Novel and mild route to phthalocyanines and 3-iminoisoindolin1-ones via N,N-diethylhydroxylamine-promoted conversion of phthalonitriles and a dramatic solvent-dependence of the reaction

Article abstract of DOI:10.1002/adsc.200700261

Refluxing a mixture of phthalonitrile C₆R¹R ²R³R⁴(CN)₂ 1 (R¹-R ⁴ = H), or its substituted derivatives 2 (R¹, R ³, R⁴ = H, R² = Me), or 3 (R¹, R⁴ = H, R², R³ = Cl) (lequiv.) and N,N-diethylhy-droxylamine, Et₂NOH, (4 equivs.) in methanol for 4 h results (Route A) in precipitation of the symmetrical (6 and 8) and an isomeric mixture of unsymmetrical (7) phthalocyanines, isolated in good (55-65 % ) yields. The reaction of phthalonitriles 1, 2, or 4 (R¹, R ³, R⁴ = H, R² = NO₂) (4 equivs.) with Et₂NOH (8 equivs.) in the presence of a metal salt MCl ₂ (M = Zn, Cd, Co, Ni) (1 equiv.) in n-BuOH or without solvent results in the formation of metallated phthalocyanine species (9-17). Upon refluxing in freshlydistilled dry chloroform, phthalonitrile 1 or its substituted analogues 2, 3 or 5 (R¹-R⁴ = F) (1 equiv.) react with N,N-diethylhydroxylamine (2 equivs.) affording 3-iminoisoindolin-1- ones 18-21 (Route B) isolated in good yields (55-80%). All the prepared compounds were characterized with C, H, and N elemental analyses, ESI-MS, IR, and compounds 18-21 also by ID (¹H, ¹³C(¹H]), and 2D (¹H,¹⁵N-HMBC and ¹H,¹³CHMQC, ¹H,¹³C-HMBC) NMR spectroscopy.

Full text of DOI:10.1002/adsc.200700261

FULL PAPERS
DOI: 10.1002/adsc.200700261
Novel and Mild Route to Phthalocyanines and 3-Iminoisoindolin-
1-ones via N,N-Diethylhydroxylamine-Promoted Conversion of
Phthalonitriles and a Dramatic Solvent-Dependence of the
Reaction
Konstantin V. Luzyanin,a,b Vadim Yu. Kukushkin,b,* Maximilian N. Kopylovich,a
Alexey A. Nazarov,c Markus Galanski,c and Armando J. L. Pombeiroa,*
a
Centro de Química Estrutural, Complexo I, Instituto Superior TØcnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon,
Portugal
Fax : (+351)-21–846 4455; E-mail: pombeiro@ist.utl.pt
St. Petersburg State University, 198504 Stary Petergof, Russian Federation
b
E-mail: kukushkin@VK2100.spb.edu
Institute of Inorganic Chemistry – Bioinorganic, Environmental and Radiochemistry, University of Vienna,
c
Währinger Str. 42, 1090, Vienna, Austria
Received: May 25, 2007; Published online: December 14, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Refluxing a mixture of phthalonitrile tilled dry chloroform, phthalonitrile 1 or its substitut-
C6R1R2R3R4(CN)2 1 (R1–R4 =H), or its substituted ed analogues 2, 3 or 5 (R1–R4 =F) (1 equiv.) react
derivatives 2 (R1, R3, R4 =H, R2 =Me), or 3 (R1, with N,N-diethylhydroxylamine (2 equivs.) affording
R4 =H, R2, R3 =Cl) (1 equiv.) and N,N-diethylhy- 3-iminoisoindolin-1-ones 18–21 (Route B) isolated in
droxylamine, Et2NOH, (4 equivs.) in methanol for good yields (55–80%). All the prepared compounds
4 h results (Route A) in precipitation of the symmet- were characterized with C, H, and N elemental anal-
rical (6 and 8) and an isomeric mixture of unsymmet- yses, ESI-MS, IR, and compounds 18–21 also by 1D
rical (7) phthalocyanines, isolated in good (55–65%) (1H, 13C{1H}), and 2D (1H,15N-HMBC and 1H,13C-
yields. The reaction of phthalonitriles 1, 2, or 4 (R1, HMQC, 1H,13C-HMBC) NMR spectroscopy.
