Copper-catalyzed direct transformation of secondary allylic and benzylic alcohols into azides and amides: An efficient utility of azide as a nitrogen source

Article abstract of DOI:10.1002/ejoc.201500010

A mild and convenient method for the synthesis of amides has been explored by using secondary alcohols, Cu(ClO₄)₂·6H₂O as a catalyst, and trimethylsilyl azide (TMSN₃) as a nitrogen source in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) at ambient temperature. This method has been successfully adapted to the preparation of azides directly from their corresponding alcohols and offers excellent chemoselectivity in the formation of ω-halo azides and the azidation of allylic alcohols in the presence of a benzyl alcohol moiety. In addition, this strategy provides an opportunity to synthesize azides that can serve as precursors to β-amino acids. A mild and convenient method for the synthesis of amides has been explored by using secondary alcohols, Cu(ClO₄)₂·6H₂O as a catalyst, and trimethylsilyl azide (TMSN₃) as a nitrogen source in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) at ambient temperature. This method has also been adapted to the preparation of azides directly from their corresponding alcohols.

Full text of DOI:10.1002/ejoc.201500010

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FULL PAPER
DOI: 10.1002/ejoc.201500010
Copper-Catalyzed Direct Transformation of Secondary Allylic and Benzylic
Alcohols into Azides and Amides: An Efficient Utility of Azide as a Nitrogen
Source
Balaji V. Rokade,[a] Karthik Gadde,[a] and Kandikere Ramaiah Prabhu*[a]
Keywords: Synthetic methods / Chemoselectivity / Alcohols / Azides / Amides / Copper
A mild and convenient method for the synthesis of amides
azides directly from their corresponding alcohols and offers
has been explored by using secondary alcohols, Cu(ClO4) excellent chemoselectivity in the formation of ω-halo azides
2·6H2O as a catalyst, and trimethylsilyl azide (TMSN3) as a
nitrogen source in the presence of 2,3-dichloro-5,6-dicyano-
p-benzoquinone (DDQ) at ambient temperature. This
method has been successfully adapted to the preparation of
and the azidation of allylic alcohols in the presence of a
benzyl alcohol moiety. In addition, this strategy provides an
opportunity to synthesize azides that can serve as precursors
to β-amino acids.
try.[26] Apart from this, azides have also been used for the
insertion of a nitrogen atom into a hydrocarbon unit to
obtain nitriles,[27] tetrazoles,[28] and amides.[29,30] Recently,
Jiao and co-workers reported an interesting method to syn-
thesize amides and acrylamides from benzyl-substitued hy-
drocarbons under FeCl2 catalysis.[30] Although this method
is attractive, it involves starting materials that are not easy
to access and require multistep synthetic sequences.[31] Re-
cently, we reported the oxidative conversion of alcohols into
their nitriles[32a] and tetrazoles (Scheme 1).[32b] During these
investigations, it was observed that the corresponding
azides were formed as an intermediate, which underwent
further oxidation in the presence of DDQ (2,3-dichloro-5,6-
dicyano-p-benzoquinone) to generate a nitrilium intermedi-
ate.[32] With this observation and in continuation of our
work on the utility of azides,[32,33] we have synthesized
amides directly from secondary alcohols, which are easily
accessible or prepared by the reduction of ketones or the
1,2-addition of Grignard reagents to aldehydes. By using
the present strategy, the successful chemoselective syntheses
of ω-halo azides and ω-hydroxy azides have also been ex-
plored.
Introduction
The construction of the carbon–nitrogen bond is an im-
portant transformation in organic synthesis because of its
prevalence in a number of biologically active compounds.
As a result, a large number of publications on this subject
have appeared in recent years.[1–3] The amide functionality
is the crucial backbone of peptide chemistry and serves as
an important precursor in a variety of organic transforma-
tions. Amides have been used as coupling partners in vari-
ous transition-metal-catalyzed coupling reactions such as
those with aryl boronic acids or aryl halides,[4] and amides
can be reduced into their amines[5] or hydrolyzed into ac-
ids.[6] In recent times, amides have been employed as direct-
ing groups in C–H functionalization strategies.[7] Tradition-
ally, amides are synthesized by coupling carboxylic acids
and carboxylic acid derivatives with an amine.[8,9] Amides
can also be accessed through a Beckmann rearrange-
ment,[10] a Schmidt rearrangement,[11] the oxidative amid-
ation of alcohols,[12–14] aldehydes,[15,16] ketones,[17] and
amines,[18] and the aminocarbonylation of aromatic hal-
ides.[19,20] Amides can also be synthesized by coupling alde-
hyde groups with amines,[21] azides,[22] or amides[23] under
metal or metal-free reaction conditions. Usually, most of
the above-mentioned methods utilize an amine as a cou-
pling partner.
Similar to amides, organic azides are also important pre-
cursors in organic synthesis.[24,25] The utility of azides has
been greatly enhanced by the development of click chemis-
[a] Department of Organic Chemistry, Indian Institute of Science,
Bangalore 560012, Karnataka, India
E-mail: prabhu@orgchem.iisc.ernet.in
http://orgchem.iisc.ernet.in/faculty/krp/group/index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500010.
Scheme 1. Previous work.
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B. V. Rokade, K. Gadde, K. R. Prabhu
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Results and Discussion
Synthesis of Amides
(Table 2, Entry 1). Alcohols that contain electron-donating
substituents such as 4-methoxy and 4-methyl on the aryl
ring furnished the corresponding amides 2b and 2f in 56
and 72% yield, respectively (Table 2, Entries 2 and 6). Sub-
strates with a halide substituent such as a 4-bromo, 4-
chloro, 4-fluoro, 2-bromo and 2-fluoro group on the aryl
ring under the optimized reaction conditions furnished the
corresponding amides 2c-2e, 2g and 2h in good to excellent
yields (Table 2, Entries 3–5, 7 and 8).
In search of suitable conditions to obtain an amide, we
began by examining the reaction between (E)-1,3-di-
phenylprop-2-en-1-ol (1a) and trimethylsilyl azide (TMSN3,
1.2 equiv.) with DDQ (1.2 equiv.) as the oxidant, Cu(ClO4)
2·6H2O as the catalyst, and water (3 equiv.) as an additive in
dichloromethane (DCM) at room temperature (Table 1).[29]
Surprisingly, this reaction resulted in the formation of
tetrazole 2aЈ as the sole product, and the formation of
amide 2a was not observed, even in trace amounts (Table 1,
Entry 1, determined by 1H NMR conversion). Changing
the solvent from DCM to CH3CN did not provide better
results (Table 1, Entries 2 and 3,). However, to our delight,
the use of acidic additives such as acetic acid (3 equiv.) was
encouraging, and the expected amide 2a was obtained in
30% yield along with tetrazole 2aЈ (70% yield) as a major
product (Table 1, Entry 4). Increasing the amount of AcOH
to 10 equiv. was not useful, as the reaction furnished a mix-
ture of amide 2a and tetrazole 2aЈ in a 50:50 ratio (Table 1,
Entry 5). Remarkably, using acetic acid as the solvent gave
a favorable result and furnished the expected amide 2a as
the sole product (Table 1, Entry 6). Therefore, the optimal
reaction conditions for the efficient oxidative transforma-
tion of alcohols into their corresponding amides involved
the combination of Cu(ClO4)2·6H2O (5 mol-%), TMSN3
(1.2 equiv.), DDQ (1.2 equiv.), and H2O (3 equiv.) in AcOH
as the solvent at ambient temperature.
Table 2. Substrate scope.[a,b]
Table 1. Optimization studies.[a]
Entry
Solvent
Additive [equiv.]
Product[b]
1
2
3
4
5
6
CH2Cl2
CH3CN
CH3CN
CH2Cl2
CH2Cl2
AcOH
none
none
AcOH (3)
AcOH (3)
AcOH (10)
none
2aЈ only
complex mixture
complex mixture
2a + 2aЈ (30:70)
2a + 2aЈ (50:50)
2a only
[a] Reagents and conditions: 1 (0.5 mmol), TMSN3 (0.6 mmol), Cu-
(ClO4)2·6H2O (0.025 mmol), DDQ (0.6 mmol), H2O (1.5 mmol),
and AcOH (2 mL) at room temp. for 1 h. [b] Isolated yield.
[a] Reagents and conditions: 1a (0.5 mmol), TMSN3 (0.6 mmol),
(0.025 mmol), DDQ (0.6 mmol), H2O
The substrate scope was further investigated by using sec-
ondary allylic alcohols with different aryl moieties at the 3-
position and a phenyl group at the 1-position. As expected,
under the optimal conditions, these reactions furnished re-
Cu(ClO4)2·6H2O
(1.5 mmol), additive, and solvent (2 mL) at room temp. for 1 h.
1
[b] Products determined by H NMR conversion.
