Intermolecular electrophilic O-amination of alcohols

Article abstract of DOI:10.1021/jo061900m

We report the first examples of an intermolecular electrophilic O-amination of aliphatic alcohols. Thus, the new reagents, fluorenone oxime tosylate, 5a, or mesylate, 5b, permit O-amination of diverse alcohols in the presence of NaH under mild conditions. By following the formation of the resulting oxime ethers, 6, the reaction was shown to be sensitive to steric effects in the alcohol. Furthermore, the presence of an aromatic ring or of a double bond in the alcohol molecule (benzyl, allyl) was found to increase the reaction rate.

Full text of DOI:10.1021/jo061900m

Previous studies have indicated that such reactions most likely
involve SN2 displacement on nitrogen by a carbanion. However,
since carbanions easily abstract protons attached to nitrogen,
resulting in the decomposition of the aminating species, the yield
of the aminated product often remains low. For a successful
amination, it is therefore desirable to have an aminating agent
that lacks a hydrogen on the nitrogen. This has led to the use,
among others, of vinyl azides,5 (phenylthio)methyl azide,6 and
diphenyl phosphorazidate7 in the amination of aromatic, het-
eroaromatic, and even alkyl-lithiated carbanions or Grignard
species.
Intermolecular Electrophilic O-Amination of
Alcohols†
Alfred Hassner,* Guy Patchornik, Tarun K. Pradhan, and
R. Kumareswaran
Department of Chemistry, Bar-Ilan UniVersity,
Ramat-Gan 52900, Israel
hassna@mail.biu.ac.il
By contrast to amination on carbon or nitrogen,2-4 amination
on oxygen is less explored. Thus O-sulfonylhydroxylamines3a
do not aminate alcohols. Rapoport et al.8 have shown that
phenolates can react in an amine exchange reaction with 1a to
produce various O-arylhydroxylamines. A nice example of an
attack by a phenolate on the N of an O-oxime sulfonate (2)
leading to benzisoxazole 3 has been reported by Kemp and
Woodward.9 Similarly, some time ago, we reported the first
examples of intramolecular N-N bond formation in the
synthesis of pyrazolines.10 Though the conversion of 2 to 3 was
an example of an intramolecular reaction with a favorable
formation of a five-membered ring, this result, as well as those
by Rapoport, encouraged us to attempt to find a reagent for the
electrophilic intermolecular amination of aliphatic alcohols.
Herein, we report the first reagents of type 5 that serve to convert
simple alcohols into O-alkylhydroxylamine derivatives.
ReceiVed September 14, 2006
We report the first examples of an intermolecular electro-
philic O-amination of aliphatic alcohols. Thus, the new
reagents, fluorenone oxime tosylate, 5a, or mesylate, 5b,
permit O-amination of diverse alcohols in the presence of
NaH under mild conditions. By following the formation of
the resulting oxime ethers, 6, the reaction was shown to be
sensitive to steric effects in the alcohol. Furthermore, the
presence of an aromatic ring or of a double bond in the
alcohol molecule (benzyl, allyl) was found to increase the
reaction rate.
Though an aldehyde oxime O-sulfonate was used in the
formation of the O-N bond in 3, our own studies and the
literature11 indicated that such aldehyde oxime species usually
lead to the facile elimination of sulfate with the formation of a
nitrile. Furthermore, many ketoxime sulfonates under basic
conditions can undergo the Neber12 or the Beckmann4,13
rearrangement. Hence, we initially chose fluorenone oxime
derivatives, 4, the rationale being not only because they possess
a good sulfate leaving group, as in Woodward’s example, but
mainly because attack by an O-nucleophile on N may proceed
via addition to the NdC, facilitated by the formation of an
intermediate 6π-electron-stabilized fluorene anion.14 Further-
more, fluorenone oxime derivatives should be stable, easily
isolable compounds, and the absence of R protons obviates the
possibility of a Neber rearrangement.
