Synthesis of 4,5-dihydroxyphthalonitrile

Article abstract of DOI:10.1023/A:1011387916186

4,5-Dihydroxyphthalonitrile was synthesized from pyrocatechol in a simple way. The compound obtained is a convenient starting reagent for the preparation of 4,5-dialkoxyphthalonitriles.

Full text of DOI:10.1023/A:1011387916186

Russian Chemical Bulletin, International Edition, Vol. 50, No. 5, pp. 919—920, May, 2001
919
Synthesis of 4,5-dihydroxyphthalonitrile
A. V. Ivanov,« P. A. Svinareva, L. G. Tomilova, and N. S. Zefirov
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119899 Moscow, Russian Federation.
Fax: +7 (095) 939 0290. E-mail: tom@org.chem.msu.su
4,5-Dihydroxyphthalonitrile was synthesized from pyrocatechol in a simple way. The
compound obtained is
alkoxyphthalonitriles.
a convenient starting reagent for the preparation of 4,5-di-
Key words: 4,5-dihydroxyphthalonitrile, 2,2-dimethyl-1,3-benzodioxole, bromination,
cyanation.
4,5-Dialkoxyphthalonitriles could be synthesized by
alkylating 4,5-dihydroxyphthalonitrile (1). In addition,
this compound can be useful in the cases when direct
introduction of cyano groups into the target molecule
according to the Rosenmund—von Braun method is
prevented by the low reactivity or instability of the
starting dihalide. However, the synthesis of compound 1
has not been reported up to the present.
We synthesized 4,5-dihydroxyphthalonitrile (1) from
pyrocatechol according to Scheme 1. The scheme in-
cludes benzodioxole protection of the hydroxy groups,
bromination of the benzene ring, cyanation of the re-
sulting dibromide 3, and elimination of the protection
group from symmetrical dinitrile 4.
amine used to bind HCl. The isolation was appreciably
facilitated by using K2CO3 as a base, the yield of
compound 2 remaining high (94%).
Benzodioxole 2 is then brominated2,3 to give 5,6-di-
bromo-2,2-dimethyl-1,3-benzodioxole (3) in high yield
(92%). We preferred this method of preparing dibromide
3 because an alternative way, namely, bromination of
pyrocatechol followed by the formation of the dioxolane
ring, provides low yields of 3 (direct bromination of
pyrocatechol4 affords 4,5-dibromopyrocatechol only in
∼30% yield).
Cyanation of dibromide 3 with copper(I) cyanide in
the ratio of 1 : 5 in boiling DMF for 3.5 h gives dinitrile
4 in 36% yield. Another reaction product, 6-bro-
mo-5-cyano-2,2-dimethyl-1,3-benzodioxole (5), is
formed in 7—8% yield. Further heating is unsuitable
since the reaction mixture turns green, and its UV-VIS
spectrum shows a characteristic peak at 680 nm, in-
dicating a cyclization of dinitrile 4 into copper
2,3,9,10,16,17,23,24-tetra(isopropylidenedioxy)phthalo-
cyanine in the presence of an excess of the copper(I) salt.
The isopropylidene protection in dinitrile 4 is effec-
tively removed under the action of conc. H2SO4 to give
the target 4,5-dihydroxyphthalonitrile (1) in 90% yield.
The use of HCl is less convenient, since the reaction
duration is extended to two days, affording phthalonitrile
1 in only 80—83% yield.
The preparation of 2,2-dimethyl-1,3-benzodioxole
(2) was described in Ref. 1, but the target product is
rather difficult to isolate in the presence of triethyl-
Scheme 1
Br2,
OH
O
Ac2O
PCl3, Me2CO
O
OH
2
CuCN,
DMF
Br
O
The structure of compound 1 was proved by 1H and
13C NMR spectroscopy and mass spectrometry; its com-
position was confirmed by elemental analysis.
O
Br
3
Thus, 4,5-dihydroxyphthalonitrile can be easily syn-
thesized from pyrocatechol by closing a dioxolane ring
to protect its hydroxy groups, brominating the benzene
ring, and cyanating the resulting dibromide.
NC
NC
O
O
H2O,
NC
OH
OH
4
H2SO4
+
Experimental
Br
NC
O
1
H and 13C NMR were recorded on Bruker AC-200 instru-
1
O
NC
ment (200 and 50.3 MHz, respectively) in CDCl3 (for com-
5
pounds 3, 4, and 5) or in (CD3)2CO (for dinitrile 1); the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 879—880, May, 2001.
1066-5285/01/5005-919 $25.00 © 2001 Plenum Publishing Corporation