After the optimization studies were complete, the sub- gioisomeric mixtures of the corresponding amides. Here,
strate scope was studied by using a variety of secondary the regioselectivity of the reaction was determined by the
allylic alcohols, and the results are summarized in Tables 2 electronic and steric factors associated with the substrate.
and 3. As shown in Table 2, secondary allylic alcohols that Alcohol 1i with a methyl substituent at the ortho position
are substituted with identical aromatic rings at the 1- and furnished amide 2i as a mixture of regioisomers in a 67:33
3-positions (i.e., 1a–1h) furnished the expected acrylamides ratio (78% yield, Table 3, Entry 1). However, alcohol 1j
(i.e., 2a–2h) in good to excellent yields (Table 2, Entries 1– with a methyl substituent at the para position of the aryl
8). Under the optimal reaction conditions, (E)-1,3-di- ring furnished amide 2j in 66% yield as a mixture of re-
phenylprop-2-en-1-ol (1a) furnished amide 2a in 93% yield gioisomers in a 27:73 ratio (Table 3, Entry 2). The effect on
2
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Azides and Amides from Allylic and Benzylic Alcohols
Table 3. Substrate scope.[a,b]
[a] Reagents and conditions: 1 (0.5 mmol), TMSN3 (0.6 mmol), Cu(ClO4)2·6H2O (0.025 mmol), DDQ (0.6 mmol), H2O (1.5 mmol), and
AcOH (2 mL) at room temp. for 1 h. [b] Isolated yield.
the regioselectivity of the reaction was then studied by hav- withdrawing substituent at the para position of the aryl ring
ing a chloro substituent at different positions of the aryl furnished the corresponding amides 2p and 2q in a re-
ring. Alcohol 1 that contains a chloro substituent at the gioisomeric ratio of 75:25 and 88:12, respectively (Table 3,
ortho or para position of the aryl ring (i.e., 1k and 1m) Entries 8 and 9). Finally, alcohols that have a naphthyl
furnished the corresponding amides 2k and 2m as a 50:50 group such as (E)-3-(naphthalen-1-yl)-1-phenylprop-2-en-1-
mixture of regioisomers in 91% yield (Table 3, Entries 3 ol and (E)-3-(naphthalen-2-yl)-1-phenylprop-2-en-1-ol fur-
and 5). However, alcohol 1l that contains a chloro substitu- nished the corresponding amides 2r and 2s in good yields
ent at the meta position yielded amide 2l as a 35:65 mixture (73 and 90%) with regioisomeric ratios of 50:50 and 27:73,
of regioisomers (79% yield, Table 3, Entry 4). Alcohol 1n respectively (Table 3, Entries 10 and 11).
that contains a bromo substituent at the meta position of
Under the optimal reaction conditions, a symmetrical
the aryl ring furnished amide 2n in a 33:67 ratio of isomers secondary benzyl alcohol such as bis(4-methoxyphenyl)
(91% yield, Table 3, Entry 6). Alcohol 1o with a fluoro sub- methanol (1t) also afforded the corresponding amide 2t in
stitution at the para position of the aryl ring did not have 78% yield (Scheme 2). However, substrates such as an all-
much impact and afforded the corresponding amide 2o as ylic-alkylic or a benzylic-alkylic alcohol were treated under
a 50:50 regioisomeric mixture (81% yield, Table 3, Entry 7). present reaction conditions but unfortunately failed to give
Additionally, alcohols 1p and 1q that contain an electron- the expected amide.
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B. V. Rokade, K. Gadde, K. R. Prabhu
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aliphatic azides are prepared by the nucleophilic substitu-
tion reaction of organic halides/mesylates/tosylates with so-
dium azide,[24] whereas aromatic azides are synthesized by
using the classical Sandmeyer reaction. Apart from these,
there have recently been a few reports on the synthesis of
azides from the benzyl methyl ether and unsymmetrical di-
benzyl ethers that are derived from secondary or tertiary
benzyl alcohols[34] and benzylic silyl ethers.[35] There are
also some reports about the azidation of alcohols.[36]
The aforementioned methods suffer from disadvantages
such as the need of additional steps to synthesize the start-
ing materials or the lack of a broad substrate scope. Be-
cause of these reasons and the significance of azides as in-
termediates in organic synthesis, there is a need to develop
efficient methods for the synthesis of azides. In our earlier
work[32] on the direct oxidative transformation of an
alcohol into a nitrile, we observed the formation of an azide
as an intermediate. It was surprising to see that highly
Lewis acidic copper salts such as Cu(ClO4)2·6H2O and
Cu(OTf)2 (OTf = trifluoromethanesulfonate) were effective
catalysts, whereas other copper catalysts such as CuCl,
CuBr, CuI, and Cu(OAc)2·H2O were detrimental to this re-
action.
Scheme 2. Reaction with benzylic alcohol. Reagents and condi-
tions: 1t (0.5 mmol), TMSN3 (0.6 mmol), Cu(ClO4)2·6H2O
(0.025 mmol), DDQ (0.6 mmol), H2O (1.5 mmol), and AcOH
(2 mL) at room temp. for 1 h.
A further application of this methodology has been
shown by carrying out the reaction on a preparative scale.
Under the present reaction conditions, alcohol 1a (1.22 g)
furnished the expected amide 2a in 70% yield (Scheme 3).
Scheme 3. Application on a preparative scale. Reagents and condi-
tions: (a) 1a (1.22 g, 5.83 mmol), TMSN3 (1.2 equiv.), Cu(ClO4)
2·6H2O (5 mol-%), DDQ (1.2 equiv.), H2O (3 equiv.), and AcOH
(10 mL) at room temp. for 1 h.
On the basis of our earlier work,[32] we established that
Cu(ClO4)2·6H2O (5 mol-%) and TMSN3 (1.2 equiv.) in
CH2Cl2 at ambient temperature were the optimal reaction
conditions for the direct conversion of alcohols into azides.
Initially, primary cinnamyl alcohol derivatives such as (E)-
3-(4-nitrophenyl)prop-2-en-1-ol (3a), (E)-3-[4-(trifluoro-
methyl)phenyl]prop-2-en-1-ol (3b), and (E)-3-(4-chloro-
phenyl)prop-2-en-1-ol (3c), which have nitro, trifluoro-
methyl, and chloro substituents at the para position of the
phenyl ring, were subjected to the reaction under optimal
reaction conditions. In these cases, the reactions led to the
formation of the corresponding azides 4a, 4b, and 4c,
respectively, in good to excellent yields (79, 81, and 72%,
respectively). Furthermore, under the optimized reaction
conditions, secondary cinnamyl alcohol derivatives such as
(E)-1,3-bis(4-chlorophenyl)prop-2-en-1-ol (1d), (E)-1,3-
bis(4-fluorophenyl)prop-2-en-1-ol (1e), (E)-1,3-di-p-tolyl-
prop-2-en-1-ol (1f), and (E)-1,3-bis(2-bromophenyl)prop-2-
en-1-ol (1g) that have chloro, fluoro, methyl, and bromo
substituents on both aromatic rings of the alcohol yielded
the corresponding azides 4d, 4e, 4f, and 4g in 90, 84, 85,
and 90%, respectively. In addition, alcohols such as (E)-4-
phenylbut-3-en-2-ol (3h) and (E)-4-(4-methoxyphenyl)but-
3-en-2-ol (3i) furnished azides 4h and 4i, respectively, as the
sole product, which can be explained by the extended stabi-
lization of the carbocation by the cinnamyl moiety
(Scheme 4).
Synthesis of Azides
Azides are important precursors and intermediates for a
variety of organic transformations, and the present study
offers an opportunity to synthesize azides directly from
alcohols (Scheme 1). Therefore, we proceeded to investigate
the synthesis of a variety of azides (Scheme 4). Generally,
Alcohols (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-ol
(1o) and (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-ol
(1o´), which are regioisomers, were subjected to the optimal
azidation conditions. Under these conditions, these iso-
meric alcohols furnished the isomeric mixture of azides 4jA
and 4jAЈ in the same ratio (50:50) in good yields
(Scheme 5). This clearly indicates that reaction of both
alcohols 1o and 1oЈ proceeds through a similar intermedi-
Scheme 4. Direct azidation of cinnamyl alcohols.
4
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Azides and Amides from Allylic and Benzylic Alcohols
ate, namely, the delocalized carbocation followed by the at- bromo substituents on a sp3-hybridized carbon atom, ex-
tack of TMSN3 to give azides 4jA and 4jAЈ as shown in hibited excellent chemoselectivity and furnished the corre-
Scheme 5.
sponding halo azides 4k and 4r in 75 and 53% yield, respec-
tively.
Scheme 5. Substrate scope. [a] Reagents and conditions: 1o or 1oЈ
(0.5 mmol), TMSN3 (0.6 mmol), Cu(ClO4)2·6H2O (0.025 mmol),
and dichloromethane (2 mL) at room temp. for 5–10 min. [b] Based
1
on H NMR conversion.
Furthermore, alcohols 1i and 1p were subjected to the
azidation reaction, which furnished the corresponding mix-
ture of azides 4jB/4jBЈ in 60:40 ratio and 4jC/4jCЈ in 71:29
ratio (Scheme 6, a and b), which are also in agreement with
the amide ratios observed in Table 3, Entries 1 and 8.
Scheme 6. Substrate scope. [a] Reagents and conditions: 1i or 1p
(0.5 mmol), TMSN3 (0.6 mmol), Cu(ClO4)2·6H2O (0.025 mmol),
and AcOH (2 mL) at room temp. for 5–10 min. [b] Based on 1H
NMR conversion.
Scheme 7. Direct azidation of benzylic alcohols (TBS = tert-butyld-
imethylsilyl, n.r.: no reaction).
