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Synlett 2004(14): 2537-2540  
DOI: 10.1055/s-2004-835621
LETTER
© Georg Thieme Verlag Stuttgart · New York

Cu-Catalysed N-Arylation of Hydrazines with Bismuthanes: Synthesis and Pinacol or Imino-Pinacol Coupling of 4-Formylphenylhydrazines and their Phenylimine Derivatives

Olavi Loog, Uno Mäeorg*
Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014, Tartu, Estonia
e-Mail: uno.maeorg@ut.ee;
Further Information

Publication History

Received 25 August 2004
Publication Date:
20 October 2004 (online)

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Abstract

Acetal protected 4-formylphenylbismuthane was prepared and used for arylation of trisubstituted hydrazines. Formylphenylhydrazines, obtained after removal of acetal group, were used in coupling reaction to give diols containing two sub­stituted hydrazino moieties and the coupling of corresponding ­phenylimine derivatives gave corresponding diamines.

Key words

hydrazine arylation - aldehydes - imines - pinacol coupling - diols

11

For the use of arylbismuthanes in arylation of hydrazine derivatives, see ref. [7] and ref. [10]

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A mixture of 2-(4-bromophenyl)-1,3-dioxolane (8.160 g, 35.6 mmol), Mg powder (0.909 g, 37.4 mmol) and THF (55 mL) was gently warmed to induce the reaction, keeping the reaction mixture temperature below 40 °C. The reaction mixture was stirred for 4 h at r.t. and cooled to -45 °C. A solution of BiCl3 (3.370 g, 10.7 mmol) in THF (55 mL) was added over the period of 20 min at -45 °C. The mixture was stirred for 35 min at the same temperature and then allowed to warm to r.t. Sat. NH4Cl solution and brine were added, the mixture was filtered through celite and the filter cake was washed with THF. The organic layer was separated and the water layer was extracted with Et2O. The combined organic layer was dried (MgSO4) and concentrated at reduced pressure. The residue was dissolved in the mixture of EtOAc and CH2Cl2 and eluted with EtOAc through a short pad of silica gel. Eluates were concentrated to about 1:3 of initial volume and about the same volume of hexane was then added. The precipitate was filtered and dried to give 4.74 g of light yellow fine crystals (mp 150.5-151.5 °C). Additional 0.16 g of product was obtained from the mother liquor by silica gel column chromatography (EtOAc-hexane). Overall yield 4.90 g (70%, purity by NMR >99%). 1H NMR (200 MHz, CDCl3): δ = 4.03 (m, 2 H), 4.10 (m, 2 H), 5.76 (s, 1 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.74 (d, J = 8.2 Hz, 2 H). 13C NMR (50 MHz): δ = 65.3, 103.9, 128.5, 137.6, 156.3. Treatment of arylbismuthane 1 with TsOH in aq THF (see ref. [29] ) gave corresponding bismuthane with free aldehyde groups; 1H NMR and 13C NMR spectra were identical with those described in ref. [12b]

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Hydrazine 2a was prepared as described in ref. [7b] (82%, mp 104.5-105.5 °C). Hydrazine 2b was prepared as described in ref. [5b] (78%, mp 109-110 °C).
Preparation of Hydrazine 2c. To the mixture of 1,2-diacetylhydrazine (0.382 g, 3.30 mmol) and MeCN (10 mL) were added Boc2O (0.756 g, 3.46 mmol) in MeCN (5 mL) and then DMAP (0.010 g, 0.083 mmol) in MeCN (0.3 mL). The mixture was stirred at r.t. for 17 h under argon. The reaction mixture was then poured into the mixture of sat. NH4Cl (10 mL) and brine (20 mL) and extracted with Et2O. The combined organic layer was washed with the mixture of sat. NH4Cl and brine (1:2), sat. NaHCO3 and brine, dried (MgSO4) and concentrated. Column chromatographic separation (silica gel, EtOAc) of the residue gave 2c as colourless oil (0.365 g, 51%), which crystallised on standing, mp 104-105 °C (purity by NMR >99%).

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Typical Procedure. CH2Cl2 (5 mL) and Et3N (0.21 mL, 1.5 mmol) were added to the mixture of hydrazine (1.0 mmol), Cu(OAc)2 (0.276 g, 1.5 mmol) and bismuthane 1 (0.985 g, 1.5 mmol) in oven-dried flask under argon. The reaction mixture was stirred at r.t. For the synthesis of 3b additional amounts of Cu(OAc)2 and Et3N were added after 22 h and 48 h [respectively 0.186 g, 1.0 mmol + 0.091 g, 0.5 mmol of Cu(OAc)2 and 0.1 mL, 1.0 mmol + 0.1 mL, 1.0 mmol of Et3N]. For the synthesis of 3c additional amounts of Cu(OAc)2 (0.276 g, 1.5 mmol) and Et3N (0.28 mL, 2.0 mmol) were added after 24 h. After indicated time (see Table [1] ) Et2O and H2O or in case of 3c also brine were added. In case of 3a only H2O was added, the mixture was filtered through celite and the residue was rinsed with CH2Cl2. The organic layer was separated and the water layer was extracted with Et2O and in case of 3a also with CH2Cl2 or in case of 3c also with EtOAc. The combined organic layer was washed with brine, dried (MgSO4) and concentrated at reduced pressure. The residue was purified by silica gel column chromatography (EtOAc-hexane). Compound 3a: Colourless oil (purity by NMR >95%). Compound 3b: Colourless oil (purity by NMR >97%). Compound 3c: Pale yellow oil (purity by NMR >98%).

