Direct Exploitation of the Ethynyl Moiety in Calcium Carbide Through Sealed Ball Milling

Article abstract of DOI:10.1002/ejoc.202000612

Ball milling of calcium carbide (CaC₂) enables the reaction of its ethynyl moiety with organic electrophiles. This was realized simply by co-milling CaC₂ with organic substrates in a sealed jar without the need for an additive or a catalyst. Various ketones including those bearing α-hydrogens were ethynylated in good yields at short reaction times. Aryl halides are also amenable substrates for this protocol as they furnish aryl ethynes through a benzyne intermediate. This method offers a practical and cheap alternative to the established procedures for introducing ethynyl functionalities.

Full text of DOI:10.1002/ejoc.202000612

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Direct Exploitation of the Ethynyl Moiety in Calcium Carbide
Through Sealed Ball Milling
Authors: Abolfazl Hosseini and Peter Richard Schreiner
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
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content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000612
Link to VoR: https://doi.org/10.1002/ejoc.202000612
01/2020

10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
Direct Exploitation of the Ethynyl Moiety in Calcium Carbide
Through Sealed Ball Milling
Abolfazl Hosseini[a] and Peter R. Schreiner*[a]
[a]
Dr. A. Hosseini, Prof. Dr. P. R. Schreiner
Institute of Organic Chemistry, Justus Liebig University Giessen
Heinrich-Buff-Ring 17, 35392 Giessen (Germany)
E-mail: prs@uni-giessen.de
Home page: https://www.uni-giessen.de/schreiner
Supporting information for this article is given via a link at the end of the document.
Abstract: Ball milling of calcium carbide (CaC2) enables the reaction
of its ethynyl moiety with organic electrophiles. This was realized
simply by co-milling CaC2 with organic substrates in a sealed jar
without the need for an additive or a catalyst. Various ketones
including those bearing α-hydrogens were ethynylated in good yields
at short reaction times. Aryl halides are also amenable substrates for
this protocol as they furnish aryl ethynes through a benzyne
intermediate. This method offers a practical and cheap alternative to
the established procedures for introducing of ethynyl functionalities.
achievement, it has yet to be demonstrated that the suggested
polyalkynylated product can be isolated using this protocol. Later
on, Borchardt and co-workers described
a
one-pot
mechanochemical synthesis of N-doped porous carbons using a
planetary ball mill.[11] The authors carefully monitored the reaction
progress and used various techniques for their product
characterization but ruled out the presence of sp-hybridized
carbon in the final product as evident from Raman spectroscopy.
Introduction
“Calcium carbide has no value for the synthetical processes of
organic chemistry” is an infamous quote of Harry C. Jones dating
back more than 120 years.[1] Even though this is not entirely true,
today we are still challenged by the problems associated with
exploring and exploiting the full potential of CaC2 as a valuable
starting material for organic synthesis.[2] Beginning with the
commercial production of calcium carbide (CaC2) in 1892,[3] the
idea lingered on how to transfer the ethynyl moiety from a
crystalline, insoluble inorganic carbide into organic molecules.[4]
The ability to construct C–C bonds in a highly efficient manner
from such a cheap, readily available, and stable starting material
has obvious synthetic utility and value.[5] Therefore, many
attempts have been devoted to utilizing CaC2 in organic synthesis
during the early decades of the 20th century.[6] Oroshnik and
Mebane showed that calcium diacetylide (HCºC-Ca-CºCH)
readily reacts with ketones to furnish the desired propargyl
alcohols,[7] but the low solubility of polymeric calcium acetylide
(i.e., CaC2) prevents the direct addition to carbonyl compounds.
Increasing the solubility of calcium carbide with additives has
become a renewed subject of investigation and various organic
transformations utilizing such a strategy were reported recently.[2b,
Scheme 1. Progress in the mechanochemical activation of calcium carbide.
The most promising result for mechano-activation of CaC2
was reported by Bolm and Hernández et al. who successfully
exploited CaC2 in a one-pot three component synthesis of 1,4-
diamino-2-butynes (Scheme 1).[12] Contrary to a previous report
for the same reaction under conventional conditions, the
disubstituted product (1,4-diamino-2-butyne) was preferentially
obtained under milling conditions. The same authors also
2c, 8]
The inherently nearly impenetrable and mechanically hard
structure of solid CaC2 evoked the idea of using ultrasound or
mechanical force ball milling techniques.[9]
Shearing and friction of solid materials induced by mechanical
energy fractures the solid into fine particles, thus enabling
materials to react. Bearing this idea in mind, Li et al. reported the
described
a
mechanochemical Favorskii-type alkynylation
reaction under solvent-free conditions using calcium carbide and
a fourfold stoichiometric ratio of KOH.[13] The method offers
direct alkynylation of polyhalogenated hydrocarbons with CaC2
10]
using a planetary ball mill.[9b,
Despite this impressive
1
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
advantages over the previous procedure where benzene and a
reaction time of several days were required.[14] Despite such
notable advances, a relatively limited substrate scope arose from
base promoted aldol condensation of ketones bearing α-
hydrogens, which limits the broad application of this method.[15]
The additive-free reactions reported by Li et al.[8h, 9b, 10b, 10c] are
indeed different from that of Bolm and Hernández who utilized a
catalyst or an additive; no reaction occurred in the absence of an
additive.[13] Therefore, the question remains whether it is possible
to transfer the ethynyl moiety directly from CaC2 without the need
for an additive or a catalyst. A way to activate neat CaC2 and
understand the fundamental issues could greatly facilitate the use
of CaC2 in organic synthesis. Here we report the ethynylation of
ketones using CaC2 directly without additive. So far, various
reagents including alkali metal acetylides or ethynyl Grignard
reagents have been utilized for ethynylation reactions, however,
the preparation of these reagents requires strong bases, dry
solvents, and acetylene gas, which makes them expensive and
cut in half when benzophenone was added to pre-milled calcium
carbide, indicating that active CaC2 readily decomposes upon
exposure to air (Table 1, entry 6). With this result, we further
optimized the molar ratio of benzophenone to CaC2 (the average
purity was taken into account); a molar ratio of 0.28:6 was by far
the best (Table 1, entries 7–9). The reaction at low impact milling
afforded high yields and better mass balance than entry 6, albeit
at longer reaction times (Table 1, entry 11).