The oldest route to amine derivatives is nucleophilic displace-
ment on carbon by nitrogen nucleophiles. Yet, over the past
few years, reagents possessing good leaving groups on N have
been developed for electrophilic amination;1 foremost among
them are hydroxylamine sulfonic acid derivatives, for instance,
1a,b.2,3 These compounds react primarily with stabilized car-
banions or with amines, which displace the good leaving group
on N. Though the yields in such reactions are often low, higher
yields can been achieved, as in the amination of stabilized
carbanions by O-diphenylphosphinyl hydroxylamine 1c.3
(5) (a) Belinka, B. A.; Hassner, A. J. Am. Chem. Soc. 1980, 102, 6185.
(b) Hassner, A.; Munger, P.; Belinka, B. A. Tetrahedron Lett. 1982, 23,
699.
(6) (a)Trost, B. M.; Pearson, W. H. J. Am. Chem. Soc. 1981, 103, 2483.
(b) Trost, B. M.; Pearson, W. H. J. Am. Chem. Soc. 1983, 105, 1054.
(7) Mori, S.; Aoyama, T.; Shiori, T. Tetrahedron Lett. 1984, 25, 429.
(8) Castellino, A. J.; Rapoport, H. J. Org. Chem. 1984, 49, 1348.
(9) Kemp, D. S.; Woodward, R. B. Tetrahedron 1965, 21, 3019.
(10) Hassner, A.; Michelson, M. J. J. Org. Chem. 1962, 27, 298.
(11) Sreith, J.; Fizet, C.; Fritz, H. HelV. Chim. Acta 1976, 59, 2786.
(12) (a) Neber, P. W.; Huh, G. Liebigs Ann. Chem. 1935, 515, 283. (b)
O’Brine, C. Chem. ReV. 1964, 64, 81.
† Dedicated to Prof. Albert Padwa on his 70th birthday.
(1) Tamura, Y.; Minamikawa, J.; Ikeda, M. Synthesis 1977, 1.
(2) Erdick, E.; Ay, M. Chem. ReV. 1989, 89, 1947.
(3) (a) Sheradsky, T. Tetrahedron Lett. 1968, 1909. (b) Sheradsky, T.;
Nir, Z. Tetrahedron Lett. 1969, 77. (c) Sheradsky, T.; Salemnick, G.; Nir,
Z. Tetrahedron 1972, 28, 3833. (d) Sheradky, T.; Yusupova, L. Tetrahedron
Lett. 1995, 36, 7701. (e) Sheradsky, T.; Itzhak, N. J. Chem. Soc., Perkin
Trans. 1 1986, 13. (f) Colvin, E. W.; Kirby, G. W.; Wilson, A. C.
Tetrahedron Lett. 1982, 23, 3835.
(13) Popp, F. D.; McEwen, W. E. Chem. ReV. 1958, 58, 321.
(14) Indeed, benzophenone oxime O-tosylate was also prepared, but its
reaction with alcohol anions did not lead to O-alkyloxime ethers.
(4) Tamura, Y.; Fujiwara, H.; Sumoto, K.; Ikeda, M.; Kita, Y. Synthesis
1973, 215.
10.1021/jo061900m CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/21/2006
658
J. Org. Chem. 2007, 72, 658-661

proceeded much more slowly, requiring 50-55 °C, and led to
ether 6b after 7 h in a 60% isolated yield. There was no
significant improvement in the yield after 14 h, and the major
side product detected after 14 h was fluorenone oxime.
Surprisingly, even the primary alcohol, n-butanol, reacted very
slowly with 5a at room temperature and required heating to
50-60 °C to provide ether 6c in 65% yield after 24 h (60%
calculated by HPLC integrations).15 There was no improvement
in yield after 48 h of reaction time. In all reactions, fluorenone
oxime was a byproduct.