Then, the scope of this azidation reaction was extended
to benzylic alcohols, and the results are summarized in
Scheme 7. A variety of benzylic alcohols with different sub-
The chemoselectivity that was observed in the formation
stituents underwent a facile transformation into their corre- of the halo azides is rare and difficult to achieve. Further
sponding azides in good to excellent yields. 3-Chloro-1- investigations showed that the reaction is versatile as 1-(4-
phenylpropan-1-ol (3k), 3-(naphthalen-1-yloxy)-1-phen- methoxyphenyl)-2-(naphthalen-2-yloxy)ethan-1-ol (3s), 1-
ylpropan-1-ol (3l), 1,2,3,4-tetrahydronaphthalen-1-ol (3m), (thiophen-2-yl)ethan-1-ol (3t), and 1-phenylbut-3-en-1-ol
and 1-([1,1Ј-biphenyl]-4-yl)ethan-1-ol (3n) under the opti- (3u) furnished the corresponding azides 4s, 4t, and 4u in
mal reaction conditions furnished the corresponding azides good yields (74, 73, and 75%, respectively). Secondary sym-
4k, 4l, 4m, and 4n in good to excellent yields. Electron- metrical benzylic alcohols such as diphenylmethanol (3v)
donating substituents on aromatic secondary alcohols such and 4,4Ј-bis(4-methoxyphenyl)methanol (3w) underwent
as 1-(4-methoxyphenyl)ethan-1-ol (3o), 1-(4-[benzyloxy] smooth transformation to furnish the corresponding azides
phenyl)ethan-1-ol (3p), and 1-{4-[(tert-butyldimethylsilyl) 4v and 4w in 77 and 84% yield, respectively. Under the reac-
oxy]phenyl}ethan-1-ol (3q) underwent a facile transforma- tion conditions, the alcohol with a propargyl moiety such
tion to yield the corresponding azides 4o, 4p, and 4q in 84, as 1-phenylpent-1-yn-3-ol (3x) afforded the expected prop-
88, and 81% yield, respectively. Furthermore, 2-bromo-1- argyl azide 4x in 52% yield. However, primary benzyl
(4-methoxyphenyl)ethan-1-ol (3r) under the similar reaction alcohol (3y) did not undergo the reaction, and the corre-
conditions afforded the corresponding azide 4r in a moder- sponding benzyl azide (4y) was not obtained (Scheme 7).
ate yield (53%). It is noteworthy that halo-substituted
Methyl 2-[hydroxy(phenyl)methyl]acrylate (5), an alcohol
alcohols such as 3k and 3r, which contain chloro and derived from the Baylis–Hilmann reaction of methyl acryl-
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B. V. Rokade, K. Gadde, K. R. Prabhu
FULL PAPER
ate with benzaldehyde, smoothly underwent the reaction to b). Interestingly, the reaction of 1-phenylprop-2-en-1-ol
provide the regioisomeric mixture of the corresponding (10), which is a allylic alcohol, under the optimal conditions
azides 6 and 6Ј in a 58:42 ratio. It was found that azide 6Ј led to the formation of the terminal azide (E)-(3-azidoprop-
will slowly convert into azide 6 through a [3,3] sigmatropic 1-en-1-yl)benzene (11) as the sole product in 72% yield
rearrangement. It is important to note that product 6 can (Scheme 9, b). Under similar reaction conditions, (Z)-cin-
be converted by reduction into a β-amino acid derivative namyl alcohol (12) furnished (E)-cinnamyl azide (11) in
(Scheme 8).
92% yield (Scheme 9, c). The results of this reaction suggest
a strong possibility of a carbocation as an intermediate.
To confirm the presence of a carbocation intermediate in
this transformation, chiral alcohol (S)-1-(4-methoxy-
phenyl)propan-1-ol (13)[37a] was subjected to the optimal re-
action conditions. As expected, azide 14 was formed in 87%
yield as a racemic mixture (Scheme 10). Because this reac-
tion is led to a racemized product, it is clear beyond a doubt
that the reaction proceeds through the corresponding
carbocation.
Scheme 8. Synthesis of β-azido esters.
The inert nature of benzyl alcohol towards azidation un-
der the present reaction conditions provided an opportunity
to investigate the chemoselective azidation of allylic
alcohols in the presence of a benzyl alcohol moiety
(Scheme 9, a). Thus, (E)-3-[4-(hydroxymethyl)phenyl]prop-
2-en-1-ol (7) that contains benzylic and allylic hydroxy
groups in the same molecule was subjected to the present
reaction conditions.
Scheme 10. Azidation of chiral alcohol 13 (er = enantiomeric ra-
tio).
Thereafter, this new azidation reaction, which is cata-
lyzed by Cu(ClO4)2·6H2O, was used in situ along with a
subsequent click reaction by adding phenyl acetylene.
Alcohol 9 was treated under the present reaction conditions
followed by the addition of phenyl acetylene to yield the
corresponding triazole 15 in 42% yield (Scheme 11).
Scheme 11. One-pot click reaction.
Reaction Mechanism
We believe that the regioselectivity of the reaction is de-
termined by the nature of the substituent that is present on
the aromatic ring. The fact that the unsymmetrically substi-
tuted alcohol preferentially furnishes the azide that is benz-
ylic to an electron-rich phenyl ring over an electron-poor
one suggests that the formation of the azide is the determin-
ing factor for the observed regioselectivity. This selectivity is
influenced by the formation of a stable carbocation. Azide I
is further oxidized to give unstable azidonium intermediate
Scheme 9. Chemoselectivity study. [a] Reagents and conditions: 7,
9, 10, or 12 (0.5 mmol), TMSN3 (0.6 mmol), Cu(ClO4)2·6H2O
(0.025 mmol), and dichloromethane (2 mL) at room temp. for 5–
10 min.
As expected, the allylic alcohol functionality underwent II followed by the migration of one of the groups and the
a selective transformation into the azide, whereas the hy- loss of nitrogen to generate nitrilium ion III. It was also
droxylbenzyl group remained intact to furnish azido observed that an aryl group migration is preferable over
alcohol (E)-[4-(3-azidoprop-1-en-1-yl)phenyl]methanol (8) that of a vinyl group, which might be from the stabilization
in 72% yield (Scheme 9, a). As expected cinnamyl alcohol of azidonium intermediate II by a phenonium ion. There-
(9) under the optimal reaction conditions furnished (E)-(3- fore, the overall observed migratory aptitude is: aryl group
azidoprop-1-en-1-yl)benzene (11) in 96% yield (Scheme 9, Ͼ vinyl group.[37b,37c]
6
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Azides and Amides from Allylic and Benzylic Alcohols
On the basis of our work in the formation of nitriles[32a]
and tetrazoles[32b] from their corresponding alcohols, a ten-
tative mechanism has been proposed in which Cu(ClO4)
2·6H2O is initially treated with the alcohol and TMSN3 to
generate azide I. In the presence of DDQ, azide I is oxidized
to give nitrilium intermediate III, which is trapped by water
to furnish the corresponding amide (Scheme 12). The exact
role of AcOH in the formation of amide product is not
clear.
tored by TLC, approximately 60 min.). The reaction mixture was
diluted with EtOAc, and Na2CO3 was added. The mixture was then
passed through alumina, and the filtrate was concentrated. The res-
idue was purified by column chromatography on silica gel.
Typical Experimental Procedure for the Synthesis of Azides from
Alcohols: TMSN3 (0.08 mL, 0.6 mmol, 1.2 equiv.) was added to a
well-stirred solution of alcohol 3a (89.6 mg, 0.5 mmol, 1 equiv.)
and Cu(ClO4)2·6H2O (9.3 mg, 0.025 mmol, 5 mol-%) in CH2Cl2
(2 mL). The mixture was stirred at room temperature until the reac-
tion reached completion (monitored by TLC, approximately
15 min.). The mixture was extracted with EtOAc or DCM (3ϫ
15 mL), and the combined organic extracts were washed with water,
dried with anhydrous Na2SO4, and concentrated. The crude prod-
uct was purified by silica gel column chromatography.
(E)-N-Phenylcinnamamide (2a):[30] White solid (103.8 mg, 93%
yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 149–151 °C; ref.[38] m.p.
151–153 °C. IR (KBr): ν = 3274, 3058, 1662, 1626, 1596, 1545,
˜
1
1493, 1443, 1351, 1250, 1189, 977 cm–1. H NMR (400 MHz, [D6]
DMSO): δ = 10.22 (s, 1 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.63–7.57
(m, 3 H), 7.47–7.39 (m, 3 H), 7.35–7.31 (m, 2 H), 7.07 (t, J =
7.2 Hz, 1 H), 6.84 (d, J = 16 Hz, 1 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 163.5, 140.2, 139.3, 134.7, 129.8, 129.0, 128.8,
127.7, 123.4, 122.3, 119.2 ppm. HRMS (ESI): calcd. for
C15H13NNaO [M + Na]+ 246.0895; found 246.0890.
(E)-N,3-Bis(4-methoxyphenyl)acrylamide (2b):[39] White solid
(79.3 mg, 56% yield); R = 0.4 (25% EtOAc/hexane). IR (KBr): ν
˜
f
= 3275, 2841, 1653, 1616, 1604, 1507, 1300, 1243, 1168, 1029, 1004,
823 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.00 (s, 1 H),
7.60 (d, J = 8.4 Hz, 2 H), 7.56 (d, J = 8.4 Hz, 2 H), 7.50 (d, J =
16 Hz, 1 H), 7.00 (d, J = 8.4 Hz, 2 H), 6.90 (d, J = 8.8 Hz, 2 H),
6.65 (d, J = 16 Hz, 1 H), 3.79 (s, 3 H), 3.73 (s, 3 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 163.4, 160.5, 155.2, 139.4, 132.6,
129.3, 127.4, 120.6, 119.8, 114.5, 113.9, 55.3, 55.2 ppm. HRMS
Scheme 12. Tentative mechanism.
Conclusions
We have reported a mild and convenient method to ac-
cess amides by starting from secondary alcohols in the pres- (ESI): calcd. for C17H17NNaO3 [M + Na]+ 306.1106; found
306.1109.
ence of TMSN3, Cu(ClO4)2·6H2O, and DDQ in a one-pot
reaction at ambient temperature. A detailed study was car-
ried out to understand the effect that various substituents
on the aromatic ring of an allylic alcohol would have on
the regioselectivity of the reaction. This methodology has
also been applied to the synthesis of azides directly from
the corresponding alcohols. One of the salient features of
this method is that it exhibits excellent chemoselectivity in
the synthesis of ω-halo azides, which are difficult to access
by conventional methods. In addition, this method offers
excellent chemoselectivity in the azidation of an allylic
alcohol in the presence of a benzylic alcohol moiety.