Table 1. Optimization of the Conditions of the Reaction of Calcium Carbide
(CaC2) with Benzophenone (1a) under Ball Milling Conditions in Different
Stainless Steel (SS) or Tungsten Carbide (WC) Jars.[a]
inconvenient to handle.[16]
Therefore, replacing traditional
Entry
1a (mmol)
CaC2
t (min)
Jar
Yield (%)[b]
(mmol)
acetylide reagents with CaC2 would be highly desirable. In theory,
the activation of CaC2 through mechanical milling seems plausible
as small particles with high surface areas are expected to be
much more reactive and even pyrophoric when exposed to air.[17]
The essential challenge is the determination of the factors of the
milling process that affect the reactivity of the formed small
reactive particles.
2a
–
3a
1
0.14
0.14
0.14
0.14
0.28
0.28
0.28
0.28
0.28
0.28
0.28
3
3
3
3
6
6
3
9
12
6
6
40
40
40
40
40
40
40
40
40
60
80
WC
WC
SS
–
2[c]
3
–
–
trace
17
19
25[h]
9
trace
36
4[d,e,f]
5[d]
6[g]
7
SS
SS
39
Results and Discussion
WC
WC
WC
WC
SS
50[h,i]
15
We began with the ball milling reaction of benzophenone with
CaC2 in a tungsten carbide (WC) jar at a frequency of 30 Hz for
40 min. However, only black insoluble carbon ensued (Table 1,
entry 1); the starting materials could not be recovered from the
reaction mixture. Only a stainless steel (SS) jar provided some
evidence for product formation upon TLC analysis (Table 1, entry
3). To avoid heating the sample through the milling process the
reaction was performed at low temperatures (Table 1, footnote d).
To our delight, the reaction progressed well with a total product
yield of 53% and a 1:2 mono:di ratio (Table 1, entry 4). This kind
of transformation has not been reported using CaC2 without the
need for an additive or a catalyst. Almost the same yield was
obtained when the amounts of starting materials were doubled
(Table 1, entry 5), implying scalability. Even though we obtained
a reasonable yield, the low mass balance (⁓70%) remained
unsatisfactory. This may be rationalized by the so-called “hot spot
theory” that assumes that local temperatures at tips of
propagating cracks may reach several hundreds or thousands of
degrees Celsius in a fraction of a second.[18] In fact, the high
frequency vibration allows some air flow into the jar, thereby
burning the organic matter in the milling process; depending on
oxygen supply, this delivers carbon monoxide or carbon black.
8
23
27
15
15
40
9
39
10
11[j]
37
WC
47[k]
[a] Reaction conditions: Crushed CaC2 and 1a placed in a 20 mL SS or WC
jar and milled for the indicated time at 30 Hz. [b] Yields determined by 1H
NMR using 1,4-dinitrobenzene as internal standard. [c] Jar sealed under Ar
atmosphere. [d] Jar cooled every 10 min by immersion into a liquid nitrogen
bath for ca. 1 min. [e] 16% of 1a remained unreacted according NMR
analysis. [f] 17% yield of products obtained when milling continued for 80
min. [g] Addition of benzophenone to milled calcium carbide at room
temperature reduced the yield to half. [h] Yield of isolated product. [i] 6% of
1a recovered. [j] Reaction performed at 25 Hz. [k] 22% of 1a remained.
Note that the mass ratio of the starting materials is critical and
a free flow powder is needed to drive the reaction. As a result,
increasing the ratio of benzophenone decreases the yield due to
the formation of a wet cohesive mixture (Table 1, entry 7). With
the optimized conditions in hand, other ketones were investigated
for the direct ethynylation with calcium carbide (Table 2). Bulky
2-naphthyl phenyl ketone gave moderate yields of isolated
products under both 30 and 25 Hz milling conditions, with
decreased selectivity for di-substituted product. Improved yields
were achieved when 0.22 mmol (0.05 g, the optimized mass ratio
according to Table 1) of 1b was employed.