Since reaction of some of the alcohols with tosylate 5a
required heating, we were searching for a more reactive substrate
that could be employed at room temperature. To this end, we
examined fluorenone oxime mesylate 5b17 and fluorenone oxime
triflate 5c18 as O-amination substrates. The triflate 5c reacted
with the Na derivative of cyclopentanol at room temperature
but furnished mainly fluorenone oxime, apparently by competi-
tive attack at the sulfonyl group. The mesylate 5b proved to be
the most desirable substrate, reacting with most alcohols at room
temperature to produce oxime ethers, 6, with negligible forma-
tion of free oxime. Excess NaH should be avoided, as it reacts
slowly with 5b to form fluorenone.19
Isolation of the Na (or K) salt 4a prepared from fluorenone
and hydroxylamine-O-sulfonic acid (HOS) proved impractical
because of its high solubility in water and the difficulty to
remove excess HOS from the product. Hence, we prepared the
tetrabutylammonium salt 4b by reaction of HOS, fluorenone,
and tetrabutylammonium hydroxide in a 3:1:2.25 ratio in
methanol-water. Reaction of 4b with the sodium salts of several
alcohols (EtOH, BnOH, cyclopentanol) led to the consumption
of the oxime sulfonate, but negligible amounts of O-aminated
products, 6, were detected; their presence was only confirmed
by mass spectra. In order to avoid the presence of the negatively
charged sulfonate group, as in 4, we prepared the neutral
fluorenone oxime O-tosylate 5a (85% yield). The oxime tosylate
5a was a stable solid, unaffected by 0.5 M HCl or 0.5 M NaOH
at room temperature for 48 h.
Preliminary studies with 5a were encouraging; heterogeneous
reaction of oxime tosylate 5a15 with sodium benzyloxide, formed
in situ from the alcohol and NaH in THF, led to O-amination
with the formation of fluorenone oxime-O-alkyl ether, 6a, at
over an 80% yield at room temperature.16 Lithium alcoholate
gave slightly lower yield, and there was slight improvement in
yield when THF-HMPA (1:1) or THF-DMSO (1:1) was used
as the solvent. Following the reaction by HPLC initially proved
to be advantageous. The disappearance of the starting oxime
tosylate 5a and the appearance of oxime ether 6a, as well as of
fluorenone oxime (the latter resulting from an attack of the
alcoholate on the tosyl group), were monitored. Optimum
reactant conditions for the reaction of oxime tosylate 5a with
benzyl alcohol were established as ROH:5a:NaH ) 1:2:2 in a
minimum of dry THF in a heterogeneous phase at room
temperature. The reaction with benzyl alcohol was allowed to
proceed for 6.5-7 h at room temperature and led to a 80%
yield of benzyl ether 6a, based on the alcohol as a limiting
reagent and determined by HPLC integrations. The actual
isolation of benzyl ether 6a by column chromatography provided
the compound in 84% yield. Thus, HPLC integration yields,
despite the fact that the reaction was heterogeneous, are fairly
representative of isolated yields. Theoretically possible double-
amination products such as 7, resulting from further addition
of the alcoholate to the NdC, were not observed. Neither was
a Beckmann rearrangement product.
Table 1 records a few examples of O-amination of alcoho-
lates, formed by treatment of each alcohol with 1.1 equiv of
NaH in THF for 30 min and then allowing them to react with
1.1 equiv of mesylate 5b in THF at 25 °C. The reactions of
some representative primary and secondary alcohols were
followed by TLC and stopped after disappearance of 5b. The
products 6, isolated after evaporation, acidification, and chro-
matography, were pure by NMR. Alcohol 9 was chosen because
its visually detectable chromophore can be useful as a universal
standard reagent.20
The general trend that emerges from our studies is that
secondary alcohols react much more slowly than primary
alcohols, and tertiary butanol did not react under these condi-
tions, which is expected for steric reasons. The presence of an
aromatic substituent, as in benzyl alcohol, as well as that of an
The structure of 6a was established by 1H and 13C NMR and
by mass spectra. In order to prove that no Beckmann rearrange-
ment to 8 (an isomer of 6a) had taken place, the structure of 6a
was verified by its independent synthesis from fluorenone and
O-benzylhydroxylamine.
However, when tosylate displacement on 5a was carried out
with a secondary alcohol, namely, cyclopentanol, the reaction
(17) Shirai, M.; Tsunooka, M. J. Photopolym. Sci. Technol. 1990, 3, 301.
