 from 1 under Various ConditionsaÞ
Synthesis of Metal-Free Phthalocyanines
Entry
HMDS
(molar ratio)bÞ
(NH4)2SO4
(molar ratio)bÞ
Reaction
time/h
Reaction
temperature/ꢁC
Yield
/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
4.0
0
0.1
0.2
0.3
0.3
1.0
0.3
—
—
0.1
0.1
—
10
24
10
24
10
10
24
24
10
24
10
10
10
24
10
24
100
100
100
100
150
150
150
150
150
150
150
150
150
150
150
100
0
59
0
68
23
56
56
72
49
0
42
50
60
64
61
3
0.1
—
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
a) An equimolar amount of DMF to 1 was used. b) The molar ratio to 1.
10), but excessive HMDS did not increase the yield of 2 (entry
9). We found that a catalytic amount of HMDS was also effec-
tive for the formation of the phthalocyanine framework. Thus,
the reaction with 1 and HMDS in a molar ratio of 1.0:0.3 gave 2
butyl)-, tetrapropoxy-, tetraphenoxy-, and tetrakis(octylthio)-
phthalocyanines 7–10 were prepared from the corresponding
4-substituted phthalonitriles 3–6 (Scheme 3, Table 2). The
reactions were performed with a catalytic amount (0.3 molar
ꢁ
ꢁ
in 64% yield by heating for 24 h at 150 C (entry 14). It is rea-
ratio) of HMDS for 24 h at 150 C, giving 7–10 in good yields
sonable that a catalytic amount of HMDS forms H2-Pc accord-
ing to the plausible reaction mechanism (Scheme 2): HMDS
promotes cyclization of phthalonitriles not only by activation
of the cyano group together with (NH4)2SO4, but also by nucle-
ophilic attack on the cyano carbon, and furthermore accelerates
subsequent intermolecular reactions. HMDS is then reproduced
at the intramolecular cyclization stage to form the phthalocya-
nine skeleton.
(entries 1, 4, and 6). The phthalocyanine derivatives 7–10 were
obtained as a mixture of regioisomers that were not separated.
The reaction of 4-tert-butylphthalonitrile 3 with an excess
amount (2.0 molar ratio) of HMDS did not significantly in-
crease the yield of 7 (entries 2 and 3). Tetraphenoxyphthalocya-
nine 9 was not formed in good yield (entry 5). Naphthalocya-
nine 12 was formed in 44% yield upon heating of a mixture
of 2,3-naphthalonitrile ꢁ11 and HMDS in a molar ratio of
1.0:2.0 for 24 h at 150 C (Scheme 4).
Various peripherally substituted H2-Pcs such as tetra(tert-
Scheme 3.
Table 2. Preparation of Peripherally Substituted H2-Pcs 7–10aÞ
Entry
Phthalonitrile
R
HMDS
(molar ratio)bÞ
Reaction
temperature/ꢁC
Phthalocyanine
Yield
/%
1
2
3
4
5
6
t-Bu
t-Bu
t-Bu
PrO
PhO
OctS
3
0.3
2.0
2.0
0.3
2.0
0.3
150
100
150
150
150
150
7
7
7
8
9
10
49
53
52
56
21
62
3
3
4
5
6
a) The molar ratio of (NH4)2SO4 to 1 was 0.1. The mixture was heated for 10 h. b) The molar ratio
to 1.

H. Uchida et al.
Bull. Chem. Soc. Jpn., 77, No. 7 (2004) 1403
Scheme 4.
diisopropylamine, triethylamine, and DBU had no significant
effect (entries 12, 14–16). Chlorotrimethylsilane and imidazole
are known to effectively catalyze the trimethylsilylation of al-
cohols, enols, and thiols with HMDS.15 This is probably the
reason why these additives promoted the formation of H2-Pc.
