Synthesis of functional acetylene derivatives from calcium carbide

Article abstract of DOI:10.1002/cssc.201100649

AHA Erlebnis: CaC₂, used to produce acetylene until several decades ago, is re-emerging as a cheap, sustainable resource synthesized from coal and lignocellulosic biomass. We report efficient catalytic protocols for the synthesis of functional acetylene derivatives from CaC₂ through aldehyde, alkyne, and amine (AAA) as well as alkyne, haloalkane, and amine (AHA) couplings, and in addition demonstrate its use in click and Sonogashira chemistry, showing that calcium carbide is a sustainable and cost-efficient carbon source.

Full text of DOI:10.1002/cssc.201100649

DOI: 10.1002/cssc.201100649
Synthesis of Functional Acetylene Derivatives from Calcium Carbide
Zhewang Lin, Dingyi Yu, Yin Ngai Sum, and Yugen Zhang*[a]
In the 1950s and 1960s, a large portion of the calcium carbide
produced worldwide was transformed in industry into millions
of tonnes of acetylene. Between 1960 and 1970, when the
worldwide production of calcium carbide-acetylene peaked, it
served as the primary feedstock for a wide variety of commodi-
ty and specialty chemicals. Since then, advances in petroleum
and olefins technology have reduced and limited the impor-
tance of acetylene. However, the diminishing reserves of hy-
drocarbons following one century of heavy industrial petrole-
um use have become a major concern for future decades.[1]
Hence, calcium carbide-acetylene is re-emerging as a viable
feedstock for the chemical industry.
tons and synthetically versatile key intermediates for nitrogen-
containing biologically active compounds.[22–24] Usually, termi-
nal alkynes are employed as nucleophilic carbon source, via CÀ
H activation. More recently a metal-catalyzed three-component
coupling of alkynes, haloalkanes, and amines (AHA) to afford
propargylamines was reported.[25–27] However, the substrates
used in these two reactions are limited to substituted terminal
alkynes and as a result, the reactions produce internal alkynes.
Although these internal alkynes, with different functional
groups, are certainly important to many organic reactions,
their internal structure limits many further important applica-
tions of functionalized alkynes. Hence the development of new
catalytic systems for the production of mono-substituted prop-
argylamines with a terminal alkyne function directly from calci-
um carbide via AAA or AHA three-component coupling reac-
tion pathways is highly desirable. By controlling the reaction
conditions, we successfully realized such mono-substituted
propargylamines in high yields under mild conditions, provid-
ing a great opportunity for the application of calcium carbide
in organic synthesis and the development of a versatile amino-
propyne product chemistry (Scheme 1).
Calcium carbide is traditionally synthesized from coal. Re-
cently, it has been demonstrated that calcium carbide can also
be synthesized from lignocellulosic biomass.[2,3] The low pro-
duction costs[4] of this new method have put calcium carbide
in a better position to serve as a sustainable resource for the
chemical industry. Due to the variety of addition reactions that
the triple bond can undergo and the fact that the weakly
acidic hydrogen atom of acetylene derivatives has been exten-
sively used in organic synthesis,[5–8] it is important to develop
efficient protocols for the synthesis of various functional acety-
lene derivatives directly from calcium carbide. This would offer
the chemical industry and organic synthesis platform chemicals
from a sustainable feedstock. Furthermore, the use of calcium
carbide in organic synthesis is more cost-efficient and safer
than the use of acetylene gas. However, its low solubility in
almost all solvents and the difficulty in controlling mono-sub-
stitution reactions are major challenges in the direct synthesis
of functionalized acetylene derivatives from CaC2.[9]
Herein, we disclose efficient catalytic protocols for the syn-
thesis of various functional acetylene derivatives from calcium
carbide. The newly developed synthetic protocols are extreme-
ly useful in organic synthesis and may promote the use of cal-
cium carbide as an alternative to petroleum.
Carbon–carbon bond formation using alkynes as a nucleo-
philic carbon source is a very useful method in synthetic
chemistry.[10–14] However, most of the alkynes reported to be in-
volved in nucleophilic attack are substituted terminal alkynes,
not acetylene or calcium carbide. For example, the well-docu-
mented, three-component aldehyde, alkyne, and amine (AAA)
coupling[15–20] is an elegant method for the synthesis and prep-
aration of propargylamines, which are frequently used as skele-
Scheme 1. a) Traditional AAA and AHA coupling reactions, and b) AAA and
AHA coupling reactions with calcium carbide.
