Base-induced transformations of ortho-nitrobenzylketones: intramolecular displacement of nitro group versus nitro-nitrite rearrangement Sergey I. Filimonov a, * , Zhanna V. Chirkova a, y , Igor G. Abramov a, y , Sergey I. Firgang b, z , Galina A. Stashina b, z , Yuri A. Strelenko b, z , Dmitriy V. Khakimov b, z , Tatyana S. Pivina b, z , Alexander V. Samet b, z , Kyrill Yu. Suponitsky c, x a Yaroslavl State Technical University, 88 Moskovsky Pr, 150023 Yaroslavl, Russian Federation b N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Pr.,119991 Moscow, Russia c A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov St.,119991 Moscow, Russia article info Article history: Received 27 February 2012 Received in revised form 27 April 2012 Accepted 8 May 2012 Available online 18 May 2012 Keywords: 4-Bromo-5-nitrophthalonitrile 4-(2-R-2-Oxoethyl)-5-nitrophthalonitriles 1,2-Benzoxazole-5,6-dicarbonitriles Alkyl 5,6-Dicyanobenzofuran-2- carboxylates 1-Hydroxyindole-5,6-dicarbonitriles Nitro-nitrite rearrangement abstract Reactions of 4-bromo-5-nitrophthalonitrile (BNPN) with enolates of alkyl 4-R-2,4-dioxobutanoates gave alkyl 3-acyl-5,6-dicyanobenzofuran-2-carboxylates, 4-(2-R-2-oxoethyl)-5-nitrophthalonitriles, or 3-acyl- 1,2-benzoxazole-5,6-dicarbonitriles. With a base, 4-(2-R-2-oxoethyl)-5-nitrophthalonitriles either un- dergo nitro-nitrite rearrangement resulting in 3-acyl-1,2-benzoxazole-5,6-dicarbonitriles or yield 2-R- benzofuran-5,6-dicarbonitriles with a nitro group displacement. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction S N Ar-reactions are of significant interest both from theoretical 1 and practical 2,3 points of view. Consecutive C-,O-nucleophilic sub- stitution of ortho-located leaving groups (Hal, NO 2 ) in various substrates with 1,3-dicarbonyl compounds results in 2,3- disubstituted benzofurans. 4e6 At the same time, 2- carboxybenzofurans were not obtained via S N Ar-reaction so far. Known methods for the synthesis of these compounds include intramolecular cyclization of the corresponding O-substituted sal- icylaldehyde derivatives 7 or ortho-alkynyl phenyl ethers. 8 Interest in the synthesis of 2-carboxybenzofurans is due to the fact that the latter are used as precursors in the synthesis of biologically active compounds. 9e11 Our work was aimed at the synthesis of previously unknown benzofuran-5,6-dicarbonitriles with alkoxycarbonyl group in 2- position via S N Ar-reaction of 4-bromo-5-nitrophthalonitrile (BNPN) with sodium enolates of alkyl 2,4-dioxobutanoates 2aed. The use of these compounds as ambident nucleophiles was not described previously. At the same time, BNPN 1 is well-known as one of the active substrates for the preparation of various heterocyclic sys- tems annulated with a phthalonitrile fragment. 12e14 ortho-Dicar- bonitriles serve as a starting material for the synthesis of macroheterocycles 15 (hexazocyclanes, phthalocyanines). 2. Results and discussion We found that, depending on the temperature, the reaction of 1 with 2 in 1:2 ratio (or reaction between 1 and alkyl 2,4- dioxobutanoates (1:1) in the presence of K 2 CO 3 ) affords either 4, 5, 6 or their mixtures. Detailed 1 H NMR study of the reaction of substrate 1 with 2a (DMSO-d 6 , 25  C) revealed the formation and accumulation of a single compound, which was assigned the structure of 3a. Such assignment is based on upfield 1 H NMR chemical shifts of the protons of phthalonitrile moiety (7.55 and 8.34 ppm) compared to those of the same protons in products 4, 5, 6. When the reaction mixture was diluted with water, enolates 3 were found to undergo hydrolytic cleavage 16e18 (retro-Claisen * Corresponding author. Fax: þ7 4852 44 07 29; e-mail addresses: filimonovsi@ ystu.ru (S.I. Filimonov), sametav@server.ioc.ac.ru (A.V. Samet). y Fax: þ7 4852 44 07 29. z Fax: þ7 495 135 53 28. x Fax: þ7 499 135 92 02. Contents lists available at SciVerse ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2012.05.034 Tetrahedron 68 (2012) 5991e5997