Synthesis, Chemistry, and Photochemistry of Methylcyanobutadiyne in the Context of Space Science

Article abstract of DOI:10.1021/acs.joc.6b00205

An alternative preparation of methylcyanobutadiyne (MeC₅N), a molecule present in the interstellar medium, was established in order to circumvent tedious steps from previous methods. The possibility of forming methylcyanoacetylene and MeC₅N by gas-phase photolysis was evaluated from relevant acetylene derivatives in the context of space science. The reactivity of MeC₅N toward simple nucleophiles was investigated. The exclusive formation of E adducts was observed, together with a solvent dependence for the regioselectivity of the addition.

Full text of DOI:10.1021/acs.joc.6b00205

Article
pubs.acs.org/joc
Synthesis, Chemistry, and Photochemistry of Methylcyanobutadiyne
in the Context of Space Science
Nicolas Kerisit,† Cedric Rouxel,† Sophie Colombel-Rouen,† Loïc Toupet,‡ Jean-Claude Guillemin,*,†
́
and Yann Trolez*,†
†Ecole Nationale Super
France
‡Institut de Physique de Rennes, UMR 6251, CNRS, Universite
France
́
ieure de Chimie de Rennes, UMR 6226, CNRS, 11 allee
́
de Beaulieu, CS 50837, 35708 Rennes cedex 7,
́
de Rennes 1, 263 avenue du General Leclerc, 35042 Rennes cedex,
́
́
S
* Supporting Information
ABSTRACT: An alternative preparation of methylcyanobutadiyne (MeC5N), a molecule present in the interstellar medium, was
established in order to circumvent tedious steps from previous methods. The possibility of forming methylcyanoacetylene and
MeC5N by gas-phase photolysis was evaluated from relevant acetylene derivatives in the context of space science. The reactivity
of MeC5N toward simple nucleophiles was investigated. The exclusive formation of E adducts was observed, together with a
solvent dependence for the regioselectivity of the addition.
pure form by removing it from the reaction mixture as it is
formed. Later, Miller and Lemmon modified this procedure by
adding sand to the mixture of amide and phosphorus
pentoxide.7
Cyanoacetylene is considered to be a key compound in the
field of the origins of life. Using HC3N, different research
groups have reported that it is possible to prepare amino acids,8
nucleobases,9 nucleosides,10 and nucleotides11 and to transform
cyanoacetylene into a phosphorylating agent.12 Cyanoacetalde-
hyde, which is prepared in almost quantitative yield from HC3N
in basic conditions,9 is also an important compound in
prebiotic chemistry and has been involved in the synthesis of
compounds of prebiotic interest.13
Although HC3N has retained a lot of attention in the
community of scientists working on the origins of life and/or
interstellar chemistry these last 50 years, the other cyanopo-
lyynes have been much less studied, most probably because of
the difficulty in synthesizing them at the hundreds of milligrams
scale. In this work, we focused on methylcyanobutadiyne
(MeC5N) that has scarcely been studied so far. We report a
new synthetic pathway that circumvents the tedious formation
of 1,3-pentadiyne that was published a few years ago.6d The
possibility of forming methylcyanobutadiyne as well as
methylcyanoacetylene by photolysis in the gas phase has also
been evaluated (the conditions used here are different from
INTRODUCTION
■
About 200 molecules have been detected in the interstellar
medium (ISM) so far.1 A wide range of compounds are present
in different regions of space, ranging from small molecules like
molecular hydrogen2 to heavier molecules like fullerenes C60
and C70.3 An interesting family of molecules, the cyanopo-
lyynes, is present in molecular clouds. The structure of
cyanopolyynes consists of conjugated triple bonds substituted
by a cyano group on one side and a hydrogen on the other side.
The general formula of cyanopolyynes is H−(CC)n−CN,
and compounds with n ranging from 1 to 5 have been detected
in the ISM.4 Because of their high permanent dipole moment,
they give strong signals in microwave spectroscopy, the method
of choice for the detection of molecules in the ISM.
Consequently, they are quite easily detected compared to
other simple molecules, even when their abundance is not high.
