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N. C. Mathur et al. / Tetrahedron Letters 44 (2003) 5141–5144
4. (a) Mathur, N. C.; Shechter, H. J. Org. Chem. 1990, 55,
range of 9–11) are assigned as trans (E)-isomers; the
5-methylenehydantoin isomers with JC,H values ranging
3
3001; (b) Mathur, N. C.; Shechter, H. Tetrahedron Lett.
1990, 31, 6965; (c) Mathur, N. C.; Shechter, H. Tetrahedron
Lett. 1991, 32, 3799; (d) 5-(Hydroxymethylene)hydantoins
42 have been previously prepared by decomposition of
5-diazo-6-hydroxydihydrouracil with rhodium(II) acetate
at 105°C.4c
from 4 to 6 Hz are assigned as cis (Z)-isomers.9b The
stereochemistries of further products of the present study
are to be investigated by NMR and crystallographic
methods; (b) The 13C NMR assignment methods are based
on that of Ref. 2a and references cited therein.
10. The 3JC,H spin coupling value between the exocyclic olefin
proton and the C-4 carbonyl carbon in 19 is 8.0 Hz.
Assignment of the stereochemistry of 19 has not yet been
made.
11. Reactions of 5-(N-pyridiniummethylene)hydantoin bro-
mides (23)12 and 3-alkyl-[5-(N-pyridiniummethylene)-
hydantoin bromides, respectively, with strong bases are of
interest with respect to advantageous generation of 5-
hydantoenylcarbenes 64 as in Eq. (1).
5. (a) Hydantoin 7 (stereochemistry unknown) was prepared
from 5-benzalhydantoin and Br2 in acetic acid.3 Synthesis
of no other 5-(a-haloalkylidene)hydantoins has been
reported; (b) The products from reactions of 7 with other
nucleophiles were not identified;3,5c (c) See Ref. 14 for
further studies of addition–eliminations of 7.
6. (a) Sprinson, D. B.; Chargaff, E. J. Biol. Chem. 1946, 164,
417; (b) Stubbe, J. A.; Kenyon, G. L. Biochemistry 1971,
10, 2669; (c) Hirschbein, B. L.; Mazenod, F. P.; Whitesides,
G. M. J. Org. Chem. 1982, 47, 3765.
7. (a) Conversions of 9 by 10 and 14 (Scheme 1) to 12 and
16, respectively, apparently involve acid-catalyzed (1) ring-
closures of 11 and 15 to their corresponding 5-bro-
momethyl-5-hydroxyhydantoins and then dehydrations
or/and (2) eliminations of H2O from 11 or 15 and then
heterocyclizations of the (E)- and (Z)-3-bromo-2-ureido-
acrylic acids generated. It is emphasized that products from
(1) intramolecular displacements of Br− in 11 or 15 and/or
(2) formation and intramolecular additions in 3-bromo-2-
ureidoacrylic acids and eliminations of Br− were not
obtained. The mechanisms of conversions of 9 by 10 and
14 to 12 and 16, respectively, will be discussed further in
a future publication; (b) 5-Methylenehydantoin (24%) has
been prepared from pyruvic acid, urea (10), hydrochloric
acid, and acetic acid and (2) 5-hydroxy-5-methylhydantoin
(69%) is obtained from pyruvic acid and aqueous urea (10)
at 20–25°C for 14 days;7c,d (c) Of note in the above
preparations of 5-methylenehydantoin and 12 is that such
methylenehydantoins are more stable than their respective
(endocyclic) 5-methyl- and 5-(bromomethyl)hydantoene
isomers; (d) Murahashi, S.; Yuki, H.; Kosai, K.; Doura,
F. Bull. Chem. Soc. Jpn. 1966, 39, 1559.
12. Pyridinium bromide 24 was obtained as follows. A solution
of bromide 16 (96.1 mg, 0.439 mol) in pyridine (10 mL)
was refluxed for 2 h, stirred at room temperature for 2 days,
cooled, and then filtered. The precipitate, on rinsing with
Et2O, gave 24 (125 mg, 96%) as a brown solid; mp
1
191–193°C; H NMR (DMSO-d6): l 9.15 (2H, d, J=4.85
Hz), 8.79 (1H, t, J=7.45 Hz), 8.30 (2H, t, J=7.50 Hz), 7.60
(1H, s), 3.05 (3H, s), 2.70 (3H, s); 13C NMR (DMSO-d6):
l 162.1, 154.7, 147.5, 146.2, 130.3, 127.8, 110.4, 28.3, 25.2;
exact mass calcd for C11H12BrN3O2 (M+−C5H5NBr) m/e
139.0507, found m/e 39.0508. Anal. calcd for
C11H12BrN3O2: C, 44.32; H, 4.06. Found C, 44.44; H, 4.03.
