Synthesis and Characterization of Cyanobutadiene Isomers-Molecules of Astrochemical Significance

Article abstract of DOI:10.1021/acs.joc.9b03388

Four cyanobutadiene isomers of considerable interest to the organic chemistry, molecular spectroscopy, and astrochemistry communities were synthesized in good yields and isolated as pure compounds: (E)-1-cyano-1,3-butadiene (E-1), (Z)-1-cyano-1,3-butadiene (Z-1), 4-cyano-1,2-butadiene (2), and 2-cyano-1,3-butadiene (3). A diastereoselective synthesis was developed to generate (E)-1-cyano-1,3-butadiene (1) (10:1 E/Z) via tandem S_N2 and E2′ reactions. The potential energy surfaces of the E2′ reactions leading to (E)- A nd (Z)-1-cyano-1,3-butadiene (1) were analyzed by density functional theory calculations, and the observed diastereoselectivity was rationalized in the context of the Curtin-Hammett principle. The preparation of pure samples of these reactive compounds enables measurement of their laboratory rotational spectra, which are the critical data needed to search for these species in space by radioastronomy.

Full text of DOI:10.1021/acs.joc.9b03388

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Synthesis and Characterization of Cyanobutadiene
IsomersMolecules of Astrochemical Significance
Samuel M. Kougias, Stephanie N. Knezz, Andrew N. Owen, Rodrigo A. Sanchez, Grace E. Hyland,
Daniel J. Lee, Aatmik R. Patel, Brian J. Esselman, R. Claude Woods, and Robert J. McMahon*
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ABSTRACT: Four cyanobutadiene isomers of considerable interest to the organic
chemistry, molecular spectroscopy, and astrochemistry communities were
synthesized in good yields and isolated as pure compounds: (E)-1-cyano-1,3-
butadiene (E-1), (Z)-1-cyano-1,3-butadiene (Z-1), 4-cyano-1,2-butadiene (2), and
2-cyano-1,3-butadiene (3). A diastereoselective synthesis was developed to
generate (E)-1-cyano-1,3-butadiene (1) (10:1 E/Z) via tandem SN2 and E2′
reactions. The potential energy surfaces of the E2′ reactions leading to (E)- and
(Z)-1-cyano-1,3-butadiene (1) were analyzed by density functional theory
calculations, and the observed diastereoselectivity was rationalized in the context
of the Curtin−Hammett principle. The preparation of pure samples of these reactive compounds enables measurement of their
laboratory rotational spectra, which are the critical data needed to search for these species in space by radioastronomy.
INTRODUCTION
■
Over 200 different molecules have been detected in the
interstellar medium (ISM) or circumstellar shells1,2 and are
theorized to be involved in complex reaction networks.3−7 The
vast majority of these detections have been made via
radioastronomy, through observation and assignment of
rotational spectra. Because of their large dipole moments,8−10
which confer intense rotational transitions, and composition of
relatively abundant elements, nitriles (R−CN) represent
realistic targets for detection by radioastronomy. Approx-
imately 10% of the known interstellar molecules are nitriles,
including recently detected benzonitrile,11 hydroxyacetoni-
trile,12 and silyl cyanide.13 Interstellar nitriles are observed in
varying degrees of hydrogenation, from highly unsaturated
cyanopolyynes, RC2n+1N (R = H, n = 1−4; R = CH3, n = 1,
2),14−20 to vinyl and phenyl derivatives (vinyl cyanide
(acrylonitrile),21 cyanoallene,22 and benzonitrile11), to com-
pounds with fully saturated backbones (acetonitrile,23
hydroxyacetonitrile,12 propyl cyanide,24 and isopropyl cya-
nide25). Spectroscopic data for the organic nitriles described
herein(E)-1-cyano-1,3-butadiene (E-1), (Z)-1-cyano-1,3-
butadiene (Z-1), 4-cyano-1,2-butadiene (2), and 2-cyano-1,3-
butadiene (3) (Figure 1)would enable radioastronomical
searches for these compounds. Each of these nitriles has been
proposed as a likely component of the ISM.26−30 Additionally,
these nitriles are acyclic isomers of the aromatic heterocycle,
pyridine, which has yet to be identified in the ISM.31 Detection
of any of these nitriles would provide additional motivation to
detect pyridine and other aromatic heterocycles. The existence
of organic nitriles in the ISM is relevant not only to our
understanding of the chemical processes in the ISM but also to
Figure 1. Cyanobutadiene isomers: (E)-1-cyano-1,3-butadiene (E-1),
(Z)-1-cyano-1,3-butadiene (Z-1), 4-cyano-1,2-butadiene (2), and 2-
cyano-1,3-butadiene (3).
our understanding of the origin of amino acids, nucleotides,
and other prebiotic compounds that are critical for life on
Earth.
Organic nitriles have also been detected in the nitrogen-rich
atmosphere of Saturn’s largest moon, Titan. Titan has been of
interest as a possible analogue to prebiotic Earth26 and has
been visited by the Cassini−Huygens probe.32 Small organic
nitriles (up to four carbon atoms) and their corresponding
anions were detected in Titan’s atmosphere.33 Electric
discharge experiments performed on various gaseous mixtures
(e.g. N2, CH4, C2H6, NH3, H2O, and H2S) simulating the
atmosphere of Titan produce a myriad of nitrile-containing
small molecules.3,34,35 It is plausible that the nitriles in Figure 1
are components of Titan’s atmosphere.
Despite the sophistication of modern synthetic chemistry,
the synthesis, purification, and isolation of the simple organic
Received: December 16, 2019
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nitriles shown in Figure 1 remain a challenge at the current
time. The new procedures reported in this work enable
detailed studies of the high-resolution rotational spectroscopy
of the four cyanobutadiene isomers (Figure 1).36 The
rotational spectrum of each of these compounds is very
complex; having a pure sample, for which spectral features are
not obscured by impurities, is critical to achieve a sophisticated
analysis of the complex spectrum. In measuring gas-phase
spectra, volatile impurities are especially problematic. Our
procedures have been designed to minimize, or eliminate,
these troubling contaminants. This work provides the
foundation for the ultimate detection of nitriles E-1, Z-1, 2,
and 3 in extraterrestrial environments. With their relevance in
the atmospheric chemistry of Titan and interstellar chemistry,
the improved isolation of these nitriles allows new spectro-
scopic measurements of broad interest to the chemistry
community.
E-1 and Z-1, but the experimental procedures for synthesis,
purification, and isolation were designed for a relatively large
scale, and these reports predate modern methods for
spectroscopic characterization.45−54
An efficient, selective synthesis of (E)-1-cyano-1,3-butadiene
(E-1) has not been described, although modern synthetic
procedures for producing a mixture of diastereomers (E-1 and
Z-1) have been reported (Scheme 1e−g). The preparation
reported by Braun et al.55 (Scheme 1e) involves the reaction of
the acetonitrile anion with acrolein and subsequent protec-
tion/elimination steps to yield diastereomers E-1 and Z-1 in a
2:1 ratio. The procedure described by Clary and Back56
(Scheme 1f) combines diethylcyanomethyl-phosphonate ylide
with acrolein in a Horner−Wadsworth−Emmons olefination
to afford diastereomers E-1 and Z-1 in a 3:1 ratio. Banert57
reported the selective preparation of Z-1 by thermolysis or
photolysis of 1-azido-cyclopentadiene (Scheme 1g). These
various procedures notwithstanding, details concerning both
purification and characterization of E-1 and Z-1 remain
incomplete because of the sensitivity and high reactivity of
these compounds under a variety of conditions.
The literature does not include any reports describing the
synthesis of 4-cyano-1,2-butadiene (2) or the determination of
its physical properties. 2-Cyano-1,3-butadiene (3) has been
prepared, typically via synthetic routes that involve a pyrolysis
reaction.51,58−60 As with the 1-cyano isomers, details
concerning both purification and characterization of 2-cyano-
1,3-butadiene (3) remain incomplete.