Two methylated cyanopolyynes, for which the general
formula is Me−(CC)n−CN, have also been detected in the
ISM (n = 1−2).5
Synthesis in the laboratory of only a few cyanopolyynes
obtained in pure form has been achieved until now,6 most
probably because of the synthetic challenge that these unstable
species represents.
The synthesis of cyanoacetylene has been known for more
than 100 years and has been described by Moureu and
Bongrand.6a It consists of preparing the corresponding amide
and, in the next step, heating the latter in the presence of
phosphorus pentoxide in order to obtain cyanoacetylene in
Received: January 28, 2016
© XXXX American Chemical Society
A
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Scheme 1. Synthesis of Methylcyanobutadiyne 6
a
Scheme 2. Photolysis Experiments Using a Mixture of Propyne and Dicyanoacetylene and the Proposed Mechanisms
a
Conditions: (a−c) Photolysis experiments in the gas phase using binary mixtures of propyne (7) and dicyanoacetylene (8) at different wavelengths;
(d) proposed radical pathways generating MeC3N (9) and MeC5N (6); (e) proposed cycloaddition pathway generating MeC3N (9).
those of the ISM but could nevertheless give some interesting
insights). Moreover, the reactivity of MeC5N toward simple
nucleophiles was investigated.
a solution of potassium hydroxide, allowing the deprotection of
the triple bond.16 Submitting 3 to the Fritsch−Buttenberg−
Wiechell rearrangement led to the formation of 1,3-
pentadiynyllithium that was then reacted with methyl
chloroformate, affording ester 4. It is important to notice that
this compound could not be separated from methyl pentanoate,
which is a byproduct from the reaction of nBuLi and methyl
chloroformate. Nevertheless, this mixture was reacted with an
aqueous solution of ammonia, leading to amide 5 in 27% yield
from 3. Finally, MeC5N 6 was obtained in 88% yield by reacting
amide 5 with an excess of phosphorus pentoxide in the
presence of sand while heating the reaction mixture from 110
to 150 °C.
RESULTS AND DISCUSSION
■
Synthesis of MeC5N. We have recently reported an
efficient synthetic pathway for methylcyanobutadiyne.6d The
synthesis involves the formation of 1,3-pentadiyne from
commercially available 1,4-dichlorobutyne, following a modified
procedure previously reported by Verkruijsse and Brandsma.14
However, this step is tedious, and the reaction is very
exothermic, which can induce safety issues in the laboratory.
To overcome this problem, another synthetic route was
developed. The synthesis starts with the commercially available
4-(trimethylsilyl)-3-butyn-2-one 1, which was reacted with
carbon tetrabromide and triphenylphosphine, allowing thus the
preparation of dibromoolefin 2 in 90% yield (Scheme 1).15
Terminal alkyne 3 was obtained in 99% yield by reacting 2 with
This alternative preparation of MeC5N differs from the
previous one6d by forming the ester 4 in another pathway and
does not require the tedious synthesis of the thermally unstable
1,3-pentadiyne. Furthermore, one of the most significant
improvements lies in the dehydration of amide 5, obtained in
B
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Article
a
Scheme 3. Photolysis Experiments Using a Mixture of Propyne and Cyanoacetylene and the Proposed Mechanisms
a
Conditions: (a−c) Photolysis experiments in the gas phase using binary mixtures of propyne (7) and cyanoacetylene (10) at different wavelengths;
(d) proposed cycloaddition pathway generating MeC3N (9); (e) proposed radical pathway generating MeC5N (6).
a yield higher than that previously published (88 vs 36%), by
using an excess of phosphorus pentoxide. The overall yield of
the sequence is 21% compared with our previously published
sequence, which only reached 8%. Additionally, this procedure
allows one to circumvent the one proposed by Kroto et al.,6f
who used a stannylated precursor and cyanogen chloride, which
are known to be toxic.
Particularly noteworthy is the thermal stability of MeC5N
compared to its parent compound cyanobutadiyne (HC5N).
Indeed, MeC5N melts at 92 °C without decomposition, and
HC5N starts to decompose from −40 °C. The same trend was
observed, to a lesser extent, between methylcyanoacetylene
(MeC3N) and HC3N. Whereas the first one is stable at room
temperature, the second one slowly decomposes at ordinary
pressure and temperature conditions and must be kept in a
freezer.