The mass loss was confirmed when the reaction time for entry
4 of Table 1 was extended to 80 min giving only 17% yield. The
airflow could be readily prevented by applying grease to seal the
circumference of the jar screw cap, and we were delighted to
isolate the desired products in 75% yield with a 1:2 mono:di ratio
(Table 1, entry 6). We also tested the reactivity of pre-milled CaC2,
however, these fine powder or nanoparticle forms are highly
sensitive to air and moisture. For instance, the yield was almost
2
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
Table 2. Ball Milling Alkynylation of Ketones using Calcium Carbide.[a]
[a] Reaction conditions: Ketone (0.28 mmol), CaC2 (6 mmol) milled for specified time in a grease sealed 25 mL tungsten carbide jar. [b] Yields determined by 1H
NMR using 1,4-dinitrobenzene as internal standard. [c] Ratio determined by NMR. [d] Yield of isolated product. [e] 0.22 mmol of ketone used. [f] 12% of 1c
remained (NMR). [g] 7% of 4,4′-dichlorobenzophenone remained (NMR). [h] 3,4,5-Trimethoxybenzaldehyde used as internal standard. [i] Jar cooled every 10
min by immersion into a liquid nitrogen bath for ca. 1 min. [j] 3f obtained as mixture of diastereomers. [k] 6.8 mmol of CaC2 used. [l] 8% of adamantanone
remained (NMR). [m] 44% of 1j remained (NMR). [n] More than 50% of substrate remained (NMR).
4,4′-Dichlorobenzophenone (1c) afforded low yield under
optimized reaction conditions with small amounts of unreacted
starting material (12% by NMR). The chlorine in 1c possibly
provides an opportunity for halogen replacement (vide infra),
leading to low yield. The side reactions could be diminished by
conducting the reaction at low impact milling, giving the
3
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
ethynylated products in 48% after 80 min. Similar results were
obtained with 4,4'-dimethylbenzophenone (1d) providing the
corresponding products in total 50% yields and a 1:1.5 mono:di
ratio. Ketone bearing heterocyclic moieties also react with CaC2
to give the corresponding products in similar yields at low impact
conditions. In contrast, high impact milling provided only low
yields with somewhat lower selectivity even at low temperature.
Notably, enolizable ketones 1f and 1g were also tolerated and
furnished the corresponding products in good yields; aliphatic
ketones were also ethynylated (Table 2, entries 1h–1j). Non-
enolizable adamantanone 1i afforded the products in 54% yield
and a 1:2.2 mono:di ratio, and the yield could be increased to 71%
under low impact conditions. A similar result was obtained in case
of bulky diamantanone 1j (Table 2). In general, benzo-fused
cyclic ketones were less reactive than the benzophenone
derivatives. The reaction of fluorenone 1k with calcium carbide
provided 2k and 3k in 38% yield and a 1:2 mono:di ratio at 25 Hz
whereas high impact milling gave lower yield with inversed
selectivity. 10,10-Dimethylanthrone 1l gave similar results and no
significant improvement was observed even after prolonged
reaction time. Xanthone 1m and 1-phenyl-2-pyrrolidinone 1n
were unreactive under our reaction conditions.
To probe this hypothesis, a control experiment was performed in
the presence of CaO. Surprisingly, 50% of anthraquinone 4p and
12% of dianthrone 5p were obtained, proving that calcium oxide
could act as a reasonably effective oxidizing agent under these
conditions (Scheme 2). This result is consistent with the previous
findings that CaC2 promotes formation of radicals at high
temperatures.[19]
Scheme 2. Ball Milling Reaction of Anthrone with CaC2 and CaO.
Stimulated by the indication of radical reactivity, we then
became interested in the chemical reactivity of CaC2 toward aryl
halides under ball milling conditions. Aryl ethynes are the building
blocks often encountered within a wide range of natural and
Our efforts to extend our protocol to aldehydes was met with
synthetic organic materials.
The Sonogashira coupling of
mixed success.
exploited as
3,4,5-trimethoxybenzaldehyde (1o) was
solid aldehyde in similar manner (see
acetylenes with aryl halides, provides a useful tool for accessing
of mono and diaryl-substituted acetylenes.[21] However, even with
considerable effort, the high cost and environmental issues
associated with the use of palladium catalysts, expensive ligands
as well as the use of protected acetylenes restrict the industrial
application of the Sonogashira method. Having established
alternative reaction conditions, we probed the feasibility of a
catalyst and ligand-free alkynylation of aryl halides under ball
milling, conditions.[22] A test reaction using 9-bromophenanthrene
(Ar-a) as a substrate showed that the reaction did produce the
desired product, 9-ethynylphenanthrene (Ar-a1), albeit in low
a
a
Supplementary Information for details) but only low product yields
along with Cannizzaro side products and an ester were obtained
after 80 min milling at 25 Hz (Scheme S1). Shortening the milling
process to 60 min at 25 Hz and utilizing low temperatures
improved the yields (Scheme S1).
In the course of our studies, an unexpected result observed
with anthrone 1p piqued our curiosity about the mechanism and
also lends support to the need of excluding air entering the system.
Instead of the desired alkynylated product, the reaction was
accompanied with the formation of anthraquinone 4p and
yield.
The competitive formation of phenanthrene (Ar-H)
dianthrone 5p in 28% and 9%, respectively.
