(Tosylimino)phenyl-λ3-iodane as a reagent for the synthesis of methyl carbamates via hofmann rearrangement of aromatic and aliphatic carboxamides

Article abstract of DOI:10.1021/jo300007c

A new, mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides using (tosylimino)phenyl-λ³-iodane, PhINTs, as a reagent is reported. Because of the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.

Full text of DOI:10.1021/jo300007c

Note
pubs.acs.org/joc
(Tosylimino)phenyl-λ3-iodane as a Reagent for the Synthesis of
Methyl Carbamates via Hofmann Rearrangement of Aromatic and
Aliphatic Carboxamides
Akira Yoshimura, Matthew W. Luedtke, and Viktor V. Zhdankin*
Department of Chemistry and Biochemistry, University of MinnesotaDuluth, Duluth, Minnesota 55812, United States
S
* Supporting Information
ABSTRACT: A new, mild procedure for the Hofmann rearrange-
ment of aromatic and aliphatic carboxamides using (tosylimino)-
phenyl-λ3-iodane, PhINTs, as a reagent is reported. Because of the
mild reaction conditions, this method is particularly useful for the
Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent
iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the
isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.
n recent years, hypervalent iodine compounds have emerged
as environmentally friendly and efficient oxidizing reagents
the reaction of p-toluamide 2a with (diacetoxyiodo)benzene,
PhI(OAc)2, gave a complex mixture of products, which,
according to NMR, contained only 71% of carbamate 4a.
Because of the mild reaction conditions and high selectivity in
the reaction of p-toluamide 2a with PhINTs, we were also able
to isolate the initially formed, labile, p-isocyanatotoluene 3a in
80% preparative yield.
I
for various synthetically useful oxidative transformations.1
Organohypervalent iodine(III) compounds are particularly
useful as the oxidants in Hofmann-type rearrangements,
which have been utilized in numerous synthetic works.2−5
The most common reagents for Hofmann-type rearrangements
include (diacetoxyiodo)benzene,2 [bis(trifluoroacetoxy)iodo]-
benzene,3 [hydroxy(tosyloxy)]iodobenzene,4 and their recycla-
ble analogues.5 All these reagents, however, are powerful
oxidants, incompatible with many functional groups and
substituted phenyl rings, such as phenol ethers. We decided
to investigate a milder oxidant, tosylimino-λ3-iodane, PhINTs,
as a potential reagent for Hofmann-type rearrangement of alkyl-
and arylcarboxamides. In recent years, PhINTs and other N-
tosyliminoiodanes, ArINTs, have found broad synthetic
application as useful reagents for the aziridination of alkenes
and the amidation reactions of various organic substrates.6
Herein, we wish to report the use of PhINTs as a mild reagent
for Hofmann rearrangement of aromatic and aliphatic
carboxamides to the respective isocyanates, which can be
subsequently trapped with methanol to afford respective
carbamates as the final isolable products. Because of the mild
reaction conditions, this method is particularly useful for the
Hofmann rearrangement of substituted benzamides, which
usually afford complex reaction mixtures in reactions with other
hypervalent iodine oxidants.2d,3b,4d,7
Using the optimized reaction conditions, we have inves-
tigated the conversion of various substituted benzamides and
alkylcarboxamides 2 to the respective carbamates 4 (Table 2).
In general, all aromatic substrates with either electron-donating
or electron-withdrawing substituents afforded products 4 in
good yields (entries 1−12). However, the reactions of
benzamides with a bulky ortho-substituent or with an
electron-withdrawing group in the phenyl ring required longer
time. In particular, the reaction of 2,4-dichlorobenzamide 4i
required 4 h and the use of 1.5 equiv of reagent 1 for
completion (entry 8). The most sterically hindered benzamide,
2,4,6-trimethylbenzamide, did not react with reagent 1 even
after 24 h of stirring at room temperature (entry 13). As
expected, various aliphatic amides, including benzylcarbox-
amides, primary, second, tertiary and cyclic alkylcarboxamides,
have also smoothly reacted with tosyliminoiodane 1 giving
respective carbamates 4 in excellent yields (entries 14−23).