Photochemical Formation of MeC3N and MeC5N. The
presence of “complex” molecules such as cyanopolyynes or
fullerenes in the interstellar medium is quite puzzling, given the
very low pressure and temperature conditions. The only
reasonable source of energy available in molecular clouds is
radiation. Therefore, we suppose that UV light (or shorter
wavelength radiations) could be responsible for breaking bonds
and thus generating radicals or simply exciting molecules and
making them react more easily than in the ground state. To
understand how MeC5N could be formed in the medium, we
submitted various binary mixtures of gases that are present or
supposed to be present in this medium to a UV irradiation. We
have already reported a preliminary study about the formation
of trace amounts of MeC5N under such conditions using a 193
nm irradiation.6d In order to gain more insights about the
mechanism of formation of this compound, we have completed
this study with an irradiation at 254 and 185 nm. In parallel, we
tried to identify traces of MeC3N in the same mixtures in order
to collect information about the mechanism of formation of
MeC5N. All experiments were performed using 100 mbar of
each gas at room temperature. These conditions are clearly far
different from the genuine interstellar conditions, but they
allow the new products to be formed in a decent time scale and
detectable amounts. To evaluate the photochemical behavior of
the different mixtures, three different irradiation conditions
were used: one with a 254 nm irradiation, another using 254
and 193 irradiations, and a last one using 254, 193, and 185 nm
irradiations. To simplify the way we distinguish these three
conditions, only the shortest wavelength is specified in the
following text.
The photolysis of propyne and dicyanoacetylene (which was
synthesized according to a procedure from the literature17) at
254, 193, or 185 nm led to the formation of MeC3N in each
case, whereas MeC5N was only formed at 193 nm (Scheme 2,
eqs a−c). At 254 nm and shorter wavelengths, dicyanoacetylene
can most likely undergo a homolytic bond cleavage of Csp−
Csp single bond, forming a CN radical on the one hand and a
C3N radical on the other hand. Addition of a CN radical on
propyne gives MeC3N (as already described in other articles18),
and addition of a C3N radical gives MeC5N (Scheme 2, eq d).
However, particularly noteworthy is the formation of MeC3N at
each wavelength contrary to MeC5N. In our previous report,6d
we suggested that propyne could also lead to a propargylic
radical below 193 nm that would inhibit the formation of
MeC5N. Nevertheless, MeC3N was formed at 185 nm, which
could suggest that the radical pathway might not be the only
possible mechanism. Actually, we could also envisage a
sequence of [2 + 2] cycloaddition−retroelectrocyclization
that would allow for the formation of MeC3N but not the
formation of MeC5N (Scheme 2, eq e). Such a mechanism has
already been suggested for the reactivity of dicyanoacetylene
with ethylene in similar experiments.19
When cyanoacetylene was used jointly with propyne, MeC3N
was observed at 254 and 193 nm (Scheme 3, eqs a and b) but
not at 185 nm (Scheme 3, eq c). MeC5N was only formed at
193 nm. According to the literature, cyanoacetylene does not
undergo Csp−H cleavage upon irradiation at a wavelength
longer than 240 nm.20 Propyne does not absorb significantly at
254 nm;21 therefore, a mechanism involving the formation of
radical species cannot be invoked to describe the irradiation
experiment at 254 nm. Nevertheless, at this wavelength,
cyanoacetylene can be brought to its excited state and react
with propyne in a cycloaddition reaction, forming a cyclo-
butadiene (Scheme 3, eq d).18 The latter intermediate can
rearrange into one molecule of MeC3N and one molecule of
acetylene after retroelectrocyclization. This observation tends
C
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Scheme 4. Photolysis Experiments Using a Mixture of 1,3-Pentadiyne and Dicyanoacetylene
to confirm the possibility of a cycloaddition pathway that is
parallel to a radical pathway (Scheme 3, eq d). Actually,
MeC5N was formed at 193 nm and cannot be formed by
cycloaddition. Addition of a cyanoethynyl radical on propyne
can lead to MeC5N (Scheme 3, eq e). Neither methylcyanoa-
cetylene nor methylcyanobutadiyne was observed at 185 nm
when a mixture of propyne and cyanoacetylene was irradiated
(Scheme 3, eq c). Since the absorption coefficient of propyne at
185 nm (about 110 amg−1 cm−1,22 at 293 K)20 is 10 times more
important than that of cyanoacetylene (about 10 amg−1 cm−1,
at 293 K),23 we suppose that the propargyl radical is mostly
formed,24 preventing thus the formation of MeC3N and
MeC5N.
