N-silyloxaziridines: Synthesis and use for electrophilic amination

Article abstract of DOI:10.1021/jo302182t

N-Silyloxaziridines were synthesized for the first time. Their tert-butyldiphenylsilyl (TBDPS) derivatives were stable reagents that were prepared on a multigram scale in three steps and in 44% overall yield from the corresponding benzylamines. They were mild electrophilic aminating reagents that reacted at room temperature with diversely substituted primary and secondary amines to produce N-monoalkyl or N,N-dialkyl benzaldehyde hydrazones in 44a-87% yield.

Full text of DOI:10.1021/jo302182t

Note
pubs.acs.org/joc
N‑Silyloxaziridines: Synthesis and Use for Electrophilic Amination
Nicolas Richy, Mohammed Ghoraf, and Joelle Vidal*
̈
Institut des Sciences Chimiques de Rennes, Universite
10A, Campus de Beaulieu, 35042 Rennes Cedex, France
́
de Rennes 1, CNRS-UMR 6226, Chimie et photonique molec
́
ulaires, Bat
̂
iment
S
* Supporting Information
ABSTRACT: N-Silyloxaziridines were synthesized for the first
time. Their tert-butyldiphenylsilyl (TBDPS) derivatives were stable
reagents that were prepared on a multigram scale in three steps and
in 44% overall yield from the corresponding benzylamines. They
were mild electrophilic aminating reagents that reacted at room
temperature with diversely substituted primary and secondary
amines to produce N-monoalkyl or N,N-dialkyl benzaldehyde
hydrazones in 44−87% yield.
Scheme 1. Synthesis of N-Silyloxaziridines 1
ecause of their three-membered strained heterocyclic ring
Band their weak N−O bond, oxaziridines possess unusual
reactivity1 that has been exploited in photochemical or thermal
rearrangements, catalyzed ring-opening,2 catalyzed asymmetric
oxyamination of olefins,3 and the widely investigated oxidation
(oxygen transfer) or amination (nitrogen transfer) of
nucleophiles.1 It has been established that the competition
between oxygen or nitrogen transfer depends on the nature of
the nucleophile and the substituents on the oxaziridine,
especially at the nitrogen atom. N-Sulfonyl-,4,5 N-perfluor-
oalkyl-,6 N-phosphinoyl-,7 N-tert-butyl-,8 and N-phosphonioox-
aziridines9 have been developed as efficient reagents for
oxidation reactions such as epoxidation of olefins, asymmetric
enolate hydroxylation, or oxidation of sulfide to sulfoxide. N-
Chloro-10 and N-methyloxaziridines8 are attacked at nitrogen
by amines to generate, respectively, tetrazines and air-sensitive
N-methylhydrazines. Electrophilic amination of amines, alco-
hols, and a wide range of sulfur and carbon nucleophiles is
performed by generally unstable N-H oxaziridines11,12 and
stable N-alkoxycarbonyl-13−18 and N-carboxamidooxaziri-
dines.19 Since aliphatic hydrazine derivatives are more difficult
to prepare than aromatic ones,20,21 the N−N bond formation
from N-H or N-alkoxycarbonyl oxaziridines and aliphatic
amines is particularly interesting. Lastly, calculations of the
transition state for aziridination of alkenes by diversely N-
substituted oxaziridines have shown concerted but highly
asynchronous nitrogen transfer and have predicted that hitherto
unknown N-silyloxaziridines would be the most favorable ones
for this reaction.22 As reagents for electrophilic amination are of
great interest in organic synthesis,23−25 we decided to prepare
N-silyloxaziridines in order to study their chemical properties.
We report here the first synthesis of N-silyloxaziridines 1
(Scheme 1) and their reactivity toward amines, thiols, and
alkenes. They are stable reagents that react under mild
conditions. In contrast with other aminating oxaziridines that
transfer their N-substituted group to nucleophiles, benzalde-
hyde hydrazones 9 or 10 instead of N-silylhydrazines are
produced in fair to very good yields from diversely substituted
primary and secondary amines.
Although silyl derivatives are very popular as protecting
groups, their use in amino group protection is mainly limited to
the bulky tert-butyldiphenylsilyl (TBDPS) group due to the
high acid and moisture sensitivity of N-silylamines.26−28 As
derivatization at the nitrogen of N-H oxaziridines by electro-
philic reagents has been reported,11,29 we attempted to
introduce the TBDPS group on the known N-H oxaziridines
330 in order to prepare 1. Oxaziridines 3 were too unstable to
be isolated from their solution and were generated from
benzaldehyde 2 and hydroxylamine-O-sulfonic acid in low
yields (18−21%, determined by iodometric titration) (Scheme
1).11 Unfortunately, treatment of crude 3 by chloro-tert-
butyldiphenylsilane at room temperature without additives or
in the presence of imidazole or DMAP resulted in complex
Received: October 4, 2012
Published: November 8, 2012
© 2012 American Chemical Society
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Table 1. Amination of Morpholine by N-Silyloxaziridines 1
a
entry
oxaziridine
solvent
reaction progress at rt (%), reaction time (h)
temp (°C)
time (h)
product
yield (%)
1
2
3
1a
1b
CHCl3
CHCl3
CH3CN
55, 21
68, 4
88, 4
20 then 45
30
15
15
7a
7b
7b
56
89
82
20
20
1b
a
1
Determined by H NMR integration of the morpholino signals in the reaction mixture (c = 0.5 mol L−1) at indicated reaction time.