(18) Okamura, H.; Sakai, K.; Tsunooka, M.; Shirai, M. J. Photopolym.
Sci. Technol. 2003, 16, 701.
(19) While 5a or 5c reacted slowly with NaH in THF in the absence of
alcohol to produce fluorenone oxime, 5b was converted after 12 h to
fluorenone (40%), apparently by hydride attack on N.
(20) For the application of analogous chromophores as universal standard
reagents, see: Patchornik, A.; Hassner, A.; Kramer, M.; Gottlieb, H. E.;
Cojocaru, M. Heterocycles 1999, 51, 1243.
(15) Shirai, M.; Kawaue, A.; Okamura, H.; Tsunooka, M. Chem. Mater.
2003, 15, 4075.
(16) Unlike in the reaction with n-butanol, the yield of benzyl alcohol
amination product 6a was not much improved when the reaction was carried
out at 50 °C.
J. Org. Chem, Vol. 72, No. 2, 2007 659

TABLE 1. Relative Yields of O-Amination Products 6 by Reaction
of 5 with ROH and NaH at Room Temperature
40% in water). After stirring the slurry for 15 min at room
temperature, solvent was removed under reduced pressure, water
was added, and the solid precipitate was filtered and washed with
tert-butyl methyl ether to give 1.28 g (75%) of tetrabutylammonium
1
9-fluorenone oxime-O-sulfate (5) (solid, mp 133 °C). H NMR
δH: 8.45-7.85 (m, 2H), 7.55-7.40 (m, 6H), 3.41-3.20 (m, 8H),
1.50-1.32 (m, 16H), 0.96-0.85 (m, 12H). 13C NMR δC: 153.9,
141.3, 140.4, 135.2, 131.2, 130.3, 130.2, 128.0, 127.6, 122.6, 119.6,
119.6, 109.0, 58.1, 23.6, 19.4, 13.4. LRMS (EI) m/z (%): 274
(MH+) (100). FAB+ m/z (%): 242 (MH+) (100).
General Procedure for Formation of Oxime Ethers, 6 (Table
1), from Corresponding Alcohols and 5b, with Fluoren-9-one
O-Benzyl Oxime (6a) as an Example. Benzyl alcohol (0.22 g, 2
mmol) and NaH (0.08 g, 2 mmol, 60% in mineral oil) were stirred
in dry THF (15 mL) for 30 min at room temperature. The solution
of fluoren-9-one O-methanesulfonyl oxime 5b, mp 150 °C (0.55
g, 2 mmol) in THF (30 mL), was added to the reaction mixture
and stirred for 3 h at room temperature. The reaction was followed
by TLC. Solvent was evaporated under reduced pressure, and the
residue was extracted with ethyl acetate (50 mL), washed with
water, and dried (Na2SO4). Oxime ether 6a was purified by silica-
gel column chromatography (eluant 1:20 ethyl acetate in n-hexane)
(yield 0.51 g, 90%, mp 55 °C). 1H NMR δH: 8.40-8.37 (m, 1H),
7.89-7.85 (m, 1H), 7.68-7.57 (m, 4H), 7.47-7.39 (m, 5H), 7.35-
7.33 (m, 2H), 5.54 (s, 2H, CH2O). 13C NMR δC: 152.5, 141.3,
140.2, 137.5, 135.6, 130.9, 130.6, 129.8, 129.3, 128.5, 128.4, 128.4,
128.1, 128.1, 128.0, 127.8, 121.7, 119.9, 119.8, 77.8. LRMS (CI,
CH4) m/z (%): 286 (MH+) (100). HRMS m/z: calcd for C20H15-
NO, 285.115; found, 286.125 (MH+). Anal. Calcd for C20H15NO:
C, 84.19; H, 5.30; N, 4.91. Found: C, 84.25; H, 5.33; N, 4.81.
The identical product (6a) was obtained in 95% yield by reaction
of 180 mg of 9-fluorenone with 285 mg (1.8 equiv) of O-
benzylhydroxylamine hydrochloride in EtOH-water and NaOH.