This result
implicate that both radical[19] and dehydrohalogenation (benzyne
formation)[22] pathways are probably involved (Scheme 3a).
apparently conflicts with the intrinsic reducing property of CaC2.[19]
Since CaO is the main impurity of CaC2, we reasoned that the
contribution from the CaO might facilitate benzylic oxidation.[20]
Scheme 3. Additive-Free Reaction of Calcium Carbide with Aryl Halides under Ball Milling Conditions.
4
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
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Aryl fluorides have less tendency to radical formation and are
more prone to generate benzyne intermediates when exposed to
base catalysts.[23] Hence, 2-fluoro-1,4-dimethoxybenzene (Ar-b)
was subjected to ethynylation under milling conditions. In a series
of test reactions, we found that performing the reaction using low
frequency with an elongated time improves the yield to 42% of
mono- and di-substituted (Scheme 3b). Clearly, this reaction is
also assisted by the formation of highly stable CaF2.
The surface morphologies of the milled CaC2 particles were
analyzed by scanning electron microscopy (SEM). The milled
CaC2 particles in grease-sealed jar are discrete and flaky in shape
with a diameter range of nm to μm (Figure 2a) whereas the CaC2
particles in an ungreased jar show amorphous morphology with
micrometer dimensions (Figure 2c). A key difference was
observed in the corresponding EDX spectra: The carbon content
of the former (15.5%) was significantly higher than the later (5.0%).
This implies that carbon content was reduced due to the diffusion
of moisture and oxygen through the jar’s screw cap during the
milling process (Figures 2b and 2d). This finding also confirms
our results above (Table 1) that tight sealing of the ball milling jar
is essential to utilize the starting materials more effectively. We
suggest that milling of CaC2 generates crystal defects on the
surface of CaC2 nanoparticles leading to formation of highly
reactive acetylide species. If unprotected from oxygen and
moisture, these activated acetylides rapidly react to give carbon
monoxide/carbon or acetylene gas that is rapidly lost. In sealed
containers, the activated acetylides react with electrophiles
instead.
100
80
60
Total Yield
40
2a
20
3a
0
0
5
1 0 1 5 2 0 2 5 3 0 3 5 4 0
Time (min)
Conclusion
Figure 1. Time/yield Profile of 1a with CaC2 under Ball Milling Conditions.
We demonstrate that CaC2 can be mechanochemically activated
through mechanical milling. Unlike all previous approaches for
the activation of CaC2, which usually require base and/or catalysts,
our method delivers the product without the need for a catalyst or
an additive. This allowed us to alkynate various ketones including
those are bearing α-hydrogens in good yields with a preference
for disubstitued products. Some selected aryl halides were
To gain preliminary insight into what happens in the ball
milling for the ketone alkynylation, we monitored the overall
reaction rate using benzophenone 1a as the test substrate in a
tungsten carbide (WC) jar at a frequency of 30 Hz. The time/yield
profile of this reaction suggests that di-substituted product 3a may
form from a doubly deprotonated (and complexed with Ca2+) 2a
adduct (Figure 1). Consequently, a reduction in the concentration
of 1a led to a decrease in the rate of the formation of 3a at around
25 min.
alkynylated with good selectivities as well.
This method
represents a practical approach for the activation of CaC2 and
opens new opportunities for its use in synthesis. A key finding is
that the ball milling jars have to be as air tight as possible to avoid
the loss of material through the escape of acetylene gas or
“burning” with oxygen.
As an outlook, we suggest that
(a)
(b)
modifications of the jars to have much tighter sealing and better
temperature control would greatly improve the efficiency of this
approach in general.
Experimental Section
General Information
(c)
(d)
Caution: Milling of calcium carbide under high frequency in an air
protected WC jar produces CaC2 nanoparticles that can
spontaneously ignite in air.
All chemicals were purchased from Aldrich, Alfa Aesar and Acros
Organics in reagent grade or better quality and used without
further purification. All of the ball milling reactions were performed
in a Retsch MM 400 mixer mill with 20 mL grinding vessels.
Analytical thin-layer chromatography (TLC) was performed on
plastic-backed silica gel 60 coated with a fluorescence indicator.
Visualization of TLC plate was performed by UV (254 nm) or
Figure 2. Scanning electron micrographs image and EDX spectrum of: (a,b)
CaC2 particles milled in a grease-sealed jar; (c,d) CaC2 particles milled in a non-
grease-sealed jar. The samples were prepared by milling at 30 Hz for 40 min
in a tungsten carbide jar and were measured under argon atmosphere.
phosphomolybdic/permanganate stains.
Flash column
chromatography was conducted using Merck silica gel 60 (0.040–
0.063 mm). 1H and 13C spectra were measured with Bruker
spectrometer Avance II 400 MHz (AV 400) and Avance III 600
MHz (AV 600), using TMS as the internal standard. Chemical
shifts are reported in parts per million (ppm). The progress of
5
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
reactions was monitored by GC-MS analyses with a Quadrupol-
MS HP MSD 5971(EI) and HP 5890A GC equipped with a J & W
Scientific fused silica GC column (30 m × 0.250 mm, 0.25 micron
DB–5MS stationary phase: 5% phenyl and 95% methyl silicone)
using He (4.6 grade) as carrier gas; T-program standard 60–
250 °C (15 °C/min heating rate), injector and transfer line 250 °C.
