Synthesis of Phthalonitriles
Using a Palladium Catalyst

Zafar Iqbal; Alexey Lyubimtsev; Michael Hanack

doi:10.1055/s-2008-1078269

LETTER

Synthesis of Phthalonitriles Using a Palladium Catalyst

Zafar Iqbal^a, Alexey Lyubimtsev^a,b, Michael Hanack*^a
^a Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Fax: +49(7071)295244; e-Mail: hanack@uni-tuebingen.de;
^b Ivanovo State University of Chemistry and Technology, Organic Chemistry Department, F. Engels Str. 7, 153460 Ivanovo, Russian Federation

Abstract

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Abstract

An easy synthetic method to obtain phthalonitriles from o-dibromobenzenes under mild conditions in high yields using Zn(CN)₂ and a catalytic amount of tris(dibenzylideneacetone)dipalladium and 1,1′-bis(diphenylphosphino)ferrocene is described.

Key words

cyanation - o-dibromobenzenes - palladium - phthalonitriles

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References

References and Notes

1a De la Torre G. Claessens CG. Torres T. Chem. Commun. 2007, 2000

1b Hanack M. Heckmann H. Polley R. Methods of Organic Chemistry (Houben-Weyl) Thieme; Stuttgart: 1997. p.717

1c Leznoff CC. Phthalocyanines: Properties and Applications VCH Publishers, Inc.; New York: 1989. p.1

1d Hanack M. Lang M. Adv. Mater. 1994, 6: 819

2 Sharman WM. Van Lier JE. In Porphyrin Handbook Vol. 15: Kadish E. Smith KM. Guilard R. Academic Press; New York: 2003. p.1

3 Friedman L. Shechter H. J. Org. Chem. 1961, 26: 2522

4 Hanack M. Drechsler U. Synlett 1998, 1207

5a Zhu Y.-Z. Cai C. Eur. J. Org. Chem. 2007, 2401

5b Weissman SA. Zewge D. Chen C. J. Org. Chem. 2005, 70: 1508

5c Sundermeier M. Zapf A. Beller M. Eur. J. Inorg. Chem. 2003, 3513

6a Tsuji J. Transition Metal Reagents and Catalysts - Innovations in Organic Synthesis John Wiley and Sons; Chichester: 2000.

6b Brandsma L. Vasilevsky SF. Verkruijsse HD. Application of Transition Metal Catalysts in Organic Synthesis Springer; Berlin, Heidelberg: 1999. p.149

6c Heck RF. Palladium Reagents in Organic Syntheses Academic Press; London: 1985.

7

Synthesis of Substituted Phthalonitriles - General Procedure A 25 mL two-neck round-bottom flask was charged with 1 mmol of o-dibromobenzene in DMAC (2 mL) and PMHS (20 mg) was added at r.t. The reaction mixture was heated to the required temperature (Table [¹] ) and Pd₂ ₍dba)₃ (20 mg, 2 mol%) and DPPF (15 mg, 2.7 mol%) were added. Afterwards, Zn(CN)₂ (117 mg, 1 mmol) was added in 4-5 portions during the time mentioned in Table [¹] till TLC indicated completion of the reaction. The reaction mixture was cooled, diluted with EtOAc and filtered. Filtrate was washed with H₂O, dried with MgSO₄, and concentrated in vacuo. The crude product was purified by column chromatography using CH₂Cl₂ as eluent.

8 Martin MT. Liu B. Cooley BE. Eaddy JF. Tetrahedron Lett. 2007, 48: 2555

9a Takagi K. Sasaki K. Sakakibara Y. Bull. Chem. Soc. Jpn. 1991, 64: 1118

9b Maligres PE. Waters MS. Fleitz F. Askin D. Tetrahedron Lett. 1999, 40: 8193

9c Jin F. Confalone PN. Tetrahedron Lett. 2000, 41: 3271

10a

Synthesis of 1,2-Dibromo-4- tert -butylbenzene ( 2a) To a solution of 1-bromo-4-tert-butylbenzene (8 g, 0.04 mol) in CCl₄ (5 mL) in the presence of a small amount of iron powder was added a solution of bromine (9.5 g, 0.12 mol) in CCl₄ (4 mL) at 5 ˚C over 10 min. The mixture was stirred at 15 ˚C for 2 h. Solvent was evaporated and product was purified by column chromatography using CH₂Cl₂-hexane (1:1) as eluent; yield 11 g (92%). ^¹H NMR (400 MHz, CDCl₃): δ = 7.59 (d, ⁴ J = 2.3 Hz, 1 H), 7.50 (d, ^³ J = 8.4 Hz, 1 H), 7.16 (dd, ^³ J = 8.4 Hz, ⁴ J = 2.3 Hz, 1 H), 1.27 (s, 9 H) ppm. MS (EI): m/z (%) = 291.8 (45) [M]⁺, 276.8 (100).