Compared to the known methods of Hofmann rearrangement
of alkylcarboxamides using other hypervalent iodanes, our
method affords products 4 in similar yields, and the reaction is
compatible with different substituents.2c,d,7c
First, we have investigated the Hofmann rearrangement of p-
toluamide 2a using PhINTs 1 (1.2 equiv) at room temperature
in different solvents. The initially formed p-isocyanatotoluene
3a was subsequently converted to the respective carbamate 4a
by treatment with methanol for 4.5 h at room temperature; the
yields of product 4a under different reaction conditions are
shown in Table 1. Out of several solvents tested (Table 1), the
reaction in dichloromethane was found to give the best results,
affording 98% of carbamate 4a after 30 min of the initial
reaction (entry 7). For comparison, under similar conditions
The mild reactions conditions and high selectivity in the
reaction of carboxamides 2 with PhINTs allow the isolation of
the initially formed isocyanates 3 or subsequent conversion of
these highly reactive intermediates to other final stable
products. For example, the trapping of isocyanate 3a with 2-
propanol or 2-methyl-2-propanol instead of methanol afforded
Received: January 2, 2012
Published: February 3, 2012
© 2012 American Chemical Society
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Note
a
Table 1. Optimization of Hofmann Rearrangement with Iminoiodane 1.
b
entry
time (h)
solvent
yield of 4a (%)
1
2
3
4
5
6
7
1.5
1.5
1.5
1.5
1.5
1.5
0.5
0.5
MeCN
MeOH
CHCl3
AcOEt
THF
(2)
(39)
(53)
c
c
d
CH2Cl2
CH2Cl2
CH2Cl2
97 (100)
d
98 (100)
e
8
(71)
a
b
All reactions were performed using 1 equiv of p-toluamide 2a and 1.2 equiv of reagent 1 at room temperature. Numbers in parentheses show
c
d
yields determined from 1H NMR spectra of reaction mixture. No reaction. Yields of products isolated by preparative TLC.
e
(Diacetoxyiodo)benzene was used instead of reagent 1.
a
Table 2. Synthesis of Carbamates by Hofmann Rearrangement with Iminoiodane 1
a
b
All reactions were performed using 1 equiv of amide and 1.2 equiv of reagent 1 at room temperature unless noted otherwise. Isolated yields; the
yields shown in parentheses correspond to the literature2d data for the synthesis of carbamates 4 from carboxamides 2 using PhI(OAc)2 in KOH/
MeOH. 1.5 equiv of reagent 1 was used. No reaction.
c
d
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Note
a period of 12 h a yellow precipitate formed, which was then filtered,
washed with hexane and dichloromethane several times, and dried in
vacuo to give 528 mg (68%) of product 1, isolated as light yellow
solid: mp 103−103.7 °C dec (lit.8 mp 104−105 °C); IR (KBr) cm−1
3422, 3056, 2925, 1594, 1444, 1266, 1131, 1124, 1081, 866, 820, 742;
1H NMR (500 MHz, DMSO-d6) δ 7.69 (d, J = 7.8, 2H), 7.59−7.41
the respective carbamates 5a and 5b in good yields, and the
treatment of isocyanate 3a with 10% aqueous HCl followed by
basic workup gave p-toluidine 5c in 89% yield (Scheme 1).
Scheme 1. Conversion of p-Toluamide 2a to Carbamates
5a,b and p-Toluidine 5c
(m, 3H), 7.33−7.26 (m, 2H), 7.06 (d, J = 7.8, 2H), 2.27 (s, 3H).
General Procedure for Hofmann Rearrangement of Carbox-
amides 2 with Imino-λ3-iodane 1. N-(4-Methylphenylsulfonyl)-
iminophenyl-λ3-iodane 1 (34 mg, 0.090 mmol) was added to a
solution of carboxamide 2 (0.075 mmol) in dichloromethane (1.5 mL)
under stirring at room temperature. A change of the initially
heterogeneous mixture to a homogeneous solution was observed
after several minutes. The reaction mixture was stirred for 0.5−4 h
(see Table 2), methanol (1.52 mL) was added, and stirring was
continued for additional 4.5 h at room temperature. Then the reaction
mixture was concentrated and separated by preparative TLC (hexane−
ethyl acetate, 2: 1 or 3: 1) to afford analytically pure carbamates 4.
Methyl N-(4-Methylphenyl)carbamate (4a).9 Reaction of p-
toluamide 2a (10 mg, 0.075 mmol) according to the general procedure
afforded 12 mg (98%) of product 4a, isolated as colorless needles
(recrystallized from dichloromethane−hexane): mp 98.3−99 °C (lit.9
Based on the previously reported mechanistic studies of
Hofmann rearrangement using other hypervalent iodine
reagents,3a,b,4f we propose that the reaction starts from the
formation of amidoiodane 6 (Scheme 2). Subsequently, the
1
mp 97−99 °C); IR (KBr) cm−1 3328, 1704, 1599, 1538, 1231; H
Scheme 2. Proposed Reaction Mechanism
NMR (500 MHz, CDCl3) δ 7.26 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 8.5
Hz, 2H), 6.52 (br s, 1H), 3.77 (s, 3H), 2.30 (s, 3H).