Calcium carbide (72-82%) was purchased from Acros Organics.
1,1,4,4-Tetrakis(4-methylphenyl)but-2-yne-1,4-diol (3d).[13] 1H NMR
(400 MHz, DMSO-d6) δ = 7.42 (d, J = 7.9 Hz, 8H), 7.09 (d, J = 7.9 Hz, 8H),
6.67 (s, 2H), 2.25 (s, 12H). 13C NMR (101 MHz, DMSO-d6) δ = 143.8,
136.0, 128.4, 125.7, 89.2, 72.7, 20.5. HRMS Calcd for C32H30O2 [M + Na]+
469.2138; Found 469.2136.
1-Phenyl-1-(pyridin-2-yl)prop-2-yn-1-ol (2e).[13] 1H NMR (400 MHz,
DMSO-d6) δ = 8.47 - 8.45 (m, 1H), 7.83 – 7.76 (m, 1H), 7.74 – 7.69 (m,
1H), 7.59 - 7.55 (m, 2H), 7.33 – 7.21 (m, 4H), 6.95 (s, 1H), 3.67 (s, 1H).
13C NMR (101 MHz, DMSO-d6) δ = 163.0, 148.3, 144.9, 137.0, 127.7,
127.2, 126.0, 122.4, 119.3, 87.1, 76.3, 73.8. HRMS Calcd for C14H11NO
[M + Na]+ 232.0733; Found 232.0736.
General procedure for reactions of ketones with calcium carbide
under ball milling conditions
Silicone grease was applied to completely fill the interstitial
spaces of the inner screw thread of a 20 mL WC jar. Crushed
CaC2 (x mmol) and ketone (y mmol) were placed into the jar as
indicated in Table 2. The jar was tightly closed and milled at
specified frequency and indicated time. The jar was then allowed
to reach room temperature and then carefully opened under fume
hood. Ethyl acetate was added to almost fill the jar and then the
rest of calcium carbide was quenched followed by slow addition
of water (the mixture must be gently stirred by means of a spatula
during the addition of water). The reaction mixture was filtered
through a pad of celite and washed with ethyl acetate. The filtrate
was washed with brine and the organic layers was dried over
Na2SO4, filtered and concentrated to give the crude products.
Pure propargyl alcohols were obtained by column
chromatography on silica gel.
1,4-Diphenyl-1,4-di(pyridin-2-yl)but-2-yne-1,4-diol (3e).[13] 1H NMR
(400 MHz, DMSO-d6) δ = 8.50 (dt, J = 4.7, 1.2 Hz, 2H), 7.86 – 7.79 (m,
4H), 7.70 – 7.62 (m, 4H), 7.33 - 7.18 (m, 8H), 6.91 (s, 2H). 13C NMR (101
MHz, DMSO-d6) δ = 163.2, 148.3, 145.30, 137.0, 127.7, 127.2, 126.3,
122.4, 119.6, 88.5, 74.1. HRMS Calcd for C26H20N2O2 [M + H]+ 393.1598;
Found 393.1596.
1-Cyclohexyl-1-phenylprop-2-yn-1-ol (2f).[25]
1H NMR (400 MHz,
DMSO-d6) δ = 7.52 - 7.47 (m, 2H), 7.36 - 7.30 (m, 2H), 7.28 - 7.20 (m,
1H), 5.88 (s, 1H), 3.51 (s, 1H), 1.85 – 1.81 (m, 1H), 1.70 - 1.50 (m, 4H),
1.44 (m, 1H), 1.12 – 0.93 (m, 5H). 13C NMR (101 MHz, DMSO-d6) δ =
144.4, 127.4, 126.9, 126.0, 86.6, 75.9, 74.4, 49.6, 27.2, 26.9, 25.9, 25.7.
HRMS Calcd for C15H18O [M + Na]+ 237.1250; Found 237.1248.
1,4-Di(cyclohexyl)-1,4-diphenylbut-2-yne-1,4-diol (3f). 1H NMR (400
MHz, DMSO-d6) δ = 7.62 – 7.56 (m, 4H), 7.36 - 7.30 (m, 4H), 7.28 – 7.22
(m, 2H), 5.83 (s, 1H), 5.81 (s, 1H), 2.04 - 1.95 (m, 2H), 1.74 - 1.69 (m,
2H), 1.64 - 1.55 (m, 6H), 1.45 - 1.36 (m, 2H), 1.26 – 0.99 (m, 10H). 13C
NMR (101 MHz, DMSO-d6) δ = 145.0, 145.0, 127.4, 126.9, 126.4, 126.3,
87.5, 87.5, 75.0, 74.9, 50.2, 50.2, 27.4, 27.4, 27.3, 27.2, 26.1, 26.1, 25.8.
HRMS Calcd for C28H34O2 [M + Na]+ 425.2451; Found 425.2448.
1,1-Diphenyl-prop-2-yn-1-ol (2a).[13] 1H NMR (400 MHz, DMSO-d6) δ =
7.54 - 7.52 (m, 4H), 7.33 - 7.29 (m, 4H), 7.24 - 7.20 (m, 2H), 6.81 (s, 1H),
3.81 (s, 1H) ppm; 13C NMR (101 MHz, DMSO-d6) δ = 146.0, 127.9, 127.1,
125.6, 87.4, 76.9, 72.6. HRMS Calcd for C15H12O [M + Na]+ 231.0780;
Found 231.0778.