In order to complete these experiments, a mixture of 1,3-
pentadiyne (detected in the interstellar medium in 198425) and
dicyanoacetylene was also subjected to photolysis (Scheme 4).
Formation of MeC3N was not observed at any of the three
wavelengths, but in each case, trace amounts of MeC5N were
detected. These experiments indicate that C−C single bonds of
1,3-pentadiyne or C−C triple bonds from both compounds
remain unchanged under these irradiation conditions. One can
suppose that MeC5N was probably formed by addition of CN
radical on pentadiyne. However, a [2 + 2] cycloaddition−
retroelectrocyclization cascade could also lead to MeC5N.
Furthermore, MeC7N might have been formed by chain
elongation during these experiments, but at the moment, we do
not have any authentic sample of this compound, which would
allow us to identify it easily out of a complex mixture. We are
currently investigating the possibility to synthesize it in pure
form in our laboratory.26,27
Addition of Nucleophiles on MeC5N. The question
“could life have emerged from space following a cascade of
chemical processes that would have started outside the Earth” is
still open. The Rosetta mission28 as well as the study of the
chemical composition of meteorites29 attempts to answer this
question, at least partially. In the same manner, numerous
studies have shown that cyanoacetylene could have played a
central role in the formation of building blocks of life on the
Primitive Earth.8−13
Following this reasoning, we have investigated the reactivity
of MeC5N toward secondary amines as a preliminary study.
Our previous study of the addition of nucleophiles on
cyanobutadiyne showed the exclusive formation of the 1,6-
addition products as a mixture of Z/E isomers.6b,30 In the
present work, MeC5N has been treated with dimethylamine or
morpholine in either methanol or tetrahydrofuran. For each
experiment, 1 equiv of amine was added at room temperature;
the compounds were reacted for 2 h, and the products were
isolated after column chromatography. Even though these
experiments are far from the Primitive Earth conditions with
water as solvent, it was important to run these reactions
because the reactivity of MeC5N was completely unknown.
This is the reason why investigating its reactivity with simple
compounds was primordial as a first step.
Formation of 1,4-adducts 13 and 15 was observed in trace
amount according to H NMR (Table 1, entries 1 and 2) but
1
Table 1. Addition of Amines on MeC5N (6)
1,6-adducts
(yield)
1,4-adducts
(yield)
entry
Nu−H
Me2NH
solvent
1
2
3
4
THF
12 (82%)
14 (93%)
12 (28%)
14 (21%)
13 (trace)
15 (trace)
13 (55%)
15 (41%)
O(CH2−CH2)2NH
Me2NH
THF
methanol
methanol
O(CH2−CH2)2NH
could not be isolated purely from these experiments. By simply
changing the solvent, using methanol instead of THF, we
observed the formation of a mixture of 1,4-addition and 1,6-
addition products (Table 1, entries 3 and 4). For these
experiments, the 1,4-addition products 13 and 15 were the
major compounds and were obtained in 55 and 41% yields,
respectively. This difference of reactivity while increasing the
polarity of the solvent can be attributed to a difference of
solvation of the dipolar activated complex, which is formed
from neutral molecules.31
Compounds 12−15 were characterized by 1H and 13C NMR
spectroscopy (HSQC, HMBC, and NOESY) as well as by high-
resolution mass spectrometry. Structures of compounds 12 and
15 were also solved by X-ray crystallography.