Currently, the most useful methods for the synthesis of ami-
nopropynes include the use of the very sensitive Grignard re-
agent HCCMgBr[28] and metal-catalyzed propargylic substitu-
tion reactions with propargylic acetates, propargylic alcohols,
and propargylic halides.[29–34] Here, we modified the AAA and
AHA reaction conditions and achieved versatile, simple, and
direct synthetic protocols for aminopropynes with calcium car-
bide as alkyne feedstock. Initial tests for the AHA reaction with
calcium carbide were carried out under the following condi-
tions: calcium carbide (1.0 mmol), dichloromethane (1.5 mmol),
[a] Z. Lin, D. Yu, Y. N. Sum, Dr. Y. Zhang
Institute of Bioengineering and Nanotechnology
31 Biopolis Way, The Nanos
Singapore 138669 (Singapore)
Fax: (+65)6478-9020
E-mail: ygzhang@ibn.a-star.edu.sg
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201100649.
ChemSusChem 2012, 5, 625 – 628
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
625

and diisopropylamine (1.5 mmol) were mixed with CuCl
(10 mol%) as catalyst at 808C in CH3CN. This afforded the
mono-substituted acetylene product diisopropylaminopropyne
(B1) in good yield (70%; Scheme 2; see Supporting Informa-
tion, Table S1, entry 1). Inspired by this result, reaction condi-
strates) may help to break down the calcium carbide’s poly-
meric structure, thereby promoting the reaction. Further reac-
tions were carried out in undried solvent. Due to the greater
structural variety, further studies were focused on AAA-type
coupling reactions with calcium carbide.
The substrate scope for the
AAA-type coupling reaction was
then investigated by using the
optimized conditions: calcium
carbide (1.2 mmol), aldehyde or
ketone
(1.0 mmol),
amine
(1.5 mmol) and CuI (10 mol%) in
CH3CN at 808C (Scheme 3). Aro-
matic aldehydes, either with
electron-donating or electron-
withdrawing groups, smoothly
underwent AAA-type coupling
Scheme 2. AHA coupling with calcium carbide.
with calcium carbide to give the
corresponding mono-substituted
tions were further optimized (Table S1). Notably, organic bases
such as triethylamine (TEA) or N-ethyl-N-isopropylpropan-2-
amine (DIEA) also delivered the mono-substituted aminopro-
pyne product in reasonably good yield (Scheme 2). Generally,
acyclic aliphatic (B1), heterocyclic (B2), and cyclic (B3) secon-
dary amines gave good product yields (Scheme 2). However,
under the same conditions reactions with inorganic base, (i.e.,
K2CO3 or Cs2CO3) produced the corresponding symmetric bis-
substituted propargylic amines with an internal alkyne struc-
ture (B4) in yields of 70% and 75% respectively (Scheme 2;
Table S1, entries 9 and 10, ). The reactions generally took
a long time probably due to the poor solubility of calcium car-
bide in the reaction system.[9]
aminopropynes in good yields (Scheme 3, C1–5). The catalytic
system was not sensitive to various functional groups, such as
ÀCN, ÀCl, ÀBr, or ÀOR. In addition, aliphatic aldehydes (C6–7)
or ketone (C8, with longer reaction times) also gave the corre-
sponding aminopropynes in good yields. When varying the
amine substrates, it was found that cyclic, heterocyclic, and
acyclic aliphatic secondary amines gave very good yields of
products under the standard reaction conditions (C9–12).
However, no reaction was observed for primary amines (C13–
14). This may due to the lower activity of imine intermediates
for primary amines compared to iminium intermediates for
secondary amines.
The mono-substituted acetylene products synthesized from
AAA- and AHA-type three-component coupling reactions with
calcium carbide could have various applications in organic syn-
thesis.[35–36] Herein, several reactions were realized to demon-
strate the versatility of mono-substituted acetylene aminopro-
pynes in synthesis and to show the untapped potential of cal-
cium carbide in synthesis and the chemical industry.