BACKGROUND
■
1-Cyano-1,3-butadiene (2,4-pentadienenitrile) (1; mixture of E
and Z isomers) was originally isolated and studied at DuPont
as a potential monomer unit by Carothers and co-workers
(Scheme 1a).37−40 Snyder et al. prepared 1 by flash vacuum
pyrolysis (Scheme 1b), separated the E and Z isomers by
careful fractional distillation,41 and investigated the reactivity
of 1 in trapping, dimerization, and polymerization reac-
tions.42−44 These early investigations contain a wealth of
useful data describing the synthesis and physical properties of
RESULTS AND DISCUSSION
■
Scheme 1. Previous Syntheses of 1-Cyano-1,3-butadiene
(1)
1-Cyano-1,3-butadiene (1). From the time of the earliest
interest in 1-cyano-1,3-butadiene (1) (Scheme 1),37−44 it has
been evident that generating this compound has not been the
obstacle to further study. Rather, the sensitivity of 1 to undergo
reaction (dimerization, polymerization) or degradation (heat,
light, strong bases, and silica/alumina gels) greatly complicates
the task of purifying and characterizing 1. Our attempts to
replicate the procedure reported by Braun et al.55 (Scheme 1e)
failed to produce an isolable amount of the expected mixture of
diastereomers. In our hands, the procedure described by Clary
and Back56 (Scheme 1f) afforded E-1 and Z-1 as components
in a rather complex mixture of products. Analysis of the crude
1H NMR spectrum revealed the presence of suspected
polymeric byproducts generated through addition reactions
between E-1/Z-1 and the strong base used to generate the
phosphonate ylide. Thus, we sought alternate synthetic
strategies to facilitate isolation, purification, and character-
ization of compound 1.
a
We replicated the conditions for the synthesis of 1-cyano-
1,3-butadiene (1) reported by the DuPont group (Scheme
1a).38,39 To prepare the requisite starting material, 4-chloro-
1,2-butadiene (7), we employed the sequence depicted in
Scheme 2a. 2-Butyne-1,4-diol (4) was monochlorinated with
SOCl2 to produce 4-chloro-2-butyn-1-ol (5), and subsequent
reduction of 5 with LiAlH4 produced 1,2-butadien-4-ol (6).61
Chlorination of 6 with SOCl2 produced 4-chloro-1,2-butadiene
(7),62 which was isolated and subjected to the reaction
conditions described by Coffman (Scheme 1a).39 Analysis of
the resulting product mixture via 1H NMR spectroscopy
revealed the presence of both E-1 and Z-1 along with several
methoxy-substituted species resulting from the addition of
methanol across one (or both) of the double bonds present in
1, as noted previously.39 We suspected that the mixed solvent
a
(a) Carothers and Berchet;38 Coffman.39 (b) Snyder et al.41 (c)
Daessle et al.48 (d) Katagiri et al.53 (e) Braun et al.55 (f) Clary and
Back.56 (g) Banert.57
B
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Scheme 2. Initial Synthetic Route to 1-Cyano-1,3-butadiene (1) from 2-Butyne-1,4-diol (4)
a
b
1
Isolated (gravimetric) yield. Yield and diastereomeric ratio determined via H NMR.
Scheme 3. Improved Synthetic Route to 1-Cyano-1,3-butadiene (Mixture E-1 and Z-1) from Propargyl Alcohol (9)
a
b
Reaction yield determined via 1H NMR using phenyltrimethylsilane (Ph-TMS) as an internal standard. Diastereomeric ratio determined via 1H
NMR.
system (H2O/MeOH) in Scheme 1a was used in an attempt to
optimize the solubility of the ionic and the organic reactants
(sodium cyanide and 4-chloro-1,2-butadiene (7), respectively),
but the formation of methanol adducts is clearly problematic.
We changed the reaction solvent to acetonitrile, which
seemed to be a more appropriate solvent for an SN2 reaction.
The solubility of alkali-metal cyanides in most polar aprotic
organic solvents is low, so a crown ether (18-crown-6)63 was
used as a phase-transfer catalyst. Although a solution of KCN
and 18-crown-6 in acetonitrile was not completely homoge-
nous, the increased solubility of cyanide was apparently
sufficient that the reaction mixture rapidly became a turbid,
dark brown color as the reaction progressed (Scheme 2b). The
13C{1H}NMR spectrum of the crude reaction mixture
contained three signals characteristic of an allenic sp-
hybridized 13C atom, indicating the presence of alcohol 6,
chloride 7, and a previously unreported allene derivative.
Further analysis via two-dimensional NMR spectroscopy
(HMBC/HSQC) showed correlation of the new allenic 13C
of unreacted starting material 7. Extending the reaction time to
4 h resulted in the formation of a polymeric material and
complete loss of both E-1 and Z-1yet, there was still
unreacted 7 present (evident via NMR). The same reaction
sequence employing the corresponding 4-bromo-1,2-butadiene
(8) afforded a better result. 4-Bromo-1,2-butadiene (8) was
prepared in two steps from propargyl alcohol (9) (Scheme
3a).61,64 When treated with the same reaction conditions as
allenic chloride 7, allenic bromide 8 reacted in a more
controlled, clean manner, yielding significantly less of the
brown polymeric material. The reaction of allenic bromide 8 to
form 2 and the subsequent isomerization of 2 to 1 were
unexpectedly slow; at room temperature and under anhydrous
conditions, isomerization of 4-cyano-1,2-butadiene (2) to 1-
cyano-1,3-butadiene (1) took 5 days (80% yield; approx-
imately 1:1 mixture of E-1 and Z-1) (Scheme 2c). Despite the
use of a phase-transfer catalyst, the reaction in acetonitrile was
not homogenous. The addition of water (∼10% v/v) to the
reaction mixture increased the solubility of KCN and
decreased the reaction time to approximately 24 h (Scheme
3b). The optimal conditions for producing a 1:1 mixture of E-1
and Z-1 with minimal byproducts are reported in Scheme 3b.
Even though the reaction efficiently produced E-1 and Z-1, we
were confounded in our efforts to separate, purify, and isolate
these isomers, as prepared using this procedure. Difficulties
included the inability to remove small amounts of acetonitrile
and propensity for dimerization and/or polymerization.
Requiring pure, neat materials in order to obtain their
rotational spectra, we turned to other synthetic strategies
that might afford a measure of selectivity in the preparation of
E-1 and Z-1.
1
signal to three H signals sharing a very similar coupling
pattern as observed in alcohol 6 and chloride 7, but with
different J-coupling frequencies and chemical shifts. We
suspected that the unassigned 13C signal was due to 4-cyano-
1,2-butadiene (2), the presumed product of initial SN2
substitution in chloro compound 7, prior to rearrangement
to 1-cyano-1,3-butadiene (1). This suspicion was later
confirmed to be true. Details concerning the optimization of
reaction conditions, isolation, and spectroscopic character-
ization of 4-cyano-1,2-butadiene (2) are discussed below.
Along with 4-cyano-1,2-butadiene (2), smaller amounts of 1-
cyano-1,3-butadiene (E-1 and Z-1) were formed in this
reaction, and the product mixture also included a large amount
C
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Scheme 4. Strategy for Diastereoselective Synthesis of (E)-1-Cyano-1,3-butadiene (E-1)
Scheme 5. Diastereoselective Synthesis of (E)-1-Cyano-1,3-butadiene (E-1) from (Z)-1,2-Dibromo-2-butene (Z-10)
a
b
c
1
1
Isolated (gravimetric) yield. Diastereomeric ratio determined via H NMR. 1,4-Dicyano-2-butene (Z-13) not observed via H NMR.