Furthermore, it has been shown that this strategy provides
an opportunity to synthesize (E)-methyl 2-(azidomethyl)-3-
phenylacrylate, which can serve as a precursor in the syn-
thesis of a β-amino acid.
(E)-N,3-Bis(4-bromophenyl)acrylamide (2c):[10c] White solid
(167.7 mg, 88% yield); Rf = 0.7 (25% EtOAc/hexane), m.p. 215–
217 °C. IR (KBr): ν = 3285, 3048, 1652, 1619, 1589, 1530, 1486,
˜
1396, 1335, 1245, 1183, 1070, 1007, 966, 815 cm–1. 1H NMR
(400 MHz, [D6]DMSO): δ = 10.36 (s, 1 H), 7.68–7.64 (m, 4 H),
7.59–7.51 (m, 5 H), 6.82 (d, J = 16 Hz, 1 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 163.4, 139.2, 138.5, 133.9, 132.0,
131.6, 129.6, 123.0, 122.8, 121.1, 115.0 ppm. HRMS (ESI): calcd.
for C15H12Br2NO [M + H]+ 379.9286; found 379.9285.
(E)-N,3-Bis(4-chlorophenyl)acrylamide
(2d):[30]
White
solid
(105.2 mg, 72% yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 207–
209 °C; ref.[40] m.p. 207 °C. IR (KBr): ν = 3279, 3109, 3038, 1654,
˜
1621, 1592, 1533, 1489, 1398, 1336, 1245, 1184, 1095, 1011, 969,
819 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 10.36 (s, 1 H),
7.72 (d, J = 8.8 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.59 (d, J =
16 Hz, 1 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.8 Hz, 2 H),
6.80 (d, J = 16 Hz, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO):
δ = 163.4, 139.1, 138.1, 134.3, 133.6, 129.4, 129.0, 128.7, 127.0,
122.8, 120.8 ppm. HRMS (ESI): calcd. for C15H11Cl2NNaO [M +
Na]+ 314.0115; found 314.0117.
Experimental Section
Typical Experimental Procedure for the Synthesis of Amides from
Alcohols: TMSN3 (0.08 mL, 0.6 mmol, 1.2 equiv.) was added to a (E)-N,3-Bis(4-fluorophenyl)acrylamide (2e):[10c]
White solid
(118.0 mg, 91% yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 156–
well-stirred solution of alcohol 1a (105.1 mg, 0.5 mmol, 1 equiv.),
Cu(ClO4)2·6H2O (9.3 mg, 0.025 mmol, 5 mol-%), and H2O (27 mg, 158 °C. IR (KBr): ν = 3295, 1654, 1622, 1602, 1534, 1506, 1407,
˜
1.5 mmol, 3 equiv.) in AcOH (2 mL). After 15 min, DDQ was 1340, 1239, 1214, 1183, 970, 830 cm–1. 1H NMR (400 MHz, [D6]
added (136.2 mg, 0.6 mmol, 1.2 equiv.), and the mixture was stirred
at room temperature until the reaction reached completion (moni-
DMSO): δ = 10.25 (s, 1 H), 7.73–7.67 (m, 4 H), 7.59 (d, J = 16 Hz,
1 H), 7.31–7.26 (m, 2 H), 7.20–7.15 (m, 2 H), 6.74 (d, J = 16 Hz,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O50010
/KAP1
Date: 06-03-15 12:48:07
Pages: 13
B. V. Rokade, K. Gadde, K. R. Prabhu
FULL PAPER
1 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 162.8 (d, J =
976 cm–1. Data for 2kA: 1H NMR (400 MHz, CDCl3): δ = 8.53 (d,
247 Hz), 163.3, 158.0 (d, J = 238 Hz), 139.0, 135.6 (d, J = 3 Hz), J = 8 Hz, 1 H), 7.82 (s, 1 H), 7.78 (d, J = 15.6 Hz, 1 H), 7.57–7.38
131.3 (d, J = 3 Hz), 129.8 (d, J = 9 Hz), 122.0, 120.9 (d, J = 7 Hz),
116.0 (d, J = 21 Hz), 115.3 (d, J = 22 Hz) ppm. 19F NMR
(376 MHz, [D6]DMSO): δ = –110.9, –118.9 ppm. HRMS (ESI):
calcd. for C15H11F2NNaO [M + Na]+ 282.0706; found 282.0707.
(m, 6 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.06 (t, J = 7.6 Hz, 1 H), 6.60
(d, J = 15.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
163.8, 143.0, 134.7, 134.4, 130.2, 129.0, 128.9, 128.1, 127.8, 124.7,
122.7, 121.7, 120.5 ppm. Data for 2kB: 1H NMR (400 MHz,
CDCl3): δ = 8.12 (d, J = 15.6 Hz, 1 H), 7.97 (s, 1 H), 7.67–7.52 (m,
3 H), 7.39–7.11 (m, 6 H), 6.62 (d, J = 15.6 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 163.5, 138.2, 137.9, 134.9, 132.9,
130.7, 130.2, 129.0, 127.6, 126.9, 124.5, 123.8, 120.0 ppm. HRMS
(ESI): calcd. for C15H12ClNNaO [M + Na]+ 280.0505; found
280.0502.
(E)-N,3-Di-p-tolylacrylamide (2f):[30] White solid (90.5 mg, 72%
yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 172–174 °C; ref.[10b] m.p.
173–175 °C. IR (KBr): ν = 3307, 2916, 1656, 1624, 1521, 1405,
˜
1337, 1241, 1171, 977, 815, 788 cm–1. 1H NMR (400 MHz, [D6]
DMSO): δ = 10.10 (s, 1 H), 7.60–7.50 (m, 5 H), 7.24 (d, J = 8 Hz,
2 H), 7.13 (d, J = 8 Hz, 2 H), 6.77 (d, J = 16 Hz, 1 H), 2.33 (s, 3
H), 2.26 (s, 3 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
163.5, 139.9, 139.6, 136.9, 132.3, 132.1, 129.7, 129.2, 127.7, 121.3,
119.2, 21.0, 20.5 ppm. HRMS (ESI): calcd. for C17H17NNaO [M
+ Na]+ 274.1208; found 274.1204.
(E)-3-(3-Chlorophenyl)-N-phenylacrylamide (2lA)[41a] and (E)-N-(3-
Chlorophenyl)cinnamamide (2lB):[41b] White solid [101.8 mg, 79%
yield; 2lA/2lB, 35:65 (determined by 1H NMR)]. IR (KBr): ν =
˜
3262, 3058, 1654, 1618, 1594, 1542, 1420, 1341, 1235, 1248, 1185,
979 cm–1. Data for 2lA: 1H NMR (400 MHz, [D6]DMSO): δ =
10.23 (s, 1 H), 7.96–7.50 (m, 11 H), 6.90 (d, J = 16 Hz, 1 H) ppm.
Data for 2lB: 1H NMR (400 MHz, [D6]DMSO): δ = 10.41 (s, 1 H),
7.96–7.50 (m, 11 H), 6.82 (d, J = 16 Hz, 1 H) ppm. HRMS (ESI):
calcd. for C15H12ClNNaO [M + Na]+ 280.0505; found 280.0506.
(E)-N,3-Bis(2-bromophenyl)acrylamide (2g): White solid (135.3 mg
71% yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 184–186 °C. IR
(KBr): ν = 3262, 3051, 1655, 1624, 1536, 1437, 1337, 1283, 1186,
˜
1026, 965, 742 cm–1. 1H NMR (400 MHz, [D6]DMSO): δ = 9.75 (s,
1 H), 7.86 (d, J = 15.6 Hz, 1 H), 7.81–7.78 (m, 2 H), 7.74–7.68 (m,
2 H), 7.51–7.47 (m, 1 H), 7.43–7.34 (m, 2 H), 7.18–7.14 (m, 1 H),
7.08 (d, J = 15.6 Hz, 1 H) ppm. 13C NMR (100 MHz, [D6]DMSO):
δ = 163.4, 138.6, 136.1, 134.2, 133.3, 132.8, 131.6, 128.4, 128.1,
127.9, 127.1, 126.7, 124.9, 124.5, 117.3 ppm. HRMS (ESI): calcd.
for C15H11Br2NNaO [M + Na]+ 401.9105; found 401.9107.
(E)-3-(4-Chlorophenyl)-N-phenylacrylamide (2mA)[10c] and (E)-N-(4-
Chlorophenyl)cinnamamide (2mB):[10c] White solid [117.4 mg, 91%
1
yield; 2mA/2mB, 50:50 (determined by H NMR)]. IR (KBr): ν =
˜
3274, 3058, 1662, 1626, 1596, 1545, 1493, 1443, 1351, 1250, 1189,
977 cm–1. Data for 2mA: 1H NMR (400 MHz, [D6]DMSO): δ =
1
10.22 (s, 1 H), 7.75–6.80 (m, 11 H) ppm. Data for 2mB: H NMR
(E)-N,3-Bis(2-fluorophenyl)acrylamide (2h): White solid (111.5 mg,
86% yield); Rf = 0.4 (25% EtOAc/hexane), m.p. 141–143 °C. IR
(400 MHz, [D6]DMSO): δ = 10.35 (s, 1 H), 7.75–6.80 (m, 11
H) ppm. HRMS (ESI): calcd. for C15H12ClNNaO [M + Na]+
280.0505; found 280.0505.