13. [(Phenylthio)methylene]hydantoin 29 was prepared by
adding tetramethylguanidine (237 mg, 2.05 mmol, 1.5
equiv.) dropwise to a solution of 16 (300 mg, 1.3 equiv.)
and thiophenol (196 mg, 1.78 mmol, 1.3 equiv.) in THF
(3 mL) at 25°C. The mixture formed a yellow precipitate
which was stirred for 24 h. Filtration and then concentra-
tion of the filtrate at reduced pressure followed by column
chromatography (1:3 ethyl acetate/petroleum ether) gave
29 as a yellow solid (290.0 mg, 85%). An analytical sample
of 29 was obtained by recrystallization from ethanol: mp
1
8. The experimental procedure for preparing 12 is described
as follows. Bromine (6.7 ml, 20.8 g, 0.13 mol) was added
to a solution of pyruvic acid (9.6 ml, 20.8 g, 0.13 mol), conc
H2SO4 (one drop), and CH2Cl2 (10 mL). The solvent and
HBr in the reaction mixture were removed in vacuo. Upon
dissolving the residue, crude bromopyruvic acid (9), in
anhydrous CH3CN (250 mL), boron trifluoride etherate (7
mL, 8.09 g, 0.05 mol), and then urea (10, 7.8 g, 0.13 mol,
15 min) were added. The mixture was refluxed for 9 h and
then cooled to room temperature. The dark precipitate
formed was suction-filtered. Additional product was
obtained upon concentrating the filtrate. The combined
solids were washed with water, dissolved in ethanol, treated
with charcoal, and crystallized from ethanol to give 12
89–91°C; H NMR (CDCl3): l 3.09 (s, 3H), 3.51 (s, 3H),
6.75 (s, 1H), 7.30–7.50 (m, 5H); 13C NMR (CDCl3): l
25.02, 28.98, 112.17, 127.21, 128.23, 129.58, 130.86, 133.51,
154.69, 161.27; exact mass calcd for C12H12N2O2S m/e
248.0619, found m/e 248.0618. Anal. calcd for
C12H12N2O2S: C, 58.05; H, 4.88. Found: C, 58.03; H, 4.91.
14. (a) Kocienski, P. J. Tetrahedron Lett. 1979, 20, 2649; (b)
Hsiao, C.-N.; Shechter, H. J. Org. Chem. 1988, 53, 2688
and references cited therein.
15. S. Negi of this laboratory has found that (1) 12 and 7 are
converted by aqueous sodium p-toluenesulfinate at 95°C
to 5-(p-toluenesulfonylmethylene)hydantoin (71%) and 5-
(a-p-toluenesulfonylbenzal)hydantoin (85%), respectively,
and (2) 7 reacts with piperidine and morpholine in dioxane
at 105–120°C to give 5-(a-N-piperidinobenzal)hydantoin
(68%) and 5-(a-N-morpholinobenzal)hydantoin (55%),
respectively. The stereochemistries of these products have
not yet been determined.
1
(11.6 g, 47%) as a white solid; mp 247–249°C; H NMR
(DMSO-d6): l 11.3 (1H, bs), 10.6 (1H, bs), 6.54 (1H, s);
MS: 192 (M+2, 98), 190 (M, 100), 149 (27), 121 (89), 119
(89). Anal. calcd for C4H3BrN2O2: C, 25.16; H, 1.58; N,
14.67; Found: C, 25.21; H, 1.61; N, 14.60.
16. For recent developments in catalytic asymmetric hydro-
genations of functionally-substituted olefins, see: Rajan-
Babu, T. V.; Casalnuovo, A. L.; Ayers, T. A.; Nomura, N.;
Jin, J.; Park, H.; Nandi, M. Curr. Org. Chem. 2003, 7, 1
and references cited therein.
9. (a) The stereochemical assignments of 16, 24, 26, 29–32,
and 34 are made by 13C NMR from the long-range 13C–1H
coupling constants between their exocyclic olefinic protons
and their C-4 carbonyl carbons.2a The present 5-methylene-
hydantoins that have 3JC,H values of 9.0 Hz and higher (a