(E)-1-Cyano-1,3-butadiene (E-1). Daessle et al. demon-
spectroscopy showed the rapid formation of E-1/Z-1 upon
the addition of KCN to Z-10. Signals corresponding to (Z)-1-
bromo-4-cyano-2-butene (Z-11) or (Z)-1,4-dicyano-2-butene
(Z-13), a potential byproduct resulting from a second SN2
strated that 1-cyano-1,3-butadiene (1) can be accessed via an
E2′ (1,4-elimination) reaction of a mixture of 1-chloro-4-
cyano-2-butenes with anhydrous ammonia (Scheme 1c).48
Katagiri et al. demonstrated that 1 can be produced in a one-
pot synthesis involving the treatment of a mixture of 1,4-
dibromo-2-butenes (10) with alkali-metal cyanides under basic
conditions (Scheme 1d).53 Although the diastereoselectivity of
these reactions was not previously investigated, we saw an
opportunity to influence the diastereoselectivity of the reaction
to favor the formation of E-1 over Z-1 via the stereochemistry
of the 1,4-dibromo-2-butene precursor Z-10 or E-10 (Scheme
4). Consistent with similar precedents,65−67 we hypothesized
that E2′ reaction of (Z)-1-bromo-4-cyano-2-butene (Z-11)
would favor the formation of E-1 over Z-1 because of a steric
preference for the cyano group to be rotated away from the cis
−CH2Br group in the transition state for the elimination
reaction. In fact, selectivity in favor of E-1 was observed, and a
computational analysis of the basis for the selectivity is
described later in this article.
(Z)-1,4-Dibromo-2-butene (Z-10), prepared from (Z)-2-
buten-1,4-diol (12) via Appel conditions,68 readily reacts with
two equivalents of KCN through tandem SN2/E2′ reactions to
form 1-cyano-1,3-butadiene (1; E/Z ratio 14:1) without the
addition of an exogenous base (Scheme 5). The best results
were observed using binary acetonitrile/water solvent systems.
Reactions performed in pure acetonitrile (via the addition of
solid KCN to the stirring reaction) proceeded slowly and never
to full conversionlikely because of the low solubility of KCN
in acetonitrile. Several other polar aprotic solvents were
investigated for use in these reactions [dimethylformamide
(DMF), tetrahydrofuran (THF), glyme, diethyl ether, poly-
ethylene glycol (PEG), and dimethyl sulfoxide (DMSO)],
although the cleanest reactions were observed with the
acetonitrile/water solvent system. DMF and DMSO accel-
erated the reaction to the point of a rapid exotherm, which
resulted in degradation of the product, likely because of the
high concentration of cyanide in these solvents. We found that
the best diastereoselectivity was observed (with near-complete
conversion) in experiments where aqueous KCN was added
slowly to a solution of Z-10 and 18-crown-6 in acetonitrile at 0
°C. Evaluation of the reaction progress via 1H NMR
1
displacement in Z-11, were not observed in the H NMR
spectrum as the reaction progressed. The rapid formation of E-
1/Z-1 and the absence of observable Z-11 and Z-13 signals in
1
the H NMR evaluation suggest that the product-forming E2′
reaction occurs more rapidly than either of these competing
reactions. The drawback of this procedure was the difficulty of
removing the residual acetonitrile solvent from the product E-
1.
The following procedure was developed with the goal of
optimizing the isolation and purification of the target
compound (E)-1-cyano-1,3-butadiene (E-1). The addition of
Z-10 to 50 mol % of 18-crown-6 resulted in a eutectic mixture,
which remained a liquid when cooled to 0 °C. Slow addition of
aqueous KCN to a rapidly stirring eutectic mixture of Z-10/18-
crown-6 at 0 °C proceeded to full conversion, while retaining
good diastereoselectivity to produce E-1. Subsequent extrac-
tion with diethyl ether and fractional distillation of the product
mixture yielded 1-cyano-1,3-butadiene (1) in 90% isolated
yield (E/Z ratio 10:1) (Scheme 6).
Scheme 6. Modified Reaction Conditions for Efficient
Synthesis and Purification of (E)-1-Cyano-1,3-butadiene (E-
a
1)
a
b
Isolated (gravimetric) yield. Diastereomeric ratio determined via
1H NMR.
(Z)-1-Cyano-1,3-butadiene (Z-1). A selective route to
produce (Z)-1-cyano-1,3-butadiene (Z-1) has been reported,57
although details of the experimental procedure and spectro-
scopic properties are not readily available. Multiple studies
describe the separation, isolation, and physical properties of Z-
1.41,69 As a counterpart to our development of a selective
process for the preparation of E-1 from Z-1,4-dibromo-2-
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butene (Z-10), we observed that subjecting E-10 to the
reaction conditions shown in Scheme 7 resulted in a mildly
Scheme 7. Modified Reaction Conditions for Semi-selective
Preparation of (Z)-1-Cyano-1,3-butadiene (Z-1) from (E)-
1,4-Dibromo-2-butene (E-10)
a
b
Reaction yield determined via 1H NMR. Diastereomeric ratio
c
1
determined via H NMR. Isolated (gravimetric) yield.
Figure 2. Computed reaction coordinate diagram for E2′ reaction of
(Z)-1-bromo-4-cyano-2-butene (Z-11) with cyanide in water. Gibbs
free energies at B3LYP/cc-pVTZ with the polarized continuum model
for the solvent (H2O) at 273 K (0 °C). Solid line: lower energy
transition state. Dashed line: higher energy transition state.
selective formation of Z-1. Although this procedure utilizes
acetonitrile as the solvent, which was problematic in the
isolation and purification of E-1, the slightly higher volatility of
Z-1 enables its separation from E-1 and acetonitrile in a
straightforward fashion. Iterative fractional distillation of the
product mixture increased the relative concentration of Z-1 in
the distillate, resulting in a reasonably pure sample of Z-1 after
three distillations. Purity was sufficient that the ratio of E to Z
by rotational spectroscopy was observed to be approximately
1:8 (E-1/Z-1).
Computational Analysis of Diastereoselectivity in the
Formation of 1-Cyano-1,3-butadiene (E-1/Z-1). The reaction
to form (E)-1-cyano-1,3-butadiene (E-1) from (Z)-1,4-
dibromo-2-butene (Z-10) is hypothesized to proceed through
(Z)-1-bromo-4-cyano-2-butene (Z-11), which, once formed,
reacts with another equivalent of cyanide to eliminate HBr in a
concerted 1,4-elimination mechanism (E2′ mechanism). Given
that the E and Z diastereomers of 1-cyano-1,3-butadiene (1)
are predicted to be very similar in energy (within 1 kcal/mol)
and the reactions of different precursor stereoisomers lead to
different product ratios, it is clear that a kinetically controlled
reaction is responsible for the observed diastereoselectivity.
Thus, the E2′ transition state barriers leading to each
diastereomer of 10 must be responsible for the selectivity, or
lack thereof, in the formation of E-1 and Z-1.
Figure 3. Computed reaction coordinate diagram for E2′ reaction of
(E)-1-bromo-4-cyano-2-butene (E-11) with cyanide in water. Gibbs
free energies at B3LYP/cc-pVTZ with the polarized continuum model
for the solvent (H2O) at 323 K (50 °C). Solid line: lower energy
transition state. Dashed line: higher energy transition state.