The copper-catalyzed alkyne–azide cycloaddition (“click”) re-
action is well-known and widely used in different fields.[37–38]
Here, a multiple-component reaction using the aminopropyne
that was synthesized from calcium carbide AAA-type coupling
reaction, sodium azide, and aryl/alkyl halide to afford 1,2,3-tria-
zole was demonstrated. A mixture of N,N-diethyl-1-phenyl-
prop-2-yn-1-amine, sodium azide, iodobenzene, CuI (10 mol%),
and N,N-dimethylethylenediamine (15 mol%) were mixed in
DMF. The functionalized triazole product, N-ethyl-N-(phenyl(1-
phenyl-1H-1,2,3-triazol-4-yl)methyl) ethanamine D1, was ob-
tained in 85% isolated yield. Interestingly, the click reaction
did not proceed with phenylazide and the aminopropyne
using the same catalytic system. Other than iodobenzene, ben-
zylic bromide (D2) and alkyl bromide (D3) also gave good tria-
zole yields (Scheme 4). The use of sodium azide and aryl/alkyl
halide instead of aryl/alkyl azide not only provides an easily ac-
cessible and versatile substrate scope, but also a safer proce-
dure for the click reaction.
Following the successful synthesis of mono-substituted ami-
nopropynes from calcium carbide via AHA coupling, the (more
versatile) three-component AAA coupling with calcium carbide
as the alkyne source was attempted. To our delight, with the
initial conditions of calcium carbide (1.2 mmol), benzaldehyde
(1.0 mmol), diisopropylamine (1.5 mmol), and CuCl (10 mol%)
at 808C in CH3CN, a moderate yield of mono-substituted AAA
product (N,N-diisopropyl-1-phenylprop-2-yn-1-amine) was ob-
tained in 72 h (Table S2, entry 1). No bis-substituted product
was observed. The optimum ratio of calcium carbide to alde-
hyde to and amine was found to be 1.2:1.0:1.5. Among the
copper catalysts screened, CuCl, CuBr, Cu(OAc)2, Cu(acac)2, and
CuCl2 gave moderate to low conversions, while CuI gave the
best isolated yield of 72% (Table S2, entries 1–6). No reaction
took place at room temperature and higher reaction tempera-
tures did not improve the product yield. Interestingly, no bis-
substituted propargylic amine product was observed even
with inorganic base present in the reaction system. Similar to
the AHA reaction protocol, the AAA-type coupling reaction in-
volving calcium carbide also required a long time (72 h) to
reach high yields, again due to poor solubility in the reaction
system. However, the reaction time could be drastically short-
ened (to 18 h) while retaining a similar yield when using un-
dried acetonitrile (containing 0.02 vol% of water) was used
(Table S2, entry 14). The trace amount of water (2 mol% of sub-
626
www.chemsuschem.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2012, 5, 625 – 628

The Sonagashira reaction is
among the most useful and im-
portant coupling reactions in or-
ganic synthesis.[39–40] The Sono-
gashira reaction of calcium car-
bide and iodobenzene has been
reported, producing bis-substi-
tuted
diphenylacetylene.[9]
Herein, a sequential AAA-Sona-
gashira coupling reaction was
successfully
developed.
As
shown in Scheme 6, N,N-diethyl-
1,3-diphenylprop-2-yn-1-amine
was obtained in 66% overall iso-
lated yield. The reaction de-
scribed here provides an effi-
cient, simple, and fast method to
construct complex alkynyl com-
pounds from calcium carbide.
In conclusion, a novel catalytic
system for the production of
propargylamines from calcium
carbide via AAA or AHA three-
component coupling reaction
pathways is described. Mono-
substituted aminopropyne prod-
ucts with a terminal alkyne func-
Scheme 3. AAA coupling reactions with calcium carbide.
tion can be produced in high
yields, under mild conditions.
Furthermore, a series of novel synthesis protocols were dem-
onstrated based on calcium carbide and aminopropyne. A click
reaction between aminopropyne and azide, a one pot sequen-
tial AAA–AHA coupling, and a AAA–Sonogashira coupling reac-
tion with calcium carbide demonstrate the versatile applica-
tions of this novel methodology in organic synthesis. Calcium
carbide directly undergoes different types of reactions and
complex structures are formed using provides versatile and
fast synthetic protocols. The direct usage of calcium carbide
Scheme 4. Three-component coupling cyclization reactions.
The aminopropynes synthe-
sized through AAA coupling
could also further undergo AHA-
type coupling to form asymmet-
ric bis-substituted propargylic
amines. Interestingly, this two-
step reaction could be conduct-
Scheme 5. One-pot AAA–AHA coupling reaction.
ed in one pot as a sequential
AAA–AHA reaction (Scheme 5).
