Full Cleavage of C≡C Bond in Electron-Deficient Alkynes via Reaction with Ethylenediamine

Article abstract of DOI:10.1071/CH17026

Reaction of 1,2-diaminioethane (ethylenediamine) with electron-deficient alkynes leads to full scission of the C≡C bond even in the absence of a keto group directly attached to the alkyne. This process involves oxidation of one of the alkyne carbons into C2 of a 2-R-4,5-dihydroimidazole with the concomitant reduction of the other carbon to a methyl group. The sequence of Sonogashira coupling with the ethylenediamine-mediated fragmentation described in this work can be used for selective formal substitution of halogen in aryl halides by a methyl group or a 4,5-dihydroimidazol-2-yl moiety.

Full text of DOI:10.1071/CH17026

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH17026
Full Cleavage of CꢀC Bond in Electron-Deficient Alkynes
via Reaction with Ethylenediamine
A D
,
A
B
Sergei F. Vasilevsky,
Maria P. Davydova, Victor I. Mamatyuk,
C
C
A
Nikolay Tsvetkov, Audrey Hughes, Denis S. Baranov,
C D
,
and Igor V. Alabugin
A
Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the
Russian Academy of Science, 3 Institutskaya Street, Novosibirsk 630090, Russia.
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian
Academy of Science, Novosibirsk 630090, Russia.
B
C
Department of Chemistry and Biochemistry, Florida State University, Tallahassee,
FL 32306, USA.
D
Corresponding authors. Email: vasilev@kinetics.nsc.ru; alabugin@chem.fsu.edu
Reaction of 1,2-diaminioethane (ethylenediamine) with electron-deficient alkynes leads to full scission of the CꢀC bond
even in the absence of a keto group directly attached to the alkyne. This process involves oxidation of one of the alkyne
carbons into C2 of a 2-R-4,5-dihydroimidazole with the concomitant reduction of the other carbon to a methyl group. The
sequence of Sonogashira coupling with the ethylenediamine-mediated fragmentation described in this work can be used
for selective formal substitution of halogen in aryl halides by a methyl group or a 4,5-dihydroimidazol-2-yl moiety.
Manuscript received: 12 January 2017.
Manuscript accepted: 11 February 2017.
Published online: 9 March 2017.
from the related alkenes.[9] Subsequently, Cheng and cow-
orkers applied this reaction to the preparation of 4(3H)-quina-
zolinones.[10] The latter transformation expands the utility of
acceptor alkyne reactants as a one-carbon electrophilic build-
ing block in the preparation of 1,3-diaza-containing
heterocycles.
Computational analysis of that fragmentation cascade in
ketoalkynes revealed interesting mechanistic features
(Scheme 3).[8a] For example, whereas the intermolecular
Michael addition was fast, the intramolecular 5-exo-trig closure
of the second amino group at the alkene was slow and thermo-
dynamically unfavourable. The presence of the carbonyl group
at the alkyne was essential in partially alleviating this thermo-
dynamic penalty by avoiding charge separation at the transition
state (TS) where the developing negative charge at the carbonyl
could serve as an acceptor for the proton from the NH2 moiety.
Furthermore, the carbonyl group is important for the final C–C
scission step where, again, it plays a key part in the six-
membered TS that avoids charge separation and makes this step
concerted.
The final step of the fragmentation cascade corresponds to a
retro-Mannich reaction. It illustrates the inherent connection
between the chemistries of alkynes and carbonyl compounds.
Because alkynes have the same oxidation level as carbonyl
compounds, one can engineer new alkyne cascade transforma-
tions by unmasking the hidden ‘carbonyl nature’ of alkynes.[11]
However, when building bridges between alkynes and car-
bonyls, one has to remember that alkynes are generally less
electrophilic than carbonyls – an expected difference that stems
Introduction
Alkynes are indispensable building blocks for the preparation of
conjugated molecules and carbon-rich materials. The unique
combination of electronic and spatial features of the triple bond
renders the alkyne moiety a useful departure point in the design
of new chemical transformations.[1] The electrophilic reactivity
of alkynes can be amplified by the presence of electron accep-
tors conjugated with the triple bond. Such compounds readily
undergo addition reactions with nucleophiles, including a vari-
ety of cyclization reactions mediated by the formation of new
C–C and C–heteroatom bonds.[2]
Fragmentation reactions continue to play an important role in
the construction of new molecular targets.[3,4] In this context, the
fragmentations of carbon–carbon bonds often provide particu-
larly elegant and conceptually unique synthetic disconnections.
