Mendeleev Communications Electronic Version, Issue 1, 2001 (pp. 1–42) Hexamethyldisilazane as an amination agent: one-pot synthesis of isoamarine and its pyridine analogue Electron A. Mistryukov N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119992 Moscow, Russian Federation. Fax: +7 095 135 5328 10.1070/MC2001v011n01ABEH001384 The ability of hexamethyldisilazane to convert aldehydes into Schiff bases was adapted to the one-pot syntheses of isoamarine and its pyridine analogue.Here, the conversion of a non-enolisable aldehyde function into a Schiff base with hexamethyldisilazane (HMDS) under LiBr catalysis via amination–dehydration is reported.1 The choice of aldehydes is connected with the synthesis of vicinal diamines such as diphenylethylenediamine and its pyridine analogue.For these purposes, two aldehydes (benzaldehyde 1a and 2-pyridinecarboxaldehyde 1b) were used as starting materials for the synthesis of isoamarine 2a† and its pyridine analogue 2b‡ as intermediates for the corresponding vicinal diaryl ethylenediamines. The reported procedure for 1,2-diphenylethylenediamine- 1,2 includes reduction and hydrolysis of 2a.2 The multistage synthesis of 2a is known,3 where the first product is bis-Schiff base 3a§ formed by deamination of a probable unstable trimeric Schiff base, sym-triazine 4a.Corresponding sym-triazine 4b, a derivative of aldehide 1b, is a stable compound.4 In the case of 1a, when HDMS is an amination agent, we found that the sequence 1a ® 4a ® 3a ® ® 5a ® 2a can be performed with a high yield by a one-pot procedure.Moreover, if 3a, 5a or 2a is the aim product, the reaction may be stopped at any intermediate stage by changing the conditions (Scheme 1). For example, if the first intermediate of aldehyde amination by HMDS (compound 3a) is to be isolated, the reaction is performed in a THF or diethyl ether solution with no basic catalyst added.Trasformation to cyclic products requires a basic catalyst and thermal treatment. The kinetic product of cyclization, cis-imidazoline 5a, may be obtained by the thermal process in DMSO with sodium hydroxide catalysis under mild conditions. The reaction of HMDS with aldehyde 1b is of special interest. Here, no catalyst addition is required, the reaction is exothermic and gives, depending on conditions, either itermediate bis-Schiff base 3b¶ or pyridoisoamarine 2b.The conversion of 3b into cyclic product 2b is to be noted. Contrary to the conversion of 3a into a cyclic product, where a thermal or catalytic reaction gives different products, cis-5a or trans-2a, compound 3b gives the same isomer (probably, trans-2b) by either catalytic (NaOH) or thermal process, although the latter is much slower (ca. 30% coversion after 1 h at 140 °C). Deep colour formation at the NaOH-catalysed conversion of 3b into 2b indicates different structures of transition states for 2a and 2b. References 1 N. Duffaut and J.-P. Dupin, Bull. Soc. Chim. Fr., 1966, 3205. 2 E. J. Corey and F. N. M. Kuhnle, Tetrahedron Lett., 1997, 38, 4466. 3 O. F. Williams and J. C.Bailer, J. Am. Chem. Soc., 1959, 81, 4466. 4 C. Harries and G. Lenart, Liebigs Ann. Chem., 1915, 410. † Synthesis of 2a, one-pot procedure. To a solution of 1a (0.1 mol, 10.13 ml) and 0.1 g of LiBr in 20 ml of DMSO (argon) HMDS (0.11 mol, 23.05 ml) was added with stirring. The spontaneous temperature raise was accompanied by ammonia evolution (T ~ 50 °C). After the exothermal stage NaOH (1 g) was added, and siloxane was distilled off by a gradual raise of temperature to 120–130 °C.After 2 h at 130 °C the cooled mixture was poured onto aqueous ammonia (50 ml), and the suspension was left to stand overnight. The product was filtered off, washed with ammonia, acetone and hexane and dried on the filter. The yield of 2a was 8.15 g (83%), mp 198–201 °C. 1HNMR (CDCl3) d: 7.97–7.26 (m, 15H), 4.93 (s, 2H, CH), 1.7 (br. s 1H NH).‡ Synthesis of 2b. One-pot procedure. A mixture of 1b (0.1 mol, 9.52 ml), 0.1 mol of HMDS (20.9 ml) and 20 ml of DMSO was stirred under argon. The temperature gradually raised to ca. 90 °C (30 min) with ammonia evolution. When the temperature started to drop, the mixture was heated to 90 °C for 15 min. To the cooled heterogeneous mixture (the upper layer of siloxane) 1.2 g NaOH was added to immediately give a deep red colour.By gradual heating up to 135 °C, siloxane was distilled off and, after 1 h at 130 °C, the cooled mixture was treated with 1.8 ml of AcOH and then 30 ml of ammonia. After 12 h at room temperature, the suspention was filtered, washed with ammonia (2×10 ml), the filter cake was dried by suction and washed with diethyl ether (2×10 ml).After drying, the product was dissolved in 60 ml of hot toluene and filtered through a silica gel bed. On cooling, the precipitated crystals of 2b were filtered off and washed with toluene and hexane. Total yield 6.8 g, mp 132–133 °C. 1H NMR (DMSO) d: 8.0 (br. s, 1H, NH), 7.2–8.7 (m, 12H, Py), 5.25 (s, 2H, CH). § Synthesis of 3a.The mixture of 0.1 mol of 1a, 0.1 g LiBr, 0.1 mol of HMDS and 20 ml of THF was stirred under argon at 50–80 °C until evolution of ammonia subsided (ca. 2 h). The solvent was removed on a rotary evaporator, and the residue was dissolved in hot hexane. The solution was filtered through a silica gel bed and cooled. After filtration, the yield of 3a3 was 9.33 g (94%), mp 101–102 °C. 1H NMR (DMSO) d: 6.05 (s, 1H, CH), 7.3–7.9 (m, 15H, ArH), 8.7 (s, 2H, CH). ¶ Synthesis of 3b. A solution of 1b (0.1 mol, 9.52 ml), 0.1 mol of HMDS (20.9 ml) in 20 ml DMSO was stirred under argon. The temperature spontaneously raised to ca. 90 °C with ammonia evolution and when the exothermal stage subsided, this temperature was kept for additional 20 min. On cooling, the two-phase reaction mixture gave copious crystals. After filtration and washing with dioxane and toluene, the yield of 3b was 7.4 g (86%), mp 149–150 °C. 1H NMR (DMSO) d: 7.7 (br. s, 1H), 6.9– 8.7 (m, 12H), 5.6 (br. s, 2H). Scheme 1 Reagents and conditions: i, HDMS, NH3, – H2O, DMSO, LiBr cat.; ii, – NH3, heat; iii, heat; iv, NaOH cat. RCHO HN N NH R R R H i ii N N R R R iii NH N R R R 1a,b 4a,b 3a,b 5a,b a R = Ph b R = 2-pyridyl NH N R R R 2a,b iv Received: 16th October 2000; Com. 00/1710