(KBr): ν = 3288, 3059, 1662, 1630, 1543, 1483, 1457, 1341, 1228,
˜
1
1105, 973, 756 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 10.10
(E)-3-(3-Bromophenyl)-N-phenylacrylamide (2nA)[10b] and (E)-N-(3-
(s, 1 H), 8.06 (m, 1 H), 7.73–7.64 (m, 2 H), 7.47–7.41 (m, 1 H),
7.29–7.25 (m, 3 H), 7.17–7.14 (m, 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 163.8, 160.6 (d, J = 250 Hz), 153.5 (d, J =
243 Hz), 133.1, 131.8 (d, J = 9.3 Hz), 129.4, 126.3 (d, J = 11 Hz),
125.4 (d, J = 8 Hz), 125.1 (d, J = 3.1 Hz), 124.6 (d, J = 4.7 Hz),
124.5 (d, J = 3.3 Hz), 123.9, 122.4 (d, J = 11.4 Hz), 116.2 (d, J =
21 Hz), 115.5 (d, J = 19 Hz) ppm. 19F NMR (376 MHz, [D6]
Bromophenyl)cinnamamide (2nB):[10b] Gummy white liquid
1
[137.4 mg, 91% yield; 2nA/2nB, 33:67 (determined by H NMR)].
IR (KBr): ν = 3356, 2619, 1638, 1398, 1240, 1026, 648 cm–1. Data
˜
for 2nA: 1H NMR (400 MHz, [D6]DMSO): δ = 10.23 (s, 1 H), 7.83
(s, 1 H), 7.70–7.25 (m, 8 H), 7.07 (t, J = 8 Hz, 1 H), 6.88 (d, J =
16 Hz, 1 H) ppm. Data for 2nB: 1H NMR (400 MHz, [D6]DMSO):
δ = 10.40 (s, 1 H), 8.08 (s, 1 H), 7.70–7.25 (m, 9 H), 6.80 (d, J =
16 Hz, 1 H) ppm. HRMS (ESI): calcd. for C15H12BrNNaO [M +
Na]+ 324.0000; found 324.0002.
DMSO):
δ = –115.6, –124.9 ppm. HRMS (ESI): calcd. for
C15H11F2NNaO [M + Na]+ 282.0706; found 282.0705.
(E)-N-Phenyl-3-(o-tolyl)acrylamide (2iA)[10c] and (E)-N-(o-Tolyl)
(E)-3-(4-Fluorophenyl)-N-phenylacrylamide (2oA)[10c] and (E)-N-(4-
Fluorophenyl)cinnamamide (2oB):[10b] White solid [97.7 mg, 81%
yield; 2oA/2oB, approximately 50:50 (determined by 1H and 19F
cinnamamide (2iB):[10c] White solid [92.6 mg 78% yield; 2iA/2iB,
1
67:33 (determined by H NMR)]. IR (KBr): ν = 3265, 3028, 1657,
˜
1622, 1542, 1451, 1348, 1253, 1198, 976 cm–1. Data for 2iA: 1H
NMR (400 MHz, [D6]DMSO): δ = 10.21 (s, 1 H), 7.83–6.73 (m, 11
H), 2.41 (s, 3 H) ppm. Data for 2iB: 1H NMR (400 MHz, [D6]
DMSO): δ = 9.47 (s, 1 H), 8.28–6.22 (m, 11 H), 2.25 (s, 3 H) ppm.
HRMS (ESI): calcd. for C16H15NNaO [M + Na]+ 260.1051; found
260.1053.
NMR)]. IR (KBr): ν = 3326, 3056, 1659, 1628, 1600, 1531, 1508,
˜
1442, 1338, 1234, 1176, 970 cm–1. Data for 2oA: 1H NMR
(400 MHz, [D6]DMSO): δ = 10.18 (s, 1 H), 7.74–6.76 (m, 11
H) ppm. Data for 2oB: 1H NMR (400 MHz, [D6]DMSO): δ =
10.26 (s, 1 H), 7.74–6.76 (m, 11 H) ppm. 19F NMR (376 MHz, [D6]
DMSO):
δ = –111.0, –119.1 ppm. HRMS (ESI): calcd. for
C15H12FNNaO [M + Na]+ 264.0801; found 264.0800.
(E)-N-Phenyl-3-(p-tolyl)acrylamide (2jA)[10c] and (E)-N-(p-Tolyl)
cinnamamide (2jB):[10c] White solid [78.3 mg, 66% yield; 2jA/2jB,
(E)-3-(4-Nitrophenyl)-N-phenylacrylamide (2pA)[42] and (E)-N-(4-
1
Nitrophenyl)cinnamamide (2pB):[42] Yellow solid [112.7 mg, 84%
27:73 (determined by H NMR)]. IR (KBr): ν = 3285, 3033, 1656,
˜
1625, 1598, 1528, 1498, 1442, 1335, 1247, 1181, 975 cm–1. Data for
2jA: 1H NMR (400 MHz, [D6]DMSO): δ = 10.12 (s, 1 H), 7.71–
6.77 (m, 11 H), 2.26 (s, 1 H) ppm. Data for 2jB: 1H NMR
(400 MHz, [D6]DMSO): δ = 10.16 (s, 1 H), 7.71–6.77 (m, 11 H),
2.33 (s, 1 H) ppm. HRMS (ESI): calcd. for C16H16NO [M + H]+
238.1232; found 238.1230.
yield; 2pA/2pB, 75:25 (determined by 1H NMR)]. IR (KBr): ν =
˜
3365, 1693, 1630, 1597, 1542, 1500, 1448, 1327, 1298, 1255, 1160,
1
1109, 992, 977 cm–1 cm–1. Data for 2pA: H NMR (400 MHz, [D6]
DMSO): δ = 10.63 (s, 1 H), 8.28–6.93 (m, 10 H), 6.86 (d, J = 16 Hz,
1 H) ppm. Data for 2pB: 1H NMR (400 MHz, [D6]DMSO): δ =
10.30 (s, 1 H), 8.28–6.93 (m, 10 H), 6.24 (d, J = 16 Hz, 1 H) ppm.
HRMS (ESI): calcd. for C15H12N2NaO3 [M + Na]+ 291.0746;
found 291.0748.
(E)-3-(2-Chlorophenyl)-N-phenylacrylamide (2kA)[10c] and (E)-N-(2-
Chlorophenyl)cinnamamide (2kB):[40] White solid [117.2 mg, 91%
yield; 2kA/2kB, 50:50 (determined by 1H NMR)]. IR (KBr): ν =
(E)-3-(4-Cyanophenyl)-N-phenylacrylamide (2qA) and (E)-N-(4-Cy-
anophenyl)cinnamamide (2qB): White solid [55.9 mg, 45% yield;
˜
3297, 3061, 1663, 1626, 1597, 1527, 1473, 1440, 1340, 1241, 1178,
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50010
/KAP1
Date: 06-03-15 12:48:07
Pages: 13
Azides and Amides from Allylic and Benzylic Alcohols
1
2qA/2qB, 88:12 (determined by 1H NMR)]. IR (KBr): ν = 3349,
IR (neat): ν = 2099 cm–1. H NMR (400 MHz, CDCl ): δ = 7.37–
˜
˜
3
3058, 2227, 1672, 1630, 1594, 1527, 1509, 1448, 1340, 1254, 1174,
7.28 (m, 8 H), 6.65 (d, J = 16 Hz, 1 H), 6.20 (dd, J = 16, 7.2 Hz,
976 cm–1. Data for 2qA: 1H NMR (400 MHz, [D6]DMSO): δ =
1 H), 5.18 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
1
10.63 (s, 1 H), 7.89–6.20 (m, 11 H) ppm. Data for 2qB: H NMR δ = 136.8, 134.2, 134.1, 134.0, 132.0, 129.0, 128.8, 128.4, 127.9,
(400 MHz, [D6]DMSO): δ = 10.30 (s, 1 H), 7.89–6.20 (m, 11 127.0, 66.4 ppm. MS: m/z = 303. HRMS: calcd. for C15H11Cl2 [M –
H) ppm. HRMS (ESI): calcd. for C16H12N2NaO [M + Na]+ N3]+ 261.0238; found 261.0235.
271.0847; found 271.0853.
(E)-4,4Ј-(3-Azidoprop-1-ene-1,3-diyl)bis(fluorobenzene) (4e): Color-
(E)-3-(Naphthalen-1-yl)-N-phenylacrylamide (2rA)[43a] and (E)-N-
less liquid (113.9 mg, 84% yield); Rf = 0.6 (10% EtOAc/hexane).
(Naphthalen-1-yl)cinnamamide (2rB):[43b] White solid [99.8 mg,
1
IR (neat): ν = 2100 cm–1. H NMR (400 MHz, CDCl ): δ = 7.39–
˜
3
1
73% yield; 2rA/2rB, 50:50 (determined by H NMR)]. IR (KBr): ν
˜
7.32 (m, 4 H), 7.10–7.00 (m, 4 H), 6.66 (d, J = 16 Hz, 1 H), 6.17
(dd, J = 16, 7.2 Hz, 1 H), 5.18 (d, J = 7.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 162.7 (d, J = 246 Hz), 162.5 (d, J =
246 Hz), 134.3, 131.9, 128.6 (d, J = 45 Hz), 128.5 (d, J = 45 Hz),
126.4, 115.8 (d, J = 11 Hz), 115.6 (d, J = 11 Hz), 66.4 ppm. 19F
NMR (376 MHz, CDCl3): δ = –113.1, –113.6 ppm. MS: m/z = 229
[M – N3]+. HRMS: calcd. for C15H12F2N [M – N2 + H]+ 244.0938;
found 244.0939.
= 3285, 3061, 1654, 1621, 1598, 1527, 1500, 1443, 1349, 1248, 1189,
971 cm–1. Data for 2rA: 1H NMR (400 MHz, [D6]DMSO): δ =
1
10.16 (s, 1 H), 8.35–6.91 (m, 14 H) ppm. Data for 2rB: H NMR
(400 MHz, [D6]DMSO): δ = 10.31 (s, 1 H), 8.35–6.91 (m, 14
H) ppm. HRMS (ESI): calcd. for C19H15NNaO [M + Na]+
296.1051; found 296.1049.