920
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 5, May, 2001
Ivanov et al.
chemical shifts (δ) are referred to tetramethylsilane. Mass
spectra were recorded on a Finnigan MAT INCOS-50 instru-
ment (EI, 70 eV, direct inlet). The compounds obtained were
analyzed by TLC using Silufol UV-254 plates. Copper cyanide
(Chemapol) was used without additional purification. Solvents
were purified according to the conventional methods.5
2,2-Dimethyl-1,3-benzodioxole (2). Phosphorus trichloride
(16.5 g, 0.12 mol) was added dropwise at 20 °C over 20 min to
a stirred solution of pyrocatechol (33 g, 0.30 mol) and Me2CO
(23 g, 0.36 mol) in 120 mL of benzene. The reaction mixture
was stirred until HCl ceased to evolve and then poured into
K2CO3 (100 g). The organic layer was filtered, and the precipi-
tate was washed with 50 mL of benzene. The benzene solution
was washed with 10% NaOH and water and dried with anhy-
drous CaCl2. Distillation gave benzodioxolane (2) (42 g, 94%).
Its physicochemical characteristics correlate with the litera-
ture data.1
6-Bromo-5-cyano-2,2-dimethyl-1,3-benzodioxole (5) was
isolated as a by-product while chromatographing the reaction
mixture obtained by the cyanation of compound 3 (see the
above experiment). The yield of 5 was 0.16 ã (8%), m.p.
153—154 °C. 1H NMR (CDCl3), δ: 1.67 (s, 6 H, C(2)Me2);
6.95, 7.03, (both s, each 1 H, Ar). 13C NMR, δ: 26.0 (Me);
110.4 (C(6)); 111.7 (CN); 112.4 (C(7)); 113.3 (C(4)); 118.3
(C(2)); 121.6 (C(5)); 147.2 (C(9)); 152.1 (C(8)). MS, m/z: 253,
255 [M]+. Found (%): C, 47.59; H, 3.40; N, 5.18. C10H8BrNO2.
Calculated (%): C, 47.27; H, 3.17; N, 5.51.
4,5-Dihydroxyphthalonitrile (1). A solution of 5,6-dicyano-
2,2-dimethyl-1,3-benzodioxole (4) (1.5 g, 0.0075 mol) in 2.5 mL
of conc. H2SO4 was poured into 10 mL of water. The precipi-
tate that formed upon cooling was filtered off, washed with
CHCl3, and dried in vacuo to give compound 1 (1.08 g, 90%) as
a colorless powder, m.p. 114—115 °C. 1H NMR ((CD3)2CO),
δ: 7.38 (s, 2 H, Ar); 9.96 (br.s, 2 H, OH). 13C NMR,
δ: 107.9 (C(1), C(2)); 116.8 (CN); 120.7 (C(3), C(6)); 150.7
(C(4), C(5)). MS, m/z: 160 [M]+. Found (%): C, 59.64;
H, 2.78; N, 17.15. C8H4N2O2. Calculated (%): C, 60.00;
H, 2.52; N, 17.49.
5,6-Dibromo-2,2-dimethyl-1,3-benzodioxole (3) was syn-
thesized as described in Refs. 2 and 3. The yield of 3 was 42 g
(92%); its characteristics are identical with the literature data.2,3
1H NMR, δ: 1.67 (s, 6 H, C(2)Me2); 6.98 (s, 2 H, Ar).
13C NMR, δ: 24.9 (Me), 111.4 (C(4), C(7)), 114.0 (C(5),
C(6)), 118.6 (C(2)), 145.3 (C(8), C(9)).
References
5,6-Dicyano-2,2-dimethyl-1,3-benzodioxole (4). A mixture
of 5,6-dibromo-2,2-dimethyl-1,3-benzodioxolane (3) (2.5 g,
0.008 mol) and CuCN (3.63 g, 0.040 mol) was refluxed in
30 mL of freshly distilled DMF for 3.5 h. The reaction mixture
was cooled to 20 °C and diluted with 75 mL of CHCl3. The
precipitate that formed was filtered off, and the filtrate was
washed with water (5½100 mL) to remove DMF, dried with
CaCl2, and concentrated on a rotary evaporator. The residue
was purified by column chromatography on silica gel in ben-
zene. The yield of 4 was 50.59 g (36%), m.p. 167—168 °C.
1H NMR, δ: 1.67 (s, 6 H, C(2)Me2); 7.03, (s, 2 H, Ar.).
13C NMR, δ: 26.1 (Me); 110.1 (C(5), C(6)); 112.5 (C(4),
C(7)); 115.7 (CN); 123.1 (C(2)); 151.3 (C(8), C(9)). MS, m/z:
200 [M]+. Found (%): C, 66.21; H, 4.28; N, 14.19. C11H8N2O2.
Calculated (%): C, 66.00; H, 4.03; N, 13.99.
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Received November 29, 2000;
in revised form February 19, 2001