1,1,4,4-Tetraphenylbut-2-yne-1,4-diol (3a).[13] 1H NMR (400 MHz,
DMSO-d6) δ = 7.59 (d, J = 7.4 Hz, 8H), 7.31 (t, J = 7.5 Hz, 8H), 7.22 (t, J
= 7.3 Hz, 4H), 6.88 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ = 146.9,
128.42, 127.5, 126.2, 89.8, 73.5. HRMS Calcd for C28H22O2 [M + Na]+
413.1512; Found 413.1522.
4-Methyl-3-phenylpent-1-yn-3-ol (2g).[24] 1H NMR (400 MHz, CDCl3) δ =
7.65 – 7.59 (m, 2H), 7.38 – 7.28 (m, 3H), 2.69 (s, 1H), 2.38 (s, 1H), 2.11
(sept, J = 6.7 Hz, 1H), 1.08 (d, J = 6.6 Hz, 3H), 0.83 (d, J = 6.8 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ = 143.4, 127.9, 127.7, 126.1, 85.0, 74.9,
40.2, 17.9, 17.3. HRMS Calcd for C12H14O [M + Na]+ 197.0937; Found
197.0939.
1-(Naphthalen-2-yl)-1-phenylprop-2-yn-1-ol (2b).[24] 1H NMR (400 MHz,
DMSO-d6) δ = 8.15 (s, 1H), 7.97 – 7.92 (m, 1H), 7.88 – 7.81 (m, 2H), 7.61
- 7.45 (m, 5H), 7.32 (t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H), 6.98 (s,
1H), 3.89 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ = 145.7, 143.3, 132.4,
132.1, 128.1, 128.0, 127.7, 127.3, 127.2, 126.3, 126.1, 125.7, 124.5, 123.4,
87.2, 77.3, 72.8. HRMS Calcd for C19H14O [M + Na]+ 281.0937; Found
281.0935.
2,7-Dimethyl-3,6-diphenyloct-4-yne-3,6-diol (3g). 1H NMR (400 MHz,
DMSO-d6) δ = 7.64 – 7.57 (m, 4H), 7.38 – 7.22 (m, 6H), 5.86 (d, 2H), 2.03
– 1.93 (m, 2H), 1.04 – 0.99 (dd, J = 6.6, 4.1 Hz, 6H), 0.78 (d, J = 6.8 Hz,
6H). 13C NMR (101 MHz, DMSO-d6) δ = 145.1, 145.0, 127.4, 127.4, 126.9,
126.3, 126.2, 87.3, 87.2, 75.4, 75.3, 40.4, 40.3, 17.9, 17.8, 17.6, 17.6.
HRMS Calcd for C22H26O2 [M + Na]+ 345.1825; Found 345.1822.
1,4-Di(naphthalen-2-yl)-1,4-diphenylbut-2-yne-1,4-diol (3b). 1H NMR
(400 MHz, DMSO-d6) δ = 8.25 - 8.22 (m, 2H), 7.89 - 7.79 (m, 6H), 7.73 –
7.67 (m, 4H), 7.64 (dt, J = 8.7, 2.1 Hz, 2H), 7.53 – 7.46 (m, 4H), 7.34 (td,
J = 7.6, 1.9 Hz, 4H), 7.27 - 7.22 (m, 2H), 7.10 (d, 2H). 13C NMR (101 MHz,
DMSO-d6) δ = 146.1, 146.1, 143.8, 143.8, 132.4, 132.1, 128.0, 127.7,
127.4, 127.2, 126.3, 126.1, 125.9, 124.7, 123.7, 89.6, 73.1. HRMS Calcd
for C19H14O [M + Na]+ 513.1825; Found 513.1827.
1,1-Dicyclohexyl-prop-2-yn-1-ol (2h).[26] 1H NMR (400 MHz, CDCl3) δ =
2.40 (s, 1H), 1.88 – 1.16 (m, 22H). 13C NMR (101 MHz, CDCl3) δ = 86.0,
76.8, 73.6, 43.6, 27.8, 26.7, 26.6, 26.5, 26.2. HRMS Calcd for C15H24O [M
+ Na]+ 243.1719; Found 243.1716.
1,1,4,4-Tetracyclohexylbut-2-yne-1,4-diol (3h). 1H NMR (400 MHz,
CDCl3) δ = 1.86 – 0.99 (m, 44H). 13C NMR (101 MHz, CDCl3) δ = 87.4,
77.0, 43.9, 28.1, 26.8, 26.7, 26.6, 26.4. HRMS Calcd for C28H46O2 [M +
Na]+ 437.3390; Found 437.3389.
1,1-Bis(4-chlorophenyl)prop-2-yn-1-ol (2c).[13] 1H NMR (400 MHz,
DMSO-d6) δ = 7.50 (d, J = 8.6 Hz, 5H), 7.39 (d, J = 8.6 Hz, 5H), 7.07 (s,
1H), 3.92 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ = 144.5, 132.0, 128.1,
127.5, 86.3, 77.7, 71.8. HRMS Calcd for C15H10Cl2O [M - H]+ 275.0036;
Found 275.0033.