mixtures. Subsequently, the synthesis of N-silyloxaziridines 1
was successful starting from N-TBDPS amines 5,31 which were
prepared in very good yields from the corresponding amines 4
(Scheme 1). According to Colvin’s method,32 N-chlorination of
N-TBDPS amines 5 by tert-butyl hypochlorite followed by
treatment with DBU afforded in 56−79% yields N-TBDPS
imines 6, which were moisture sensitive. Attempts to oxidize
imine 6a by anhydrous Li-m-CPBA, which was very efficient in
the synthesis of N-alkoxycarbonyl oxaziridines,13 did not supply
the desired oxaziridine 1a. Modification of Ruano’s conditions33
using a dry solution of m-CPBA in the presence of solid KOH
led within 1.5 h at 0 °C to oxaziridines 1a,b from N-TBDPS
imines 6. Purification of 1 by chromatography over silica gel
resulted in extensive decomposition, even in the presence of
triethylamine. We found that pretreatment of silica by
chlorotrimethylsilane followed by heating at 190 °C under
vacuum, minimized decomposition during flash chromatog-
raphy and so allowed purification of 1. Oxaziridines 1 were
obtained as solids on a multigram scale and in 66−82% yield
from 6. They were stable for several months when kept at 4 °C.
Their NMR spectra showed one characteristic heterocyclic CH
signal at ca 4.6 ppm (1H NMR) and ca. 75 ppm (13C NMR),
indicating the sole presence of the trans diasteromer due to the
bulky TBDPS substituent. The carbons of the TBDPS
diastereotopic phenyl groups displayed distinct signals in the
13C NMR spectrum. Oxaziridine 1b was quite stable in the
presence of moisture since 1H NMR monitoring of a mixture of
1b (c = 0.1 mol l−1) and water (3.5 equiv) in CDCl3/CD3CN
(5:2) showed only 10% decomposition after 14 days at room
temperature.
Table 2. Amination of Amines 8 by N-Silyloxaziridine 1b
Next, we studied the reactivity of oxaziridines 1 toward
morpholine as a model for amines (Table 1). The reaction was
1
monitored by H NMR using integration of the morpholino
signals. With oxaziridine 1a, the reaction was slow at room
temperature (55% progress after 21 h at room temperature)
and produced hydrazone 7a (56% isolated yield) and tert-
butyldiphenylsilanol34 (Table 1, entry 1). Moderate heating was
needed in order to complete the reaction. Reaction of
oxaziridine 1b was faster in similar conditions (Table 1, entry
2). The yield of hydrazone 7b was also higher (89%). An
increase in the rate of morpholine amination with an electron-
withdrawing substituent of the 3-phenyl group was also
observed in the case of N-alkoxycarbonyloxaziridines.13 The
use of a polar solvent such as acetonitrile increased the reaction
rate and had little influence on the yield in 7b (Table 1, entry
3).
a
Reaction was run at 45 °C for 72 h.
preferably chosen as the solvent, and the reaction was run
overnight at room temperature, except in the case of aniline
derivatives 8a and 8d which needed heating (entries 1 and 4).
In many cases (entries 1, 4, 8, and 9) hydrazones 9a, 9d, 9h,
and 9i were isolated as solids after crystallization in the
appropriate solvent. Extensive decomposition of hydrazone 9
was generally observed during purification by silica gel
chromatography and was minimized using basic alumina in
Reaction of aliphatic or aromatic amines 8 with the more
reactive oxaziridine 1b was then investigated and supplied
hydrazones 9 or 10, except in the case of the less basic
diphenylamine or imidazole which gave no reaction after
extended heating at 45 °C (Table 2). Acetonitrile was
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the case of N,N-disubstituted hydrazones 9b,c (entries 2 and
3). Instability of hydrazones 9e−g required further acylation of
the monosubstituted nitrogen (R2 = H) in order to isolate the
stable products 10e−g (entries 5−7). As the reaction did not
involve asymmetric centers, it provided access to chiral
enantiopure hydrazones 9b, 9c, and 9i (entries 2, 3, and 9)
from enantiopure amines 8b, 8c, and 8i. Yields in 4-
nitrobenzaldehyde hydrazones 9 or 10 were higher than that
of the corresponding cyclohexanone hydrazones obtained from
the unstable 3,3-pentamethyleneoxaziridine, which generally
reacted at higher temperature.11
Reaction of oxaziridine 1b with some other nucleophiles was
also studied. 4-Chlorothiophenol was aminated in mild
conditions to afford 4-nitrobenzylidene sulfenamide 11 in fair
yield due to decomposition during silica gel purification
(Scheme 2). We also tested the reaction of stilbene or
C1 for the transfer of the N-(alkoxycarbonyl) group to amines
producing 12 and 2 (Scheme 3).13 When R3 = TBDPS, the