Fluoren-9-one O-Cyclopentyl Oxime (6b). 1H NMR δH: 8.37-
8.32 (m, 1H), 7.85-7.78 (m, 1H), 7.68-7.62 (m, 4H), 7.34-7.28
(m, 2H), 5.04-4.93 (m, 1H, CH-O), 2.15-1.65 (m, 8H). 13C NMR
δC: 151.7, 141.1, 139.9, 135.7, 130.5, 129.8, 129.4, 128.8, 128.0,
127.6, 121.4, 119.7, 119.6, 87.1, 32.3, 32.3, 23.8, 23.8. LRMS (CI,
CH4) m/z (%): 264 (MH+) (100), 196 (M-C5H8) (35). HRMS
m/z: calcd for C18H17NO, 264.138; found, 264.138.
a Heating at 55 °C.
olefinic double bond, as in allyl alcohol or 3-butene-1-ol, appears
to enhance the reactivity compared to that in the presence of
n-butanol, but acetylenic alcohols are slower to react. An
R-carbethoxy group, as in lactate, does not interfere. Since
cyclopentanol required heating even with mesylate 5b, we also
examined its reaction with the mesylate of 5,7-dinitrofluoren-
9-one oxime, which was expected to involve a more stable
fluorene anion intermediate, but the reaction was less clean and
led to a mixture of products. Finally, we showed that hydrolysis
of the oxime ethers proceeds well upon heating with 6 N HCl
in acetic acid to provide O-alkylhydroxylamines; for example,
O-benzylhydroxylamine was isolated in 60% yield as its
hydrochloride, and O-allylhydroxylamine was isolated in 65%
yield.
1
Fluoren-9-one O-Butyl Oxime (6c). H NMR δH: 8.20-8.17
(m, 1H), 7.68-7.65 (m, 1H), 7.67-7.47 (m, 2H), 7.29-7.15 (m,
4H), 4.31 (t, J ) 7 Hz, 2H, O-CH2CH2), 1.78-1.69 (m, 2H), 1.45
(m, 2H), 0.90 (t, J ) 7 Hz, 3H, CH2CH3). 13C NMR δC: 159.1,
141.2, 140.1, 135.7, 130.7, 130.3, 129.6, 129.1, 128.1, 127.8, 121.5,
119.8, 119.7, 75.7, 31.3, 19.2, 13.9. LRMS (CI, NH3) m/z (%):
252 (MH+) (100). HRMS m/z: calcd for C17H17NO, 251.131; found,
251.131.
In conclusion, we have shown that O-amination of aliphatic
alcohol anions is possible by using the electrophilic N reagents
5a or, preferably, 5b to produce oxime ethers, 6, which can be
hydrolyzed to O-alkylhydroxylamines. Such O-aminations might
prove of interest in enzyme inhibition studies.
Fluoren-9-one O-Heptyl Oxime (6d). 1H NMR δH: 8.38-8.30
(m, 1H), 7.75-7.71 (m, 1H), 7.60-7.51 (m, 2H), 7.45-7.30 (m,
4H), 4.40 (t, J ) 7 Hz, 2H, O-CH2CH2), 1.85-1.78 (m, 2H),
1.60-1.21 (m, 10H), 0.9 (t, J ) 7 Hz, 3H, CH2CH3). 13C NMR
δC: 151.7, 141.2, 140.0, 135.7, 130.6, 129.5, 129.0, 128.0, 127.76,
121.4, 119.7, 119.7, 76.0, 31.8, 29.2, 29.1, 26.0, 22.6, 14.0. LRMS
(CI, NH3) m/z (%): 294 (MH+) (100). HRMS m/z: calcd for C20H30-
NO, 293.178; found, 294.185 (MH+).
Experimental Section
General. All of the solvents were dried according to standard
procedures. All of the fine chemicals were commercial and were
used as such without further purification. NMR spectra were
recorded on a 300 MHz instrument in CDCl3 (unless otherwise
stated), and chemical shifts are reported relative to TMS. Mass
spectra were recorded on a Finnigan 4021 spectrometer. All new
compounds, except where melting points are given, were isolated
as oils. Flash chromatography was carried out on silica gel (60H).