Methyl N-(2-Methylphenyl)carbamate (4b).9 Reaction of o-
toluamide 2b (10 mg, 0.075 mmol) according to the general
procedure afforded 12 mg (97%) of product 4b, isolated as a colorless
oil: 1H NMR (500 MHz, CDCl3) δ 7.77 (brs, 1H), 7.21 (t, J = 7.5 Hz,
1H), 7.16 (d, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz, 2H), 6.38 (brs, 1H),
3.78 (s, 3H), 2.25 (s, 3H).
Methyl N-(3-Methylphenyl)carbamate (4c).10 Reaction of m-
toluamide 2c (10 mg, 0.075 mmol) according to the general procedure
afforded 12 mg (98%) of product 4c, isolated as colorless needles
(recrystallized from dichloromethane−hexane): mp 69−69.3 °C (lit.11
1
mp 70−72 °C); H NMR (500 MHz, CDCl3) δ 7.24−7.12 (m, 3H),
6.88 (d, J = 7 Hz, 1H), 6.57 (br s, 1H), 3.77 (s, 3H), 2.33 (s, 3H).
Methyl N-Phenylcarbamate (4d).12 Reaction of benzamide 2d
(9 mg, 0.075 mmol) according to the general procedure afforded 11
mg (96%) of product 4d, isolated as a white amorphous solid: IR
(KBr) 3314, 1702, 1604, 1546, 1237 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.38 (d, J = 8 Hz, 2H), 7.31 (t, J = 8 Hz, 2H), 7.07 (t, J = 8
Hz, 1H), 6.61 (br s, 1H), 3.78 (s, 3H).
reductive elimination of iodobenzene and the 1,2-alkyl or -aryl
shift to the electron-deficient nitrenium nitrogen atom in the
intermediate 7 afford isocyanate 3. Subsequent addition of an
alcohol to isocyanate 3 gives the final carbamate 4.
In summary, we have reported a new, mild procedure for the
Hofmann rearrangement of aromatic and aliphatic carbox-
amides using iminoiodane PhINTs as a reagent. Because of the
mild reaction conditions, this method is particularly useful for
the Hofmann rearrangement of substituted benzamides, which
usually afford complex reaction mixtures in the reactions with
other hypervalent iodine oxidants. The mild reaction conditions
and the high selectivity in the reaction of carboxamides with
PhINTs allow the isolation of the initially formed labile
isocyanates or their subsequent conversion to stable carbamates
by treatment with alcohols.
Methyl N-(4-Methoxyphenyl)carbamate (4e).12 Reaction of p-
methoxybenzamide 2e (11 mg, 0.075 mmol) according to the general
procedure afforded 12 mg (90%) of product 4e, isolated as colorless
needles (recrystallized from dichloromethane−hexane): mp 87.8−89.3
°C (lit.13 mp 88 °C); H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 9
1
Hz, 2H), 6.85 (d, J = 9 Hz, 2H), 6.45 (brs, 1H), 3.79 (s, 3H), 3.76 (s,
3H).
Methyl N-(3-Methoxyphenyl)carbamate (4f).14 Reaction of m-
methoxybenzamide 2f (11 mg, 0.075 mmol) according to the general
procedure afforded 13 mg (96%) of product 4f, isolated as a white
1
amorphous solid: H NMR (500 MHz, CDCl3) δ 7.19 (t, J = 7.8 Hz,
EXPERIMENTAL SECTION
1H), 7.12 (br s, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.62 (dd, J = 7.8, 2.5
Hz, 1H), 6.60 (b rs, 1H), 3.80 (s, 3H), 3.78 (s, 3H).
■
All reactions were performed under dry nitrogen atmosphere with
flame-dried glassware. All commercial reagents were ACS reagent
grade and used without further purification. Carboxamides 2 were
from commercial sources. Dichloromethane was distilled from CaH2
immediately prior to use. Diethyl ether was distilled from Na/
benzophenone. NMR spectra were recorded at 500 MHz (1H NMR)
and 125 MHz (13C NMR). Chemical shifts (δ) are reported in parts
per million and referenced relative to tetramethylsilane.