increase of the reaction rate in a polar solvent or in the
presence of the aryl electron-withdrawing group of 1b (Table
1) still supports the proposal for TS or Int. As N-TBDPS
hydrazine 12 is not produced, concerted fragmentation of
transition state TS (reaction A) can be excluded. So, pathway B
conducting to intermediate Int can be examined. Intermediate
Int may be considered as an aza-analogue of the β-
hydroxysilane intermediate formed in the Peterson olefina-
tion35 (reaction from an α-silyl organometallic reagent and a
ketone). Its fragmentation follows a new pathway (C3)
producing hydrazone 9 because of the affinity of oxygen for
silicon,35 instead of pathway C1 postulated with N-
(alkoxycarbonyl)-13 or N-methyloxaziridines8 (hydrazine for-
mation, R3 = alkoxycarbonyl or methyl) or pathway C2
producing hydroxyl amine 14 which is obtained in the case of
N-sulfonyloxaziridines (R3 = sulfonyl).36
Scheme 2. Amination of 4-Chlorothiophenol by 1b
In conclusion, the first preparation of N-silyloxaziridine is
described in an efficient way. N-TBDPS oxaziridines 1a,b are
stable and mild aminating reagents that react at room
temperature with diversely substituted primary and secondary
amines to produce hydrazones 9 or 10 in 44−87% yield. This
new access to N-monoalkyl or N,N-dialkyl hydrazones 9 and
especially to enantiopure chiral ones, may stimulate develop-
ment of their very diverse reactivity.37,38 For instance,
hydrazones 9 may find applications in the synthesis of chiral
pyrazolidinones,39 may improve chemical diversity in the
reaction of 1,1-dialkylhydrazones with arynes40,41 or may be
used in the synthesis of 1,3,4-trisubstituted pyrazoles.42
dimethylmaleate with N-TBDPS oxaziridine 1b because
calculations have predicted that N-(trimethylsilyl)oxaziridines
would be good targets for alkene aziridination.22 Unfortunately,
no reaction occurred after 72 h at 50 °C (neat reagents),
perhaps because of the steric hindrance of the bulky TBDPS
group.
An N−N bond is created during reaction of 1 with amines,
but unlike the other N-substituted aminating oxaziridines,13 the
transfer of the silylated nitrogen of 1 to amines producing N-
TBDPS hydrazine 12 (R3 = TBDPS) was not observed
(Scheme 3, reaction A). As N-TBDPS hydrazine 12 might react
EXPERIMENTAL SECTION
■
4-Nitrobenzenemethanamine (4b). Prepared according to the
literature:43 mp 134−136 °C; H NMR (300 MHz, CDCl3) δ 1.42
1
Scheme 3. Plausible Mechanism for Amination of Amines
with Oxaziridines
(brs, 2H), 3.92 (s, 2H), 7.42 (d, 2H, J = 8.6 Hz), 8.11 (d, 2H, J = 8.6
Hz); 13C NMR (75 MHz, CDCl3) δ 45.7 (CH2), 123.7 (CH), 127.7
(CH), 146.9 (C), 150.5 (C).
N-[(1,1-Dimethylethyl)diphenylsilyl]benzenemethanamine
(5a). Prepared according to the literature:31 1H NMR (300 MHz,
CDCl3) δ 1.22 (s, 9H), 1.39 (br s, 1H), 4.12 (d, 2H, J = 7.7 Hz),
7.33−7.53 (m, 11H), 7.90 (m, 4H). 13C NMR (75 MHz, CDCl3) δ
18.6 (C), 27.5 (CH3), 46.7 (CH2), 126.5 (CH), 127.0 (CH), 127.6
(CH), 128.3 (CH), 129.2 (CH), 135.1 (C), 135.8 (CH), 143.7 (C).
N-[(1,1-Dimethylethyl)diphenylsilyl]-4-nitrobenzeneme-
thanamine (5b). 4-Nitrobenzenemethanamine (4b) (4.38 g, 28.7
mmol) in anhydrous acetonitrile (50 mL) was reacted under nitrogen
with triethylamine (6.1 mL, 43.4 mmol) and tert-butylchlorodiphe-
nylsilane (7.92 g, 28.8 mmol). After 15 h at room temperature and
filtration through Celite, the solution was concentrated. The resulting
solid was dissolved in a 4:1 mixture of n-pentane/AcOEt (200 mL)
and the organic phase was washed with aqueous 1 M NaHCO3, water,
then was dried over MgSO4, filtered, and concentrated. After
crystallization in n-hexane, N-[(1,1-dimethylethyl)diphenylsilyl]-4-
nitrobenzenemethanamine (5b) was obtained as a yellow solid (9.46
g, 84% yield): mp 74−76 °C; 1H NMR (300 MHz, CDCl3) δ 1.00 (s,
9H), 1.30 (brs, 1H), 3.98 (s, 2H), 7.26−7.33 (m, 8H,), 7.59−7.63 (m,
4H), 8.05 (d, 2H, J = 8.8 Hz); 13C NMR (75 MHz, CDCl3) δ 18.7
(C), 27.5 (CH3), 46.3 (CH2), 123.6 (CH), 127.5 (CH), 127.7 (CH),
129.5 (CH), 134.5 (C), 135.8 (CH), 146.7 (C), 151.4 (C). HRMS
(ESI) for C23H26N2O2SiNa [M + Na]+ calcd 413.1661, found
413.1640.
with the electrophilic benzaldehyde 2 to give hydrazone 9
(Scheme 3, reaction D), an authentic sample of tert-
butyldimethylsilylamino morpholine 13 was prepared32 in
order to check this hypothesis. The reaction of 13 at room
temperature with 1 equiv of 2b in anhydrous CDCl3 (c = 1 mol
1
L−1) was monitored by H NMR. As only 8% of 13 was
transformed after 8 days, the intermediary formation of N-
TBDPS hydrazine 12 during the reaction of amine and 1 was
ruled out.
