Dihydrobenzoxazines and tetrahydroquinoxalines by a tandem reduction‐reductive amination reaction

Abstract

A tandem reduction‐reductive amination reaction has been applied to the synthesis of 3,4‐dihydro‐2H‐1,4‐benzoxazines and 1‐acetyl‐1,2,3,4‐tetrahydroquinoxalines. The nitroketones required for the benzoxazine ring closures were prepared by (A) alkylation of the anion derived from 2‐nitrophenol with an allylic halide or (B) nucleophilic aromatic substitution of an allylic alkoxide on 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the quinoxalines were prepared by alkylation of the anion of 2‐nitroacetanilide with an allylic halide followed by ozonolysis. Catalytic hydrogenation of the nitroketones using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a reduction‐reductive amination sequence. The N‐methyl derivatives for both ring systems were easily prepared by adding 5‐10 equivalents of aqueous formaldehyde prior to the reduction. The dihydrobenzoxazines were isolated in high yield following purification by chromatographic methods; tetrahydroquinoxalines were isolated in a similar manner and possessed differentiated functionality on the two nitrogens.

Iron‐Catalysed Direct Aromatic Amination withN‐Chloroamines

“…Purification by column chromatography, eluting with 10 % EtOAc in hexane afforded 2p (25 mg, 0.15 mmol, 20 %) as a colourless oil. The NMR data is in accordance with the literature . 1 H NMR signals for the major product reported (300 MHz, CDCl 3 ) δ = 6.92–6.84 (1H, m, ArC H ), 6.83–6.77 (1H, m, ArC H ), 6.69–6.61 (2H, m, 2 × ArC H ), 4.21 (1H, dd, J = 10.5, 2.6, C H 2 ), 4.04 (1H, dd, J = 10.5, 2.6, C H 2 ), 3.44–3.33 (1H, m, C H ), 2.89 (3H, s, NC H 3 ), 1.22 (3H, d, J = 6.5, C H 3 ); 13 C NMR signals for the major product reported (101 MHz, CDCl 3 ) δ = 144.2, 126.6, 121.8, 116.6, 116.4, 111.7, 69.2, 52.1, 36.1, 14.1; IR υ max (neat) /cm –1 : 3065, 3039, 2972, 2929, 2875, 2820, 1604, 1499; LCMS (ESI + ): C 19 H 22 NO [M + H] + : calculated 164.2, found 164.4.…”

Synthesis and Crystal Structure of Novel N-Acyl-N′-Dichloroacetyl-6,7-Dichloro-1,2,3,4-Tetrahydroquinoxalines Derivatives

“…Cl (1) 120.38(19) N(2)-C(11)-C (12) 116.64 (18) Synthesis of 3; general procedure Acyl chloride was added dropwise to a well stirred mixture of 2 (10 mmol) and Na 2 CO 3 (12 mmol) in 30 mL of benzene, at room temperature. After stirring about 1-4 h (monitored by TLC), the solvent was removed under reduced pressure.…”

“…8,9 Some substituted 1,2,3,4-tetrahydroquinoxaline were also obtained through a sequential procedure, including substitution, reduction and cyclisation. [10][11][12][13] However, it is hard to obtain mono-substituted 1,2,3,4-tetrahydroquinoxaline with the two nitrogen being the same. Many attempts had been made to monoalkylate or monoacylate 1,2,3,4-tetrahydroquinoxaline with a number of halides, alkyl p-toluenesulfonates, acetic anhydride, acetyl chloride, ketene, acetamide and benzoyl chloride, at temperatures ranging from -70 to 300 °C.…”

Structures of the racemate and (S)-enantiomer of 7,8-difluoro-3-methyl-2,3-dihydro-4H-[1,4]benzoxazine

“…1,4- 6 The known methods for the synthesis of enantiomer (S) 1 can be divided into two main groups. The first group includes the methods for asymmetric synthesis: (a) asym metric reduction of imines by the action of chiral reducing agents 7 and chiral catalysts based on the Ir I complexes and (b) asymmetric synthesis using chiral synthones, viz., diols 9 and alaninol derivatives.…”