(E)-3-(Naphthalen-2-yl)-N-phenylacrylamide (2sA) and (E)-N-
(Naphthalen-2-yl)cinnamamide (2sB):[44] White solid [123.0 mg,
(E)-4,4Ј-(3-Azidoprop-1-ene-1,3-diyl)bis(methylbenzene) (4f): Color-
1
90% yield; 2sA/2sB, 27:73 (determined by H NMR)]. IR (KBr): ν
˜
less liquid (111.9 mg, 85% yield); Rf = 0.8 (10% EtOAc/hexane).
= 3455, 3057, 1627, 1525, 1438, 1328, 1254, 1169, 971 cm–1. Data
for 2sA: 1H NMR (400 MHz, [D6]DMSO): δ = 10.43 (s, 1 H), 8.44
(s, 1 H), 7.99–7.06 (m, 12 H), 6.92 (d, J = 15.6 Hz) ppm. Data for
1
IR (neat): ν = 2098 cm–1. H NMR (400 MHz, CDCl ): δ = 7.30–
˜
3
7.11 (m, 8 H), 6.66 (d, J = 15.6 Hz, 1 H), 6.23 (dd, J = 15.6, 7.2 Hz,
1 H), 5.15 (d, J = 7.2 Hz, 1 H), 2.35 (s, 3 H), 2.33 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 138.1, 138.0, 135.6, 133.2, 132.6,
129.4, 129.3, 127.0, 126.6, 126.0, 67.1, 21.2, 21.1 ppm. MS: m/z =
221 [M – N3]+. HRMS: calcd. for C17H17 [M – N3]+ 221.1330;
found 221.1328.
1
2sB: H NMR (400 MHz, [D6]DMSO): δ = 10.26 (s, 1 H), 8.14 (s,
1 H), 7.99–7.06 (m, 12 H), 6.98 (d, J = 16 Hz, 1 H) ppm. HRMS
(ESI): calcd. for C19H15NNaO [M + Na]+ 296.1051; found
296.1053.
4-Methoxy-N-(4-methoxyphenyl)benzamide (2t):[30] White solid
(100.3 mg, 78% yield); Rf = 0.3 (25% EtOAc/hexane), m.p. 200–
(E)-2,2Ј-(3-Azidoprop-1-ene-1,3-diyl)bis(bromobenzene) (4g): Color-
less liquid (176.9 mg, 90% yield); Rf = 0.7 (10% EtOAc/hexane).
202 °C; ref.[45] m.p. 201–202 °C. IR (KBr): ν = 3332, 2954, 1644,
˜
1
IR (neat): ν = 2101 cm–1. H NMR (400 MHz, CDCl ): δ = 7.60–
˜
1607, 1515, 1414, 1301, 1246, 1230, 1177, 1030, 823, 763, 666 cm–1.
1H NMR (400 MHz, [D6]DMSO): δ = 9.97 (s, 1 H), 7.95 (d, J =
8 Hz, 2 H), 7.66 (d, J = 8 Hz, 2 H), 7.05 (d, J = 8 Hz, 2 H), 6.91
(d, J = 8 Hz, 2 H), 3.83 (s, 3 H), 3.74 (s, 3 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 164.5, 161.7, 155.4, 132.4, 129.4,
127.1, 122.0, 113.7, 113.5, 55.4, 55.1 ppm. HRMS (ESI): calcd. for
C15H15NNaO3 [M + Na]+ 280.0950; found 280.0949.
3
7.46 (m, 4 H), 7.37 (t, J = 7.6 Hz, 1 H), 7.26–7.10 (m, 4 H), 6.11
(dd, J = 15.6, 6.8 Hz, 1 H), 5.73 (d, J = 6.8 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 137.5, 136.0, 133.1, 133.0, 132.4,
129.7, 129.4, 128.6, 128.4, 128.0, 127.5, 127.3, 123.9, 123.3,
65.5 ppm. MS: m/z = 351 [M – N3]+. HRMS and elemental analysis
of this compound was unsuccessful. We believe that this is a result
of the instability of this compound under the employed conditions
for analysis.
(E)-1-(3-Azidoprop-1-en-1-yl)-4-nitrobenzene
(4a):[46]
Yellow
gummy liquid (80.7 mg, 79% yield); Rf = 0.8 (10% EtOAc/hexane).
(E)-(3-Azidobut-1-en-1-yl)benzene
(4h):[36f]
Colorless
liquid
IR (neat): ν = 2104 cm–1. H NMR (400 MHz, CDCl ): δ = 8.20
1
˜
3
(68.4 mg, 79% yield); R = 0.7 (10% EtOAc/hexane). IR (neat): ν
˜
f
(d, J = 8.8 Hz, 2 H), 7.54 (d, J = 8.8 Hz, 2 H), 6.73 (d, J = 16 Hz,
1 H), 6.41 (dt, J = 16, 6 Hz, 1 H), 4.03 (d, J = 6 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 147.3, 142.4, 131.7, 127.5, 127.2,
124.0, 52.5 ppm. HRMS (ESI): calcd. for C9H8N4O2 [M]+
204.0647; found 204.0641.
= 2098 cm–1. H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8 Hz,
1
2 H), 7.33 (t, J = 8 Hz, 2 H), 7.26 (t, J = 8 Hz, 1 H), 6.60 (d, J =
16 Hz, 1 H), 6.14 (dd, J = 16, 8 Hz, 1 H), 4.20–4.13 (m, 1 H), 1.37
(d, J = 8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.0,
132.1, 128.6, 128.3, 128.0, 126.6, 59.6, 20.2 ppm. MS: m/z = 131
[M – N3]+.
(E)-1-(3-Azidoprop-1-en-1-yl)-4-(trifluoromethyl)benzene
(4b):[47]
Colorless liquid (92.0 mg, 81% yield); Rf = 0.8 (10% EtOAc/hex-
ane). IR (neat): ν = 2103 cm–1. H NMR (400 MHz, CDCl ): δ =
1
˜
(E)-1-(3-Azidobut-1-en-1-yl)-4-methoxybenzene (4i):[49] Colorless li-
3
7.59 (d, J = 8 Hz, 2 H), 7.49 (d, J = 8 Hz, 2 H), 6.68 (d, J = 16 Hz,
1 H), 6.33 (dt, J = 16, 6.4 Hz, 1 H), 3.99 (d, J = 6.4 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 139.4, 132.7, 129.9 (q, J =
33 Hz), 126.8, 125.6 (q, J = 4 Hz), 125.2, 124.0 (q, J = 270 Hz),
52.7 ppm. 19F NMR (376 MHz, CDCl3): δ = –62.6 ppm. MS: m/z
= 228 [M + H]+.
quid (84.3 mg, 83% yield); Rf = 0.6 (10% EtOAc/hexane). IR
1
(neat): ν = 2100 cm–1. H NMR (400 MHz, CDCl ): δ = 7.33 (d, J
˜
3
= 8.4 Hz, 2 H), 6.87 (d, J = 8.8 Hz, 2 H), 6.54 (d, J = 15.6 Hz, 1
H), 6.01 (dd, J = 15.6, 7.6 Hz, 1 H), 4.18–4.12 (m, 1 H), 3.81 (s, 3
H), 1.36 (d, J = 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 159.5, 131.7, 128.7, 127.8, 126.0, 114.0, 59.9, 55.3, 20.3 ppm.
MS: m/z = 203 [M]+.
(E)-1-(3-Azidoprop-1-en-1-yl)-4-chlorobenzene (4c):[48] Colorless li-
quid (69.7 mg, 72% yield); Rf = 0.8 (10% EtOAc/hexane). IR
(E)-1-(3-Azido-3-phenylprop-1-en-1-yl)-4-fluorobenzene (4jA) and
(E)-1-(1-Azido-3-phenylallyl)-4-fluorobenzene (4jAЈ): Colorless li-
quid [107.6 mg, 85% yield by starting from 1o; 103.8 mg, 82% yield
by starting from 1oЈ; 4jA/4jAЈ, approximately 50:50 (determined by
1
(neat): ν = 2098 cm–1. H NMR (400 MHz, CDCl ): δ = 7.34–7.28
˜
3
(m, 4 H), 6.60 (d, J = 15.6 Hz, 1 H), 6.21 (dd, J = 16, 6.4 Hz, 1
H), 3.94 (d, J = 6.4 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 134.5, 133.8, 133.1, 128.8, 127.8, 123.1, 52.8 ppm. HRMS:
calcd. for C9H8Cl [M – N3]+ 151.0315; found 151.0313.
1H and 19F NMR)]; R = 0.7 (10% EtOAc/hexane). IR (neat): ν =
˜
f
2099 cm–1. Data for mixture of 4jA and 4jAЈ: 1H NMR (400 MHz,
CDCl3): δ = 7.41–7.24 (m, 7 H), 7.09–6.99 (m, 2 H), 6.72–6.65 (m,
1 H), 6.28–6.18 (m, 1 H), 5.18 (d, J = 8 Hz, 1 H) ppm. 19F NMR
(E)-4,4Ј-(3-Azidoprop-1-ene-1,3-diyl)bis(chlorobenzene) (4d): Color-
less liquid (136.9 mg, 90% yield); Rf = 0.8 (10% EtOAc/hexane).
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O50010
/KAP1
Date: 06-03-15 12:48:08
Pages: 13
B. V. Rokade, K. Gadde, K. R. Prabhu
1-(1-Azidoethyl)-4-(benzyloxy)benzene Gray liquid
(4p):[34]
FULL PAPER
(376 MHz, CDCl3): δ = –113.4, –113.7 ppm. HRMS (ESI): calcd.
for C15H12F [M – N3]+ 211.0923; found 211.0927.