In the case of N-(alkoxycarbonyl)oxaziridines, we formerly
proposed a mechanism postulating transition state TS or
intermediate Int (R3 = alkoxycarbonyl) and reactions A, B, and
N-[(1,1-Dimethylethyl)diphenylsilyl]benzaldimine (6a).
Under argon and at 0 °C, a solution of tert-butyl hypochlorite44 (2.0
g, 20 mmol) in anhydrous THF (5 mL) was added dropwise to N-
[(1,1-dimethylethyl)diphenylsilyl]benzenemethanamine (5a) (6.3 g,
18 mmol) in anhydrous THF (30 mL). After 2 h at 0 °C, the mixture
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was concentrated. The residue was dissolved in anhydrous ether (30
mL). Then, DBU (2.7 g, 18 mmol) in ether (3 mL) was added at 0 °C
under argon. The mixture was left at room temperature overnight,
filtered through anhydrous Celite, and concentrated. After Kugelrohr
distillation N-[(1,1-dimethylethyl)diphenylsilyl]benzaldimine (6a)
(3.52 g, 56% yield) was obtained as a pale yellow oil, which solidified
CH2Cl2 (0.5 mL) by acetyl chloride (19 μL, 0.26 mmol) and
anhydrous pyridine (22 μL, 0.26 mmol). After 1 h at 0 °C and 3 h at
room temperature, the mixture was diluted by CH2Cl2 (5 mL), washed
by 10% aqueous citric acid and by water, dried over Na2SO4, filtered,
concentrated, and purified.
N-(Benzylidene amino)morpholine (7a). From morpholine (45
μL, 0.51 mmol) and oxaziridine 1a (375 mg, 0.58 mmol) in CH2Cl2 (1
mL) at 45 °C for 30 h, the general procedure afforded hydrazone 7a as
an orange solid (51.1 mg, 56% yield) after chromatography over silica
gel (ether/n-pentane = 1:4): mp 91−92 °C (lit.11 mp 88−89 °C, lit.40
mp 90−91 °C); Rf (1:4 ether/ n-pentane) 0.13; 1H NMR (300 MHz,
CDCl3) δ 3.11 (t, 4H, J = 4.9 Hz), 3.83 (t, 4H, J = 4.9 Hz), 7.21−7.31
(m, 3H), 7.52−7.55 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 51.9
(CH2), 66.5 (CH2), 126.2 (CH), 128.4 (CH), 128.6 (CH), 135.9 (C),
136.3 (CH).
N-(4-Nitrobenzylideneamino)morpholine 7b. From morpho-
line (23 μL, 0.26 mmol) and oxaziridine 1b (107 mg, 0.27 mmol) in
CHCl3, the general procedure afforded hydrazone 7b as an orange
solid (55.3 mg, 89% yield) after chromatography over silica gel
(CH2Cl2/n-pentane = 2:3): mp 150−152 °C (lit.45 mp 149−151 °C);
Rf (2:3 CH2Cl2/n-pentane) 0.07; 1H NMR (300 MHz, CDCl3) δ 3.20
(t, 4H, J = 5.0 Hz), 3.83 (t, 4H, J = 5.0 Hz), 7.46 (s, 1H), 7.64 (d, 2H,
J = 9.0 Hz), 8.23 (d, 2H, J = 9.0 Hz); 13C NMR (75 MHz, CDCl3) δ
51.3 (CH2), 66.3 (CH2), 124.0 (CH), 126.2 (CH), 131.6 (CH) 142.4
(C) 147.0 (C). Anal. Calcd for C11H13N3O3: C, 56.16; H, 5.57; N,
17.86. Found: C, 56.10; H, 5.56; N, 17.62.
4-Nitrobenzaldehyde N-Methyl-N-phenylhydrazone (9a).
From N-methylaniline (27 μL, 0.25 mmol) and oxaziridine 1b (101
mg, 0.25 mmol) at 45 °C for 3 days, the general procedure afforded
hydrazone 9a as an orange solid (48.6 mg, 76% yield) after
crystallization in ether/n-pentane: mp 132−133 °C (lit.46 mp 133−
134 °C); 1H NMR (300 MHz, CDCl3) δ 3.50 (s, 3H), 7.03 (t, 1H, J =
6.7 Hz),7.35−7.43 (m, 4H), 7.48 (s, 1H), 7.80 (d, 2H, J = 8.9 Hz),
8.23 (d, 2H, J = 8.9 Hz); 13C NMR (75 MHz, CDCl3) δ 33.7 (CH3),
116.0 (CH), 122.0 (CH), 124.1 (CH), 126.0 (CH), 128.7 (CH),
129.2 (CH), 143.2 (C), 146.5 (C), 147.2 (C). Anal. Calcd for
C14H13N3O2, 0.25 H2O: C, 64.73; H, 5.24; N, 16.18. Found: C, 64.44;
H, 5.12; N, 16.17.