Such fragmentations can be mediated by metals,[5] or proceed in
a metal-free fashion (Scheme 1).[6,7] Furthermore, fragmenta-
tions can be further separated into oxidative or redox-neutral
processes. For the latter type, the transformation often proceeds
via internal disproportionation where one of the carbons at the
breaking bond is oxidized whereas the other one is reduced.
We described earlier the complete scission of the triple bond
of a-acetylenyl ketones induced by ethylenediamine with the
formation of the respective methyl aryl ketones and 2-R-
imidazolines (Scheme 2).[8] This reactivity pattern contrasts
drastically with reports of the (formally) single C(O)–alkyne
bond scission in reactions with other nucleophiles. Nenajdenko
and coworkers illustrated that this transformation is applicable
to strongly polarized CF3-substituted alkynes generated in situ
Journal compilation ꢀ CSIRO 2017
www.publish.csiro.au/journals/ajc

B
S. F. Vasilevsky et al.
Metal-free
Metal-catalyzed
Ar
Mo(CO)6
resorcinol
H
N
Ph
Ar
Ph
Ar
Ar
NH
O
R
RЈ
Ar
ϩ
Ph
O
O
H2N NH2
Mortreux,
Blanchard
redox-neutral
O
C
C
R
RЈ
N
H
O
Ag-catalyst
TMSN3, air
Vasilevsky, Alabugin
oxidative
R
H
R
N
Jiao
oxidative
R
OLi
R
R
O
O
Pd(OAc)2
ZnCl2, O2
ϩ
ϩ
R
RЈ
R
RЈ
OLi
OH
C
C
ORЉ
ORЉ
R
OLi
OLi
Jiang
oxidative
Shindo
redox-neutral
I
OH
R
Ph
R
O
ICl
R
Ru-catalyst
Pr
ϩ
ϩ
Ph
C
H
O
n-PrOH
I
C O
R
Liang
oxidative
Liu
redox-neutral
Scheme 1. Selected examples of alkyne fragmentations. The colour code illustrates the redox features of these processes (red, an
oxidized carbon; blue, a reduced carbon; grey, no change in the formal oxidation state).
C–C cleavage
Results and Discussion
O
In the first stage, we concentrated on 1- and 2-phenylethynyl-
9,10-anthraquinones (1a, b). In these vinylogs of a-ketoalkynes,
the carbonyl group is removed further away from the triple bond.
Variation of solvents, reagent ratios, and temperatures revealed
that the fragmentation proceeds most effectively in refluxing
pyridine with a 50-fold excess of the nucleophile (Scheme 4).
The fragmentation of 1-phenylethynyl-9,10-antraquinone
(1a) was complete after 3 h. Chromatographic purification of
the reaction products led to the isolation of the two alkyne
scission products – 1-methyl-9,10-anthraquinone (2a, 69 %) and
2-phenyl-4,5-dihydroimidazol (3a, 68 %) (Scheme 5).
In addition, we isolated the 6-endo-dig cyclization product
2-phenyl-7H-dibenzo[de,h]quinolin-7-one (4) in a yield of
12 %. The formation of the latter product can be described
analogously to the earlier published cyclizations of 1-pheny-
lethynyl-9,10-anthraquinones with N-polynucleophiles (hydra-
zine, guanidine, urea, thiourea), leading to 2-R-7H-dibenzo[de,
h]quinolin-7-ones (Scheme 6).[12] It is possible that anchimeric
assistance[13] (via a homoanomeric[14] interaction with the lone
pair of the remote nitrogen atom, as shown with the dashed
arrow) is involved in the C–N scission step.