R3, R4 =H, R2 =NO2) (4 equivs.) with Et2NOH
(8 equivs.) in the presence of a metal salt MCl2 (M=
Zn, Cd, Co, Ni) (1 equiv.) in n-BuOH or without sol- Keywords: N,N-diethylhydroxylamine; 3-iminoisoin-
vent results in the formation of metallated phthalo- dolin-1-ones; metal-free phthalocyanines; metallated
cyanine species (9–17). Upon refluxing in freshly dis- phthalocyanines; phthalonitriles; solvent dependence
Introduction
obtained from Pcs and an Ln compound[5] are by an
order of magnitude higher than in the template syn-
Since their discovery, metal-free (Pcs) and metallated thesis[6]). In addition, the reaction between Pcs and
phthalocyanines (M-Pcs) have become compounds of metal sources to afford M-Pcs proceeds under much
a great importance with a wide range of applications milder conditions in comparison with the convention-
in industry, laboratory, and medicine,[1,2] e.g., as dyes/ al template synthesis; the former is particularly useful
pigments,[1,2] molecular and photoconductors,[3] liquid for the preparation of thermally unstable M-Pcs.
crystalline mesophases,[3] oxidation catalysts,[2] and
agents in anticancer photodynamic therapy.[4]
The synthetic routes to metal-free Pcs have not
changed substantially since the early works by Lin-
Pcs are commonly the parent compounds for a stead,[7] and usually involve cyclotetramerization of
series of phthalocyanine species and from a synthetic the so-called phthalogenes (1,2-disubstituted ben-
viewpoint they are even more important than M-Pcs. zenes),[1] e.g., 1,3-diiminoisoindoline, o-cyanobenz-
Indeed, Pcs are employed for the preparation of M- amide or phthalonitrile (Pn). The reaction of Pns
Pcs, especially those which are not directly accessible occurs upon reflux in C3–C8 alcohols, 2-(N,N-dimethyl-
via template synthesis (e.g., yields of lanthanide-Pcs amino)ethanol or without solvent at 100–3008C for
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Scheme 1.
prolonged time and requires the presence of a nucleo-
It is clear from Scheme 1 that the cyclotetrameriza-
phile, e.g., ORÀ or DBU (1,8-diazabicyclo- tion of Pns (I) to yield Pcs (II) involves the donation
[5.4.0]undec-7-ene).[1,2]
of two protons from the oxime and a 2eÀ reduction.
Another route to Pcs is the demetallization of M- In addition, the promoter should exhibit nucleophilic
Pcs, obtained by template synthesis, on their heating properties to lower the kinetic barrier toward cyclote-
in concentrated H2SO4.[1,2] Thus, the majority of meth- tramerization by forming intermediate III. All this
ods for the preparation of Pcs are typically performed means that the search for novel efficient promoters
at elevated temperatures, are energy- and/or time- should include H+ donors exhibiting higher nucleo-
consuming, involve moisture-sensitive or dangerous philic/reducing properties.
reagents (e.g., Na or Li) and dry solvents or require
demetallization.
Recently we found that, in the addition to metal-ac-
tivated nitriles, dialkyl-substituted hydroxylamines are
Recently, within our ongoing project on metal- ca. 104 times better protic nucleophiles than the corre-
mediated and/or metal-catalyzed reactions of RCN sponding oximes.[13] Taking into account the known
(the topic surveyed in a number of articles and re- higher reducing abilities of hydroxylamines vs.
views[8–10] including those written by some of us[8,10]), oximes,[14] we have decided to investigate the promot-
we have discovered a novel method for the synthesis ing ability of the former species in the conversion of
of M-Pcs starting from Pns,[11,12] which employs Pns to Pcs and observed that a dialkylhydroxylamine,
oximes (R2C=NOH) as highly efficient promoting viz., N,N-diethylhydroxylamine (Et2NOH), can so
agents. This reaction proceeds via the formation of an greatly enhance the cyclotetramerization of Pns in al-
intermediate complex (III) (generated by the double cohols that this reaction could even proceed without a
nucleophilic addition to a cyano-carbon), which in metal source. We have found that this reaction pro-
turn reacts further with 2 equivs. of o-phthalonitriles vides a mild and expedient protocol for the facile
to form NiPcs (Scheme 1).
preparation of metal-free Pcs in MeOH, while in
However, when this method is applied to the prepa- CHCl3 it proceeds in another direction furnishing 3-
ration of metal-free Pcs, it becomes much less effec- iminoisoindolin-1-ones and all this study is reported
tive insofar as it requires prolonged heating (8–24 h) herein.
followed by purification of the target compounds.