Methyl N-(4-Chlorophenyl)carbamate (4g).9 Reaction of p-
chlorobenzamide 2g (12 mg, 0.075 mmol) according to the general
procedure afforded 13 mg (94%) of product 4g, isolated as a colorless
needles (recrystallized from dichloromethane−hexane): mp 115.6−
116.1 °C (lit.9 mp 114−115 °C); IR (KBr) cm−1 3345, 1701, 1606,
1546, 1238, 1092; 1H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 8.8 Hz,
2H), 7.27 (d, J = 8.8 Hz, 2H), 6.59 (br s, 1H), 3.78 (s, 3H).
Methyl N-(2-Chlorophenyl)carbamate (4h).9 Reaction of o-
chlorobenzamide 2h (12 mg, 0.075 mmol) according to the general
procedure afforded 13 mg (94%) of product 4h, isolated as a colorless
oil; 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J = 8 Hz, 1H), 7.34 (d, J =
8 Hz, 1H), 7.27 (t, J = 8 Hz, 1H), 7.15 (br s, 1H), 6.99 (t, J = 8 Hz,
1H), 3.81 (s, 3H).
N-(4-Methylphenylsulfonyl)imino-phenyl-λ3-iodane (1).8 1-
Diacetoxy-phenyl-λ3-iodane (670 mg, 2.1 mmol) was added to a
stirred mixture of potassium hydroxide (292 mg, 2.1 mmol) and p-
toluenesulfonamide (356 mg, 5.2 mmol) in methanol (7.8 mL). The
resulting clear yellow solution was stirred for 2.5 h at 0 °C and 0.5 h at
room temperature and then poured into distilled water (49 mL). Over
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Note
Methyl N-(2,4-Dichlorophenyl)carbamate (4i).15 Reaction of
2,4-dichlorobenzamide 2i (14 mg, 0.075 mmol) according to the
general procedure afforded 13 mg (80%) of product 4i, isolated as
colorless needles (recrystallized from dichloromethane−hexane): mp
MHz, CDCl3) δ 4.46 (br s, 1H), 3.80 (m, 1H), 3.65 (s, 3H), 1.15 (d, J
= 6.5 Hz, 6H).
Methyl N-tert-Butylcarbamate (4u).21 Reaction of trimethyla-
cetamide 2u (15 mg, 0.15 mmol) according to the general procedure
67.6−68.3 °C (lit.15 mp 58−62 °C); H NMR (500 MHz, CDCl3) δ
1
1
afforded 14 mg (72%) of product 4u, isolated as a colorless oil: H
NMR (500 MHz, CDCl3) δ 4.60 (br s, 1H), 3.62 (s, 3H), 1.32 (s,
8.13 (d, J = 9 Hz, 1H), 7.36 (d, J = 3 Hz, 1H), 7.25 (dd, J = 9, 3 Hz,
1H), 7.09 (br s, 1H), 3.81 (s, 3H).
9H).
Methyl N-Cyclohexylcarbamate (4v).7c Reaction of cyclo-
hexanecarboxamide 2v (10 mg, 0.075 mmol) according to the general
procedure afforded 10 mg (85%) of product 4v, isolated as colorless
needles (recrystallized from dichloromethane−hexane): mp 74.6−75.2
°C (lit.7c mp 73.5−74.5 °C); IR (KBr) cm−1 3346, 2934, 1695, 1538,
Methyl N-(4-Bromophenyl)carbamate (4j).16 Reaction of p-
bromobenzamide 2j (15 mg, 0.075 mmol) according to the general
procedure afforded 17 mg (98%) of product 4j, isolated as a white
solid (recrystallized from dichloromethane−hexane: mp 125.1−125.7
°C; 1H NMR (500 MHz, CDCl3) δ 7.41 (d, J = 8.8 Hz, 2H), 7.28 (d, J
= 8.8 Hz, 2H), 6.58 (brs, 1H), 3.78 (s, 3H).
1
1229; H NMR (500 MHz, CDCl3): δ 4.53 (br s, 1H), 3.65 (s, 3H),
Methyl N-(4-Trifluoromethylphenyl)carbamate (4k).17 Reac-
tion of p-trifluoromethylbenzamide 2k (14 mg, 0.075 mmol)
according to the general procedure afforded 14 mg (85%) of product
4k, isolated as colorless needles (recrystallized from dichloro-
3.48 (br s, 1H), 1.98−1.86 (m, 2H), 1.75−1.65 (m, 2H), 1.64−1.56
(m, 1H), 1.40−1.28 (m, 2H), 1.22−1.06 (m, 3H).