Hydroquinone is also sometimes effective in the preparation
of H2-Pcs.9 Bu3SnH and hydroquinone were examined, and
good yields of 2 were obtained in the reaction without
(NH4)2SO4 (entries 17, 18, and 19) and also in the presence
of (NH4)2SO4 (entry 20). Since hydroquinone was supposed
to be silylated by the action of HMDS during the reaction,
1,4-bis(trimethylsiloxy)benzene16 was examined and found to
be effective as well in the presence of (NH4)2SO4 (entry 21),
but not effective without (NH4)2SO4 (entry 22). When the reac-
Table 3. Preparation of H2-Pc 2 in the Presence of Various
AdditivesaÞ
Entry
Additive
Reaction Yield
time/h
/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
—
—
10
24
10
24
48
10
24
10
24
10
24
10
24
10
10
10
10
10
24
24
10
10
17
62
61
56
48
52
49
54
47
62
57
37
64
39
27
34
56
65
51
62
60
0
p-TsOH H2O
ꢂ
p-TsOH H2O
ꢂ
p-TsOH H2O
ꢂ
TfOH
TfOH
TMSCl
TMSCl
ꢁ
imidazole
imidazole
pyridine
pyridine
i-Pr2NH
Et3NbÞ
DBU
Bu3SnH
tion was performed with HMDS for 24 h at 150 C, H2-Pc 2
was obtained in good yield even without an additive (entry
2). Unfortunately, the yields obtained by heating for 24 h at
ꢁ
150 C with any additives did not significantly exceed those
without an additive. Most of the additives listed in Table 3,
whether they are acidic or basic, increased the yield of H2-Pc
2 when compared with those obtained by heating for 10 h at
ꢁ
150 C without an additive.
hydroquinone
hydroquinone
hydroquinone/(NH4)2SO4
1,4-(TMSO)2C6H4/(NH4)2SO4
1,4-(TMSO)2C6H4
Conclusion
cÞ
We have developed a new and efficient protocol for the pro-
duction of unsubstituted and substituted H2-phthalocyanines
that can be performed under substantially neutral and mild
conditions. Some additives were effective in the preparation
of H2-Pcs with HMDS.
dÞ
a) A mixture of 1, HMDS, an additive, and DMF in a molar ra-
ꢁ
tio of 1.0:0.3:0.1:1.0 was heated at 150 C unless otherwise
noted. b) A mixture of 1, HMDS, Et3N, aꢁnd DMF in a molar
ratio of 1.0:2.0:0.1:1.0 was heated at 150 C. c) A mixture of
1, HMDS, hydroquinone, (NH4)2SO4, and DMF in a molar ra-
tio of 1.0:0.6:0.3:0.1:1.0 was heated. d) A mixture of 1, HMDS,
1,4-(TMSO)2C6H4, (NH4)2SO4, and DMF in a molar ratio of
1.0:0.3:0.1:0.1:1.0 was heated.
Experimental
General. HMDS was distilled before use. DMF was distilled
from P2O5 and stored over MS 4A. Phthalonitrile and naphthaloni-
trile were purchased from TCI. 4-Substituted phthalonitriles were
synthesized according to the methods reported in the literature.17
Additives were dried under vacuum before use. All solvents for ex-
traction and other reagents were used without additional purifica-
tion. UV–vis spectra were measured with a JASCO V-530 spec-
trometer. 1H NMR spectra were taken on a Varian Gemini-200
spectrometer using tetramethylsilane as an internal standard.
MALDI-TOF MS were recorded on a Perseptive Biosystems Voy-
ager RN spectrometer without a matrix via external calibration us-
ing commercially available metal-free phthalocyanine and zinc
naphthalocyanine as calibrants. Microanalyses were performed
with a Perkin Elmer-240.
We examined some other additives in place of (NH4)2SO4.
We reported earlier that the formation of metal–Pcs with
HMDS was promoted by p-TsOH and H2SO4.12 The reaction
was performed by using 1 and HMDS in a molar ratio of
1.0:0.3 (Table 3). p-TsOH and TfOH were effective in the for-
mation of H2-Pc as compared with the yields in the reaction
ꢁ
without an additive for 10 h at 150 C (entry 1 vs entries 3
and 6), but heating for a longer time decreased the yield (entries
4, 5, and 7).ꢁChlorotrimethylsilane increased the yield of 1 for
10 h at 150 C (entry 8). The weakly basic imidazole also ac-
celerated the formation of H2-Pc (entry 10), whereas pyridine,
Preparation of Phthalocyanine (2).8 Method A: A glass tube
was charged with phthalonitrile (300 mg, 2.34 mmol), (NH4)2SO4

1404 Bull. Chem. Soc. Jpn., 77, No. 7 (2004)
Synthesis of Metal-Free Phthalocyanines
(31 mg, 0.234 mmol), HMDS (0.99 mL, 4.69 mmol), and DMF
(0.18 mL, 2.33 mmol) under an argon atmosphere. The tube was
sealed and heated to 150 C. A dark purple solid immediately ap-
Structure and Function,’’ Cambridge University Press, Cambridge
(1998). e) M. Hanack, H. Heckmann, and R. Polley, ‘‘Methods of
Organic Chemistry,’’ ed by E. Schaumann, Georg Thieme Verlag,
Stuttgart (1998), Vol. E9d, p. 717–846. f) G. Torre, C. G.