(111.5 mg, 88% yield); R = 0.6 (10% EtOAc/hexane). IR (neat): ν
˜
f
= 2102 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.44–7.37 (m, 4 H),
7.33 (d, J = 8 Hz, 1 H), 7.25 (d, J = 8 Hz, 2 H), 6.97 (d, J = 8 Hz,
2 H), 5.06 (s, 2 H), 4.56 (q, J = 8 Hz, 1 H), 1.50 (d, J = 8 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.6, 136.8, 133.1,
128.6, 128.0, 127.7, 127.5, 115.0, 70.0, 60.6, 21.4 ppm. MS: m/z =
211 [M – N3]+.
(E)-1-(3-Azido-3-phenylprop-1-en-1-yl)-2-methylbenzene (4jB) and
(E)-1-(1-Azido-3-phenylallyl)-2-methylbenzene (4jBЈ): Colorless li-
quid [108.3 mg, 87% yield; 4jB/4jBЈ, approximately 60:40 (deter-
1
mined by H NMR)]; R = 0.8 (10% EtOAc/hexane). IR (neat): ν
˜
f
= 2096 cm–1. H NMR (400 MHz, CDCl3, major isomer 4jB): δ =
1
7.42–7.16 (m, 9 H), 6.93 (d, J = 15.6 Hz, 1 H), 6.16 (dd, J =
15.6 Hz, 7.2 Hz, 1 H), 5.22 (d, J = 7.6 Hz, 1 H), 2.37 (s, 3 H) ppm.
[4-(1-Azidoethyl)phenoxy](tert-butyl)dimethylsilane (4q): Colorless
1H NMR (400 MHz, CDCl3, minor isomer 4jBЈ): δ = 7.42–7.16 (m, liquid (112.4 mg, 81% yield); Rf = 0.8 (10% EtOAc/hexane). IR
1
9 H), 6.67 (d, J = 15.6 Hz, 1 H), 6.26 (dd, J = 16.0 Hz, 6.8 Hz, 1 (neat): ν = 2104 cm–1. H NMR (400 MHz, CDCl ): δ = 7.18 (d, J
˜
3
H), 5.39 (d, J = 6.8 Hz, 1 H), 2.38 (s, 3 H) ppm. MS: m/z = 221
= 8 Hz, 2 H), 6.83 (d, J = 8 Hz, 2 H), 4.55 (q, J = 8 Hz, 1 H), 1.50
(d, J = 8 Hz, 3 H), 0.98 (s, 9 H), 0.20 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 155.5, 133.4, 127.6, 120.2, 60.7, 25.6, 21.4,
18.2, –4.4 ppm. MS: m/z = 235 [M – N3]+. HRMS: calcd. for
C14H23OSi [M – N3]+ 235.1518; found 235.1519.
[M – N2]+.
(E)-1-(3-Azido-3-phenylprop-1-en-1-yl)-4-nitrobenzene (4jC) and
(E)-1-(1-Azido-3-phenylallyl)-4-nitrobenzene (4jCЈ): Pale yellow li-
quid [114.8 mg, 82% yield; 4jC/4jCЈ, approximately 71:29 (deter-
1
mined by H NMR)]; R = 0.6 (10% EtOAc/hexane). IR (neat): ν
1-(1-Azido-2-bromoethyl)-4-methoxybenzene (4r):[53] Colorless li-
˜
f
= 2101 cm–1. H NMR (400 MHz, CDCl3, major isomer 4jC): δ =
quid (67.9 mg, 53% yield); Rf = 0.8 (10% EtOAc/hexane). IR
1
1
8.18 (d, J = 8.4 Hz, 2 H), 7.57–6.76 (m, 8 H), 6.46 (dd, J = 16.0 Hz,
(neat): ν = 2099 cm–1. H NMR (400 MHz, CDCl ): δ = 7.25 (d, J
˜
3
1
6.8 Hz, 1 H), 5.26 (d, J = 6.8 Hz, 1 H) ppm. H NMR (400 MHz,
= 8.4 Hz, 2 H), 6.93 (d, J = 8.4 Hz, 2 H), 4.72 (t, J = 6.8 Hz, 1 H),
CDCl3, minor isomer 4jCЈ): δ = 8.23 (d, J = 8.8 Hz, 2 H), 7.57–
3.82 (s, 3 H), 3.54–3.52 (m, 2 H) ppm. 13C NMR (100 MHz,
6.76 (m, 8 H), 6.21 (dd, J = 16.0, 8.0 Hz, 1 H), 5.32 (d, J = 8.0 Hz, CDCl3): δ = 161.1, 129.0, 128.1, 114.4, 66.4, 55.3, 35.1 ppm. MS:
1 H) ppm. MS: m/z = 238 [M – N3]+.
m/z = 214 [M – N3]+. HRMS: calcd. for C9H10BrO [M – N3]+
212.9915; found 212.9910.
(1-Azido-3-chloropropyl)benzene (4k):[35] Colorless liquid (73.4 mg,
75% yield); Rf = 0.8 (10% EtOAc/hexane). IR (neat): ν =
2-[2-Azido-2-(4-methoxyphenyl)ethoxy]naphthalene (4s): Colorless
˜
1
2099 cm–1. H NMR (400 MHz, CDCl3): δ = 7.43–7.32 (m, 5 H), liquid (118.2 mg, 74% yield); Rf = 0.8 (10% EtOAc/hexane). IR
1
4.77–4.74 (m, 1 H), 3.68–3.62 (m, 1 H), 3.51–3.46 (m, 1 H), 2.28–
(neat): ν = 2102 cm–1. H NMR (400 MHz, CDCl ): δ = 7.77–7.67
˜
3
2.20 (m, 1 H), 2.13–2.08 (m, 1 H) ppm. 13C NMR (100 MHz, (m, 3 H), 7.42 (t, J = 7.2 Hz, 1 H), 7.34–7.32 (m, 3 H), 7.19–7.11
CDCl3): δ = 138.5, 129.0, 128.6, 126.9, 63.0, 41.3, 38.9 ppm. MS:
(m, 1 H), 7.10 (s, 1 H), 6.94 (d, J = 8.4 Hz, 2 H), 4.95 (t, J = 6 Hz,
1 H), 4.24 (d, J = 6.4 Hz, 2 H), 3.82 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.9, 156.1, 134.3, 129.6, 128.4, 128.1,
127.6, 126.7, 126.4, 123.9, 118.7, 114.3, 106.9, 71.7, 64.1, 55.3 ppm.
MS (m/z): 277 [M – N3]+. HRMS: calcd. for C19H17N3NaO2 [M +
Na]+ 342.1218; found 342.1217.
m/z = 153 [M – N3]+.
1-(3-Azido-3-phenylpropoxy)naphthalene (4l): Colorless liquid
(115.3 mg, 76% yield); R = 0.6 (10% EtOAc/hexane). IR (neat): ν
˜
f
= 2097 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J = 7.2 Hz,
1 H), 7.74–7.72 (m, 1 H), 7.49–7.12 (m, 9 H), 6.93 (d, J = 8.4 Hz,
1 H), 4.36–4.27 (m, 3 H), 2.46–2.39 (m, 1 H), 2.16–2.10 (m, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 150.3, 145.9, 133.4,
128.7, 128.4, 128.3, 127.4, 126.4, 126.0, 125.3, 125.2, 121.7, 119.6,
2-(1-Azidoethyl)thiophene (4t): Colorless liquid (55.9 mg, 73%
yield); R = 0.7 (10% EtOAc/hexane). IR (neat): ν = 2104 cm–1. 1H
˜
f
NMR (400 MHz, CDCl3): δ = 7.29–7.28 (m, 1 H), 7.03–6.98 (m, 2
117.6, 63.8, 40.9, 31.8 ppm. HRMS (ESI): calcd. for C19H17N3NaO H), 4.82 (q, J = 8 Hz, 1 H), 1.62 (d, J = 8 Hz, 3 H) ppm. 13C NMR
[M + Na]+ 326.1269; found 326.1263.
(100 MHz, CDCl3): δ = 143.8, 126.7, 125.3, 124.9, 56.4, 21.7 ppm.
MS: m/z = 111 [M – N3]+. HRMS: calcd. for C6H7S [M – N3]+
111.0268; found 111.0265.
(1-Azidobut-3-enyl)benzene (4u):[54] Colorless liquid (65.0 mg, 75%
1-Azido-1,2,3,4-tetrahydronaphthalene (4m):[50] Colorless liquid
(79.7 mg, 92% yield); R = 0.8 (10% EtOAc/hexane). IR (neat): ν
˜
f
= 2095 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.31–7.12 (m, 4 H),
4.57–4.56 (m, 1 H), 2.88–2.70 (m, 2 H), 2.02–1.97 (m, 3 H), 1.82–
yield); Rf = 0.9 (10% EtOAc/hexane). IR (neat): ν = 2096,
˜
1
1.56 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 137.3, 133.7, 1246 cm–1. H NMR (400 MHz, CDCl3): δ = 7.39–7.29 (m, 5 H),
129.4, 129.1, 128.1, 126.1, 59.4, 29.1, 28.7, 18.9 ppm. MS: m/z =
5.79–5.69 (m, 1 H), 5.15–5.08 (m, 2 H), 4.49 (t, J = 7.2 Hz, 1 H),
2.63–2.48 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.2,
133.7, 128.7, 128.3, 126.9, 118.2, 65.8, 40.5 ppm. MS: m/z = 131
[M – N3]+. HRMS (ESI): calcd. for C10H11 [M – N3]+ 131.0861;
found 131.0867.
131 [M – N3]+.