H
KOH
ϩ
RCOOK
R
RЈ
RЈ
Vereshchagin
O
O
O
NHMe
OH
ϩ
HO
N
F3C
F3C
Me
Ar
Me
Ar
Vasilevsky,
Nenajdenko
C
C cleavage
H2N
Overall:
RЈ
R
O
:
NH2
H
NH
C
C
H
RϩЈ
N
Y
H
R
X
Reduced
O
Oxidized
Vasilevsky,
Alabugin, 2009
NH
N
H
ϩ
H
Y
Ar
F3C
H
In the next step, we investigated the reactivity of 2-pheny-
lethynyl-9,10-anthraquinone (1b), an isomeric substrate where
both carbonyl groups are located away from the alkyne but
conjugation is maintained via the p-system (Scheme 7).
Although the reaction occurs more slowly (5 h), it still leads to
full triple-bond scission with the formation of 2-methyl-9,10-
anthraquinone (2b, 94 %) and 2-phenylimidazoline (3a, 93 %)
(Scheme 4). Because the C=O and CꢀC functional groups are
not in the peri-arrangement, the 2-phenyl-7H-dibenzo[de,h]-
quinolin-7-one side product is not formed.
Nenajdenko,
2010
X
O
metal-free, redox-neutral
H2N
O
O
H2N
R
H
ϩ
N
H
H
O
N
R
Cheng, 2015
Scheme 2. Metal-free C–C fragmentations in ketoalkynes and related
molecules promoted by bifunctional nucleophiles.
Next, we explored the possibility of expanding the alkyne
fragmentation reactions to compounds with other functional
groups also positioned away from the alkyne moiety by focus-
sing on the family of nitro-substituted diaryl alkynes with
different positions of the acceptor NO2 group (Scheme 8).
The presence of a single para-nitro group in substrate 5a
renders it quite reactive. This compound undergoes triple-bond
from the inherently lower polarity of the hydrocarbon function-
ality. In the present work, we investigate the reactivity of a
broader selection of polarized alkynes towards ethylenedia-
mine. Our goal is to explore the limits of this remarkable
transformation by expanding it to systems where the above
assistance from the carbonyl group is unavailable.

Alkyne Fragmentations
C
H
H
H2N
H
N
H
O
N
R
O
O
ΔG‡ ϭ 23.2
:
NH2
NH
R
N
H
TS1: 5-exo-trig
cyclization coupled
to proton transfer
Y
X
ΔG ϭ ϩ14. 8
‡
H
H
O
N
O
N
TS2: fragmentation is assisted
by cyclic delocalization and
donation from the ‘exocyclic’
N lone pair
N
N
H
Y
X
ΔG‡ ϭ 21.8
Overall:
H
R
RЈ
O
N
NH
H
H
ϩ
N
NH
H
C
C
R
H
H
Y
X
RЈ
Oxidized
Reduced
ΔG ϭ Ϫ8.6
Energies in kcal molϪ1 at B3LYP/6-31ϩG(d,p) level with SCRF (THF)
Scheme 3. The sequence of steps in the alkyne fragmentation in the reaction of ketoalkynes and ethylenediamine
(1 kcal molꢁ1 ¼ 4.186 kJ molꢁ1).
Ph
Ph
O
O
N
NH2
Me
Ph
NH
H2N
N
ϩ
ϩ
pyridine, 115ЊC
O
O
O
3a
68, 93 %
1-Phenylethynyl-9,10-aq 1a
2-Phenylethynyl-9,10-aq 1b
1-Methyl-9,10-aq 2a
2-Methyl-9,10-aq 2b
69, 94 %
4 from 1a
12 %
Scheme 4. Fragmentation of phenylethynyl-9,10-anthraquinones 1a, b. aq ¼ anthraquinone.
Ph
NH
H2N
O
N
NH
Ph
H
O
O
O
Ph
NH2
H2N
1a
O
O
O
Me
OH CH2
Ph
NH
N
ϩ
3a
2a
O
O
Scheme 5. Possible mechanism of fragmentation of 1a.
scission in the reaction with 1,2-diaminoethane after 3 h, yield-
ing the expected fragmentation products, 1-methyl-4-nitroben-
zene (6a, 68 %) and 2-phenylimidazoline (3a, 61 %).