10b Ashton P. Girreser U. Giuffrida D. Kohnke FH. Mathias JP. Raymo FM. Slawin AMZ. Stoddart JF. Williams DJ. J. Am. Chem. Soc. 1993, 115: 5422

10c Andersh B. Murphy DL. Olson RJ. Synth. Commun. 2000, 30: 2091

10d Wenderski T. Light KM. Ogrin D. Bott SG. Harlan CJ. Tetrahedron Lett. 2004, 45: 6851

10e Ivanov AV. Svinareva PA. Tomilova LG. Zefirov NS. Russ. Chem. Bull. Int. Ed. 2001, 50: 919

11

Synthesis of 1,2-Dibromo-4-acetanilide ( 8a)
3-Bromoacetanilide was brominated with NBS in acetone with catalytic amounts of HCl [¹0c] to give after purification by column chromatography 1,2-dibromo-4-acetanilide (8a) in 90% yield. ^¹H NMR (400 MHz, CDCl₃): δ = 7.84 (s, 1 H), 7.50 (d, ^³ J = 8.8 Hz, 1 H), 7.38 (br s , 1 H), 7.30 (d, ^³ J = 8.8 Hz, 1 H), 2.15 (s, 3 H) ppm. MS (EI): m/z (%) = 293.0 (100) [M]⁺.

12a

Synthesis of tert -Butyl-(3,4-dibromophenoxy)dimethylsilane ( 9a) and 3,4-Dibromophenol ( 10a)
The hydroxy group in 3-bromophenol was protected with tert-butyldimethylsilyl chloride in the presence of imidazole to give tert-butyl(3-bromophenoxy)dimethylsilane quantitatively. [¹²b] ^¹H NMR (400 MHz, CDCl₃): δ = 7.09-7.04 (m, 2 H), 7.01-6.96 (m, 1 H), 6.79-6.70 (m, 1 H), 0.96 (s, 9 H), 0.18 (s, 6 H) ppm. MS (EI): m/z (%) = 286.0 (20) [M]⁺, 231.0 (100), which was brominated with NBS. [¹0c] After purification by column chromatography tert-butyl(3,4-dibromophenoxy)dimethylsilane (9a) was obtained in 78% yield. ^¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, ^³ J = 7.5 Hz, 1 H), 7.10 (d, ⁴ J = 2.5 Hz, 1 H), 6.64 (dd, ^³ J = 7.5 Hz, ⁴ J = 2.5 Hz, 1 H), 0.95 (s, 9 H), 0.18 (s, 6 H) ppm. MS (EI): m/z (%) = 365.9 (40) [M]⁺, 308.9 (100). tert-Butyldimeth-ylsilyl group in 9a was deprotected with tetrabutyl-ammonium fluoride [¹²b] to give 3,4-dibromophenol (10a) in 92% yield. ^¹H NMR (400 MHz, CDCl₃): δ = 7.28 (d, ^³ J = 8.6 Hz, 1 H), 7.02 (s, 1 H), 6.55 (d, ^³ J = 8.6 Hz, 1 H) ppm. MS (EI): m/z (%) = 252.0 (100) [M]⁺.

12b Tew GN. Pralle MU. Stupp SI. J. Am. Chem. Soc. 1999, 121: 9852

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16a

Synthesis of 6,7-Dibromo-2,2-dimethylnaphtho[2,3- d ][1,3]dioxole ( 19a)
To 5.6 g (17.6 mmol) of 2,3-dibromo-6,7-dihydroxy-naphthalene [¹6b] dissolved in toluene (40 mL) toluene and anhydrous acetone (5 mL) was added P₂O₅ in three portions during 48 h while the reaction mixture was heated at 50 ˚C. The solution was diluted with toluene (50 mL), washed with H₂O, 10% NaOH soln, H₂O and brine. Combined organic phase was concentrated with a rotary evaporator. Purification of the crude product was carried out by column chromatography using dichloromethane as eluent; yield 3.42 g (57%). ^¹H NMR (400 MHz, CDCl₃): δ = 7.88 (s, 2 H), 6.87 (s, 2 H), 1.71 (s, 6 H) ppm. MS (EI): m/z (%) = 357.9 (60) [M]⁺, 342.8 (100).

16b Youssev TE. Hanack M. J. Porphyrins Phthalocyanines 2002, 6: 571

17

Compound 19b: ^¹H NMR (400 MHz, CDCl₃): δ = 8.05 (s, 2 H), 7.10 (s, 2 H), 1.77 (s, 6 H) ppm. MS (EI): m/z (%) = 250.0 (40) [M]⁺, 235.0 (100), 210.0 (50).