The proposed E2′ substrates, (Z)- and (E)-1-bromo-4-
cyano-2-butene (11), exhibit multiple conformational isomers,
which are analyzed in detail (see Supporting Information). The
isomerization barriers for all conformations of both diaster-
eomers are less than 6 kcal/mol. Contour plots and the
detailed analysis of the complete conformational potential
energy surfaces of Z-11 and E-11 are provided in the
Supporting Information. For the reaction of each diastereomer
(Z-11 or E-11) with cyanide ion, calculations predict two pairs
of E2′ transition states leading to products (E-1 and Z-1)
(Figures 2 and 3). In each of the transition state geometries, an
acidic hydrogen atom at C-4 is perpendicular to the plane of
the adjacent alkene unit. The bromide leaving group at C-1 can
be in an anti or syn orientation with respect to the acidic
hydrogen atom at C-4. The cyano substituent at C-4 may
occupy a syn-periplanar conformation relative to the alkene
moiety, which leads to the formation of (Z)-1-cyano-1,3-
butadiene (Z-1), or an antiperiplanar conformation, which
leads to the formation of (E)-1-cyano-1,3-butadiene (E-1).
Each transition state was verified to connect one diastereomer
of the starting material (11) to one diastereomer of the
product (1), using an intrinsic reaction coordinate (IRC)
calculation. Attempts to explore a stepwise pathway beginning
with deprotonation of Z-11 or E-11 failed to obtain an anionic
intermediate as a stationary point. Therefore, a stepwise
mechanism was not considered further.
For either diastereomer of 1-bromo-4-cyano-2-butene (E-11
or Z-11), the computed activation barriers of the E2′ transition
states are significantly higher (by 7−14 kcal/mol) than the
activation barriers for conformational interconversion. Thus,
the diasteroselectivity in the elimination reaction is interpreted
in terms of the Curtin−Hammett principle.70 Product
selectivity is governed by the difference in energy between
the competing product-forming transition states (ΔΔG⧧);
conformational equilibrium in the starting materials is rapid
and does not govern the composition of products. As such, the
potential energy surfaces for the E2′ reactions shown in
Figures 2 and 3 contain a simplified surface for the
E
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conformational isomerization of each 1-bromo-4-cyano-2-
butene (E-11 or Z-11).
reaction; minimal isomerization of 2 is observed. The rate of
substitution, however, is too slow to be useful. The addition of
water to the reaction mixture increases the solubility of
cyanide, increases the rate of substitution, and increases the
rate of isomerization of 2 to 1. (Ultimately, the rate becomes
very rapid and results in a noticeable exotherm.) At a reaction
temperature of 0 °C, the isomerization is slow enough such
that 4-cyano-1,2-butadiene (2) can be isolated (Scheme 8a). In
In the E2′ reaction of (Z)-1-bromo-4-cyano-2-butene (Z-
11) with cyanide in water at 273 K (0 °C) (Figure 2), the
transition states TS2a and TS2b that lead to (Z)-1-cyano-1,3-
butadiene (Z-1) are higher in energy than the transition states
TS1a and TS1b that lead to (E)-1-cyano-1,3-butadiene (E-1).
Thus, the computational analysis is in qualitative accordance
with the experimental observation of diastereoselectivity
favoring the formation of (E)-1-cyano-1,3-butadiene (E-1).
The difference in transition state energies (ΔΔG⧧) appears to
arise from a steric interaction in the transition states involving
the −CH2CN group. Both transition states leading to Z-1
(TS2a and TS2b) have a larger interaction between −CN and
−CH2Br, relative to the transition states leading to E-1 (TS1a
and TS1b). The small energy difference between the E-1-
forming transition states TS1a and TS1b (0.8 kcal/mol) is
likely due to a subtle difference in electrostatic interactions
(repulsion) between the bromo and cyano substituents in the
anti versus syn E2′ elimination pathways. Natural bond orbital
(NBO) analysis of each transition state did not reveal any
obvious hyperconjugation contribution to the energy differ-
ences among TS1a, TS1b, TS2a, and TS2b. Assuming that this
potential energy surface reasonably models this reaction, the E-
1/Z-1 ratio derived from the ΔΔG⧧ between TS1a and TS2a
(2.4 kcal/mol) is expected to be ca. 60:1. This result is in
qualitative agreement with the experimental observation of an
E-1/Z-1 ratio of 10:1. This does indicate, however, that the
computational prediction of ΔΔG⧧ is larger than its true value
by about 1 kcal/mol.
In a similar fashion, the potential energy surface of the E2′
reaction of (E)-1-bromo-4-cyano-2-butene (E-11) with
cyanide in water at 323 K (50 °C) is presented in Figure 3.
Unlike the reaction of the isomeric system (Z-11), the
transition states for the E2′ reaction of E-11 leading to (E)-
and (Z)-1-cyano-1,3-butadiene (1) are computed to be
virtually isoergic (ΔΔG⧧ = 0.1 kcal/mol favoring the formation
of E-1). With the −CH2CN and −CH2Br groups in a trans
orientation in the ground state of E-11, there is no significant
preference for the −CN substituent to adopt one conformation
over the other. This situation is also manifested in the
transition states (TS3a, TS3b, TS4a, and TS4b); the relative
energies of the transition states reveal no preference for the
stereochemical course of the reaction. Thus, the rates of
product formation would be expected to afford a diastereo-
meric ratio of nearly 1:1. This prediction is consistent with the
experimentally observed product ratio of E-1/Z-1 (E/Z ratio
2:3). The deviation of the experimental ratio from 1:1 reveals
that there is a slight energetic preference (<1 kcal/mol) for the
transition states leading to the Z diastereomer. Our computa-
tional model is not expected to be of sufficient accuracy to
account for such a small energetic difference.
Scheme 8. Preparation of 4-Cyano-1,2-butadiene (2)
a
b
Reaction yield determined via 1H NMR. Isolated (gravimetric)
yield.
the absence of aqueous acidic or basic conditions, 2 is stable
when isolated. The slow addition of an organic-soluble cyanide
source [tetrabutylammonium cyanide (TBAC)], under anhy-
drous conditions, allows for an efficient SN2 reaction and
isolation of pure 2 without significant isomerization (Scheme
8b). Once the cyanide is consumed, exposure to water in the
subsequent extraction (to remove the polar aprotic solvent)
does not promote significant isomerization of 2. In fact, neat 2
can be left at ambient conditions for weeks without observable
isomerization. Nitrile 2 is sufficiently stable that it can be
distilled under a relatively low vacuum (100 Torr) without
noticeable degradation. In contrast to the regioselectivity
exhibited in the rearrangement of the corresponding allenic
halides,71 the isomerization of allenic nitrile 2 yields exclusively
1-cyano-1,3-butadiene (1). 2-Cyano-1,3-butadiene (3) is not
observed, which is attributable to the absence of cyanide
dissociation/recombination previously observed for the
corresponding allenic halides.
2-Cyano-1,3-butadiene (3). Although 2-cyano-1,3-buta-
diene (3) has been prepared previously, synthetic routes often
involve a pyrolysis reaction as the last step.51,58−60 Preferring
to avoid a pyrolysis reaction, we prepared 2-cyano-1,3-
butadiene (3) using a combination of literature procedures
from Strub et al.72 and Nonaka et al.73−75 (Scheme 9).
Scheme 9. Preparation of 2-Cyano-1,3-butadiene (3)
a
4-Cyano-1,2-butadiene (2). As described earlier, we
observed 4-cyano-1,2-butadiene (2) as an intermediate during
the preparation of 1-cyano-1,3-butadiene (1) from 4-halo-1,2-
butadienes (7 or 8) (Scheme 2). In order to optimize
conditions for the preparation and isolation of 2, it was
necessary to avoid the isomerization of 2 to 1a process that
is typically observed under conditions that utilize both water
and cyanide (a weak base) at ambient temperature. When the
reaction of 4-bromo-1,2-butadiene (8) is performed under
anhydrous conditions (dry solvent, vacuum-dried crown ether,
and vacuum-dried KCN), bromide 8 undergoes slow SN2
Isolated (gravimetric) yield.