The introduction of two donor methyl groups into the nitro-
substituted aromatic ring led, as expected, to a slower reaction
(6 h). However, the nature of the products did not change and
both 1,2,4-trimethyl-5-nitrobenzene (6b) and imidazoline 3a
were formed in high yields (87 and 81 % respectively).
However, the fragmentation is not observed for substrates 5c
and 5d where the nitro group does not electronically communi-
cate with the alkyne. For the meta-nitro-substituted substrate 5c,
the starting material was recovered in 80 % yield after 40 h of
reflux. For compound 5d, the combined activating effects of the
nitro and alkyne groups activate the OMe moiety towards
nucleophilic substitution, with the formation of the substitution
product 8 (Scheme 8).

D
S. F. Vasilevsky et al.
H2N
Ph
Ph
Ph
N
O
N
O
O
O
HO
NH2
H2N
– NH2(CH2)2OH
4
1a
Scheme 6. Possible route of formation of 2-phenyl-7H-dibenzo[de,h]quinolin-7-one (4).
this fragmentation in the absence of pyridine solvent by simply
using 10 equiv. of neat ethylenediamine and found that 76 % of
the two fragmentation products were formed after 20 h at 1208C
in the expected 1 : 1 ratio.
The transformation of2-phenylethynylpyridine(7b) proceeds
in a drastically different manner. Even after 40 h of reflux in
pyridine, no fragmentation products were detected. According to
NMR analysis, reaction of ethylenediamine with the diaryl
alkyne 7b leads to the formation of 33% of the enamine 10
(Scheme 10) along with unidentified products. The enamine can
be hydrolyzed to give 1-phenyl-2-(pyridin-2-yl)ethanone (11),
which was identified as the 2,4-dinitrophenylhydrazone (see
experimental section).
Ph
H2N
O
O
O
O
NH2
Ph
HN
1b
H2N
O
O
Ph
ϪPyHϩ
:Py
H
N
Ph
HN
Ϫ
HN
N
O Ϫ
O
O
O
3a
Ϫ
PyHϩ
ϪPy
Me
ϩ
Computational Analysis
O
O
2b
We wanted to gain additional insights into the origin of the
observed trends in reactivity by calculating alkyne polarization
for the key diaryl alkynes discussed above. We also included the
parent diphenyl alkyne, tolane, for comparison. At this stage, we
limited ourselves to the analysis of the starting materials instead
of the full reaction potential energy profiles. However, even this
simple analysis still provided valuable quantitative information
regarding the acceptor ability of the different aryl groups
(Table 1). The natural bond orbital (NBO) charge on the alkyne
carbons of tolane is close to zero (0.006 e). The short strong
p-bonds of the alkyne moiety are not easily polarized but
introduction of a p-nitro group at one of the alkyne carbons
increases the positive charge by a factor of 10 (to 0.060 e). The
electron-withdrawing effect of a p-nitrophenyl group is com-
parable with that of the 4-pyridine moiety. The effect of
anthracene-9,10-dione and the m-nitrophenyl group are inter-
mediate whereas the 2-pyridinyl substituent is the least with-
drawing of all the aryls investigated in the present work.
The table also includes occupancies and polarizations of the
alkyne p-bonds quantified by NBO analysis. The alkyne p-bond
conjugated to the acceptor moieties is noticeably depleted of
electron density (1.87–1.85 electrons) in comparison with the
other p-bond, which is twisted out of the conjugation. However,
polarizations of the two p-bonds are generally identical, and
p-electron density is increased at the carbon adjacent to the
acceptor moiety. The only exception is 2-(phenylethynyl)pyri-
dine, where polarizations of the two p-bonds were found to be
opposite, most likely due to the through-space donation from the
lone pair of pyridine nitrogen to the in-plane p-system.[15]
In summary, we have shown that reaction of electron-deficient
alkynes with ethylenediamine is a general transformation that can
involve not only a-acetylenic ketones but other suitably activated
alkynes. From a preparative perspective, the combination of
Sonogashira cross-coupling and fragmentation presented in this
work opens the door for two, albeit non-atom-economical, but
potentially useful synthetic transformations: introduction of
methyl groups to electron-deficient aryl halides or triflates or
Scheme 7. Possible route of fragmentation of 1b.