HPLC was performed using a UV detector set at 256 nm with a
flow rate of 1 mL/min. HPLC separations were carried out on a
C-18 column, using elution with a 3:7 water/acetonitrile solution.
Melting points were determined in an open capillary.
1
Fluoren-9-one O-Allyl Oxime (6e). H NMR δH: 8.27-8.25
(m, 1H), 7.74-7.71 (m, 1H), 7.57-7.48 (m, 2H), 7.34-7.17 (m,
4H), 6.21-6.13 (m, 1H, CHdCH2), 5.43-5.24 (m, 2H, CHdCH2),
4.88-4.86 (m, 2H, OCH2). 13C NMR δC: 152.3, 141.3, 140.2,
135.6, 134.6, 133.9, 130.9, 129.8, 129.3, 128.1, 127.8, 121.6, 119.9,
119.8, 118.0, 76.6. HRMS m/z: calcd for C16H13NO, 235.100;
found, 235.100 (M+) (100).
Fluoren-9-one O-{2-[4-(2,4-Dinitrophenyl)piperazin-1-yl]-
ethyl} Oxime (6g). Solid, mp 57 °C. 1H NMR δH: 8.72-8.65 (m,
1H), 8.01-8.3 (m, 2H), 7.71-7.60 (m, 3H), 7.42-7.30 (m, 4H),
7.10-7.02 (m, 1H), 4.61-4.55 (m, 2H), 3.41-3.30 (m, 4H), 2.95-
2.75 (m, 6H). 13C NMR δC: 152.4, 149.2, 141.3, 140.1, 138.1,
Tetrabutylammonium 9-Fluorenone Oxime-O-sulfate (4b). To
a stirred solution of 9-fluorenone (0.60 g, 3.3 mmol) in methanol
(4 mL) were added hydroxylamine-O-sulfonic acid (HOS) (1.025
g, 9 mmol) and tetrabutylammonium hydroxide (4.5 mL, 6.8 mmol,
660 J. Org. Chem., Vol. 72, No. 2, 2007

137.9, 135.4, 131.0, 130.4, 129.9, 129.0, 128.1, 127.9, 123.7, 121.5,
119.9, 119.1, 73.5, 56.8, 52.7, 50.6. MS (CI, CH4) m/z (%): 474
(MH+) (9), 444 (M-NO) (5), 180 (M-C13H8N) (100). HRMS
m/z: calcd for C25H23N5O5, 474.170; found, 474.168.
129.7, 128.3, 127.8, 121.9, 119.9, 119.8, 79.1, 61.0, 17.3, 14.2.
HRMS (CI, CH4) m/z (%): calcd for C18H17NO3, 295.129; found,
295.129 (M+) (100), 296.139 (M++1) (50), 222.091 (M+-CO2-
Et) (40).
Fluoren-9-one O-But-3-ynyl Oxime (6h). 1H NMR δH: 8.36-
8.33 (m, 1H), 7.80-7.77 (m, 1H), 7.67-7.60 (m, 2H), 7.44-7.29
(m, 4H), 4.54 (t, J ) 7 Hz, 2H), 4.25 (s, 1H), 2.83-2.77 (m, 2H).
13C NMR δC: 152.7, 141.4, 140.3, 135.5, 131.0, 130.9, 129.9,
129.4, 128.2, 127.8, 121.7, 119.9, 119.8, 80.8, 73.2, 63.8, 19.5.
HRMS (CI, CH4) m/z (%): calcd for C17H13NO, 247.100; found,
247.102 (M+) (49), 248.113 (M++1) (16), 217.071 (M+-NO)
(100).