Moreover, the method is not applicable to Pns with
donor substituents (e.g., R=Me).
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Novel and Mild Route to Phthalocyanines and 3-Iminoisoindolin-1-ones
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Results and Discussions
metrical (6 and 8) and an isomeric mixture of the un-
symmetrical (7) Pcs which were isolated in good
Reaction of Phthalonitriles and N,N-Diethylhydroxyl- yields (60% for 6, 65% for 7 and 55% for 8). The
amine in Methanol
formulations of 6–8 (see Experimental Section) are
based on elemental analyses (C, H, N), electrospray
For this work we addressed, on one hand, phthaloni- ionization mass-spectrometry (ESI-MS), IR, and
triles (1–5; Table 1) bearing a substituent with various 1H NMR spectroscopy. In addition, 6 was identified
donor/acceptor properties to investigate their influ- by comparison with a sample commercially available
from Aldrich.
The increase of reaction time (up to 24 h) does not
affect the yield but results in significant contamina-
Table 1. Phthalonitriles employed as starting materials.
tion of 6–8 with some by-products. The reactions with
Pns containing strong electron-acceptor groups, for
example, C6F4(CN)2 5 or (NO2)C6H3(CN)2 4, does not
afford Pcs; the first reaction leads to 3-iminoisondo-
lin-1-one species (see later), while the later case re-
1
2
3
R1 to R4 =H
4
5
R1 =R3 =R4 =H, R2 =NO2
R1 to R4 =F
sults in the known oxidation of Et2NOH by the NO2
group.[14,15]
R1 =R3 =R4 =H, R2 =Me
R1 =R4 =H, R2 =R3 =Cl
For 1–3, the best results were obtained with a
Pn:Et2NOH ratio of 1:4; with lower amounts of
Et2NOH the yields of Pcs strongly decreased, while
the change of the Pn:Et2NOH molar ratio to 1:8 does
ence on proceeding reactions and, on the other hand, not significantly affect the reaction. In chlorinated
the most common and cheap dialkyl-substituted hy- solvents, e.g., CHCl3, the interaction between the Pcs
droxylamine, i.e., N,N-diethylhydroxylamine (avail- and Et2NOH proceeds in another direction to yield 3-
able under the commercial name PENNSTOPꢁ).
iminoisoindolin-1-ones (Route B, Scheme 2). The re-
Refluxing a mixture of 1–3 (1 equiv.) and N,N-di- placement of methanol by ethanol decreases drastical-
ethylhydroxylamine (4 equivs.) in methanol for 4 h re- ly the yields, and only traces of 7 were isolated along
sults (Route A, Scheme 2) in precipitation of the sym- with unreacted 2 and 3-iminoisoindolin-1-one 19
(Scheme 2), while in the cases of 1 and 3 the reaction
does not proceed at all. All these observations togeth-
er demonstrate the dramatic role of the solvent in the
Et2NOH-promoted conversions of Pcs.
The most common and so far the most useful
method for the preparation of metal-free phthalocya-
nines is based on the heating of phthalogens in the
presence of such organic bases as DBU (1,8-
diazabicyclo
diazabicyclo
C
or
DBN
(1,5-
longed reflux of a phthalonitrile and the base in
EtOH to furnish metal-free Pcs in low/moderate
yields [20% (DBU) or 42% (DBN) after 18 h].[16]
Hence, our method has at least triple benefits, i.e., it
requires a lower temperature, it is less time-consum-
ing, and gives metal-free Pcs in better yields.
