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

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.

hydrazine arylation - aldehydes - imines - pinacol coupling - diols

References

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4f Pietruszka J. Witt A. Synlett  2003,  91 

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8a Ley SV. Thomas AW. Angew. Chem. Int. Ed.  2003,  42:  5400 

8b Elliott GI. Konopelski JP. Tetrahedron  2001,  57:  5683 

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11

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

Arylbismuthanes provide interest not only as arylating reagents but also as for example:

12a Therapeutic agents: Matano Y. Aratani Y. Miyamatsu T. Kurata H. Miyaji K. Sasako S. Suzuki H. J. Chem. Soc., Perkin Trans. 1  1998,  2511 

12b Building blocks for three-dimensional organometallics: Murafuji T. Nishino K. Nagasuke M. Tanabe A. Aono M. Sugihara Y. Synthesis  2000,  1208 ; and references therein

13a Stijve T. Pittet A. Deutsche Lebensmittel-Rundschau  2000,  96:  251 ; Chem. Abstr. 2000, 133, 134478

13b Chulija AJ. Bernillon J. Favre-Bovin J. Kaouadji M. Arpin N. Phytochemistry  1988,  27:  929 

14 Gompper R. Walther P. Tetrahedron  1996,  52:  14607 

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16 Slouka J. Pharmazie  1971,  26:  466 

17 Yanagisawa H, and Ho KS. inventors; Eur. Pat. Appl. EP  1168066.  ; Chem. Abstr. 2002, 136, 61567

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19 Rittersdorf W, Rey H, and Rieckmann PS. inventors; African ZA  6806903.  ; Chem. Abstr. 1970, 72, 29743

20 Takai H. Yoshida M. Iida T. Matsubara I. Shirahata K. J. Antibiot.  1976,  29:  1253 

21 Stodola FH. J. Org. Chem.  1972,  37:  178 

22a Vysochin VI. Barkhash VA. Vorozhtsov NN. Zh. Obsh. Khim.  1969,  39:  1607 ; Chem. Abstr. 1969, 71, 112563

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22c Wiley RH. Irick G. J. Org. Chem.  1959,  24:  1925 

22d

Antibiotic XK-90 [N-acetyl-N′-(3-formyl-4-hydroxyphenyl)hydrazine] has been produced microbiologically from Streptomyces chibasis, see ref. [20]

23a

2-(4-Bromophenyl)-1,3-dioxolane was prepared from 4-bromobenzaldehyde (obtained from 4-bromotoluene by treatment with CrO₃/Ac₂O) [23b] in 66% yield (mp 33.5-34.0 °C). [24]

23b Lieberman SV. Connor R. Org. Synth.  1938,  18:  61 

24 Hon Y.-S. Lee C.-F. Chen R.-J. Szu P.-H. Tetrahedron  2001,  57:  5991 

25 Combes S. Finet J.-P. Synth. Commun.  1996,  26:  4569 

26

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]

27

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%).

28

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%).

29

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%).

For the use of Zn/Cu couple in condensations of imines, see:

30a Vellemäe E. Tubrik O. Loog O. Mäeorg S. Mäeorg U. Proc. Estonian Acad. Sci. Chem.  2003,  52:  91 ; Chem. Abstr. 2003, 139, 325020

30b Sergeeva EV. Rozenberg VI. Antonov DYu. Vorontsov EV. Starikova ZA. Hopf H. Tetrahedron: Asymmetry  2002,  13:  1121 

30c Shimizu M. Iida T. Fujisawa T. Chem. Lett.  1995,  609 

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%].

32 Gansäuer A. Bauer D. J. Org. Chem.  1998,  63:  2070 

33

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%].

For 1,2-diols see:

34a Tsukinoki T. Kawaij T. Hashimoto I. Mataka S. Tashiro M. Chem. Lett.  1997,  26:  235 ; and references therein

34b For 1,2-diamines ¹H NMR, see: Eisch JJ. Kaska DD. Peterson CJ. J. Org. Chem.  1966,  31:  453 

34c ¹³C NMR: Periasamy M. Srinivas G. Karunakar GV. Bharathi P. Tetrahedron Lett.  1999,  40:  7577 

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%].

Deprotection conditions for Boc groups which were probed:

38a CF₃COOH in CH₂Cl₂, see for example: Mäeorg U. Pehk T. Ragnarsson U. Acta. Chem. Scand.  1999,  53:  1127 

38b

Aq HCl in CH₃CN.

38c BF₃·Et₂O in HOAc, see: Hiskey RG. Beacham LM. Matl VG. Smith JN. Williams EB. Thomas AM. Wolters ET. J. Org. Chem.  1971,  36:  488 

38d SnCl₄ in EtOAc, see: Miel H. Rault S. Tetrahedron Lett.  1997,  38:  7865 

39 Similarly, it has been found that removal of Boc groups from 1,2-di-Boc-1,2-diarylhydrazines under usual conditions resulted in cleavage of the N-N bond, to give rise to the corresponding arylamines: Kim K.-Y. Shin J.-T. Lee K.-S. Cho C.-G. Tetrahedron Lett.  2004,  45:  117