2-[4-(2,4-Dinitrophenyl)piperazin-1-yl] Ethanol (9). To a
stirred solution of 1-(2-hydroxyethyl)piperazine (0.70 g, 5.4 mmol)
in dichloromethane (4 mL) was added 2,4-dinitrofluorobenzene (0.3
mL, 2.36 mmol). After 15 min, the solvent was evaporated under
reduced pressure. The residue was dissolved in ethyl acetate, washed
with aqueous K2CO3 and water, and dried (MgSO4). Removal of
1
solvent gave 0.67 g (97%) of product, mp 92 °C. H NMR δH:
8.5-8.6 (m, 1H), 8.23-8.26 (m, 1H), 6.93-7.10 (m, 1H), 3.53-
3.70 (m, 2H), 3.41-3.30 (m, 4H), 2.82-2.7 (m, 4H), 2.65-2.63
(m, 2H). 13C NMR δC: 149.2, 138.4, 138.2, 128.2, 123.6, 119.3,
57.8, 52.4, 59.2, 50.6. LRMS (CI, NH3) m/z (%): 297 (M) (100),
267 (M-NO) (70), 237 (M-2NO) (35). HRMS m/z: calcd for
C12H16N4O5, 297.119; found, 297.113 (M+) (65).
Fluoren-9-one O-Pent-2-ynyl Oxime (6i). 1H NMR δH: 8.39-
8.36 (m, 1H), 7.85-7.82 (m, 1H), 7.64-7.58 (m, 2H), 7.46-7.27
(m, 4H), 4.05 (s, 2H), 2.33 (q, J ) 7 Hz, 2H), 1.23 (t, J ) 7 Hz,
3H). 13C NMR δC: 152.8, 141.4, 140.3, 135.5, 131.0, 130.6, 129.9,
129.6, 128.2, 127.8, 121.9, 119.9, 119.8, 89.2, 75.1, 64.0, 13.7,
12.7. HRMS (CI, CH4) m/z (%): calcd for C18H15NO, 261.115;
found, 261.114 (M+) (100), 262.126 (M++1) (36).
Hydrolysis of Oxime Ethers 6a and 6e. To a solution of oxime
ether (1 mmol) in 30 mL of hot glacial AcOH was added 6 N HCl
(2 mL), and heating continued for 24 h. The solvent was removed
under reduced pressure, and benzene was added to remove
fluorenone and unreacted oxime ether. The solid was crystallized
from EtOH to yield 60-65% of the corresponding O-alkylhydroxyl-
amine hydrochloride salt, identical to the authentic material by NMR
and mp.
Fluoren-9-one O-(1-Methylallyl) Oxime (6j). 1H NMR δH: 8.37
(d, J ) 7.5 Hz, 1H), 7.69-7.63 (m, 2H), 7.50-7.27 (m, 5H), 6.21-
6.09 (m, 1H, O-CH), 5.43 (d, J ) 17 Hz, 1H), 5.28 (d, J ) 10
Hz, 1H), 5.09-5.01 (m, 1H), 1.56 (d, J ) 6 Hz, 3H). 13C NMR
δC: 152.0, 141.4, 140.2, 139.3, 130.8, 130.7, 129.7, 129.4, 129.3,
128.2, 127.8, 121.7, 119.9, 119.8, 116.0, 81.6, 19.8. HRMS (CI,
CH4) m/z (%): calcd for C17H15NO, 249.115; found, 249.116 (M+)
(100), 250.123 (M++1) (74), 219.110 (M+-NO) (61).
2-(Fluoren-9-ylidene aminooxy) Propionic Acid Ethyl Ester
(6k). 1H NMR δH: 8.44-8.41 (m, 1H), 7.78-7.75 (m, 1H), 7.64-
7.58 (m, 2H), 7.43-7.27 (m, 4H), 5.05 (q, J ) 6 Hz, 1H), 4.30 (q,
Acknowledgment. Support of this research by the Marcus
Center for Medicinal and Pharmaceutical Chemistry at Bar-Ilan
University is gratefully acknowledged.
J ) 7 Hz, 2H), 1.73 (d, J ) 6 Hz, 3H), 1.32 (d, J ) 7 Hz, 3H). 13
C
NMR δC: 172.2, 153.2, 141.5, 140.4, 135.4, 131.1, 130.5, 130.1,
JO061900M
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