1
on standing: mp 52−56 °C; Eb = 135−140 °C (p = 0.1 mbar); H
NMR (300 MHz, CDCl3) δ 1.08 (s, 9H), 7.28−7.41 (m, 10H), 7.57−
7.61 (m, 3H), 7.78−7.82 (m, 2H), 8.78 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 18.9 (C), 27.3 (CH3), 127.6 (CH), 128.5 (CH), 128.7
(CH), 129.4 (CH), 131.5 (CH), 133.7 (C), 136.0 (CH), 138.9 (C),
171.3 (CH); HRMS (ESI) for C23H25NSiNa [M + Na]+ calcd
366.1654, found 366.1655.
N-[(1,1-Dimethylethyl)diphenylsilyl]-4-nitrobenzaldimine
(6b). Under argon and at 0 °C, a solution of tert-butylhypochlorite44
(2.72 g, 25.1 mmol) in anhydrous CHCl3 (4 mL) was added dropwise
to N-[(1,1-dimethylethyl)diphenylsilyl]-4-nitrobenzenemethanamine
(5b) (6.50 g, 16.6 mmol) in anhydrous CHCl3 (25 mL). After 3 h
at 0 °C, the mixture was concentrated. The residue was dissolved in
anhydrous ether (30 mL) and reacted at 0 °C with DBU (3.2 mL, 21.4
mmol) under argon. The mixture was left at room temperature
overnight, filtered, and concentrated. The resulting residue was
recrystallized under argon from anhydrous boiling cyclohexane to
afford N-[(1,1-dimethylethyl)diphenylsilyl]-4-nitrobenzaldimine (6b)
1
(5.11 g, 79% yield) as a yellow solid: mp 96−97 °C; H NMR (300
MHz, CDCl3) δ 1.10 (s, 9H), 7.30−7.38 (m, 6H), 7.55−7.58 (m, 4H),
7.94 (d, 2H, J = 8.8 Hz), 8.23 (d, 2H, J = 8.8 Hz), 8.81 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 18.9 (C), 27.3 (CH3), 123.9 (CH), 127.8
(CH), 129.3 (CH), 129.8 (CH), 132.8 (C), 136.0 (CH), 143.2 (C),
149.5 (C), 168.8 (CH); HRMS (EI) for C19H15N2O2Si [M − t-Bu]+
calcd 331.0903, found 331.0930.
N-[(1,1-Dimethylethyl)diphenylsilyl]-3(4-nitrophenyl)-
oxaziridine (1b). To a freshly prepared m-CPBA solution in CH2Cl2
(0.45 M, 27 mL, 12.1 mmol, dried over MgSO4 and then filtered)13
under argon were added at 0 °C KOH (2.16 g, 38.5 mmol) and a
solution of N-[(1,1-dimethylethyl)diphenylsilyl]-4-nitrobenzaldimine
(6b) (4.28 g, 11.02 mmol) in anhydrous CH2Cl2 (5 mL). The slurry
was stirred for 1.5 h at 0 °C and then filtered through Celite. After
concentration in vacuo, the residue was divided in four fractions.
Before chromatography, silica gel (25 g) in petroleum ether (50 mL)
was reacted with TMSCl (2.7 g) for 30 min. The solvent was removed
in vacuo, and the silanized silica was heated at 190 °C for 2 h under
vacuum (0.1 mbar). Each fraction was purified by flash chromatog-
raphy under nitrogen over silanized silica gel (25 g, anhydrous
CH2Cl2/n-pentane = 2:3). N-[(1,1-Dimethylethyl)diphenylsilyl]-3(4-
nitrophenyl)oxaziridine (1b) (2.92 g, 66% yield) was obtained as a
pale yellow solid: mp 79−80 °C; Rf (2:3 CH2Cl2/n-pentane) 0.40; 1H
NMR (300 MHz, CDCl3) δ 1.15 (s, 9H), 4.57 (s, 1H), 7.37−7.53 (m,
6H), 7.62−7.67 (m, 4H), 7.74 (d, 2H, J = 8.1 Hz), 8.23 (d, 2H, J = 8.1
Hz); 13C NMR (75 MHz, CDCl3) δ 19.4 (C), 27.5 (CH3), 74.4 (CH),
123.6 (CH), 127.8 and 128.0 (CH), 128.8 (CH), 129.9 and 130.2 (C),
130.4 and 130.5 (CH), 136.1 and 136.2 (CH), 143.3 (C), 149.0 (C);
HRMS (ESI) for C23H24N2O3SiNa [M + Na]+ calcd 427.1454, found
427.1456. Anal. Calcd for C23H24N2O3Si: C, 68.29; H, 5.98. Found: C,
68.50; H, 6.12.