For example, an asymmetric bis-
substituted product, N1,N1,N4,N4-
tetraisopropyl-1-phenylbut-2-
yne-1,4-diamine, was obtained in
70% overall isolated yield
(Scheme 5). It should be noted
that a reversed sequential AHA–
AAA reaction did not occur.
Scheme 6. One-pot AAA–Sonogashira coupling reaction.
ChemSusChem 2012, 5, 625 – 628
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
627

[6] Modern Acetylene Chemistry (Eds.: P. J. Stang, F. Diederich), VCH, Wein-
heim, 1995.
[7] Acetylene Chemistry (Eds.: F. Diederich, P. J. Stang, R. R. Tykwinski), Wiley-
VCH, Weinheim, 2005.
[8] L. Brandsma, Synthesis of Acetylenes, Allenes and Cumulenes: Methods
and Techniques, Elsevier: Amsterdam, 2004.
[9] W. Zhang, H. Wu, Z. Liu, P. Zhong, L. Zhang, X. Huang, J. Cheng, Chem.
Commun. 2006, 4826–4828.
also avoids many protection and de-protection steps that
greatly reduce the number of synthetic steps, resulting in
more efficient and greener organic synthesis. The new synthet-
ic methods presented here demonstrate that calcium carbide
could play a major role as a sustainable and cost efficient
carbon source in modern organic synthesis.
[10] J. F. Traverse, A. H. Hoveyda, M. L. Snapper, Org. Lett. 2003, 5, 3273–
3275.
Experimental Section
[11] C. M. Rao, P. Vogel, Org. Lett. 2009, 11, 1701–1704.
[12] D. Yu, Y. G. Zhang, Proc. Natl. Acad. Sci. USA 2010, 107, 20184.
[13] D. Yu, Y. G. Zhang, Green Chem. 2011, 13, 1275.
[14] Y. G. Zhang, S. N. Riduan, Angew. Chem. 2011, 123, 6334; Angew. Chem.
Int. Ed. 2011, 50, 6210.
[15] C. Wei, L. Zhang, C. J. Li, Synlett 2004, 1472–1483.
[16] M. K. Patil, M. Keller, B. M. Reddy, P. Pale, J. Sommer, Eur. J. Org. Chem.
2008, 26, 4440–4445.
All solvents were purchased from Aldrich or Fluka. All starting ma-
terials were commercially available and used as-received unless in-
dicated otherwise. Calcium carbide was purchased from Aldrich
(purity 80%). Reactions were monitored by thin layer chromatogra-
phy using 0.25 mm E. Merck silica gel coated glass plates (60F-254)
with UV light. Chemical yields refer to pure, isolated substances.
Gas chromatography–mass spectrometry (GC–MS) was performed
with Shimadzu GC-2010 instrument coupled to a GCMS–QP2010.
1H and 13C NMR spectra were obtained by using a Bruker AV-400
(400 MHz) spectrometer. In the Supporting Information, chemical
shifts are reported in ppm relative to tetramethylsilane, with the
solvent resonance as internal standard. Data are reported in the
following order: chemical shift (d, in ppm), multiplicity [indicated
by br (broadened), s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), mc (centered multiplet)]; coupling constants (J, in Hz);
integration; assignment.
[17] X. Zhang, A. Corma, Angew. Chem. 2008, 120, 4430–4433; Angew.
Chem. Int. Ed. 2008, 47, 4358–4361.
[18] Y. Zhang, P. Li, M. Wang, L. Wang, J. Org. Chem. 2009, 74, 4364–4367.
[19] N. Gommermann, C. Koradin, K. Polborn, P. Knochel, Angew. Chem.
2003, 115, 5941–5944; Angew. Chem. Int. Ed. 2003, 42, 5763–5766.
[20] T. F. Knçpfel, P. A. Aschwanden, T. Ichikawa, T. Watanabe, E. M. Carreira,
Angew. Chem. 2004, 116, 6097–6099; Angew. Chem. Int. Ed. 2004, 43,
5971–5973.
[21] K. A. Bisai, V. K. Singh, Org. Lett. 2006, 8, 2405–2408.
[22] M. Konishi, H. Ohkuma, T. Tsuno, T. Oki, G. D. VanDuyne, J. Clardy, J. Am.