2-Ethynyl adamantan-2-ol (2i).[27] 1H NMR (400 MHz, DMSO-d6) δ = 5.35
(s, 1H), 3.30 (s, 1H), 2.14 - 2.02 (m, 4H), 1.82 – 1.62 (m, 8H), 1.46 - 1.41
(m, 2H). 13C NMR (101 MHz, DMSO-d6) δ =89.6, 74.2, 70.2, 37.8, 37.2,
34.6, 31.1, 26.3, 26.3. HRMS Calcd for C12H16O [M + Na]+ 199.1093;
Found 199.1090.
1,1,4,4-Tetrakis(4-chlorophenyl)but-2-yne-1,4-diol (3c).[13] 1H NMR
(400 MHz, DMSO-d6) δ = 7.54 (d, J = 8.7 Hz, 8H), 7.40 (d, J = 8.7 Hz, 8H),
7.17 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ = 144.7, 132.1, 128.1,
127.5, 88.8, 72.1. HRMS Calcd for C28H18Cl4O2 [M + Cl]- 562.9725; Found
562.966.
2,2'-(Ethyne-1,2-diyl)bis(adamantan-2-ol) (3i).[28] 1H NMR (400 MHz,
DMSO-d6) δ = 5.15 (s, 2H), 2.14 - 2.08 (m, 8H), 1.82 – 1.62 (m, 16H), 1.46
- 1.41 (m, 4H). 13C NMR (101 MHz, DMSO-d6) δ = 88.9, 70.3, 38.2, 37.4,
34.8, 31.3, 26.5, 26.4. HRMS Calcd for C22H30O2 [M + Na]+ 349.2138;
Found 349.2136.
1,1-Bis(4-methylphenyl)prop-2-yn-1-ol (2d).[13] 1H NMR (400 MHz,
DMSO-d6) δ = 1H NMR (400 MHz, DMSO) δ = 7.37 (d, J = 8.3 Hz, 4H),
7.11 (d, J = 8.0 Hz, 4H), 6.65 (s, 1H), 3.75 (s, 1H), 2.26 (s, 6H). 13C NMR
(101 MHz, DMSO-d6) δ = 143.3, 136.1, 128.4, 125.5, 87.7, 76.5, 72.3, 20.5.
HRMS Calcd for C17H16O [M + Na]+ 259.1093; Found 259.1095.
3-Ethynyl-3-diamantanol (2j). 1H NMR (400 MHz, DMSO-d6) δ = 5.26 (s,
1H), 3.27 (s, 1H), 2.12 – 1.96 (m, 4H), 1.76 – 1.53 (m, 13H), 1.38 (dt, J =
6
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
12.3, 2.8 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ = 89.3, 74.3, 71.0,
46.6, 37.2, 36.9, 36.9, 36.5, 35.6, 35.6, 35.6, 34.8, 34.4, 31.7, 30.7, 25.5.
HRMS Calcd for C16H20O [M + Na]+ 251.1406; Found 251.1403.
127.0, 122.9, 122.8, 118.7, 82.1, 81.7. HRMS Calcd for C16H10 [M + H]+
203.0946; Found 203.0948.
Phenanthrene (Ar-H).[36] 1H NMR (400 MHz, CDCl3) δ = 8.71 (d, J = 8.1
Hz, 2H), 7.90 (dd, J = 7.8, 1.2 Hz, 2H), 7.75 (s, 2H), 7.70 – 7.58 (m, 4H).
13C NMR (101 MHz, CDCl3) δ = 132.3, 130.5, 128.8, 127.1, 126.8, 122.9.
HRMS Calcd for C14H10 [M + H]+ 179.0855; Found 179.0853.
3,3'-(Ethyne-1,2-diyl)bis(3-diamantanol) (3j). 1H NMR (400 MHz,
CDCl3) δ = 2.32 (s, 2H), 2.13 – 1.56 (m, 34H), 1.51 – 1.42 (m, 2H). 13C
NMR (101 MHz, CDCl3) δ = 89.4, 73.3, 47.8, 37.9, 37.7, 37.5, 37.3, 36.9,
36.4, 36.3, 36.00, 35.6, 32.4, 31.7, 26.3. HRMS Calcd for C30H38O2 [M +
Na]+ 453.2764; Found 453.2763.
1-Ethynyl-2,5-dimethoxybenzene (Ar-b1).[37] 1H NMR (400 MHz, CDCl3)
δ = 7.01 (d, J = 3.0 Hz, 1H), 6.88 (dd, J = 9.0, 3.0 Hz, 1H), 6.82 (d, J = 9.0
Hz, 1H), 3.86 (s, 3H), 3.76 (s, 3H), 3.30 (s, 1H). 13C NMR (101 MHz,
CDCl3) δ = 155.3, 153.3, 118.9, 116.4, 112.1, 111.8, 81.2, 80.2, 56.6, 55.9.
HRMS Calcd for C10H10O2 [M + Na]+ 185.0573; Found 185.0575.