Morita−Baylis−Hillman addition of acrylonitrile (14) and
acetaldehyde using catalytic 1,4-diazabicyclo[2.2.2]octane
(DABCO) afforded 3-hydroxy-2-methylenebutanenitrile (15)
in quantitative yield.72 Subsequent dehydration of 15 was
performed using catalytic K2CO3. The resulting 2-cyano-1,3-
butadiene (3) was distilled from the reaction mixture under
vacuum and collected as an aqueous emulsion that separated
upon cooling. Compound 3 is prone to undergo polymer-
ization, even at −20 °C.
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(collection flask cooled to −78 °C and distillation flask cooled to 0
°C). The distillate consisted of a mixture of E and Z isomers of 1-
cyano-1,3-butadiene (1) in a ratio of 2:1 in addition to residual THF.
1H NMR (400 MHz, CDCl3): E-isomer δ 6.31 (ddt, 1H, J = 16, 11,
<1 Hz), 5.74 (tt, 1H, J = 10, <1 Hz), 4.94 (dm, 1H, J = 17, <1, <1
Hz), 4.93 (dm, 1H, J = 10, <1, <1 Hz), 4.65 (dd, 1H, J = 16, <1 Hz)
ppm; Z-isomer δ 6.59 (dtd, 1H, J = 17, 10, <1 Hz), 6.03 (tt, 1H, J =
10, <1 Hz), 5.03 (dm, 1H, J = 17, <1, <1 Hz), 5.02 (dm, 1H, J = 10,
<1, <1 Hz), 4.55 (dd, 1H, J = 10, <1 Hz). HRMS (ASAP-Q-IT)81 m/
z: [M + H]+ calcd for C5H6N, 80.0495; found, 80.0493.
SUMMARY
■
We describe the synthesis, isolation, purification, and
spectroscopic characterization of four cyano-butadiene iso-
mers: (E)-1-cyano-1,3-butadiene (E-1), (Z)-1-cyano-1,3-buta-
diene (Z-1), 4-cyano-1,2-butadiene (2), and 2-cyano-1,3-
butadiene (3). These molecules are of considerable signifi-
cance to the field of astrochemistry, as possible constituents of
both planetary atmospheres and interstellar space. Because of
the general experimental difficulties in handling these reactive
compounds, the literature data concerning the spectroscopic
characterization [NMR, IR, and mass spectrometry (MS)] of
these simple organic molecules are remarkably sparse. Our new
procedures enable isolation and purification of these
compounds, affording high quality NMR, IR, and MS data,
for the first time. The preparation of pure samples of these
molecules enables the measurement of their laboratory
rotational spectrathe critical data needed to search for
these species in space by radioastronomy.
The procedure involves the formation of a phosphonate ylide
followed by reaction with acrolein in a Horner−Wadsworth−
Emmons-type olefination.56 Although this reaction appears to be
1
straightforward, the resulting H NMR spectrum does not agree with
that described in the literature.56 Upon closer investigation, the
1
previously reported H NMR data do not account for all hydrogen
atoms in the molecule. Although each isomer (E-1 and Z-1) should
have five signals in the spectrum, the E-isomer (E-1) has four reported
signals and the Z-isomer (Z-1) has only three.56 Additionally, the
reaction inherently undergoes a side reaction, and not all signals in the
crude spectrum are attributable to 1. The combination of the two
issues combined with challenges encountered in purification created
confusion in characterization and complicated the optimization and
troubleshooting processes. These issues are discussed in greater detail
in the Supporting Information section.
COMPUTATIONAL METHODS
■
Geometry optimizations and harmonic frequency calculations were
conducted with density functional theory using the B3LYP func-
tional76,77 and the cc-pVTZ basis set,78 correcting for water as a
solvent by employing the polarizable continuum model as
implemented in Gaussian 16.79 Thermally corrected Gibbs free
energies for all species were obtained from the harmonic frequency
calculations at 273, 298, and 323 K and are summarized in the
Supporting Information. Conformational analyses of the local minima
are included in the Supporting Information along with the Cartesian
coordinates of the optimized stationary points. Additional calculations
were conducted for the E2′ (1,4-elimination) transition states: IRC
calculations verified that each transition state smoothly connects one
diastereomer of the starting material to one diastereomer of the
product. Natural Bond Orbital (NBO) and Natural Resonance
Theory (NRT) calculations80 were used to analyze the electronic
structure, bonding, hyperconjugation, and relative energies of energy
minima and transition states on the potential energy surfaces.
Isolation of E- and Z-Isomers of 1-Cyano-1,3-butadiene (1). One
of the challenges encountered during the isolation of neat E-1/Z-1
originates from its volatility and its tendency to form azeotropes with
acetonitrile. The complete removal of acetonitrile was necessary for
obtaining accurate spectra and isolated yields of the product. Solvent
removal via rotary evaporation drastically reduced product yields
because of the azeotropic losses. We found that most acetonitrile
could be removed through aqueous washes of the crude ethereal
extract during reaction workup. Remaining traces of acetonitrile could
be fully removed from the products by low-temperature vacuum
distillation (∼100−500 mTorr, 0 °C). Attempts to remove
acetonitrile via careful vacuum fractional distillation were marginally
effective, as a small amount of acetonitrile always codistilled with the
product diastereomers. We found that highly volatile solvents (such as
the diethyl ether used during the biphasic extraction of the reaction
mixture) were more easily removed via fractional distillation through
a packed column under atmospheric pressure without codistilling any
E-1 and Z-1. Additionally, product losses resulting from polymer-
ization of E-1 and Z-1 during the distillation process were minimized
via the addition of a phenolic polymerization inhibitor. We found that
hydroquinone was ideal for our purposes because its high boiling
point and extremely low volatility prevented its codistillation with E-1
and Z-1 during the final purification.
(Z)-1,4-Dibromo-2-butene (Z-10). In a modification of literature
procedures,83−85 52.55 g (200 mmol) of PPh3 was added to 300 mL
of acetonitrile in a 500 mL round-bottom flask equipped with a 100
mL dropping funnel. The reaction vessel was sealed with a septum
and cooled to 0 °C on ice. The reaction vessel and contents were
subjected to three vacuum pump/N2 purge cycles. Br2 (10.2 mL,
197.8 mmol) was added dropwise to the stirring PPh3 suspension via
the dropping funnel. (Z)-2-Buten-1,4-diol (12) (9.04 g, 103 mmol)
was rapidly added to the stirring suspension via a syringe. The cooling
bath was removed, and the reactants were stirred for 1 h. After the
elapsed reaction time, approximately half of the acetonitrile solvent
was removed by rotary evaporation. The resulting triphenylphosphine
oxide precipitate was removed via vacuum filtration. The filtrate was
then evaporated to dryness. The resulting orange solids were
dissolved in 50 mL of 1:4 EtOAc/n-hexane and filtered through a
silica plug (5 cm) to remove any remaining triphenylphosphine oxide.
The solvent was removed in vacuo to yield 18.07 g (88%) of (Z)-1,4-
dibromo-2-butene (Z-10) as a pale-yellow oil. CAUTION: (Z)-1,4-
Dibromo-2-butene is a potent lachrymator and vesicant and must be
handled with caution. Samples of (Z)-1,4-dibromo-2-butene will
isomerize upon heating and should be stored in a freezer (−20 °C).
1H NMR (CDCl3, 500 MHz):δ (ppm) complex spin system, 5.89 (m,
EXPERIMENTAL SECTION
■
General Experimental Methods. All commercial reagents were
purchased from Sigma-Aldrich, Acros, or Oakwood and used as
received, unless otherwise noted. 1H NMR spectra (400 or 500 MHz)
and 13C{1H}-NMR spectra (100 or 125 MHz) were obtained in
CDCl3, CD3CN, or C6D6 on a Bruker 400 MHz AVANCE III or
Bruker 500 MHz DCH AVANCE III spectrometer; chemical shifts
(δ) are reported as ppm downfield from internal standard SiMe4.