Claessesns, and T. Torres, Eur. J. Org. Chem., 2000, 2821.
2 For example, see: a) V. F. Borodkin, J. Appl. Chem. USSR
(Engl. Transl.), 31, 803 (1958). b) B. I. Kharisov, L. M. Blanco, L.
´
M. Torres-Martinez, and A. Garcıa-Luna, Ind. Eng. Chem. Res.,
38, 2880 (1999).
ꢁ
peared. After heating for 24 h, the mixture was cooled and filtered.
The solid was washed with methanol and then dissolved in conc.
H2SO4 (10 mL). The resulting solution was poured into water
(200 mL) to give a blue precipitate. The precipitate was filtered
and washed thoroughly with water. The solid was further purified
by a soxhlet extractor with methanol to give 217 mg (72%) of 2.
Method B: The reaction was performed as described in Method
A except for the use of phthalonitrile (300 mg, 2.34 mmol),
(NH4)2SO4 (31 mg, 0.234 mmol), HMDS (0.15 mL, 0.71 mmol),
and DMF (0.18 mL, 2.33 mmol) to give 192.5 mg (64%) of 2.
3
a) H. Tomoda, S. Saito, S. Ogawa, and S. Shiraishi, Chem.
Lett., 1980, 1277. b) H. Tomoda, S. Saito, and S. Shiraishi, Chem.
Lett., 1983, 313. c) D. Wohrle, G. Schnurpfeil, and G. Knothe,
¨
Dyes Pigm., 18, 91 (1992).
4
Preparation of Tetra(tert-butyl)phthalocyanine (7).18
A
For example, see: a) P. J. Brach, S. J. Grammatica, O. A.
mixture of 4-tert-butylphthalonitrile (300 mg, 1.63 mmol),
(NH4)2SO4 (21 mg, 0.158 mmol), HMDS (0.69 mL, 3.27 mmol),
and DMF (0.13 mL, 1.68 mmol) was heated as above. Then the
mixture was cooled, filtered, and washed with methanol. The solid
was purified by silica gel column chromatography (toluene/AcOEt
= 99.5:0.5) to give 157 mg (52%) of 7.
Ossanna, and L. Weinberger, J. Heterocycl. Chem., 7, 1403
(1970). b) N. Kobayshi and A. B. P. Laver, J. Am. Chem. Soc.,
109, 7433 (1987).
5
K. Kitahara, T. Asano, S. Tokita, and H. Nishi, J. Hetero-
cycl. Chem., 26, 1887 (1989).
a) C.-H. Lee and D. K. P. Ng, Tetrahedron Lett., 43, 4211
6
Preparation of Tetrapropoxyphthalocyanine (8).3c The re-
action was the same as described for 7 except for the use of a mix-
ture of 4-propoxyphthalonitrile (300 mg, 1.61 mmol), (NH4)2SO4
(21 mg, 0.158 mmol), HMDS (0.10 mL, 0.47 mmol), and DMF
(0.12 mL, 1.55 mmol) giving 168 mg (56%) of 8.
Preparation of Tetraphenoxyphthalocyanine (9).19 The re-
action was the same as described for 7 except for the use of a mix-
ture of 4-phenoxyphthalonitrile (280 mg, 1.27 mmol), (NH4)2SO4
(17 mg, 0.126 mmol), HMDS (0.54 mL, 2.56 mmol), and DMF
(0.10 mL, 1.29 mmol) giving 58 mg (21%) of 9.