However, the ‘push–pull’ alkyne 5e, where the NO2 acceptor
and the OMe donor are positioned at the para-positions of the
two rings at the opposite alkyne termini, does undergo the full
fragmentation. Although the lowered electron deficiency of the
alkyne leads to longer reaction time (8 h is needed to reach full
conversion), the isolated yields of 1-methyl-4-nitrobenzene (6a)
and 2-(4-methoxyphenyl)-imidazoline (3b) were 62 and 66 %
respectively.
The electron-deficiency of the alkyne moiety is more impor-
tant thanalkyne polarization. Forexample, 1,2-bis(4-nitrophenyl)
ethyne (5f), a symmetric alkyne with two acceptor groups, reacts
faster(1h), yielding 51% 1-methyl-4-nitrobenzene (6a) and 55%
imidazoline 3c.
As expected, a polarized but electron-rich alkyne 1-methoxy-
4-(phenylethynyl)benzene (5g), containing a donor OCH3
group, was unreactive. In this case, the starting material was
recovered in 85 % yield after 50 h.
We also explored the possibility of expanding this chemistry
to polarized heterocycles. Considering the acceptor nature of the
pyridine moiety, it was interesting to test whether the pyridine
group can mimic the activating effect of the nitro group on
the triple bond.
Under analogous conditions (refluxing pyridine in a closed
vial at 1208C), the reaction of 4-phenylethynyl pyridine (7a) is
significantly slower. After 6 h, the fragmentation is incomplete –
NMR analysis of the reaction mixture revealed the intermediate
Michael addition product, 4-methylpyridine (picoline, 9) and
2-phenyl-4,5-dihydroimidazole (3a) in a 1.4 : 1 : 1 ratio. It took
additional 14 h under the same conditions to complete the full
transformation and produce a 70 % mixture with a 1 : 1 ratio of
the two fragmentation products according to the NMR analysis
(Scheme 9). We did not attempt to isolate the methylpyridine 9
owing to its volatility. We also tested the possibility of inducing

Alkyne Fragmentations
E
Z
X
Me
Y
N
ϩ
for 5a,b,5e,5f
NH
O2N
3a–c
55–81 %
6a,b
51–87 %
X ϭ Y ϭ H, 6a
Z ϭ H 3a
Z ϭ OMe 3b
Z ϭ NO2 3c
X ϭ 2-Me, Y ϭ 4-Me, 6b
Z
NH2
X
H2N
for 5c
pyridine, 115ЊC
Y
5c
80 %
O2N
5a–f
NO2
4-NO2, X ϭ Y ϭ H, Z ϭ H 5a
4-NO2, X ϭ 2-Me, Y ϭ 5-Me, Z ϭ H 5b
3-NO2, X ϭ Y ϭ H, Z ϭ H 5c
5-NO2, X ϭ 2-OMe Y ϭ H, Z ϭ H 5d
4-NO2, X ϭ Y ϭ H, Z ϭ OMe 5e
4-NO2, X ϭ Y ϭ H, Z ϭ NO2 5f
O2N
for 5d
NH2
N
H
8
74 %
Scheme 8. Fragmentation of nitro-substituted diaryl acetylenes 5a–f.
NH
2
NH2
Me
H2N
N
N
HN
ϩ
ϩ
9 ϩ 3a
N
pyridine, 120ЊC
NH
ϩ14 h
N
7a
6 h
9
3a
1:1
(70 %)
1.4
:
1
:
1
Scheme 9. Fragmentation of diaryl acetylene 7a.