(2S)-N-(4-Nitrobenzylideneamino)-2-methoxymethylpyrroli-
dine (9b). From 2(S)-(methoxymethyl)pyrrolidine (45 μL, 0.36
mmol) and oxaziridine 1b (158 mg, 0.39 mmol) in CH3CN, general
procedure afforded hydrazone 9b as an orange solid (42.73 mg, 45%
yield) after chromatography over basic alumina (CH2Cl2/n-pentane =
15:85): mp 78−79 °C; Rf (3:7 CH2Cl2/n-pentane) 0.17; [α]23
=
D
1
−231 (c = 0.6, CH2Cl2); H NMR (300 MHz, CDCl3) δ 1.91−2.13
(m, 4H), 3.16−3.23 (m, 1H), 3.41 (s, 3H), 3.41−3.43 (m, 1H), 3.48
(dd, J = 6.3 Hz, J = 9.3 Hz, 1H), 3.58 (dd, J = 3.6 Hz, J = 9.3 Hz, 1H),
3.75 (m, 1H), 7.09 (s, 1H), 7.61 (d, 2H, J = 8.9 Hz), 8.15 (d, 2H, J =
8.9 Hz); 13C NMR (75 MHz, CDCl3) δ 22.3 (CH2), 26.9 (CH2), 48.3
(CH2), 59.3 and 63.0 (CH or CH3), 74.3 (CH2), 124.1 (CH), 124.9
(CH), 127.4 (CH), 144.1 (C), 145.7 (C); HRMS (EI) for
C13H17N3O3 [M]+ calcd 263.1270, found 263.1253.
(1R-2S)-N-(4-Nitrobenzylideneamino)ephedrine (9c). From
(1R,2S)-ephedrine (57.8 mg, 0.35 mmol) and oxaziridine 1b (150
mg, 0.36 mmol) in CH3CN at rt overnight, the general procedure
afforded hydrazone 9c as a viscous oil after chromatography over basic
alumina (CH2Cl2/n-pentane = 1:1) (69.06 mg, 63% yield): Rf (1:1
CH2Cl2/n-pentane) 0.20; [α]23D = −165 (c = 0.5, CH2Cl2); 1H NMR
(300 MHz, CDCl3) δ 1.14 (d, 3H, J = 6.9 Hz, CH3), 2.86 (s, 3H), 3.51
(qd, 1H, J = 6.9 Hz, J = 3.7 Hz), 3.67 (brs, 1H), 5.08 (d, 1H, J = 3.7
Hz), 7.04 (s, 1H), 7.16−7.32 (m, 5H), 7.50 (d, 2H, J = 8.9 Hz), 8.09
(d, 2H, J = 8.9 Hz); 13C NMR (75 MHz, CDCl3) δ 11.8 (CH3), 37.6
(CH3), 68.2 (CH), 76.7 (CH), 124.2 (CH), 125.2 (CH), 126.2 (CH),
127.2 (CH), 127.5 (CH), 128.3 (CH), 141.7 (C),143.2 (C), 146.0
(C); HRMS (ESI) for C17H19N3O3Na [M + Na]+) calcd 336.1324,
found 336.1321.
N-[(1,1-Dimethylethyl)diphenylsilyl]-3-phenyloxaziridine
(1a). The same procedure as used for 1b afforded expected oxaziridine
1a (0.361 g, 82% yield) from N-[(1,1-dimethylethyl)diphenylsilyl]-
1
benzaldimine (6a) (0.419 g, 1.22 mmol): mp 74−77 °C; H NMR
(300 MHz, CDCl3) δ 1.28 (s, 9H), 4.67 (s, 1H), 7.40−7.55 (m, 11H),
7.72 (m, 2H), 7.80 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 19.4 (C),
27.5 (CH3), 75.9 (CH), 127.8 and 127.9 (CH), 128.4 (CH), 129.8
(CH), 130.1 and 130.2 (CH), 130.4 and 130.8 (C), 135.5 (CH), 136.0
(C), 136.2 and 136.3 (CH); HRMS (ESI) for C23H25NOSiNa [M +
Na]+ calcd 382.1603, found 382.1604.
General Procedure for Amination of Amines by Oxaziridine
1b. To a solution of oxaziridine 1b (101 mg, 0.25 mmol) in anhydrous
acetonitrile (0.5 mL) was added the amine (0.25 mmol). The mixture
was stirred overnight at room temperature and concentrated before
purification or acylation. The crude product was acylated at 0 °C in
4-Nitrobenzaldehyde N-Phenylhydrazone (9d). From aniline
(23 μL, 0.25 mmol) and oxaziridine 1b (104 mg, 0.26 mmol) in
CH3CN at 50 °C for 3 days, general procedure afforded hydrazone 9d
as a solid after crystallization in n-pentane/isopropyl oxide (17.8 mg,
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The Journal of Organic Chemistry
Note
44% yield): mp 148−151 °C (lit.47 mp 156−158 °C); 1H NMR (300
MHz, CDCl3) δ 6.96 (t, 1H, J = 7.3 Hz),7.16 (d, 2H, J = 8.6 Hz), 7.33
(t, 2H, J = 8.5 Hz), 7.71 (s, 1H), 7.78 (d, 2H, J = 8.9 Hz), 7.99 (brs,
1H), 8.23 (d, 2H, J = 8.9 Hz); 13C NMR (75 MHz, CDCl3) δ 113.1
(CH), 121.2 (CH), 124.1 (CH), 126.2 (CH), 129.4(CH), 133.8
(CH), 141.7 (C), 143.6 (C), 146.9 (C).