Mass spectra were acquired using electrospray ionization (ESI) or the
atmospheric solids analysis probe (ASAP)81 on a Thermo Scientific
Q-Exactive Plus mass spectrometer. GC/MS analysis was performed
on a Shimadzu GCMS-2010S. IR spectra were obtained on a Bruker
TENSOR Fourier transform infrared instrument as neat samples using
an attenuated total reflectance accessory (Bruker PLATINUM ATR).
1-Cyano-1,3-butadiene (1). Our preliminary studies concerning
the preparation, isolation, and identification of 1-cyano-1,3-butadiene
(1) provide some context for the experimental difficulties
encountered and detail concerning the spectroscopic assignments.82
Following the procedure of Clary and Back:56 to a suspension of
sodium hydride (2.88 g, 120 mmol) in freshly distilled THF (500
mL) was added diethyl cyanomethylphosphonate (8.1 mL, 50.1
mmol) dropwise via a syringe at 0 °C. After stirring for 1 h, freshly
distilled acrolein (3.6 mL, 53.9 mmol) was added dropwise. The
reactants were stirred for 5 h at 0 °C, warmed to room temperature,
and quenched with saturated aqueous NH4Cl solution. The solution
was extracted with diethyl ether, washed with saturated aqueous
NaCl, and dried over MgSO4. After removal of the drying agent by
filtration, ether was removed under reduced pressure at room
temperature, and the resulting mixture was fractionally distilled
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2H), 4.02 (m, 4H). 13C{1H}-NMR (CDCl3, 125 MHz): δ (ppm)
129.9, 24.7.
(w). HRMS (ESI) m/z: [M + H]+ calcd for C5H6N, 80.0495; found,
80.0494.
4-Chloro-2-butyne-1-ol (5). In a slight modification of literature
procedures,86−89 59.75 g (0.69 mol, 1 equiv) of 2-butyne-1,4-diol (4),
70 mL of dry dichloromethane, and 62 mL (770 mmol, 1.1 equiv) of
dry pyridine were added to a 1 L flame-dried three-neck round-
bottom flask under a N2 atmosphere. The stirring reaction vessel was
cooled to 0 °C on ice, and 56 mL (92 g, 772 mmol) of SOCl2 was
added dropwise over a time of 4 h via a pressure-equalizing addition
funnel. A white precipitate formed over the course of the SOCl2
addition. The reactants were then poured onto 200 mL of ice water
and subsequently extracted with dichloromethane (3 × 150 mL). The
combined organic layers were washed with saturated aqueous
NaHCO3 (1 × 100 mL) and saturated aqueous NaCl (1 × 100
mL) and dried over anhydrous Na2SO4. After removal of the drying
agent by gravity filtration, dichloromethane was removed in vacuo to
yield a deep red oil. The crude product was purified by vacuum
distillation using a short-path apparatus to yield 42.32 g (58%) of
colorless 4-chloro-2-butyne-1-ol (5), bp 50 °C (0.5 Torr).
CAUTION: 4-chloro-2-butyne-1-ol is highly explosive and a powerful
skin irritantcare must be taken when handling.90 1H NMR (CDCl3,
500 MHz): δ (ppm) 4.33 (t, 2H, 5J = 2 Hz), 4.19 (t, 2H, 5J = 2 Hz).
13C{1H}-NMR (CDCl3, 125 MHz): δ (ppm) 84.6, 80.5, 51.1, 30.3.
HRMS (ESI) m/z: [M + H]+ calcd for C4H5ClO; [35Cl]-isotopologue
calcd, 105.0107; found, 105.0102; [37Cl]-isotopologue calcd,
107.0078; found, 107.0072.
(E)-1-Cyano-1,3-butadiene (E-1) ((E)-2,4-Pentadienenitrile). (Z)-
1,4-Dibromo-2-butene (Z-10; 5.38 g, 25.2 mmol), 3.36 g (12.7
mmol) of 18-crown-6, and 57 mg (0.52 mmol) of hydroquinone were
added to a 50 mL single-neck round-bottom flask. The reaction vessel
was sealed with a septum and purged with N2 via a syringe needle
inlet. The vessel was then cooled to 0 °C on ice. Potassium cyanide
(4.09 g, 62.8 mmol) was dissolved in 10 mL of deionized H2O and
delivered to the cooled reaction dropwise via a syringe pump over the
course of 2 h with vigorous stirring. As the addition completed, the
reaction became biphasic with an orange top organic layer and a tan
bottom aqueous layer. The reactants were stirred for an additional 15
min at 0 °C after the addition was complete and then allowed to
warm to room temperature. The reaction mixture was rinsed into a
separatory funnel with 10 mL of diethyl ether and 10 mL of deionized
H2O, the organic layer was separated, and the aqueous layer was
extracted with diethyl ether (4 × 10 mL). The combined organic
layers were washed with 10 mL of saturated aqueous NaCl and dried
over anhydrous CaCl2. After removal of the drying agent by gravity
filtration, hydroquinone (97 mg) was added to the filtrate and the
ethereal solvent was removed by fractional distillation at atmospheric
pressure (45 cm Vigreux column). The crude product was cooled to
room temperature, and a vacuum of ∼400 Torr was applied to remove
residual ether. The remaining yellow concentrate was purified via
bulb-to-bulb (Kugelrohr) distillation to yield 1.80 g of 1-cyano-1,3-
butadiene (1) (90%, 10:1 E/Z) as a colorless oil. Compound E-1 is
indefinitely stable as a neat substance at −80 °C or in a dilute solution
of diethyl ether with the hydroquinone inhibitor to prevent
polymerization. 1H NMR (C6D6, 500 MHz): δ (ppm) E-1: 6.34
(dd, 1H, J = 16, 10 Hz), 5.79 (dt, 1H, J = 17.1, 10.3 Hz), 5.01 (d, 1H,
J = 2.4 Hz), 4.99 (d, 1H, J = 2.7 Hz), 4.69 (d, 1H, J = 16 Hz).
13C{1H}-NMR (C6D6, 125 MHz): δ (ppm) 150.0, 134.3, 125.9,
117.8, 100.2. IR (neat): (cm−1) 3054 (w), 2218 (m), 1629 (w), 1589
(m), 1417 (w), 1292 (w), 1258 (w), 1001 (s), 955 (m), 932 (m), 835
(m), 475 (w). HRMS (ESI) m/z: [M + H]+ calcd for C5H6N,
80.0495; found, 80.0494.
1,2-Butadien-4-ol (6). Early Method.87,88 Lithium aluminum
hydride (6.09 g, 16 mmol) and dry diethyl ether (80 mL) were
added to a flame-dried 250 mL three-neck round-bottom flask fitted
with a dry ice condenser under a N2 atmosphere and stirred to
generate a slurry. 4-Chloro-2-butyne-1-ol (5) (4.19 g, 40 mmol) was
diluted with 16 mL of dry diethyl ether and delivered dropwise via a
syringe to the stirring LAH slurry at a rate sufficient to maintain a
gentle reflux. After the addition of 5, the reactants were stirred for 30
min at 25 °C. The reaction was cooled to 0 °C on ice, and the septa
were removed. The reaction was quenched via Fieser workup: (slow
addition of 6 mL of deionized H2O, then 6 mL of 15% aqueous
NaOH, and finally 18 mL of deionized H2O). A scoop of anhydrous
Na2SO4 was added to promote aggregation of the precipitated
aluminum salts, and the vessel was stirred overnight at 25 °C. The
reaction mixture was filtered, and the organic layer was separated. The
aqueous layer was extracted with diethyl ether (3 × 25 mL). The
combined organic extracts were then dried over anhydrous Na2SO4
and filtered, and the solvent was removed in vacuo. The crude product
was purified by vacuum distillation using a short-path apparatus to
yield 1.99 g (71%) of colorless 1,2-butadien-4-ol (6), bp 60 °C (40
Torr).