NH2
NH2
H
H2N
N
N
pyridine, 115ЊC
N
O
N
7b
10
38 %
11
Scheme 10. Reaction of 2-(phenylethynyl)pyridine (7b) with 1,2-diaminoethane.
introduction of masked carboxyl (imidazoline) groups into neutral
or donor aryl halides or triflates (Scheme 11). These approaches
suggest the retrosynthetic equivalency of alkynes and one-carbon
synthons in the most reduced and oxidized forms of the latter.
General Procedure: Synthesis of Alkynes 1a–b, 5a–g, 7a–b
A mixture ofthe appropriate iodide(bromide) (4.5mmol), alkyne
(4.5mmol), PdCl2(PPh3)2 (0.014mmol), CuI (0.026mmol), and
Et3N (19.3 mmol) in benzene was stirred under an argon
atmosphere at 658C for 2–10 h.[18] The volatiles were evapo-
rated under vacuum and the residues were purified on silica
(hexane/toluene) to give 1a–b, 5a–g, 7a–b.
Experimental
Melting points were determined with a Kofler apparatus. Com-
bustion analysis was performed with a CHN- Carlo Erba Model
1106 analyser. IR spectra were recorded in KBr pellets on a
Vector 22 instrument. NMR spectra were recorded on Bruker
AV-400 spectrometer at 400.13 (1H) and 100.61 MHz (13C) in
CDCl3. Column chromatography was performed on SiO2 (Merck
60 (0.063–0.2 mm)). Analytical TLC was performed with Merck
silica gel 60 F254 plates. Ethane-1,2-diamine, PdCl2(PPh3)2, CuI,
and Et3N were commercially available reactants.
1-(Phenylethynyl)-9,10-anthraquinone (1a)
Yield 89 %, mp 158–1608C (lit. 159–1608C[19]).
2-(Phenylethynyl)-9,10-anthraquinone (1b)
Yield 93 %, mp 213–2148C (lit. 214.5–215.58C[20]).
All calculations were performed using the software package
Gaussian ’09.[16] Structures were optimized using the B3LYP/
6–31þG(d,p) level of theory, and evaluated using NBO 3.0.[17]
1-Nitro-4-(phenylethynyl)benzene (5a)
Yield 80 %, mp 120–1228C (lit. 118–1208C[21]).

F
S. F. Vasilevsky et al.
Table 1. Natural bond order (NBO) analysis of diaryl alkyne polarization at B3LYP/6–311G(d,p) level of theory
2 B
Alkyne
Occupancy
1.97
Polarization coefficientsA
cA
Charge
1,2-Diphenylethyne
C1, p (Ph)
C2, p (Ph)
50.00 %
50.00 %
50.00 %
50.00 %
50.24 %
49.76 %
51.34 %
48.66 %
50.51 %
49.49 %
50.95 %
49.04 %
50.00 %
50.00 %
50.00 %
50.00 %
50.04 %
49.96 %
51.93 %
48.08 %
50.01 %
49.98 %
51.05 %
48.94 %
49.87 %
50.13 %
50.81 %
49.18 %
50.17 %
49.83 %
51.07 %
48.94 %
0.006
0.006
1.87
1.97
1.85
1.97
1.87
1.97
1.85
1.97
1.85
1.97
1.86
1.96
1.86
1.97
1.85
C1, p (Ph)
C2, p (Ph)
1-Nitro-4-(phenylethynyl)benzene (5a)
1-Nitro-3-(phenylethynyl)benzene (5c)
1,2-Bis(4-nitrophenyl)ethyne (5f)
C1, p (pNO2Ph)
C2, p (Ph)
ꢁ0.022
0.060
C1, p (pNO2Ph)
C2, p (Ph)
C1, p (mNO2Ph)
C2, p (Ph)
0.007
0.034
C1, p (mNO2Ph)
C2, p (Ph)
C1, p (pNO2Ph)
C2, p (pNO2Ph)
C1, p (pNO2Ph)
C2, p (pNO2Ph)
C1, p (PhNO2)
C2, p (PhOMe)
C1, p (PhNO2)
C2, p (PhOMe)
C1, p (4-Py)
C2, p (Ph)
0.031
0.033
1-Methoxy-4-((4-nitrophenyl)ethynyl)benzene (5e)
4-(Phenylethynyl)pyridine (7a)
ꢁ0.011
0.056
ꢁ0.016
0.055
C1, p (4-Py)
C2, p (Ph)
2-(Phenylethynyl)pyridine (7b)
C1, p (2-Py)
C2, p (Ph)
0.008
0.013
C1, p (2-Py)
C2, p (Ph)
2-(Phenylethynyl)anthracene-9,10-dione (1b)
C1, p (Anth)
C2, p (Ph)
0.001
0.031
C1, p (Anth)
C2, p (Ph)
AFunctional groups in parentheses indicate which carbon of the alkyne is being referred to, C1 or C2.