4-Nitrobenzaldehyde N-Acetyl-N-butylhydrazone (10e).
From n-butylamine (35 μL, 0.35 mmol) and oxaziridine 1b (149
mg, 0.37 mmol) in CH3CN at rt overnight and subsequent acetylation
with acetyl chloride (26 μL, 0.36 mmol) and pyridine (29 μL, 0.36
mmol), the general procedure afforded hydrazone 10e as a yellow solid
(40.5 mg, 43% yield) after chromatography over silica gel (CH2Cl2/n-
pentane = 1:1): mp 110−111 °C; Rf (1:1 CH2Cl2/n-pentane) 0.20; 1H
NMR (300 MHz, CDCl3) δ 0.90 (t, 3H, J = 7.2 Hz), 1.27−1.39 (m,
2H), 1.44−1.56 (m, 2H), 2.40 (s, 3H), 3.93 (t, 2H, J = 7.5 Hz, CH2),
7.63 (s), 7.75 (d, 2H, J = 8.9 Hz), 8.21 (d, 2H, J = 8.9 Hz); 13C NMR
(75 MHz, CDCl3) δ 13.8 (CH3), 20.2 (CH2), 21.8 (CH3), 27.5
(CH2), 40.1 (CH2), 124.1 (CH), 127.6 (CH), 135.0 (CH), 141.0 (C),
148.0 (C), 172.9 (C); HRMS (ESI) for C13H17N3O3Na [M + Na]+:
calcd 286.1168, found 286.1168.
1H NMR (300 MHz, CDCl3) δ 3.35−3.40 (m, 2H), 3.72 (s, 3H),
4.57−4.59 (q, 1H, J = 8 Hz), 6.17 (d, 1H, J = 8 Hz), 7.06 (d, 1H, J =
2.5 Hz), 7.14 (t, 1H, J = 8 Hz), 7.23 (t, 1H, J = 8 Hz), 7.38 (d, 1H, J =
8 Hz), 7.58−7.64 (m, 3H), 8.08 (br s, 1H), 8.17 (d, 2H, (d, 1H, J = 8.7
Hz); 13C NMR (75 MHz, CDCl3) δ 27.5 (CH2), 52.3 and 62.3 (CH
or CH3), 110.3 (C), 111.3 (CH), 118.6 (CH), 119.7 (CH), 122.3
(CH), 122.9 (CH), 123.9 (CH), 126.2 (CH), 127.5 (C), 136.2 (C),
136.3 (CH), 141.7 (C), 147.0 (C), 173.3 (C); Anal. Calcd for
C19H18N4O4, 0.25 H2O: C, 61.53; H, 5.03; N, 15.11. Found: C, 61.68;
H, 4.99; N, 14.71. HRMS (ESI) for C19H18N4O4Na [M + Na]+ calcd
389.1226, found 389.1224.
N-(4-Nitrobenzylidene)-4-chlorobenzenesulfenamide (11).
4-Chlorothiophenol (50.45 mg, 0.3495 mmol) and oxaziridine 1b
(151.1 mg, 0.374 mmol) were reacted overnight at room temperature
in anhydrous acetonitrile (0.8 mL). After chromatography over silica
gel (petroleum ether/CH2Cl2 = 4:1 to 0:1) N-(4-nitrobenzylidene)-4-
chlorobenzenesulfenamide (11) was afforded as a yellow solid (40.1
mg, 39% yield): mp 135−136 °C; Rf (petroleum ether/CH2Cl2 3:2)
0.41; 1H NMR (300 MHz, CDCl3) δ 7.44 (d, 2H, J = 8.7 Hz), 7.54 (d,
2H, J = 8.7 Hz), 7.84 (d, 2H, J = 8.7 Hz), 8.29 (d, 2H, J = 8.7 Hz),
8.53 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 124.1 (CH), 127.8
(CH), 128.6 (CH), 129.5 (CH), 133.8 (C), 134.7 (C), 141.1 (C),
148.5 (C), 154.0 (CH); HRMS (ESI) for C13H1035ClN2O2S [M + H]+
calcd 293.01515, found 293.0155.
N-(tert-Butyldimethylsilyl)aminomorpholine (13). According
to the literature procedure,32 a solution of N-aminomorpholine (1.02
g, 10 mmol), triethylamine (1.53 mL, 11 mmol), and DMAP (24.4 mg,
0.2 mmol) in anhydrous ether (7 mL) was reacted at 0 °C with tert-
butylchlorodimethylsilane (1.658 g, 11 mmol) in ether (5 mL). The
resulting mixture was stirred for 48 h at room temperature and then
filtered through anhydrous Celite. After distillation under vacuum, N-
(tert-butyldimethylsilyl)aminomorpholine (13) (1.43 g, 66% yield)
was afforded as a colorless liquid: Eb = 56−57 °C (p = 0.1 mbar); 1H
NMR (200 MHz, CDCl3) δ − 0.03 (s, 3H), 0.87 (s, 9H), 2.10 (br s,
1H), 2.47 (t, 4H, J = 5.4 Hz), 3.65 (t, 4H, J = 5.4 Hz); 13C NMR (50
MHz, CDCl3) δ − 5.2 (CH3), 17.5 (C), 26.5 (CH3), 61.2 (CH2), 67.1
(CH2).