Methyl N-(1-Adamantanyl)carbamate (4w).7c Reaction of 1-
adamantanecarboxamide 2w (13 mg, 0.075 mmol) according to the
general procedure afforded 13 mg (83%) of product 4w, isolated as
colorless needles (recrystallized from dichloromethane−hexane): mp
118.4−118.9 °C (lit.7c mp 118−120 °C); 1H NMR (500 MHz,
CDCl3) δ 4.51 (br s, 1H), 3.61 (s, 3H), 2.08 (s, 3H), 1.93 (s, 6H),
1.67 (s, 6H).
methane−hexane): mp 128.3−129 °C (lit.17 mp 129−130 °C); H
1
NMR (500 MHz, CDCl3) δ 7.57 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.5
Hz, 2H), 6.74 (br s, 1H), 3.80 (s, 3H).
Methyl N-(4-Nitrophenyl)carbamate (4l).17 Reaction of p-
nitrobenzamide 2l (12 mg, 0.075 mmol) according to the general
procedure afforded 11 mg (75%) of product 4l, isolated as yellow
needles (recrystallized from dichloromethane−hexane): mp 177.2−
178 °C (lit.18 mp 176−177 °C); IR (KBr) cm−1 3391, 1740, 1595,
1508, 1326, 1219; 1H NMR (500 MHz, CDCl3) δ 8.21 (d, J = 7.8 Hz,
2H), 7.56 (d, J = 7.8 Hz, 2H), 6.93 (br s, 1H), 3.83 (s, 3H).
Methyl N-Benzylcarbamate (4n).7c Reaction of 2-phenyl-
acetamide 2n (10 mg, 0.075 mmol) according to the general
procedure afforded 12 mg (97%) of product 4n, isolated as colorless
needles (recrystallized from dichloromethane−hexane): mp 62.2−62.9
°C (lit.7c mp 63−65 °C); 1H NMR (500 MHz, CDCl3) δ 7.37 (t, J =
7.8 Hz, 2H), 7.31−7.25 (m, 3H), 4.98 (br s, 1H), 4.37 (d, J = 5.5 Hz,
2H), 3.70 (s, 3H).
p-Isocyanatotoluene (3a). N-(4-Methylphenylsulfonyl)-
iminophenyl-λ3-iodane 1 (34 mg, 0.09 mmol) was added to a solution
of p-toluamide 2a (10 mg, 0.075 mmol) in dichloromethane (1.5 mL)
and stirred at room temperature for 0.5 h. After completion of the
reaction, the mixture was concentrated and separated by preparative
TLC (hexane−ethyl acetate = 2: 1) to afford 8 mg (80%) of p-
1
isocyanatotoluene 3a, isolated as a brown oil: H NMR (500 MHz,
CDCl3) δ 7.22 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.5 Hz, 2H), 2.33 (s,
3H). The obtained product is identical to a commercially available
sample.
Isopropyl N-(4-Methylphenyl)carbamate (5a).22 Reaction of p-
toluamide 2a (10 mg, 0.075 mmol) according to the general procedure
with isopropanol instead of methanol afforded 13 mg (90%) of
Methyl N-(1-Phenylpropyl)carbamate (4o).19 Reaction of 2-
phenylbutanamide 2o (12 mg, 0.075 mmol) according to the general
procedure afforded 14 mg (97%) of product 4o, isolated as a light
1
product 5a, isolated as colorless oil; H NMR (500 MHz, CDCl3) δ
7.25 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 6.46 (br s, 1H), 5.00
(sept, J = 6.2 Hz, 1H), 1.29 (d, J = 6.2 Hz, 6H).
1
brown oil: H NMR (500 MHz, CDCl3) δ 7.35 (t, J = 7.5 Hz, 2H),
tert-Butyl N-(4-Methylphenyl)carbamate (5b).23 Reaction of p-
toluamide 2a (10 mg, 0.075 mmol) according to the general procedure
with 2-methyl-2-propanol instead of methanol afforded 11 mg (71%)
of product 5b, isolated as colorless needles (recrystallized from
dichloromethane−hexane): mp 85.4−86 °C (lit.23 mp 86 °C); 1H
NMR (500 MHz, CDCl3) δ 7.23 (d, J = 8 Hz, 2H), 7.09 (d, J = 8 Hz,
2H), 6.37 (br s, 1H), 2.29 (s, 3H), 1.51 (s, 9H).