Products of 1,4-addition on the one hand and products of
1,6-addition on the other hand were unambiguously distin-
guished by the characteristic 13C carbon shifts of their methyl
and cyano groups. Indeed, methyl groups (CH3−Csp) of
compounds 13 and 15 have a 4.4 ppm chemical shift (Table 2,
entries 3 and 5), which is consistent with the chemical shift of
other methylacetylenic compounds such as compound 6 (4.7
ppm, Table 2, entry 1). Methyl groups (CH3−Csp2) of
compounds 12 and 14 are much more downfield shifted,
reaching 18 ppm (Table 2, entries 2 and 4), and are analogous
to enyne 18,32 for instance (18.5 ppm, Table 2, entry 8). Cyano
groups also showed very characteristic chemical shifts. For
compounds 13 and 15, a signal at 121 ppm was observed,
corresponding to a cyano group connected to a Csp2 carbon
(Table 2, entries 3 and 5), and was in the same range as
compound 1733 (120.3 ppm, Table 2, entry 7). In the case of
compounds 12 and 14, a signal at 108 ppm was measured,
which is typical of a cyano group directly connected to a
carbon−carbon triple bond (Table 2, entries 2 and 4), fitting
the chemical shifts measured for 6 and 16,6b which are 105.5
and 107.6 ppm, respectively (Table 2, entries 1 and 6).
Additionally, absolute stereochemical determination of
compounds 12−15 was evidenced by NOESY experiments.
The addition of dimethylamine or morpholine on MeC5N in
THF gave the corresponding 1,6-adducts 12 and 14 in 82 and
93% yields, respectively, as major products of this reaction.
D
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Table 2. Chemical Shifts of Methyl and Cyano Carbons for New Molecules 12−15 and Reported Molecules 6, 16, 17, and 18
a
a
entry
compound
δ13C methyl group CH3−Csp2 or CH3−Csp (ppm)
δ13C cyano group (ppm)
1
2
3
4
5
6
7
8
6
4.7
18.5
4.4
105.5
108.3
121.8
107.7
120.6
107.6
120.3
12
13
14
15
16
17
18
18.2
4.4
18.5
a
All 13C spectra were recorded in CDCl3.
Figure 1. X-ray structures of compound 12 (left) and 15 (right). Hydrogen atoms were omitted for clarity.35
Each time, the exclusive formation of the E isomer was
observed, most likely because it is less sterically hindered than
the Z isomer and, therefore, is most likely to be formed.
X-ray-quality crystals were grown for compounds 12 and 15
by slow evaporation of n-pentane/acetone and chloroform
solutions, respectively. They unambiguously confirmed the
structures determined on the basis of 1H and 13C NMR
spectroscopy.
The π-system of compound 12 is completely planar, showing
good delocalization of electrons from the electron-donating
dimethylamino group to the electron-withdrawing cyano group
(Figure 1). As a consequence, conjugated single bonds are
short: the C3−C4 single bond is 1.394(2) Å long, and C5−C6
is 1.365(2) Å, whereas nonconjugated single bonds are
generally about 1.54 Å.34 The C2−C3 double bond
(1.379(2) Å) is slightly longer than a nonconjugated double
bond, which is generally about 1.34 Å. The triple bond C4−C5
(1.214(2) Å) is less affected and is just slightly longer than a
nonconjugated triple bond (ca. 1.18 Å).
Similar to that of compound 12, the π-system of compound
15 is also mostly planar, with the torsion angle C4−C1−C2−
C3 being 0.2°. The morpholine six-membered ring adopts a
chair conformation. Delocalization of electrons from the
nitrogen atom of the morpholine moiety toward the cyano
group can be evidenced by carbon−carbon bond lengths. The
length of C1−C2 double bond is 1.364(3) Å, which is slightly
longer than a nonconjugated double bond, and the C2−C3
simple bond is 1.421(3) Å long, which is much shorter than a
nonconjugated simple bond.
CONCLUSION
■
The alternative synthesis of MeC5N described in this work
makes this compound easily accessible for organic chemists.
Additionally, the large improvement of the last step of the
formation of this compound allows its preparation at the gram
scale, which is also a fairly relevant point for further study of the
latter, for spectroscopic purposes, and also extensive reactivity
studies.
Photolysis experiments in the gas phase, using different
binary mixtures of acetylenes, evidenced the formation of
MeC5N and MeC3N in such conditions. The use of acetylenic
derivatives detected in planetary atmospheres, in the interstellar
medium, or simply assumed to be present in space but not
detected yet allowed us to sharpen our understanding of the
formation of these compounds in the gas phase. In particular,
these experiments suggested that two different pathways could
be at stake in our reaction conditions: cycloaddition and radical
processes.