2
BcA ¼ polarization coefficient squared.
Alkyne as a reduced one-carbon synthon
1-Nitro-3-(phenylethynyl)benzene (5c)
Yield 70 %, mp 67–698C (lit. 68–708C[22]).
NH2
H
H2N
H
X
EAG
EAG
Pd cat,
CuI,
H
pyridine, 115ЊC
1-Methoxy-4-nitro-2-(phenylethynyl)benzene (5d)
X ϭ Cl, Br, OTf
Yield 75 %; the product was obtained as a yellow oil.[23] dH
(CDCl3) 3.89 (s, 3H), 6.94 (d, J 9.2, 1H), 7.30–7.32 (m, 3H),
7.53–7.55 (m, 2H), 8.20 (dd, J 9.2, 2.8, 1H), 8.40 (d, J 2.4, 1H).
base
Alkyne as an oxidized one-carbon synthon
max (KBr)/cmꢁ1 2225 (CꢀC).
NH2
O2N
n
H2N
N
R
X
R
Pd cat,
CuI,
base
N
H
pyridine, 115ЊC
1-Methoxy-4-((4-nitrophenyl)ethynyl)benzene (5e)
Yield 83 %, mp 121–1238C (lit. 122–1248C[24]).
Scheme 11. Use of cross-coupling and fragmentation strategies for the
introduction of methyl and imidazoline groups to aromatics. EAG ¼ electron
accepting group.
1,2-Bis(4-nitrophenyl)ethyne (5f)
Yield 67 % mp 219–2208C (lit. 221–221.58C[24]).
1,4-Dimethyl-2-nitro-5-(phenylethynyl)benzene (5b)
1-Methoxy-4-(phenylethynyl)benzene (5g)
Yield 52 %, mp 61–628C (lit. 63–648C[24]).
Yield 80 %, mp 86–888C (hexane). dH (CDCl3, 400 MHz)
2.54 (s, 3H, m-Me), 2.57 (s, 3H, o-Me), 7.39 (m, 3H, Ph), 7.45 (s,
1H, m-HAr), 7.55 (m, 2H, Ph), 7.89 (s, 1H, o-HAr). dC (CDCl3,
100 MHz) 20.22, 20.31 (2Me), 86.72, 97.39 (CꢀC), 122.63,
125.65, 128.67, 129.21, 131.14, 131.86, 135.87, 139.14 (CAr),
147.94 (C–NO2). nmax (KBr)/cmꢁ1 1340, 1517 (NO2), 2208
(CꢀC). Found: C 76.60, H 5.23, N 5.41. C16H13NO2 requires C
76.48, H 5.21, N 5.57 %.
4-(Phenylethynyl)pyridine (7a)
Yield 68 %, mp 90–928C (lit. 92–938C[25]).
2-(Phenylethynyl)pyridine (7b)
Yield 78 %, mp 318C (lit. 328C[26]).

