LETTER
Tetrahedron Lett. 2001, 42, 1945. (c) Zhu, H.-J.; Lu, K.-T.;
Sum, G.-R.; He, J.-B.; Li, H.-Q.; Pittman, C. U. Jr. New J.
Chem. 2003, 27, 409. (d) Fisher, G. B.; Fuller, J. C.;
Harrison, J.; Alvarez, S. G.; Burkhardt, E. R.; Goralski,
C. T.; Singaram, B. J. Org. Chem. 1994, 59, 6378. (e) Cha,
J. S.; Brown, H. C. Org. Prep. Proced. Int. 1994, 26, 459.
(12) Lustig, E.; Benson, W. R.; Duy, N. J. Org. Chem. 1967, 32,
851.
Anionic ortho-Fries Rearrangement to Mannich Bases
2781
°C (as HCl salt); Rf 0.14 (hexane–Et2O, 3:7). IR (KBr): 3330
cm–1. 1H NMR (400 MHz, CDCl3): d = 1.16 (t, J = 7.2 Hz, 6
H), 2.69 (q, J = 7.2 Hz, 4 H), 3.92 (s, 2 H), 7.07 (d, J = 8.0
Hz, 1 H), 7.28 (d, J = 8.0 Hz, 1 H), 7.41–7.49 (m, 2 H), 7.74
(m, 1 H), 8.22–8.28 (m, 1 H), 11.15 (br s, 1 H). 13C NMR
(100 MHz, CDCl3): d = 11.3 (2 × C), 46.5 (2 × C), 57.2,
114.4, 118.0, 122.0, 124.7, 125.0, 125.8, 126.4, 127.3,
133.8, 154.0. ES–MS: m/z = 230.24 [M + 1]+. Anal. Calcd
for C15H19NO: C, 78.56; H, 8.35; N, 6.11. Found: C, 78.25;
H, 8.64; N, 5.74.
(13) Conversion of Carbamates to Amides (Table 1); General
Procedure: n-BuLi (3.8 mL, 1.6 M sol in hexane) was added
dropwise to a stirred solution of diisopropylamine (0.607 g,
6 mmol), in anhyd THF (6 mL) at –78 °C under a nitrogen
atmosphere. After 20 min at –78 °C a solution of the
appropriate carbamate (5 mmol) in anhyd THF (6 mL) was
added. The reaction mixture was stirred for 30 min at –78 °C,
allowed to warm to r.t., stirred for a further 6 h and then
quenched with sat. NH4Cl (5 mL). The reaction mixture was
extracted with Et2O (3 × 20 mL) and the combined organic
extracts were washed with brine (25 mL) and then dried
(Na2SO4). The solvent was removed in vacuo and the crude
product was purified by silica flash column chromatography
(hexane–Et2O, 6:4) to give the corresponding amide. The
structures of the products were confirmed by comparison of
their mp, TLC, IR or 1H NMR data with authentic samples
obtained commercially or prepared by literature methods.
N,N-Diethyl-1-hydroxy-2-naphthamide (Table 1, entry
8): Obtained as colourless microcrystals (EtOAc–hexane);
yield: 0.87 g (72%); mp 50–52 °C; Rf 0.48 (hexane–Et2O,
3:7). IR (KBr): 3443, 3067, 2982, 2934, 1635 cm–1. 1H NMR
(400 MHz, CDCl3): d = 1.29 (t, J = 7.2 Hz, 6 H), 3.54 (q,
J = 7.2 Hz, 4 H), 7.25–7.33 (m, 2 H), 7.45–7.58 (m, 2 H),
7.78 (d, J = 6.8 Hz, 1 H), 8.41 (d, J = 7.6 Hz, 1 H), 11.41 (br
s, 1 H). 13C NMR (100 MHz, CDCl3): d = 13.6, 42.4, 110.6,
117.7, 123.7, 123.8, 125.7, 125.8, 127.4, 128.4, 135.6,
157.8, 172.8. ES–MS: m/z = 244.66 [M + 1]+. Anal. Calcd
for C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C, 73.78;
H, 7.20; N, 5.69.
(22) Pochini, A.; Puglia, G.; Ungaro, R. Synthesis 1983, 906.
(23) Boehme, H.; Hartke, K. Chem. Ber. 1963, 96, 604.
(24) Tanaka, Y.; Hasui, T.; Suginome, M. Org. Lett. 2007, 9,
4407.
(25) Dilman, A. D.; Arkhipov, D. E.; Belyakov, P. A.;
Struchkova, M. I.; Tartakovsky, V. A. Russ. Chem. Bull.
2006, 55, 517.
(26) Matsumoto, K.; Joho, K.; Mimori, S.; Iida, H.; Hamana, H.;
Kakehi, A. Heterocycles 2008, 76, 1061.
(27) Blade-Font, A.; De Mas Rocabayera, T. J. Chem. Soc.,
Perkin Trans. 1 1982, 841.
(28) Moehrle, H.; Troester, K. Arch. Pharm. (Weinheim, Ger.)
1982, 315, 397.
(29) For the synthesis of compound 5, see: (a) Call, G.; Morey,
J.; Costa, A.; Saá, J. M. J. Org. Chem. 1988, 53, 5345.