Addition of simple nucleophiles on MeC5N, such as
morpholine and dimethylamine, was also examined. Products
of the 1,6-addition of amines on methylcyanobutadiyne were
obtained as the exclusive addition products of these reactions in
tetrahydrofuran, showing in each case only an E configuration
for the newly formed double bond. Switching from
tetrahydrofuran to methanol indicated the formation of the
E
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Synthesis. 1,1-Dibromo-2-methylbut-1-en-3-yne (3). Dibromoo-
lefin 2 (3.63 g, 12.3 mmol) was dissolved in a mixture of THF (90
mL) and methanol (28 mL), and a solution of KOH (37 mL, 1 M)
was added slowly. The reaction mixture was stirred at rt for 40 min.
Then the aqueous layer was extracted with CH2Cl2, and the combined
organic layers were dried over MgSO4, filtered, and concentrated in
vacuo. Compound 3 was obtained as a pale yellow oil in 99% yield
(2.71 g, 12.1 mmol). The spectroscopic data were in accordance with
those from the literature.15
1,4-addition products, also possessing systematically an E
configuration. In these conditions, 1,4-addition products were
found to be the major products.
In the frame of prebiotic chemistry, the relative stability of
MeC5N (which melts at 92 °C without decomposition)
compared to that of its cyanopolyyne counterpart cyanobuta-
diyne HC5N (which decomposes from −40 °C) is interesting
and opens the possibility to envisage this compound as a
carbon provider during the late heavy bombardment the Earth
underwent 3.8 billion years ago, namely, just before the
emergence of life on Earth on a geological time scale. Indeed, it
could have survived the passage of carbonaceous meteorites (or
comets) through the atmosphere which implies a quite
important heating, depending on the size of the meteorite. If
MeC5N could have reached the Earth at that time, the question
of its future in the conditions of the Primitive Earth remains
open. Did it play any role in the formation of the building
blocks of life? This is what we are currently investigating in our
laboratory, as well as related compounds such as cyanohexa-
triyne (HC7N) and methylcyanohexatriyne (MeC7N). We are
also interested in studying the physical properties of
cyanopolyynes. With our collaborators, we were able to record
the gas-phase infrared spectrum of MeC5N, which gives a
reference for its future detection and quantification in comets
or planetary atmospheres.36
Hexa-2,4-diynamide (5).6d A solution of compound 3 (4.90 g, 21.9
mmol) in dry n-pentane (110 mL) was placed into a three-neck flask
under an argon atmosphere at −80 °C. nBuLi (31.5 mL of a 1.6 M
solution in n-hexane, 50.4 mmol) was added dropwise. The
temperature was maintained at −80 °C (solution A). The resulting
solution was allowed to reach to −60 °C and was then cooled again to
−80 °C. In parallel, a solution of methyl chloroformate (5.1 mL, 65.7
mmol) in dry n-pentane (180 mL) was placed into another three-neck
flask. This solution (solution B) was cooled to −80 °C, and solution A
was added dropwise to solution B. The resulting solution was allowed
to reach rt. After being stirred overnight at rt, the solution was
quenched with a saturated aqueous solution of ammonium chloride
and extracted five times with diethyl ether. The organic layers were
combined and washed with brine once. The organic layer was dried
over MgSO4 and filtered, and the solvent was evaporated. The residue
was purified by column chromatography (SiO2, n-pentane/diethyl
ether 95:5). 1.4 g of a mixture of compound 4 and methyl valerate in a
ratio of 65/35 was obtained and used subsequently without further
purification. Then, a 32% aqueous solution of ammonia (120 mL) was
immersed in a liquid nitrogen bath. The flask was allowed to warm.
When the aqueous solution became a liquid, a solution of the previous
mixture of compound 4 and methyl valerate (1.4 g) in a minimum of
methanol was added dropwise. After 1.5 h of stirring, the solution was
evaporated. The residue was purified by column chromatography
(SiO2, gradient of elution with DCM/acetone from 10:0 to 9:1).