Alkyne Fragmentations
G
Table 2. Reaction yields and product melting points
Starting alkyne
Duration of reaction [h]
3
Products
Yield [%]
Melting point [8C]
1a
2a
3a
4
69
172–173 (lit. 173[27]
93–95 (lit. 92–94[28]
204–205 (lit. 207–208[29]
175–177 (lit. 176–176.5[30]
)
)
)
68
12
)
1b
5a
5b
5
3
6
2b
3a
6a
3a
6b
3a
5c
8
94
93
92–94 (lit. 92–94[28]
53–54 (lit. 51–55[31]
93–95 (lit. 92–94[28]
)
)
)
68
61
87
64–66 (lit. 70–70.5[32]
)
81
94–95 (lit. 92–94[28]
66–68 (lit. 68–70[22]
120–122
)
)
5c
5d
5e
40
4
80
74
8
6a
3b
6a
3c
5g
9
62
52–54 (lit. 51–55[31]
136–138 (lit. 138–139[33]
51–52 (lit. 51–55[31]
241–243 (lit. 242–243[33]
60–62 (lit. 63–64[23]
)
66
)
5f
1
51
)
55
)
5g
7a
50
40
85
)
27 (GC-MS)
70
Not isolated
91–93 (lit. 92–94[28]
Not isolated
3a
10
11
)
7b
40
48 (GC-MS)
42 (GC-MS)
Not isolated
Reaction of Alkynes with Ethylenediamine – General
Procedure
(c) K. Gilmore, I. V. Alabugin, Chem. Rev. 2011, 111, 6513. doi:10.
1021/CR200164Y
(d) S. F. Vasilevsky, T. F. Mikhailovskaya, V. I. Mamatyuk, G. E.
Salnikov, G. A. Bogdanchikov, M. Manoharan, I. V. Alabugin, J. Org.
Chem. 2009, 74, 8106. doi:10.1021/JO901551G
(e) A. M. Thomas, A. Sujatha, G. Anilkumar, RSC Adv. 2014, 4, 21688.
doi:10.1039/C4RA02529F
(f) Y. N. Kotovshchikov, G. V. Latyshev, N. V. Lukashev, I. P.
Beletskaya, Org. Biomol. Chem. 2015, 13, 5542. doi:10.1039/
C5OB00559K
A mixture of alkyne 1a–b, 5a–g, 7a–b (1.6 mmol) and ethyle-
nediamine (5 ml, 75.0 mmol) in pyridine was refluxed for
1–50 h. Solvent was removed under reduced pressure and the
crude reaction mixture was purified by column chromatography
(toluene/ethyl acetate) to give pure products (Table 2).
In the case of 2-(phenylethynyl)pyridine (7b), the reaction
mixture was treated with an ethanolic solution of 2,4-dinitro-
phenylhydrazine to afford (Z)-2-(2-(2-(2,4-dinitrophenyl)
hydrazono)-2-phenylethyl)pyridine; yield 35%, mp 196–1988C
(lit. 192–1948C[34]).
[3] C–C bond fragmentations: seminal work: (a) A. Eschenmoser,
A. Frey, Helv. Chim. Acta 1952, 35, 1660. doi:10.1002/HLCA.
19520350532
(b) C. A. Grob, P. W. Schiess, Angew. Chem. Int. Ed. Engl. 1967, 6, 1.
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doi:10.1021/JO01020A537
(d) M. Tanabe, D. F. Crowe, R. L. Dehn, Tetrahedron Lett. 1967, 8,
Supplementary Material
NMR data and conditions for the reactions of 5d and 7a with
ethylenediamine and the optimized energies and geometries of
starting materials are available on the Journal’s website.
3943. doi:10.1016/S0040-4039(01)89757-4
Recent reviews: (e) M. A. Drahl, M. Manpadi, L. J. Williams,
Angew. Chem. Int. Ed. 2013, 52, 11222. doi:10.1002/ANIE.
201209833
(f) K. Prantz, J. Mulzer, Chem. Rev. 2010, 110, 3741. doi:10.1021/
CR900386H
Selected recent examples: (g) S. Kamijo, G. B. Dudley, J. Am. Chem.
Acknowledgements
This work was supported by Russian Foundation for Basic Research (grant
no. 16–03–00589), Chemical Service Centre of the Siberian Branch of the
Russian Academy of Science. Work at Florida State University was sup-
ported by the National Science Foundation (grant CHE-1465142).
Soc. 2005, 127, 5028. doi:10.1021/JA050663M
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