Preparation of Tetrakis(octylthio)phthalocyanine (10). The
reaction was the same as described for 7 except for the use of a
mixture of 4-octylthiophthalonitrile (300 mg, 1.10 mmol),
(NH4)2SO4 (15 mg, 0.111 mmol), HMDS (0.07 mL, 0.33 mmol),
and DMF (0.09 mL, 1.16 mmol) giving 186 mg (62%) of 10. UV–
vis (CHCl3) ꢀmax 716, 683, 355 nm; 1H NMR (CDCl3) ꢁ 8.05–
7.36 (m, 12H), 3.31–3.21 (brm, 8H), 2.01–1.25 (brm, 48H),
1.01–0.99 (br, 12H); MS (MALDI): m/z 1091.4 [M + Hþ]; Anal.
Calcd for C64H82N8S4: C, 70.41; H, 7.57; N, 10.26%. Found: C,
70.35; H, 7.48; N 10.13%.
Preparation of Naphthalocyanine (12).20 The reaction was
the same as described for 2 except for using a mixture of 2,3-naph-
thalonitrile (121 mg, 0.680 mmol), (NH4)2SO4 (9 mg, 0.070
mmol), HMDS (0.29 mL, 1.37 mmol), and DMF (0.05 mL,
0.65 mmol) affording 54 mg (44%) of 12.
(2002). On the other hand, Ce–phthalocyanine is formed in good
yields under similar reaction conditions, see: b) L. G. Tomilova,
E. V. Chernykh, T. B. Nikolaeva, V. V. Zelentsov, and E. A.
Luk’yanets, J. Gen. Chem. USSR (Engl. Transl.), 54, 1494
(1984). c) H. Isago and M. Shimoda, Chem. Lett., 1992, 147. d)
M. S. Haghighi, C. L. Teske, and H. Z. Homborg, Z. Anorg. Allg.
Chem., 608, 73 (1992).
7 P. A. Barrett, C. E. Dent, and R. P. Linstead, J. Chem. Soc.,
1936, 1719.
8 G. T. Byrne, R. P. Linstead, and A. R. Lowe, J. Chem. Soc.,
1934, 1017.
9
a) A. W. Snow and N. L. Jarvis, J. Am. Chem. Soc., 106,
4706 (1984). b) J. A. Tompson, K. Murata, D. C. Miller, J. L.
Stanton, W. E. Broderick, B. M. Hoffman, and J. A. Ibers, Inorg.
Chem., 32, 3546 (1993). For the preparation of H2-Pcs under high
pressure, see: c) S. J. Edmondson, J. S. Hill, N. S. Isaacs, and C. H.
Mitchell, J. Chem. Soc., Dalton Trans., 1990, 1115.
10 G. A. Timokhin, B. I. Kissin, and N. N. Faeshkina, J. Appl.
Chem. USSR (Engl. Transl.), 42, 2187 (1969).
11 H. Uchida, H. Tanaka, H. Yoshiyama, P. Y. Reddy, S.
Nakamura, and T. Toru, Synlett, 2002, 1649.
12 H. Uchida, P. Y. Reddy, S. Nakamura, and T. Toru, J. Org.
Chem., 68, 8736 (2003).
13 H. Uchida, H. Yoshiyama, P. Y. Reddy, S. Nakamura, and
T. Toru, Synlett, 2003, 2083.
14 Formation of H2-Pcs was not observed in the absence of
DMF. H2-Pcs were also obtained by using DMAc in place of DMF.
15 a) C. C. Sweeley, R. Bentley, M. Makita, and W. W. Wells,
J. Am. Chem. Soc., 85, 2497 (1963). b) S. Torkelson and C.
Ainsworth, Synthesis, 1976, 722. c) R. S. Glass, J. Organomet.
Chem., 61, 83 (1973).
This work was partly supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas (A) ‘‘Exploitation of Multi-
Element Cyclic Molecules’’ (No. 14044040) from the Ministry
of Education, Culture, Sports, Science and Technology, and a
grant from the NITECH 21st Century COE Program ‘‘World
Ceramics Center for Environmental Harmony’’.
16 G. Beaumont, C. Eaborn, and R. A. Jackson, J. Chem. Soc.
B, 1970, 1624.
17 D. Wohrle, M. Eskes, K. Shigehara, and A. Yamada,
¨
Synthesis, 1993, 194.
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