4-Nitrobenzaldehyde N-Acetyl-N-cyclohexylhydrazone
(10f). From cyclohexylamine (40 μL, 0.35 mmol) and oxaziridine
1b (152 mg, 0.37 mmol) in CH3CN at rt overnight and subsequent
acetylation with acetyl chloride (26 μL, 0.36 mmol) and pyridine (29
μL, 0.36 mmol), the general procedure afforded hydrazone 10f as a
yellow solid (70.9 mg, 70% yield) after chromatography over silica gel
1
(CH2Cl2): mp 149−150 °C; Rf (CH2Cl2) 0.1; H NMR (300 MHz,
CDCl3) δ 1.11−1.39 (m, 3H), 1.65−1.69 (m, 3H), 1.81−1.85 (m,
2H), 2.13−2.27 (m, 2H), 2.35 (s, 3H), 4.22 (brs, 1H), 7.74 (d, 2H, J =
1
8.9 Hz), 7.95 (brs, 1H), 8.19 (d, 2H, J = 8.9 Hz, Ar); H NMR (300
MHz, DMSO, 45 °C) δ 1.19−1.46 (m, 3 H), 1.42−1.46 (m, 3H),
1.63−1.67 (m, 2H), 2.18−2.22 (m, 2H), 2.23 (s, 3H), 4.30 (m, 1H),
7.99 (d, 2H, J = 8.9 Hz), 8.28 (d, 2H, J = 8.9 Hz), 8.39 (s, 1H); 13C
NMR (125 MHz, CDCl3) δ 23.4 (CH3), 25.4 (CH2), 26.4 (CH2),
30.0 (CH2), 55.6 (br, CH), 124.1 (CH), 127.3 (CH), 135.3 (br, CH),
141.4 (C), 148.0 (C), 173.1 (br, C); HRMS (ESI) for C15H19N3O3Na
[M + Na]+ calcd 312.1324, found 312.1323. Anal. Calcd for
C15H19N3O3: C, 62.27; H, 6.62. Found: C, 62.07; H, 6.62.
4-Nitrobenzaldehyde N-Acetyl-N-tert-butylhydrazone (10g).
From tert-butylamine (37 μL, 0.35 mmol) and oxaziridine 1b (151 mg,
0.37 mmol) in CH3CN at rt overnight and subsequent acetylation with
acetylchloride (26 μL, 0.36 mmol) and pyridine (29 μL, 0.36 mmol),
the general procedure afforded hydrazone 10g as a yellow solid (40.5
mg, 44% yield) after chromatography over silica gel (CH2Cl2/n-
ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental methods and copies of 1H and 13C NMR
spectra for all prepared compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
pentane = 1:1 then CH2Cl2): mp 112−113 °C; Rf (CH2Cl2) 0.1; H
AUTHOR INFORMATION
Corresponding Author
*E-mail: joelle.vidal@univ-rennes1.fr.
Notes
NMR (300 MHz, CDCl3) δ 1.43 (s, 9H), 1.91 (s, 3H), 7.89 (d, 2H, J
= 8.8 Hz), 8.21 (s, 1H), 8.25 (d, 2H, J = 8.8 Hz); 13C NMR (75 MHz,
CDCl3) δ 25.1 (CH3), 28.8 (CH3), 61.5 (C), 124.2 (CH), 129.0
(CH), 138.6 (C), 149.6 (C), 162.2 (CH), 168.8 (C); HRMS (ESI) for
C13H17N3O3Na [M + Na]+ calcd 286.1168, found 286.1167.
■
The authors declare no competing financial interest.
4-Nitrobenzaldehyde N-Benzylhydrazone (9h). From benzyl-
amine (39 μL, 0.25 mmol) and oxaziridine 1b (151 mg, 0.36 mmol) in
CH3CN at rt overnight, the general procedure afforded hydrazone 9h
as an orange solid (34.7 mg) after filtration. Concentration of the
filtrate and crystallization in n-pentane afforded a second crop (44.2
ACKNOWLEDGMENTS
■
M.G. thanks the “Minister
de la Recherche” for financial support. Philippe Jeh
Fabian Lambert (CRMPO, Universite
̀
e de de l’Enseignement Super
an and
de Rennes 1) are
́
ieur et
́
mg, 87% total yield): mp 124−126 °C (lit.48 mp 131 °C); H NMR
1
́
(300 MHz, CDCl3) δ 4.51 (d, J = 4.9 Hz, 2H), 6.17 (br t, 1H), 7.34−
7.40 (m, 5H), 7.56 (s, 1H), 7.67 (d, 2H, J = 8.9 Hz), 8.20 (d, 2H, J =
8.9 Hz); 13C NMR (75 MHz, CDCl3) δ 52.9 (CH2), 124.0 (CH),
125.8 (CH), 127.9 (CH), 128.1 (CH), 128.9 (CH), 132.1 (CH),
137.1 (C), 142.6 (C), 146.6 (C); HRMS (EI) for C14H13N3O2 [M]+
calcd 255.1008, found 255.1033. Anal. Calcd for C14H13N3O2: C,
65.87; H, 5.13. Found: C, 66.18; H, 5.24.
acknowledged for mass spectra recording.
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