(Z)-1-Cyano-1,3-butadiene (Z-1) ((Z)-2,4-Pentadienenitrile). Po-
tassium cyanide (9.88 g, 152 mmol, 3 equiv) and 18-crown-6 (6.66 g,
25 mmol, 50 mol %) were dissolved in 20 mL of deionized H2O in a
100 mL three-neck round-bottom flask. Hydroquinone (110 mg, 1
mmol) was added to the flask to inhibit polymerization of the
product. The flask was purged with N2 and sealed with rubber septa.
The vessel was heated to 50 °C in an oil bath. Under positive N2
pressure, one septum was removed from the reaction vessel and solid
(E)-1,4-dibromo-2-butene (E-10) (10.72 g, 50.1 mmol, 1 equiv) was
added in ∼2 g increments to the vigorously stirring KCN/18-crown-6
solution over the course of 15 min. The reaction mixture darkened to
a reddish-brown color during the addition of E-10. The reaction was
cooled to room temperature and rinsed into a separatory funnel with
10 mL of diethyl ether and 10 mL of deionized H2O. The organic
layer was separated, and the aqueous layer was extracted with diethyl
ether (4 × 25 mL). The combined organic layers were washed with
saturated aqueous NaCl (1 × 25 mL) and dried over anhydrous
CaCl2. The drying agent was removed by gravity filtration, and the
ethereal solvent was removed by fractional distillation at atmospheric
pressure (45 cm glass bead packed column). The product was purified
by vacuum distillation through the same apparatus to yield 1-cyano-
1,3-butadiene (1) (34%, 2:3 E/Z) as a colorless oil (bp 75 °C, 100
Torr). Subsequent fractional distillations through the same apparatus
can be performed to further separate Z-1 from E-1. Compound Z-1
exhibits greater thermal stability than E-1, presumably because of
Primary Method.64,90 A flame-dried 5 L three-neck round-bottom
flask was equipped with a reflux condenser (open to air),
thermometer, and mechanical stirrer. To this vessel were added CuI
(115.37 g, 605 mmol, 50 mol %), paraformaldehyde (59.53 g, 1.98
mol, 1.6 equiv), and 2.4 L of dry THF. The mechanical stirrer was
started, and dry diisopropylamine (240 mL, 1.71 mol, 1.4 equiv) was
addedthe reaction mixture appeared faint green. Propargyl alcohol
(9) (74 g, 76 mL, 1.3 mol) was added to the reaction mixture. The
addition of propargyl alcohol resulted in an immediate exotherm
(increase from 20 to 30 °C), and the reaction color changed to bright
orange. The reaction was heated with a mantle to reflux for 24 h. After
cooling to 25 °C, most of the THF solvent was removed via rotary
evaporation. The concentrated reaction mixture was slowly added to a
stirred, cooled (0 °C) solution of diethyl ether (1 L) and 12 N HCl
(120 mL), resulting in the formation of a viscous brown precipitate.
The stirring was stopped, and the mixture was allowed to separate.
The supernatant ether was decanted, and the brown precipitate was
extracted with diethyl ether (2 × 1 L). The combined ether extracts
were filtered through a silica plug (ø = 80 mm × 50 mm), dried over
anhydrous Na2SO4, and concentrated in vacuo. The crude product
was purified by vacuum distillation using a short-path apparatus to
yield 47.2 g (52%) of colorless 1,2-butadien-4-ol (6), bp 60 °C (40
1
lower reactivity with respect to dimerization or polymerization. H
NMR (C6D6, 500 MHz): δ (ppm) Z-1: 6.58 (dt, 1H, J = 16.8, 10.6
Hz), 5.98 (t, 1H, J = 10.9 Hz), 5.02 (d, 1H, J = 16.8 Hz), 5.0 (d, 1H, J
= 10.2 Hz), 4.48 (d, 1H, J = 10.7 Hz). 13C{1H}-NMR (C6D6, 125
MHz): δ (ppm) 148.7, 132.7, 126.2, 115.9, 98.4. IR (neat): (cm−1)
3071 (w), 2216 (m), 1628 (w), 1574 (m), 1428 (w), 1359 (w), 1296
(w), 1229 (w), 1001 (m), 934 (s), 778 (m), 667 (s), 487 (w), 444
1
Torr). H NMR (CDCl3, 500 MHz): δ (ppm) complex spin system,
H
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5.34 (apparent quint, 1H, J = 6.4 Hz), 4.85 (m, 2H, J = 3 Hz), 4.14
(m, 2H, J = 3 Hz), 2.4 (br s, 1H). 13C{1H}-NMR (CDCl3, 125
MHz): δ (ppm) 207.9, 90.8, 77.0, 60.2.
quint, 1H, J = 6.4 Hz), 4.97 (m, 2H, J = 3.3 Hz), 3.09 (m, 2H, J = 3.3
Hz). 13C{1H}-NMR (CDCl3, 125 MHz): δ (ppm) 209.0, 117.3, 81.2,
78.6, 17.5. IR (neat): (cm−1) 2252 (w), 1960 (w), 1417 (w), 913 (w),
852 (s), 731 (w), 678 (w), 521 (w), 467 (w). HRMS (ESI) m/z: [M
+ H]+ calcd for C5H6N, 80.0495; found, 80.0495.
4-Chloro-1,2-butadiene (7).62,86,88 SOCl2 (16.97 g, 10.4 mL,
143 mmol, 1.25 equiv), 11.28 g of dry pyridine (11.5 mL, 143 mmol,
1.25 equiv) and 50 mL of dry diethyl ether were added to a flame-
dried, three-neck 500 mL round-bottom flask equipped with a
pressure-equalizing addition funnel and reflux condenser under a N2
atmosphere. The vessel was cooled to 0 °C on an ice bath. A solution
of 1,2-butadien-4-ol (6) (7.97 g, 114 mmol, 1 equiv) in 70 mL of dry
diethyl ether was delivered dropwise to the stirring reaction via an
addition funnel over 15 min. A white precipitate formed over the
course of the addition. The reaction was heated to reflux in an oil bath
for 2 h. The reaction was cooled to room temperature and quenched
via the addition of 15 mL of deionized H2O. The organic layer was
separated, and the aqueous layer was extracted with diethyl ether (3 ×
15 mL). The combined organic layers were dried over anhydrous
Na2SO4 and filtered. The ethereal solvent was removed by fractional
distillation at atmospheric pressure (45 cm Vigreux column). The
fractionating column was removed, and the product was purified by
distillation at atmospheric pressure using a short-path apparatus to
yield 6.10 g (60%) of 4-chloro-1,2-butadiene (7) as a colorless oil. bp
3-Hydroxy-2-methylenebutanenitrile (15). Acrylonitrile (14)
(13.64 g, 257 mmol, 1 equiv), acetaldehyde (11.4 g, 259 mmol, 1
equiv), and 1,4-diazabicyclo[2.2.2]octane (DABCO) (5.64 g, 50
mmol, 20 mol %) were added to a 250 mL single-neck round-bottom
flask. The vessel was sealed with a septum and stirred for 96 h. The
1H NMR spectrum of a reaction aliquot showed complete conversion
after 96 h. The crude product was put on a vacuum line (∼100 Torr)
to remove unreacted acrylonitrile and acetaldehyde, and the crude 3-
hydroxy-2-methylenebutanenitrile (15) was used in the next synthetic
step without further purification (clear amber liquid). 1H NMR
(CDCl3, 500 MHz): δ (ppm) 6.0 (d, 1H, J = 1.4 Hz), 5.94 (s, 1H),
4.38 (qt, 1H, J = 6.4, 1.2 Hz), 3.90 (br s, 1H), 1.41 (d, 3H, J = 6.5
Hz). 13C{1H}-NMR (CDCl3, 125 MHz): δ (ppm) 128.9, 128.4,
117.3, 68.0, 22.3.
