4-Cyanophenylboronic acid

Description

4-Cyanophenylboronic acid can be used for palladium catalyzed Suzuki cross-coupling reactions to synthesize 6-acryl-2,4-diamino-pyrimidines and triazines. It is used as precursor in the synthesis of inhibitors such as Tpl2 kinase inhibitors and P2X7 antagonists used in the treatment of pain. It is also a reagent used for preparation of himbacine analogs as thrombin receptor antagonists and potential antiplatelet agents, trisulfonated calixarene upper-rim sulfonamido and their complexation with trimethyllysine epigenetic mark, antimalarial compounds via Suzuki cross-coupling, and deoxyuridine derivatives.

Reference

• G. Cooke, H. A. de Cremiers, V. M. Rotello, B. Tarbit, P. E. Vandersträten, Synthesis of 6-aryl-2,4-diamino-pyrimidines and triazines using palladium catalysed Suzuki cross-coupling reactions, Tetrahedron, 2001, vol. 57, pp. 2787-2789
• N. Ni, H. Chou, J. Wang, M. Li, C. Lu, P. C. Tai, B. Wang, Identification of boronic acids as antagonists of bacterial quorum sensing in Vibrio harveyi, Biochemical and Biophysical Research Communications, 2008, vol. 369, pp. 590-594

Chemical Properties

white to yellow powder

Uses

Intermediates of Liquid Crystals

Uses

suzuki reaction

Uses

4-Cyanophenylboronic Acid is a reactant used in the synthesis of (AMG-8718), an inhibitor of β-site amyloid precursor protein cleaving enzyme (BACE1).

Synthesis

623-00-7

126747-14-6

The general procedure for the synthesis of 4-cyanobenzeneboronic acid from 4-bromobenzonitrile was as follows: 4-bromobenzonitrile (91 g, 0.50 mol) was dissolved in THF (1.1 L) at room temperature, and activated 3molecular sieves were added for drying. After completion of drying, the solution was filtered and cooled to -100 °C. A hexane solution of 1.6 M n-butyllithium (355 mL, 0.567 mol) was slowly added over 15 min while maintaining an internal temperature between -105 °C and -93 °C. Subsequently, trimethyl borate (81 g, 0.78 mol) was added to the reaction mixture over 3 min, at which time the reaction temperature briefly increased to -72 °C. The reaction mixture was re-cooled to -100 °C over 5 min, followed by a slow warming to room temperature over 2.3 h. The reaction temperature was then increased to -100 °C over 2.3 h. The reaction temperature was then increased to -100 °C over 3 min. Upon completion of the reaction, the reaction mixture was acidified to pH 2.2 with 4N HCl and diluted with CH2Cl2 (200 mL). After separation of the aqueous layer, the organic layer was washed with brine (2 x 200 mL), dried over anhydrous MgSO4, filtered and the solvent was removed under reduced pressure to give a light yellow solid. The solid was purified by dissolving in 1N NaOH and extracting with CH2Cl2/THF (1:1, 2 × 200 mL). The aqueous phase was again acidified to pH 2.2 with 4N HCl and extracted with CH2Cl2/THF (1:1, 500 mL). The organic extracts were combined and concentrated to give a crude solid (64.6 g), which was ground with ether (160 mL) and dried under vacuum to give 4-cyanobenzeneboronic acid (44.0 g, 59.9% yield) in white powder form.1H NMR (d6-acetone, 300 MHz) data were as follows: δ 8.03 (d, 2H, J = 8.1), 7.75 (d, 2H, J = 8.4) , 7.54 (s, 2H).

References

[1] Organic Letters, 2011, vol. 13, # 17, p. 4479 - 4481
[2] Tetrahedron, 2002, vol. 58, # 29, p. 5779 - 5787
[3] Dyes and Pigments, 2011, vol. 88, # 3, p. 274 - 279
[4] Patent: US2004/6114, 2004, A1. Location in patent: Page 63
[5] Patent: US7034045, 2006, B1. Location in patent: Page/Page column 37