Reaction of Phthalonitriles and N,N-Diethylhydroxyl-
amine in Chloroform
Phthalonitrile (1) or its substituted analogues (2, 3, 5)
react with N,N-diethylhydroxylamine in refluxing
freshly distilled dry chloroform (the distillation is
needed to remove EtOH added to commercially
available chloroform as a stabilizer), giving precipi-
tates of 18–21 (Scheme 2; compound 19 is obtained as
an isomeric mixture) isolated in good yields (65, 50,
Scheme 2.
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Konstantin V. Luzyanin et al.
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80, 51%, respectively). In the presence of added
water, the yield of the reaction decreases (e.g., 50%
for 18). In non-distilled commercially available
CHCl3, the 3-iminoisoindolin-1-one product is strong-
ly contaminated with phthalocyanines. The substitu-
tion of CHCl3 with CH2Cl2 decreases the yield (e.g.,
to 20% for 18 upon reflux from 4 to 8 h), while in
acetone or acetonitrile the formation of 18 has been
detected but its high solubility in these solvents com-
plicates the isolation and purification. The replace-
ment of CHCl3 by CH2ClCH2Cl decreases drastically
the selectivity and the yield and only traces of 18
Scheme 3.
were detected by TLC upon reflux in 1,2-dichloro- formed at elevated temperatures (130–2008C),
ethane for 8 h.
reached by the use of high boiling point solvents (e.g.,
The best results were obtained with a phthaloni- PhNO2[19a,b]) and in some methods requires toxic and
trile:HONEt2 molar ratio of 1:2; with lower amounts environmentally dangerous gaseous NH3.[19a,b] The
of HONEt2, e.g., 1:0.5, the yields of the target com- synthesis proceeds in a moderate yield (30–45%), it is
pounds strongly decreased, while the change of the not selective and typically results in formation of a
phthalonitrile:HONEt2 molar ratio to 1:3 did not sig- mixture of 18 (30–40%) and isoindoline-1,3-diimine
nificantly affect the reaction.
(Scheme 3; up to 60% yield) and some unidentified
The 3-iminoisoindolin-1-ones (18–21) precipitate heterocyclic species. Consequently, this method re-
from the reaction mixture in a pure form and they do quires separation and purification of 18. A high-yield
not require further recrystallization. They give satis- laboratory method for the conversion of phthalamide
factory C, H, and N elemental analyses and the ESI- into 18 is also known[19c] but it is based on the hazard-
MS of 18–21 display molecular ion peaks. In the IR ous Pinner synthesis utilizing great amounts of toxic
spectra, 18–21 show no bands in the interval between HCl.
2200 and 2300 cmÀ1 specific for n
brations, but display two (21) or three (18–20) ly transformed to 18 and relevant substituted 3-imi-
A
Thus, we have now found that Pns can be effective-
medium intensity bands in the range of 1730– noisoindolin-1-ones (19–21) in CHCl3 via a novel pro-
1630 cmÀ1 assigned to n
N
G
1
(1H, 13C{1H}), 2D (1H,15N-HMBC and H,13C-HMQC, 18 was described in a Japanese patent application[20a]
1H,13C-HMBC) NMR spectra of 18–21 are in good the reaction between Pn, water, hydrogen peroxide,
agreement with the proposed structures. and ammonia or amines led to 3-iminoisoindolin-1-
:
It is worth noting that the preparation of imino- one. We believe that there is a similarity between this
isoindolinones is an area of avid attention owing to method and that found by us and it might be antici-
their great utility in versatile chemical transforma- pated that, in the former case, hydroxylamines are
tions, including industrial applications. Various heter- generated in situ from the amines and hydrogen per-
ocyclic compounds containing the iminoisoindolinone oxide.