Compound 5 was obtained as a white solid in 27% yield from 3 (619
mg, 5.78 mmol): 1H NMR (400 MHz, (CD3)2CO) δ = 7.47 (br s, 1H;
NH), 7.04 (br s, 1H; NH), 2.02 (s, 3H; CH3); 13C NMR (100 MHz,
(CD3)2CO) δ = 153.7, 83.0, 69.5, 68.6, 63.0, 3.8.
EXPERIMENTAL SECTION
■
General. Reactions were monitored by thin layer chromatography
and visualized under UV irradiation at 254 nm and KMnO4 staining
solution. Compounds were purified by flash column chromatography
using Geduran silica gel 60 (0.040−0.063 nm). NMR spectra were
recorded on a 400 MHz spectrometer. Spectra were recorded in
deuterochloroform referenced to CHCl3 (1H, 7.26 ppm) or CDCl3
(13C, 77.16 ppm) or deuteroacetone referenced to (CD3) (CD2H)CO
(1H, 2.05 ppm) or (CD3)2CO (13C, 29.84). Chemical shifts (d) are
reported in parts per million and coupling constants (J) are reported in
hertz. The following abbreviations are used to describe multiplicity: s,
singlet; br s, broad singlet; t, triplet. HRMS experiments were carried
out on a Q-ToF spectrometer.
Hexa-2,4-diynenitrile (6). Compound 5 (1.30 g, 12.1 mmol) was
placed in a flask containing P4O10 (17.2 g, 60.7 mmol) and sand (17.2
g). The flask was placed under vacuum and gradually heated from 110
to 150 °C over 1.5 h. The product was collected in a trap immersed in
a bath at −20 °C. Compound 6 was obtained as pure white powder in
Photochemistry. Photolyses were performed using a low-pressure
mercury lamp with a principal emission at 254 nm or another low-
pressure mercury lamp with principal emissions at 254, 193, and 185
nm. Experiments were performed in 4 × 19 cm cylindrical cells of 240
cm3, one in ordinary quartz, which absorbed most of the 185 nm
irradiation, and one with a Suprasil window, which let 254, 193, and
185 nm wavelengths pass through. Therefore, there were three
different kinds of irradiation experiments: one using the 254 nm
wavelength (with the first lamp), another one using the 254 and 193
nm wavelengths (with the second lamp and the quartz cell), and a
third one using the 254, 193, and 185 nm wavlengths (with the second
lamp and the Suprasil cell). In a standard experiment, 100 mbar of
each gas was used. At the end of the photolysis, the cell was connected
to a vacuum line and the gaseous phase was condensed with a
cosolvent on a cooling finger filled with liquid nitrogen. Analysis was
6d
1
88% yield (950 mg, 10.7 mmol): H NMR (400 MHz, CDCl3) δ =
2.05 (s, 3H; CH3); 13C NMR (100 MHz, CDCl3) δ = 105.5, 82.0,
68.4, 63.1, 47.6, 4.7.
Reactivity of MeC5N with Dimethylamine in Methanol (Com-
pounds 12 and 13). To a solution of methylcyanobutadiyne 6 (35
mg, 0.39 mmol) in methanol (1 mL) was added a solution of
dimethylamine in methanol (0.205 mL, 2 M, 0.41 mmol). The
reaction mixture was stirred at rt for 2 h. Then, the solution was
concentrated in vacuo. Purification by flash chromatography (alumina,
n-pentane/acetone 95/5) afforded compound 12 as a yellow-orange
solid in 28% yield (14.8 mg, 0.11 mmol) and compound 13 (29 mg,
1
55%) as a colorless oil. Characterization of compound 12: H NMR
(400 MHz, CDCl3) δ = 4.08 (s, 1H), 2.93 (s, 6 H; NMe2), 2.17 (s, 3
H; Me); 13C NMR (100 MHz, CDCl3) δ = 164.7, 108.3, 90.6, 68.7,
65.0, 40.2, 18.5; HRMS (ESI) m/z calcd for C8H10N2Na+ 157.07417
[M + Na]+, found 157.0744. Crystal data: C6H5NO, M = 134.18 g
1
performed by H NMR spectroscopy. The presence of MeC3N 9 and
MeC5N 6 was confirmed or invalidated by comparison of spectra
before and after subsequent addition of an authentic sample in the
NMR tube.