7.32−7.28 (m, 3H), 5.11 (br s, 1H), 4.68−4.54 (m, 1H), 3.66 (s, 3H),
1.92−1.72 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H).
Methyl N-(4-Methylbenzyl)carbamate (4p).7c Reaction of 2-(p-
tolyl)acetamide 2p (11 mg, 0.075 mmol) according to the general
procedure afforded 12 mg (91%) of product 4p, isolated as colorless
needles (recrystallized from dichloromethane−hexane): mp 71.5−72.2
°C (lit,7c mp 68−70 °C); 1H NMR (500 MHz, CDCl3) δ 7.18 (d, J =
7.5 Hz, 2H), 7.14 (d, J = 7.5 Hz, 2H), 4.92 (brs, 1H), 4.33 (d, J = 5.5
Hz, 2H), 3.70 (s, 3H), 2.34 (s, 3H).
p-Toluidine (5c).24 N-(4-Methylphenylsulfonyl)iminophenyl-λ3-
iodane 1 (67 mg, 0.18 mmol) was added to a solution of p-toluamide
2a (20 mg, 0.15 mmol) in dichloromethane (3 mL) and stirred at
room temperature for 0.5 h. Then 10% HCl (3 mL) was added and
the resulting reaction mixture stirred at 50 °C for 1 h. After
completion of the reaction, the mixture was extracted with
dichloromethane. The aqueous layer was treated with 20% NaOH,
and then the mixture was extracted with dichloromethane. The organic
layer was dried over anhydrous sodium sulfate, concentrated, and then
separated by preparative TLC (hexane−ethyl acetate, 3:1) to afford 14
mg (89%) of analytically pure p-toluidine 5c, isolated as a brown solid
(recrystallized from dichloromethane−hexane): mp 45.8−46.5 °C
Methyl N-(4-Methoxybenzyl)carbamate (4q).7c Reaction of 2-
(p-methoxyphenyl)acetamide 2q (12 mg, 0.075 mmol) according to
the general procedure afforded 13 mg (86%) of product 4q, isolated as
colorless needles (recrystallized from dichloromethane−hexane): mp
73−73.8 °C (lit.7c mp 73−74 °C); H NMR (500 MHz, CDCl3) δ
1
7.21 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 4.91 (br s, 1H), 4.30
(d, J = 6 Hz, 2H), 3.80 (s, 3H), 3.69 (s, 3H).
Methyl N-[(1-Naphthyl)methyl]carbamate (4r).7c Reaction of
1-naphthaleneacetamide 2r (14 mg, 0.075 mmol) according to the
general procedure afforded 16 mg (95%) of product 4r, isolated as
colorless needles (recrystallized from dichloromethane−hexane): mp
86.2−86.6 °C (lit.7c mp 84−86 °C); IR (KBr) cm−1 3304, 1696, 1547,
1262; 1H NMR (500 MHz, CDCl3): δ 8.03 (d, J = 8 Hz, 1H), 7.88 (d,
J = 8.5 Hz, 1H), 7.81 (d, J = 9 Hz, 1H), 7.58−7.48 (m, 2H), 7.47−7.40
(m, 2H), 4.97 (br s, 1H), 4.83 (d, J = 6 Hz, 2H), 3.71 (s, 3H).
Methyl N-Pentylcarbamate (4s).20 Reaction of hexanamide 2s
(9 mg, 0.075 mmol) according to the general procedure afforded 10
(lit.24 mp 41−44 °C); H NMR (500 MHz, CDCl3) δ 6.96 (d, J = 8
1
Hz, 2H), 6.61 (d, J = 8 Hz, 2H), 3.56 (br s, 2H), 2.28 (s, 3H).
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of NMR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
mg (92%) of product 4s, isolated as a colorless oil: H NMR (500
MHz, CDCl3) δ 4.62 (br s, 1H), 3.66 (s, 3H), 3.22−3.06 (m, 2H),
1.49 (quint, J = 7 Hz, 2H), 1.38−1.24 (m, 4H), 0.90 (t, J = 7 Hz, 3H).
Methyl N-Isopropylcarbamate (4t).7c Reaction of isobutyramide
2t (13 mg, 0.15 mmol) according to the general procedure afforded 13
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: vzhdanki@d.umn.edu.
1
mg (74%) of product 4t, isolated as a colorless oil: H NMR (500
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by a research grant from the National
Science Foundation (CHE-1009038).
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