skeleton exhibit important biological properties, such
as antihypertensive, antipsychotic, anti-inflammatory,
anesthetic, antiulcer, vasodilatory, antiviral, antileuke- Detection of Intermediates and Plausible Mechanism
mic, cytotoxic, and hypolipidemic activities.[17] More- for the Reaction between Pns and N,N-Diethyl-
over, 3-iminoisoindolin-1-one (18), as the parent com- hydroxylamine
pound of the series, is a common precursor for the
synthesis of other heterocycles and it is also useful for The study of solvent-dependence of the reactions de-
the manufacture of pigments (e.g., phthalocyanines), picted in Scheme 2 and the detection of some inter-
heat-sensitive colorants, some components for ther- mediates were done by NMR and ESI-MS. Thus,
mal-recording sheets, charge-controlling agents for phthalonitrile 1 reacts with N,N-diethylhydroxylamine
electrophotographic toners, stabilizers for plastics, in methanol or chloroform giving a mixture of imino
pharmaceuticals, and cosmetics.[1,18]
species 22 and 23 (Route C, Scheme 4), derived from
Despite the interest in alternative syntheses of 18, the nucleophilic addition, with concomitant hetero-
the most recognized and industrially used method, cyclization, of 1 or 2 equivs. of Et2NOH to Pn; al-
which is based on a reaction between phthalic anhy- though the latter species are unstable, they were de-
dride or phthalamide and a nitrogen source such as tected in ESI+-MS. If the reaction is performed in
urea or ammonia (Scheme 3), is not free from a CDCl3 or purified CHCl3, both 22 and 23 are subject
number of disadvantages. The reaction is usually per- to further transformations (Route D) to furnish 3-imi-
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Novel and Mild Route to Phthalocyanines and 3-Iminoisoindolin-1-ones
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Scheme 4.
noisoindolin-1-ones 18 and the known[21] imine (Figure 1). In the TOCSY NMR spectrum, shift corre-
MeCH2N=C(H)Me as well as the starting Et2NOH lation signals of the CH proton (quartet in the typical
which thus is regenerated. The imine has been detect- region at 6.82 ppm) to both methyl protons (2.02 and
ed by ESI (found m/z=93 [M + Na]; calcd.: m/z= 1.48 ppm) as well as to the CH2 protons (3.83 ppm)
93) and 2D TOCSY and 1H,13C- and 1H,15N- could be detected. 13C NMR signals were found at
HMBC NMR.
13.1 (CHMe), 13.7 (MeCH2), 60.3 (MeCH2) and
In the case of 23, its conversion proceeds via the 134.0 ppm (N=CH), respectively. Furthermore, long-
amino tautomer of isoindolinone, which then under- range coupling of both CH3 protons and the CH
goes the known tautomerization[22] to the more stable proton to the same nitrogen atom at 269 ppm (mea-
imino form 18. The double addition of a nucleophile sured relative to NH4Cl, which is equivalent to
at a single cyano group is very rare[11,23] but it has À84 ppm relative to nitromethane) finally unequivo-
been ascertained in our previous study[11] on the con- cally proved the release of MeCH2N=C(H)Me.
version of phthalonitriles into phthalocyanines medi-
ated by an oxime (also an HON nucleophile).
In methanol, the Route D is not dominant and the
reaction proceeds mostly via Route E, furnishing 6
In the case of the formation of 19, the reaction was through the intermediate formation (with regenera-
followed directly in the NMR tube. Besides the two tion of Et2NOH) of 24, which was also detected by
isomers of the isoindolinone (ratio nearly 1:1) with R2 ESI+-MS (found m/z=183 [M + Na]; calcd.: m/z=
or R3 being a methyl group, one equivalent of 183). Furthermore, 24 is subject to cyclotetrameriza-
MeCH2N=C(H)Me was released and unequivocally tion with regeneration of MeOH; this 2eÀ/2H+ pro-
identified by NMR spectroscopy via 2D TOCSY, cess requires a protic reducing agent, and Et2NOH,
1H,13C-, and 1H,15N-HMBC NMR measurements
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Table 2. Reaction of phthalonitriles with N,N-diethylhydrox-
ylamine in the presence of a metal source.[a]
M
M source Phthalo- Solvent
nitrile
T [8C] Yield M-Pc
[%]
Zn ZnCl2
Zn ZnCl2
Cd CdCl2
Co CoCl2
Co CoCl2
Co CoCl2
Ni NiCl2
Ni NiCl2
Ni NiCl2
1
2
1
1
2
4
1
2
4
-
-
80
120
45
55
9
10
11
12
13
14
15
16
17
n-BuOH reflux 50
n-BuOH reflux 55
-
-
n-BuOH reflux 40
-
-
80
120
65
65
120
120
45
45
[a]
In all cases Et2NOH is used as promoter and the reaction
time is 15 min.