9-Ethynyl-9H-fluoren-9-ol (2k).[29] 1H NMR (400 MHz, DMSO-d6) δ =
7.77 (d, J = 7.1 Hz, 2H), 7.63 (d, J = 7.1 Hz, 2H), 7.43 – 7.33 (m, 4H), 6.57
(s, 1H), 3.36 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ = 147.8, 138.4,
129.2, 128.2, 124.3, 120.2, 85.7, 73.3, 72.7. HRMS Calcd for C16H13O [M
- OH + MeOH]+ 221.0961; Found 221.0990.
Bis(2,5-dimethoxyphenyl)acetylene (Ar-b2).[38] 1H NMR (400 MHz,
CDCl3) δ = 7.08 (d, J = 2.7 Hz, 2H), 6.87 – 6.81 (m, 4H), 3.89 (s, 6H), 3.79
(s, 6H). 13C NMR (101 MHz, CDCl3) δ = 154.7, 153.4, 118.2, 116.0, 113.4,
112.4, 89.9, 56.8, 56.0. HRMS Calcd for C18H18O4 [M + Na]+ 321.1097;
Found 321.1095.
9,9'-(Ethyne-1,2-diyl)bis(9H-fluoren-9-ol) (3k).[29] 1H NMR (400 MHz,
DMSO-d6) δ = 7.74 (d, J = 7.1 Hz, 4H), 7.55 (d, J = 7.0 Hz, 4H), 7.42 -
7.30 (m, 8H), 6.44 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ = 147.9,
138.4, 129.1, 128.3, 124.3, 120.2, 83.0, 73.5. HRMS Calcd for C28H18O2
[M + Na]+ 409.1199; Found 409.1198.
9-Ethynyl-10,10-dimethyl-9,10-dihydroanthracen-9-ol (2l). 1H NMR
(400 MHz, DMSO-d6) δ = 7.91 (dd, J = 7.5, 1.8 Hz, 2H), 7.64 (dd, J = 7.7,
1.6 Hz, 2H), 7.40 – 7.30 (m, 4H), 6.59 (s, 1H), 3.56 (s, 1H), 1.70 (s, 3H),
1.55 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ = 141.9, 137.9, 128.1,
127.5, 126.2, 125.5, 89.4, 75.7, 65.2, 37.5, 33.2, 31.3. HRMS Calcd for
C18H16O [M + Na]+ 271.1093; Found 271.1110.
Acknowledgements
This work was supported in part by the US Department of Energy,
Office of Science, Basic Energy Sciences, Materials Sciences
and Engineering Division, under contract DE-AC02-76SF00515.
9,9'-(Ethyne-1,2-diyl)bis(10,10-dimethyl-9,10-dihydroanthracen-9-ol)
(3l). 1H NMR (400 MHz, DMSO-d6) δ = 7.79 (dd, J = 7.8, 1.4 Hz, 4H), 7.57
(dd, J = 7.9, 0.9 Hz, 4H), 7.34 – 7.29 (m, 4H), 7.24 (m, 4H), 6.32 (s, 2H),
1.61 (s, 6H), 1.35 (s, 6H). 13C NMR (101 MHz, DMSO-d6) δ = 142.6, 138.6,
128.4, 128.1, 126.5, 125.8, 90.4, 66.4, 38.1, 32.9, 32.1. HRMS Calcd for
C34H29O [M - OH]+ 453.2213; Found 453.2191.
Keywords: Alkynylation • Ball milling • Calcium carbide •
Mechanochemistry • Solvent-free
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3.64 (s, 6H). 13C NMR (101 MHz, DMSO-d6) δ = 152.6, 138.0, 136.8,
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(400 MHz, DMSO-d6) δ = 7.28 (s, 2H), 6.80 (s, 2H), 5.27 (s, 2H), 3.83 (s,
6H), 3.78 (s, 6H), 3.74 (s, 3H), 3.66 (s, 3H). 13C NMR (101 MHz, DMSO-
d6) δ = 165.2, 152.9, 152.8, 141.9, 137.2, 131.7, 124.7, 106.5, 105.3, 66.4,
60.1, 60.0, 56.00, 55.9. HRMS Calcd for C20H24O8 [M + Na]+ 415.1363;
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4H), 7.83 – 7.78 (m, 4H). 13C NMR (101 MHz, CDCl3) δ = 183.2, 134.1,
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Bianthrone (5p).[34] 1H NMR (400 MHz, CDCl3) δ = 8.03 – 7.84 (m, 4H),
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9-Ethynylphenanthrene (Ar-a1).[35] 1H NMR (400 MHz, CDCl3) δ = 8.72
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7.73 – 7.66 (m, 3H), 7.64 – 7.58 (m, 1H), 3.48 (s, 1H). 13C NMR (101 MHz,
CDCl3) δ = 133.1, 131.3, 131.1, 130.6, 130.2, 128.8, 127.9, 127.3, 127.1,
7
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
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10.1002/ejoc.202000612
European Journal of Organic Chemistry
FULL PAPER
O
Sealed High Energy Ball Milling
R1
R2
OH
R2
R1
HO
R1 R2
R2
HO
+
No Additive
No Solvent
R1
Sealed ball milling provides a novel way of activation of calcium carbide where no additive is required to transfer the acetylide moiety
to organic molecules. Various ketones and even aryl halides can thereby be ethynylated.
Institute and/or researcher Twitter usernames: prsgroupjlu (Schreiner research group).
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This article is protected by copyright. All rights reserved.