4-(1-Azidoethyl)-1,1Ј-biphenyl (4n):[51] Colorless liquid (96.0 mg,
86% yield); Rf = 0.8 (10% EtOAc/hexane). IR (neat): ν =
˜
1
2099 cm–1. H NMR (400 MHz, CDCl3): δ = 7.61–7.57 (m, 4 H),
7.46–7.33 (m, 5 H), 4.65 (q, J = 8 Hz, 1 H), 1.56 (d, J = 8 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 141.0, 140.5, 139.8,
128.8, 127.5, 127.4, 127.1, 126.8, 60.8, 21.5 ppm. MS: m/z = 223.
HRMS (ESI): calcd. for C14H13 [M – N3]+ 181.1017; found
181.1015.
(Azidomethylene)dibenzene (4v):[34] Colorless liquid (80.6 mg, 77%
yield); R = 0.8 (10% EtOAc/hexane). IR (neat): ν = 2097 cm–1. 1H
˜
f
NMR (400 MHz, CDCl3): δ = 7.37–7.23 (m, 10 H), 5.70 (s, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.5, 128.7, 128.0,
127.4, 68.5 ppm. MS: m/z = 167 [M – N3]+.
1-(1-Azidoethyl)-4-methoxybenzene (4o):[52] Colorless liquid
4,4Ј-(Azidomethylene)bis(methoxybenzene) (4w):[55] Colorless liquid
(74.4 mg, 84% yield); R = 0.8 (10% EtOAc/hexane). IR (neat): ν (113.1 mg, 84% yield); R = 0.5 (10% EtOAc/hexane). IR (neat): ν
˜
˜
f
f
= 2103 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.8 Hz,
= 2096 cm–1. H NMR (400 MHz, CDCl3): δ = 7.21 (d, J = 8 Hz,
1
2 H), 6.90 (d, J = 8.4 Hz, 2 H), 4.56 (q, J = 6.8 Hz, 1 H), 3.81 (s,
4 H), 6.87 (d, J = 8 Hz, 4 H), 5.63 (s, 1 H), 3.78 (s, 6 H) ppm.
3 H), 1.50 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): 13C NMR (100 MHz, CDCl3): δ = 159.2, 132.0, 128.5, 113.9, 67.6,
δ = 159.4, 132.8, 127.6, 114.0, 60.6, 55.2, 21.4 ppm. MS: m/z = 177
55.2 ppm. HRMS (ESI): calcd. for C15H16NO2 [M – N2 + H]+
242.1181; found 242.1180.
[M]+.
10
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50010
/KAP1
Date: 06-03-15 12:48:08
Pages: 13
Azides and Amides from Allylic and Benzylic Alcohols
[2]
[3]
[4]
[5]
[6]
A. M. Martinez, N. Rodriguez, R. G. Arrayas, J. C. Carretero,
Chem. Commun. 2014, 50, 2801–2803.
T. Morofuji, A. Shimizu, J. Yoshida, J. Am. Chem. Soc. 2014,
136, 4496–4499.
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13, 2818–2821.
Y. Yamamoto, H. Nasu, K. Tomioka, Tetrahedron 2013, 69,
3836–3840.
B. Gutmann, D. Obermayer, B. Reichart, B. Prekodravac, M.
Irfan, J. M. Kremsner, C. O. Kappe, Chem. Eur. J. 2010, 16,
12182–12194.
B. Li, J. Ma, N. Wang, H. Feng, S. Xu, B. Wang, Org. Lett.
2012, 14, 736–739.
T.-X. Metro, J. Bonnamour, T. Reidon, J. Sarpoulet, J. Marti-
nez, F. Lamaty, Chem. Commun. 2012, 48, 11781–11783.
D. S. MacMillan, J. Murray, H. F. Sneddon, C. Jamieson,
A. J. B. Watson, Green Chem. 2013, 15, 596–600.
a) Y. Furuya, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc.
2005, 127, 11240–11241; b) J. Qiu, R. Zhang, Org. Biomol.
Chem. 2013, 11, 6008–6012; c) J. Qiu, R. Zhang, Org. Biomol.
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15, 2680–2684.
(3-Azidopent-1-yn-1-yl)benzene (4x): Colorless liquid (48.2 mg,
52% yield); Rf = 0.8 (10% EtOAc/hexane). IR (neat): ν =
˜
1
2098 cm–1. H NMR (400 MHz, CDCl3): δ = 7.48–7.46 (m, 2 H),
7.33–7.32 (m, 3 H), 4.26 (t, J = 8 Hz, 1 H), 1.85–1.78 (m, 2 H),
1.09 (t, J = 8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
131.9, 128.7, 128.3, 122.1, 87.1, 84.4, 54.9, 28.8, 10.1 ppm. MS: m/z
= 185. HRMS (ESI): calcd. for C11H11 [M – N3]+ 143.0861; found
143.0861.
(E)-Methyl 2-(Azidomethyl)-3-phenylacrylate (6):[56] Colorless li-
quid (82.5 mg, 76% yield); Rf = 0.5 (10% EtOAc/hexane). IR
[7]
1
(neat): ν = 2109 cm–1. H NMR (400 MHz, CDCl ): δ = 7.98 (s, 1
˜
3
H), 7.44–7.39 (m, 5 H), 4.19 (s, 2 H), 3.89 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.5, 144.5, 134.1, 129.6, 129.5, 128.7,
126.6, 52.4, 47.0 ppm. HRMS (ESI): calcd. for C11H11N3NaO2 [M
+ Na]+ 240.0749; found 240.0747.
[8]
[9]
[10]
(E)-[4-(3-Azidoprop-1-en-1-yl)phenyl]methanol (8): White solid
(68.1 mg, 72% yield); Rf = 0.2 (20% EtOAc/hexane), m.p. 38–
1
40 °C. IR (neat): ν = 2101 cm–1. H NMR (400 MHz, CDCl ): δ =
˜
3
7.40–7.32 (m, 4 H), 6.64 (d, J = 16 Hz, 1 H), 6.27–6.20 (m, 1 H),
4.67 (s, 2 H), 3.94 (d, J = 6.8 Hz, 2 H), 1.87 (br. s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 140.8, 135.3, 134.1, 127.2, 126.8,
122.4, 64.9, 53.0 ppm. MS: m/z = 189. HRMS (ESI): calcd. for
C10H11O [M – N3]+ 147.0810; found 147.0807.
[11]
[12]
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(E)-(3-Azidoprop-1-en-1-yl)benzene (11):[57] Colorless liquid
(76.4 mg, 96% yield by starting from 9; 57.3 mg, 72% yield by
starting from 10; 73.2 mg, 92% yield by starting from 12); Rf = 0.8
(10% EtOAc/hexane). IR (neat):
ν =
˜
2100 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 7.41–7.25 (m, 5 H), 6.65 (d, J = 16 Hz, 1
H), 6.26–6.22 (m, 1 H), 3.94 (d, J = 8 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 136.0, 134.5, 128.6, 128.2, 126.6, 122.4,
53.0 ppm. MS: m/z = 159 [M]+.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
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1-(1-Azidopropyl)-4-methoxybenzene (14):[58] Colorless liquid
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(83.2 mg, 87% yield); R = 0.8 (10% EtOAc/hexane). IR (neat): ν
˜
f
= 2095 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.22 (d, J = 8.8 Hz,
2 H), 6.90 (d, J = 8.4 Hz, 2 H), 4.29 (t, J = 7.2 Hz, 1 H), 3.81 (s,
3 H), 1.90–1.70 (m, 2 H), 0.91 (t, J = 7.6 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.4, 131.6, 128.1, 114.0, 67.4, 55.2, 29.1,
10.8 ppm. MS: m/z = 191 [M]+.
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1-Cinnamyl-4-phenyl-1H-1,2,3-triazole (15):[59] Yellow solid
(54.8 mg, 42% yield); Rf = 0.1 (10% EtOAc/hexane), m.p. 133–
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˜
1
1074, 970 cm–1. H NMR (400 MHz, CDCl3): δ = 7.84–7.80 (m, 3
Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu, X. Wan, Angew. Chem.
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3289.
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5374.
H), 7.43–7.38 (m, 4 H), 7.36–7.25 (m, 4 H), 6.69 (d, J = 15.6 Hz,
1 H), 6.37 (dt, J = 16, 6.8 Hz, 1 H), 5.16 (dd, J = 6.8, 1.2 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.1, 135.4, 135.3,
130.6, 128.8, 128.7, 128.5, 128.1, 126.7, 125.7, 121.9, 119.3,
52.4 ppm. HRMS (ESI): calcd. for C17H15N3Na [M + Na]+
284.1164; found 284.1165.
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Acknowledgments
The authors thank the Indian Institute of Science (IISc), the Coun-
cil of Scientific and Industrial Research (CSIR), New Delhi
[01(2415)/10/EMR-II], and RL Fine Chem for their financial sup-
port. Dr. A. R. Ramesha (RL Fine Chem) is thanked for the useful
discussions. B. R. thanks the CSIR for a fellowship.
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/KAP1
Date: 06-03-15 12:48:08
Pages: 13
B. V. Rokade, K. Gadde, K. R. Prabhu
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Received: January 6, 2015
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50010
/KAP1
Date: 06-03-15 12:48:08
Pages: 13
Azides and Amides from Allylic and Benzylic Alcohols
Synthetic Methods
B. V. Rokade, K. Gadde,
K. R. Prabhu* ................................. 1–13
Copper-Catalyzed Direct Transformation
of Secondary Allylic and Benzylic Alcohols
into Azides and Amides: An Efficient Util-
ity of Azide as a Nitrogen Source
A mild and convenient method for the syn-
thesis of amides has been explored by using
secondary alcohols, Cu(ClO4)2·6H2O as a
catalyst, and trimethylsilyl azide (TMSN3)
as a nitrogen source in the presence of
2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ) at ambient temperature. This
method has also been adapted to the
preparation of azides directly from their
corresponding alcohols.
Keywords: Synthetic methods / Chemo-
selectivity / Alcohols / Azides / Amides /
Copper
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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13