All the reactions involving the metal salts proceed
for ca. 15–30 min and the highest yields (45–65%)
were obtained under the conditions depicted in
Table 2. The compounds were isolated by filtration
and purified by washing with organic solvents and
5M hydrochloric acid (see Experimental Section),
while some of them were purified by sublimation (9,
10, 15) under ca. 10 mm vacuum at 200–3008C.
Figure 1. Selected regions of the TOCSY (left) and the long-
1
range H,15N-HMBC (optimized at 10 Hz, right) NMR spec-
Thus, our fast and relatively low-temperature proto-
col for the preparation of 9–17 is among the most ad-
vantageous methods for the synthesis of M-Pcs and
tra.
being oxidized to the known nitrone Me(H)C=N+- gives well-comparable yields with those known for
A
other methods.[1]
nol; (ii) pure 3-iminoisoindolin-1-ones do not trans- Conclusions
form to Pcs in the presence Et2NOH under the reac-
tion conditions employed although they can be con- The results from this study can be considered from
verted to Pcs via cyclotetramerization in the presence three perspectives. First, we found a novel and effi-
of strong bases or DBU and urea.[1,2] Based on these cient method for the preparation of metal-free Pcs
observations and those described above we believe with both donor and moderate acceptor R substitu-
that the function of N,N-diethylhydroxylamine is dual ents, which starts from low-cost reagents, such as Pns
and it includes lowering the kinetic barrier toward ad- in MeOH, and is promoted by the widely comercially
dition of MeOH (thus acting as a catalyst) and reduc- available and industrially employed (for other purpos-
tion with concomitant H+ donation when phthalogene es) N,N-diethylhydroxylamine, operates at low tem-
24 cyclotetramerizes to the corresponding Pc.
peratures, requires only a short reaction time and
does not need purification of the Pcs products. The
employment of Et2NOH as an HON nucleophile al-
Reaction of Phthalonitriles and N,N-Diethylhydroxyl- ternative to an oxime[11,12] (Scheme 1) enhances the
amine in the Presence of a Metal Source
reactivity of Pns to such a degree that the tetrameri-
zation proceeds fast in a single pot and the intermedi-
In the presence of a metal center, the reaction does ate similar to III (Scheme 1) could not be detected.
not show the above solvent-dependence and the forma- Second, a protocol identical to that for generation
tion of M-Pcs (Table 2) in the reaction of various Pns of metal-free Pcs further provides a convenient
(1, 2, 4) with Et2NOH and MCl2 (M=Zn, Cd, Co, Ni) method for the synthesis of metallated phthalocya-
is observed in n-BuOH or without solvent. When nines (M-Pcs), when the reactions of the correspond-
methanol is used as the solvent the reaction does not ing Pns with Et2NOH are performed in the presence
occur, while in chloroform a mixture of 3-iminoisoindo- of a metal source.
lin-1-one with yet unidentified products was obtained.
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Novel and Mild Route to Phthalocyanines and 3-Iminoisoindolin-1-ones
FULL PAPERS
Third, we also discovered that the conversion of the Reaction of Phthalonitriles and N,N-Diethylhydroxyl-
Pns promoted by N,N-diethylhydroxylamine shows a amine in the Presence of a Metal Source; General
dramatic solvent dependence and in CHCl3 leads to Procedure for the Synthesis of Metallated Pcs (9–17)
various 3-iminoisoindolin-1-ones instead of Pcs. The
latter route for the preparation of 3-iminoisoindolin-
1-ones, taking into account its simplicity, low-cost of
Et2NOH and purity of the final products, may have a
broad application both in laboratory and in industry.
All starting Pns (1, 2, and 4) and the corresponding M-Pcs
are shown in Table 2.
A mixture of phthalonitrile 1
(4 mmol) or its corresponding substituted derivative (2, 4)
and MCl2 (1 mmol; M=Zn, Co, Cd, Ni), and Et2NOH
(8 mmol, 0.75 g) was placed in
a round-bottom flask
equipped with a magnetic stirrer and, if required, a reflux
condenser and stirred at room temperature for ca. 10 min.