2-Cyano-1,3-butadiene (3). K2CO3 (0.19 g, 1.4 mmol, 1.8 mol
%) and 1.2 mL of deionized H2O were added to a 50 mL round-
bottom flask containing the crude 3-hydroxy-2-methylene-butaneni-
trile (15) from the preceding synthetic step. Hydroquinone (20 mg)
was added to the mixture to inhibit polymerization during the
subsequent distillation. The vessel was connected to a short-path
distillation apparatus, and a vacuum of 100 Torr was applied to the
system. The boiling flask was immersed in an oil bath at 100 °C, and
the reactants were stirred vigorously to break the surface tension. The
distillation-head temperature increased to 52 °C as the colorless
distillate immediately started condensing as a biphasic mixture. A total
of 8.6 g of biphasic distillate was collected over 1 h. Over the elapsed
collection time, the contents of the boiling flask darkened to a dark
red color and the collection rate slowed. The colorless product (the
organic layer of the distillate) was separated and dried over anhydrous
Na2SO4/activated charcoal. The drying and decolorizing agents were
removed by filtration through a fine glass frit to yield 3.21 g (51%) of
2-cyano-1,3-butadiene (3) as a colorless oil. When stabilized with
hydroquinone, 3 can be purified via vacuum distillation (bp 55 °C,
100 Torr). Compound 3 is prone to undergo polymerization, even at
1
88 °C (760 Torr). H NMR (CDCl3, 500 MHz): δ (ppm) complex
spin system, 5.36 (m, 1H, J = 7.7, 6.6 Hz), 4.91 (dt, 2H, J = 6.6, 2.2
Hz), 4.08 (dt, 2H, J = 7.7, 2.2 Hz). 13C{1H}-NMR (CDCl3, 125
MHz): δ (ppm) 209.5, 89.0, 77.5, 66.0.
4-Bromo-1,2-butadiene (8).88 PBr3 (21.6 g, 10.4 mL, 80 mmol),
7.89 g of dry pyridine (8 mL, 100 mmol), and 20 mL of dry diethyl
ether were added to a flame-dried, single-neck 250 mL round-bottom
flask equipped with a pressure-equalizing addition funnel under a N2
atmosphere. The vessel was cooled to 0 °C on an ice bath. A solution
of 1,2-butadien-4-ol (6) (14.01 g, 200 mmol, 1 equiv) in 20 mL of dry
diethyl ether was delivered dropwise over 15 min to the stirring
reaction via an addition funnel, and stirring was continued for 24 h.
The reaction was allowed to warm to room temperature and
quenched with 100 mL of deionized H2O. The layers were separated,
and the aqueous layer was extracted with diethyl ether (4 × 75 mL).
The combined organic extracts were washed with saturated aqueous
NaCl (1 × 75 mL) and dried over anhydrous Na2SO4. After removal
of the drying agent by filtration, the solvent was removed in vacuo.
The crude product was purified by vacuum distillation using a short-
path apparatus to yield 17.73 g (67%) of colorless 4-bromo-1,2-
butadiene (8), bp 62 °C (100 Torr). 1H NMR (CDCl3, 500 MHz): δ
(ppm) complex spin system, 5.45 (m, 1H, J = 8.1, 6.5 Hz), 4.93 (dt,
2H, J = 6.6, 2.2 Hz), 3.96 (dt, 2H, J = 8.2, 2.0 Hz). 13C{1H}-NMR
(CDCl3, 125 MHz): δ (ppm) 209.8, 89.5, 77.5, 30.1.
1
−20 °C. H NMR (CDCl3, 500 MHz): δ (ppm) 6.35 (dd, 1H, J =
17.2, 10.4 Hz), 5.94 (s, 1H), 5.86 (s, 1H), 5.73 (d, 1H, J = 17.2 Hz),
5.47 (d, 1H, J = 10.4 Hz). 13C{1H}-NMR (CDCl3, 125 MHz): δ
(ppm) 132.2, 130.5, 122.5, 120.7, 115.9. IR (neat): (cm−1) 2986 (w),
2233 (w), 1736 (m), 1582 (w), 1378 (m), 1244 (m), 1045 (w), 983
(m), 924 (s), 492 (m). HRMS (ESI) m/z: [M + H]+ calcd for
C5H6N, 80.0495; found, 80.0494.
4-Cyano-1,2-butadiene (2) (2,3-Pentadienenitrile). 4-Bromo-
1,2-butadiene (8; 3.38 g; 25.4 mmol), was added to a flame-dried 100
mL single-neck round-bottom flask. The reaction vessel was then
sealed with a septum and purged with N2 via the syringe needle inlet.
Dry acetonitrile (10 mL) was added via a syringe, and the stirring
vessel was cooled to 0 °C on ice. A solution of 6.70 g (24.99 mmol) of
tetrabutylammonium cyanide (TBAC) in 15 mL of dry acetonitrile
was delivered dropwise to the vigorously stirring reaction over 1 h via
a syringe pump. The reaction was allowed to stir at 0 °C for 15 min
after the TBAC addition had completed. The 1H NMR spectrum of a
reaction aliquot showed complete conversion of 2 with minimal
(<2%) isomerization to E-1 and Z-1. The reaction was then rinsed
into a separatory funnel with 50 mL of diethyl ether and 30 mL of
cold deionized H2O (0 °C). The organic layer was separated, and the
aqueous layer was extracted with diethyl ether (3 × 25 mL). The
combined organic layers were washed with deionized H2O (5 × 25
mL) and saturated aqueous NaCl (1 × 25 mL) and dried over
anhydrous Na2SO4. After removal of the drying agent by gravity
filtration, the ethereal solvent was removed by fractional distillation at
atmospheric pressure via a short-path apparatus. From the resulting
concentrate, 4-cyano-1,2-butadiene (2) was purified either by flash
column chromatography (SiO2, 3:1 n-pentane/Et2O, Rf = 0.5) or by
distillation (bp 94 °C, 100 Torr). Isolated yield: 62%. 1H NMR
(CDCl3, 500 MHz): δ (ppm) complex spin system; 5.13 (apparent
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b03388.
Computational details and H- and 13C{1H}-NMR, IR,
and mass spectra for all compounds (PDF)
1
AUTHOR INFORMATION
■
Corresponding Author
Robert J. McMahon − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States; orcid.org/0000-0003-1377-5107;
Email: robert.mcmahon@wisc.edu
Authors
Samuel M. Kougias − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States; orcid.org/0000-0002-9877-0817
I
https://dx.doi.org/10.1021/acs.joc.9b03388
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pubs.acs.org/joc
Article
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Stephanie N. Knezz − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States; orcid.org/0000-0001-9445-2953
Andrew N. Owen − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
Rodrigo A. Sanchez − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
Grace E. Hyland − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
Daniel J. Lee − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
Aatmik R. Patel − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
Brian J. Esselman − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
R. Claude Woods − Department of Chemistry, University of
Wisconsin−Madison, Madison, Wisconsin 53706-1322, United
States
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Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b03388
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Science Foundation
for support of this project (CHE-1664912, CHE-1362264).
We thank the following organizations and individuals for
support of shared departmental facilities: departmental
computing resources (NSF CHE-0840494), Bruker AVANCE
400 NMR spectrometer (NSF CHE-1048642), Bruker
AVANCE 500 NMR spectrometer (gift from Paul J. and
Margaret M. Bender), and Thermo Scientific Q Exactive Plus
mass spectrometer (NIH 1S10 OD020022-1). We thank Dr.
Timothy S. Zwier for stimulating discussions.
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Cyanide (Acrylonitrile). Astrophys. J. 1975, 195, L127−L130.
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E. Hyperfine Structure Identification of Interstellar Cyanoallene
Toward TMC-1. Astrophys. J. 2006, 637, L37−L40.
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