(b) Buisson, J.-P.; Roner, R. J. Heterocycl. Chem. 1988, 25,
539. (c) Ellinger, C. A. Org. Prep. Proced. Int. 1985, 17,
419.
(30) The anionic ortho-Fries rearrangement usually takes place
upon warming the lithiation reaction to room temperature.
See: (a) Kauch, M.; Hoppe, D. Can. J. Chem. 2001, 79,
1736. (b) Wang, W.; Snieckus, V. J. Org. Chem. 1992, 57,
424. (c) Van Doorn, A. R.; Bos, M.; Harkema, S.;
Van Eerden, J.; Verboom, W.; Reinhoudt, D. N. J. Org.
Chem. 1991, 56, 2371. (d) The only other known example of
this rearrangement, occurring under similar conditions, is
that of the o-migration of the tetrazole from its aryloxy
precursor. See: Dankwardt, J. W. J. Org. Chem. 1988, 63,
3753.
(14) Cohen, T.; Moran, R. M. Jr.; Sowinski, G. J. Org. Chem.
1961, 26, 1.
(15) (a) Kawski, P.; Kochel, A.; Perevozkina, M. G.; Filarowski,
A. J. Mol. Struct. 2006, 790, 65. (b) Sigma-Aldrich cat. no.
644234.
(16) Saitama, H. W. J. Am. Chem. Soc. 2007, 129, 15102.
(17) Sigma-Aldrich cat. no. 642932.
(31) ‘Fast’ reacting electrophiles such as TMSCl and aryl
aldehydes, when present, did not quench the lithiated
species. See: Schnürch, M.; Spina, M.; Khan, A. F.;
Mihovilovic, M. D.; Stanetty, P. Chem. Soc. Rev. 2007, 36,
1046.
(18) Katritzky, A. R.; Singh, S. K.; Cai, C.; Bobrov, S. J. Org.
(32) (a) Pittelkow, M.; Boas, V.; Jass, M.; Jensen, K. J.;
Christensen, J. B. Org. Biomol. Chem. 2005, 3, 508.
(b) Karacar, A.; Freytag, M.; Thönnessen, H.; Jones, P. G.;
Barts, R.; Schmutzler, R. J. Organomet. Chem. 2002, 68,
643. (c) Kirby, A. J.; Percy, A. C. Tetrahedron 2002, 58,
6901. (d) Balasubramaniyan, V. Chem. Rev. 1966, 66, 567.
(33) 2-[(Diethylamino)methyl]-8-(1,3-dioxolan-2-yl)-1-
naphthol (8b): Prepared by reducing 8-(1,3-dioxolan-2-yl)-
N,N-diethyl-1-hydroxy-2-naphthamide (7b) with LiAlH4
according to the general procedure.29 Obtained as a
colourless semi-solid; yield: 42 mg (74%); Rf 0.38 (hexane–
Et2O, 1:4). IR (KBr): 3330 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.26 (t, J = 7.2 Hz, 6 H), 3.50 (q, J = 7.2 Hz, 4
H), 3.82 (s, 2 H), 4.08–4.18 (m, 5 H), 7.27–7.90 (m, 5 H),
11.45 (br s, 1 H). 13C NMR (100 MHz, CDCl3): d = 13.22,
41.75, 42.10, 65.09, 102.16, 114.00, 119.06, 124.16, 126.84,
129.50. ES–MS: m/z = 302.3 [M + 1]+. Anal. Calcd for
C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C, 71.48; H,
7.54; N, 4.51.
Chem. 2006, 71, 3364.
(19) Milne, G. W. A. Drugs: Synonyms and Properties; Ashgate:
Brookfield VT, 2000.
(20) Hasegawa, I.; Sakka, S. Bull. Chem. Soc. Jpn. 1988, 61,
4087.
(21) Conversion of Amides to Mannich Bases (Table 2);
General Procedure: A solution of appropriate amide (1.25
mmol) in anhyd THF (50 mL) was added to a stirred solution
of LiAlH4 (0.244 g, 6.25 mmol) in anhyd THF (25 mL) at 0
°C. The reaction mixture was allowed to warm to r.t., stirred
for 3 h and then treated successively with H2O (10 mL), 15%
aq NaOH (10 mL) and H2O (40 mL). The reaction mixture
was extracted with Et2O (3 × 30 mL) and the combined
organic extracts were dried (Na2SO4), filtered and
concentrated in vacuo. The crude product was purified by
silica flash column chromatography eluting with Et2O to
give the corresponding Mannich base. The structure of the
products was confirmed by comparison of their mp, TLC,
IR or 1H NMR data with authentic samples obtained
commercially or prepared by literature methods.
(34) 7-[(Diethylamino)methyl]-8-hydroxy-1-naphthaldehyde
(9b): Compound 8b (0.04 g, 0.13 mmol) was dissolved in a
mixture of 10% aq HCl (10 mL) and THF (10 mL) and
heated under reflux for 1 h. After cooling, 10% aq K2CO3
2-[(Diethylamino)methyl]-1-naphthol (Table 2, entry 8):
Obtained as a dark red oil; yield: 0.18 g (65%), mp 149–150
Synlett 2009, No. 17, 2777–2782 © Thieme Stuttgart · New York