mol−1, T = 140 K, triclinic, space group = P1, a = 4.1693(5) Å, b =
̅
8.6870(10) Å, c = 10.729(2) Å, α = 95.442(10)°, β = 90.247(10)°, γ =
95.864(10)°, V = 384.78 (10) Å3, Z = 2, Dc = 1.158 g cm−3, absorption
coefficient = 0.071 mm−1, F(000) = 144, reflections collected = 2771,
independent reflections = 1676 (Rint = 0.0398), data/restraints/
parameters = 1676/0/94. Final R indices (I > 2σ): R1 = 0.0529. R
indices (all data): wR2 = 0.1622, goodness-of-fit on F2 of 1.065.
Crystallography. All measurements were made in the omega-
scans technique on a diffractometer with graphite monochromatized
Mo Kα radiation. The structure was solved by direct methods using
the program SIR-97.37 The non-hydrogen atoms were refined
anisotropically by the full-matrix least-squares techniques using the
program SHELXL97. All hydrogen atoms bonded to carbon atoms
were located geometrically and treated using a riding model, with C−
H = 0.95−1.00 Å and Uiso(H) = 1.2 or 1.5 Ueq(C).
1
Characterization of compound 13: H NMR (400 MHz, CDCl3) δ =
3.97 (s, 1H), 2.95 (s, 6H; NMe2), 2.10 (s, 3H; Me); 13C NMR (100
MHz, CDCl3) δ = 147.1, 121.8, 96.6, 72.4, 67.2, 40.1, 4.4; HRMS
F
DOI: 10.1021/acs.joc.6b00205
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(ESI) m/z calcd for C8H10N2Na+ 157.07417 [M + Na]+, found
157.0742.
Higher Education for allowing a Ph.D. fellowship. We also
thank the PCMI program (INSU-CNRS) and the CNES
(Centre National d’Etudes Spatiales) for their financial support.
Reactivity of MeC5N with Dimethylamine in THF (Compound
12). To a solution of methylcyanobutadiyne 6 (35 mg, 0.39 mmol) in
THF (1 mL) was added a solution of dimethylamine in THF (0.20
mL, 2 M, 0.40 mmol). The reaction mixture was stirred at rt for 2 h.
The solution was then concentrated in vacuo. Purification by flash
chromatography (alumina, n-pentane/acetone 95/5) afforded com-
pound 12 as a yellow-orange solid in 82% yield (43 mg, 0.32 mmol).
Reactivity of MeC5N with Morpholine in Methanol (Compounds
14 and 15). To a solution of methylcyanobutadiyne 6 (44 mg, 0.49
mmol) in methanol (1.5 mL) was added a solution of morpholine in
methanol (1.0 mL, 0.5 M, 0.50 mmol). The reaction mixture was
stirred at rt for 2 h. The solution was then concentrated in vacuo.
Purification by flash chromatography (alumina, n-pentane/acetone
from 95/5 to 85/15) afforded compound 14 as a yellow solid in 21%
yield (18 mg, 0.10 mmol) and compound 15 as a white solid in 41%
yield (35 mg, 0.20 mmol). Characterization of compound 14: 1H
NMR (400 MHz, CDCl3) δ = 4.33 (s, 1H), 3.72 (t, 3J(H,H) = 5.0 Hz,
4H; OCH2), 3.20 (t, 3J(H,H) = 5.0 Hz, 4H; NCH2), 2.15 (s, 3H; Me);
13C NMR (100 MHz, CDCl3) δ = 164.3, 107.7, 88.7, 72.0, 66.2, 65.6,
DEDICATION
■
Dedicated to the memory of Professor James P. Ferris
(Rensselaer Polytechnic Institute).
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00205.
■
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AUTHOR INFORMATION
Corresponding Authors
*E-mail: jean-claude.guillemin@ensc-rennes.fr.
*E-mail: yann.trolez@ensc-rennes.fr. Fax: (+33)2-23-23-81-08.
Tel: (+33)2-23-23-80-69.
■
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Notes
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ACKNOWLEDGMENTS
■
This study is a part of the project ANR-13-BS05-0008
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J. Org. Chem. XXXX, XXX, XXX−XXX