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Acetal groups were removed similarly to the procedure described in ref. [24] ; 0.4 equiv of TsOH were used in solvent mixture THF-H2O 25:1. Compound 4a: Colourless oil (purity by NMR >98%). 1H NMR (200 MHz, CDCl3): δ = 1.49 (s, 9 H), 1.52 (s, 9 H), 7.11-7.88 (m, 9 H), 9.94 (s, 1 H). 13C NMR (50 MHz): δ = 28.16, 28.20, 82.9, 83.5, 121.2, 122.3, 125.7, 128.7, 130.4, 133.0, 141.0, 146.8, 152.5, 152.7, 190.9. Compound 4b: Colourless crystals, mp 96.5-98.5 °C (purity by NMR >97%). Compound 4c: Colourless oil (purity by NMR >98%).

31

The Zn/Cu couple was prepared and used as described in ref. [30a] ; products were separated by silica gel column chromatography (EtOAc-hexane). Compound 6a′: Colourless oil [purity by NMR >99%, by C18 HPLC (MeOH-H2O, UV 254 nm) >95%].

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Compound 5a: Off-white solid foam [purity by NMR >97%, by C18 HPLC (MeOH-H2O, UV 254 nm) >97%, dl/meso = 80:20]. 1H NMR (200 MHz, CDCl3): δ = 1.47 (s, 36 H), 3.04 [br s, -OH(dl)], 4.59 (dl, major) and 4.69 (meso, minor) (2 × s, 2 H), 6.97-7.50 (m, 18 H). 13C NMR (50 MHz): δ = 28.2, 78.4, 82.4, 122.4, 123.0, 125.6, 127.2, 128.6, 137.1, 141.1, 141.4, 153.1. Compound 5b: White solid foam [purity by NMR >97%, by C18 HPLC (MeOH-H2O, UV 254 nm) >98%, dl/meso = 80:20]. Compound 6b: White solid foam [purity by NMR >98%, by C18 HPLC (MeOH-H2O, UV 254 nm) >97%]. Compound 5c: White solid foam [purity by NMR >94% (ca. 5% Et2O), by C18 HPLC (MeOH-H2O, UV 254 nm) >96%, by 1H NMR dl/meso = 10:1]. Compound 6c: White solid foam [purity by NMR >98%, by C18 HPLC (MeOH-H2O, UV 254 nm) >96%].

35

Gansäuer and Bauer (see ref. [32] ) found that in order to obtain good dl-selectivity, the concentration of aldehyde must be kept low, which was achieved by its very slow addition.

36

Compounds 7a-c were obtained by treatment of compounds 4a-c with aniline (1.2-2.0 equiv) in CH2Cl2 at r.t. in the presence of MgSO4 followed by filtration through the pad of celite and concentration at reduced pressure. Compound 7a: Slightly yellow viscous oil (purity by NMR >98%). Compound 7b: Light yellowish solid, mp 133-134 °C (purity by NMR >99%). Compound 7c: Colourless oil (purity by NMR >95%).

37

The Zn/Cu couple was prepared and used as described in ref. [30a] ; products were purified by silica gel column chromatography (EtOAc-hexane). Compound 8a (1:1 mixture of dl- and meso-isomers): Colourless oil [purity by NMR >94% (ca. 4% Et2O), by C18 HPLC (MeOH-H2O, UV 254 nm) >97%]. 1H NMR (200 MHz, CDCl3): δ = 1.40-1.57 (m, 36 H), 4.49 [br, 3 H, dl-NCH (1 H) and NH (2 H)], 4.88 (br s, 1 H, meso-NCH), 6.42-7.50 (m, 28 H). 13C NMR (50 MHz): δ = 28.2, 61.8 (meso), 63.3 (dl), 82.4, 113.9 (meso), 114.2 (dl), 118.0 (meso), 118.3 (dl), 122.7, 125.6, 127.6, 127.7, 128.6, 129.1, 129.2, 135.4 (meso), 137.0 (dl), 141.0, 141.3, 146.5, 147.0, 153.0. Compound 8b (1:1 mixture of dl- and meso-isomers): Colourless glass [purity by NMR >82% (ca. 15% 7b), by C18 HPLC (MeOH-H2O, UV 254 nm) >86%].