In the case of Pn=1 and M=Cd, Co and Ni, n-BuOH was
added (10 mL), while in all other cases the reaction pro-
ceeded without solvent. The mixture was heated at tempera-
tures shown in Table 2, or upon reflux of the solvent for ca.
15 min. The reaction mixture was then cooled to 20–258C,
stirred additionally for ca. 10 min, the precipitate was fil-
tered off, washed with five 5-mL portions of methanol, two
5-mL portions of warm 5M hydrochloric acid, and with five
5-mL portions of acetone. The yields of 9–17 are 40–65%.
Experimental Section
All starting materials and solvents were obtained from com-
mercial sources and used as received, besides chloroform
and methanol that were purified by conventional methods
over calcium hydride and activated magnesium, respectively.
Spectroscopic and analytical data for the compounds made
are available in the electronic Supporting Information file.
Reaction of Phthalonitriles and N,N-Diethylhydroxyl-
amine in MeOH; General Procedure for the
Synthesis of Metal-Free Pcs (6–8)
Acknowledgements
A mixture of phthalonitrile 1 (0.010 mol) or any of the cor-
responding substituted phthalonitriles (2, 3) and Et2NOH
(0.040 mol, 1.80 g) in methanol (7 mL) was placed in a
round-bottom flask equipped with a magnetic stirrer and
reflux condenser and refluxed for 4 h. On heating, the solid
phthalonitrile dissolved, and the color of the solution
changed from slightly yellow to dark green followed by pre-
cipitation of a dark blue solid. The reaction mixture was
cooled to 20–258C, stirred additionally for ca. 1 h, the pre-
cipitate was filtered off, washed with five 5-mL portions of
methanol, and with five 5-mL portions of acetone. The
yields are 60% (for 6), 65% (for 7) and 55% (for 8).
This work has been partially supported by the Fundażo
para a CiÞncia e a Tecnologia (FCT), Portugal, and its POCI
2010 program (FEDER funded). K.V. L. and M. N. K ex-
press gratitude to FCT and the POCI program (FEDER
funded), Portugal, for the fellowships (grants SFRH/BPD/
27094/2006 and SFRH/BPD/14465/2003 correspondingly).
V. Yu. K. is very much obliged to the Russian Fund for Basic
Research (grants 06–03–32065 and 06–03–90901), the Scien-
tific Council of the President of the Russian Federation
(grant MK-1040.2005.3), Government of St.Petersburg for a
grant (46/06), and the FCT (Cientista Convidado/Professor at
the Instituto Superior TØcnico, Portugal). M. G. and A. A. N.
thank the Austrian Science Fund (FWF).
Reaction of Phthalonitriles and N,N-Diethylhydroxyl-
amine in CHCl3; General Procedure for the Synthesis
of 3-Iminoisoindolin-1-ones (18–21)
References
A mixture of phthalonitrile 1 (0.010 mol) or any of the cor-
responding substituted phthalonitriles (2, 3, 5) and Et2NOH
(0.020 mol, 1.80 g) in freshly distilled dry CHCl3 (7 mL) was
placed in a round-bottom flask equipped with a magnetic
stirrer and reflux condenser and refluxed for 4 h. On heat-
ing, the solid phthalonitrile dissolved, and the color of the
solution changed from slightly yellow to orange-green in the
case of 1, or to dark yellow in the case of 2 and 3, and 5, fol-
lowed by precipitation of an almost colorless slightly green-
ish solid. The reaction mixture was cooled to 20–258C,
stirred additionally for ca. 1 h, the precipitate was filtered
off, washed with five 5-mL portions of cold (108C) chloro-
form. An additional quantity of 1.8–2.0 g (ca. 15%) was ob-
tained upon evaporation of the filtrate to dryness. Treatment
of the residue with a 1:1 mixture of diethyl ether and chloro-
form (20 mL) resulted in precipitation of the 3-iminoisoin-
dolin-1-ones (18–21), which are separated by filtration and
washed with five 5-mL portions of cold (108C) chloroform.
Both fractions of 18–21 were combined and dried in air at
room temperature. Overall yields are 50–80%.
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