Chem. Soc. 1990, 112, 3715–3716.
[23] G. Dyker, Angew. Chem. 1999, 111, 1808–1822; Angew. Chem. Int. Ed.
1999, 38, 1698–1712.
General Procedure for AAA coupling: A mixture of calcium carbide
(1.2 mmol, 77 mg), benzaldehyde (1.0 mmol, 106 mg), diisopropyla-
mine (1.5 mmol, 151.5 mg), and CuI catalyst (0.1 mmol, 20.0 mg)
was added to a reaction tube (10 mL) with 2 mL CH3CN. After stir-
ring at 808C for 18 h, the mixture was diluted with H2O (10 mL)
and the aqueous layer was extracted with diethyl ether (2ꢁ10 mL),
dried over Na2SO4, and concentrated under vacuum to give the
crude product. This crude was further purified by column chroma-
tography on silica gel (ethyl acetate/hexane 1:4) to afford the cor-
responding pure aminopropyne. All products gave satisfactory
spectroscopic data.
[24] T. Napta, H. Takaya, S. Murahashi, Chem. Rev. 1998, 98, 2599–2660.
[25] D. Yu, Y. G. Zhang, Adv. Synth. Catal. 2011, 353, 163–169.
[26] Z. Lin, D. Yu, Y. G. Zhang, Tetrahedron Lett. 2011, 52, 4967.
[27] D. Aguilar, M. Contel, E. P. Urriolabeitia, Chem. Eur. J. 2010, 16, 9287–
9296.
[28] A. Guerinot, G. Lepesqueux, S. Sable, S. Reymond, J. Cossy, J. Org. Chem.
2010, 75, 5151–5163.
[29] Y. Nishibayashi, S. Uemura, Curr. Org. Chem. 2006, 10, 135–150.
[30] G. W. Kabalka, M.-L. Yao, Curr. Org. Synth. 2008, 5, 28–32.
[31] N. Ljungdahl, N. Kann, Angew. Chem. 2009, 121, 652–654; Angew.
Chem. Int. Ed. 2009, 48, 642–644.
[32] Y. Miyake, S. Uemura, Y. Nishibayashi, ChemCatChem 2009, 1, 342–356.
[33] R. J. Detz, H. Hiemstra, J. H. van Maarseveen, Eur. J. Org. Chem. 2009,
6263–6276.
Acknowledgements
[34] K. M. Nicholas, Acc. Chem. Res. 1987, 20, 207–214.
[35] D. Tejedor, S. Lꢂpez-Tosco, F. Cruz-Acosta, G. Mꢃndez-Abt, F. Garcꢄa-Tella-
do, Angew. Chem. 2009, 121, 2124–2131; Angew. Chem. Int. Ed. 2009,
48, 2090–2098.
[36] C. A. de Parrodi, P. J. Walsh, Angew. Chem. 2009, 121, 4773–4776;
Angew. Chem. Int. Ed. 2009, 48, 4679–4682.
This work was funded by the Institute of Bioengineering and
Nanotechnology (Biomedical Research Council), Agency for Sci-
ence, Technology and Research, Singapore).
[37] M. Morten, T. C. Wenzel, Chem. Rev. 2008, 108, 2952.
[38] J. E. Hein, V. V. Fokin, Chem. Soc. Rev. 2010, 39, 1302.
[39] K. Okuro, M. Furuune, M. Enna, M. Miura, M. Nomura, J. Org. Chem.
1993, 58, 4716.
Keywords: amines · calcium · carbides · renewable resources ·
synthetic methods
[1] A. P. C. Faaij, Energy Policy 2006, 34, 322–342.
[2] G. Li, Q. Liu, Z. Liu, Z. C. Zhang, C. Li, W. Wu, Angew. Chem. 2010, 122,
8658–8661; Angew. Chem. Int. Ed. 2010, 49, 8480–8483.
[3] J. Lehmann, Nature 2007, 447, 143–144.
[40] E. Gwilherm, B. Nicolas, T. Mathieu, Chem. Rev. 2008, 108, 3054.
Received: October 18, 2011
[4] The market price for calcium carbide is about 300~500 US$/T.
[5] L. Brandsma, Preparative Acetylene Chemistry, 2nd ed., Elsevier, Amster-
dam, 1988.
Revised: November 24, 2011
Published online on February 29, 2012
628
www.chemsuschem.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2012, 5, 625 – 628