Metal/catalyst/reagent free hydration of alkynes up to gram scale under temperature and pressure controlled condition

Article abstract of DOI:10.1016/j.tetlet.2018.04.044

A new green water-mediated metal/catalyst/reagent-free methodology for hydration of alkyne is devised. The remarkable yields of various ketones were achieved when alkynes were heated at 150 °C under 11 bar pressure in an autoclave for 14 h in water-methanol solution. Outstanding functional group compatibility for both the terminal and internal alkynes was established. This methodology produces excellent yields up to gram scale under optimised reaction condition.

Full text of DOI:10.1016/j.tetlet.2018.04.044

Accepted Manuscript
Metal/Catalyst/Reagent free hydration of alkynes up to gram scale under tem-
perature and pressure controlled condition
Munsaf Ali, Avinash K. Srivastava, Raj K. Joshi
PII:
S0040-4039(18)30514-8
https://doi.org/10.1016/j.tetlet.2018.04.044
TETL 49907
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 March 2018
16 April 2018
18 April 2018
Please cite this article as: Ali, M., Srivastava, A.K., Joshi, R.K., Metal/Catalyst/Reagent free hydration of alkynes
up to gram scale under temperature and pressure controlled condition, Tetrahedron Letters (2018), doi: https://
doi.org/10.1016/j.tetlet.2018.04.044
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
Leave this area blank for abstract info.
Metal/Catalyst/Reagent free hydration of
alkynes up to gram scale under temperature
and pressure controlled condition
Munsaf Alia, Avinash K. Srivastavaa, Raj K. Joshia*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Metal/Catalyst/Reagent free hydration of alkynes up to gram scale under
temperature and pressure controlled condition
Munsaf Alia, Avinash K. Srivastavaa, Raj K. Joshia*
a
Department of Chemistry, Malaviya National Institute of Technology, Jaipur 302017, Rajasthan, India
Email: rkjoshi.chy@mnit.ac.in, Phone: +91 141 2713279
ARTICLE INFO
ABSTRACT
Article history:
Received
A new green water-mediated metal/catalyst/reagent-free methodology for hydration of alkyne is
devised. The remarkable yields of various ketones were achieved when alkynes were heated at
150 ˚C under 11 bar pressure in an autoclave for 14 hr in water-methanol solution. Outstanding
functional group compatibility for both the terminal and internal alkynes was established. This
methodology produces excellent yields up to gram scale under optimised reaction condition.
Received in revised form
Accepted
Available online
Keywords:
Metal-free
Autoclave
Alkynes
Hydration
Ketone
2009 Elsevier Ltd. All rights reserved.
substrates are a precursor for hydration reactions, and the
applications of obtained carbonyls in organic syntheses7 is an
Introduction
Increasing the amount of product with minimising the role of
catalyst and raw material is one of the critical aspects among the
12 principles of green chemistry.1 There were many reports
available that demonstrate the applications of green and
sustainable methodologies for laboratory and industrial
productions. Practising various inexpensive and environmentally
benign reaction methodologies have unveiled a new era in the
field of chemistry.2 Optimizing reaction conditions to accomplish
without any chemical activation, i.e. without using chemical
reagents or catalyst to perform chemical changes; this
phenomenon is interesting as well as significantly crucial from
commercial and economic perspective. Reordering the physical
parameters (temperature and pressure) associated with the
reaction may lead to new insights in catalyst-free organic
transformation. The use of autoclave technique for
hydrogenation3, hydration4 and various other reactions is quite
common. Moreover, these methodologies outstandingly reduce
the cost and formation of undesired by-products and chemical
waste in the reaction.
essential aspect of traditional synthetic chemistry. Transition
metals and other metal complexes are extensively used for
hydration reactions. Before 1980’s mercury compounds such as
8a
Hg(OTf)2, HgSO4,8b and Hg(OAc)28c were utilised for hydration
reactions. While due to the toxicity and hazards to the
environment; search for the green, and the economic catalyst is
undergoing from many years. There is surplus literature
congregated in last two decades representing alkyne hydrations
from a variety of transition metals such as Pd9, Pt10, Rh11, Ru12,
Au13. However, these metal catalysts are rare and not
economically viable. Although some economical alternatives of
metal catalyst such as Ag14, Fe15, Co16, Sn and W mix-oxides17
also been reported in recent past. In some recent reports, acid
catalyzed18 and para-methoxybenzenetellurinic acid anhydride19
indicates that alkyne hydration can be done by metal-free
conditions. However, most of the reactions have suffered from at
least one or more following drawbacks: (i) Use expensive
transition metals (Ru, Rh, Pd, Pt, Au, Ir, Ag) predominantly the
recovery and reusability of catalysts and the indispensable use of
acid co-catalysts, additives, and promoter; (ii) High price and the
light sensitivity of silver salts; (iii) Narrow functional group
compatibility; (iv) Large excess of acidic additive besides the
metal complexes if any.
The Wacker oxidation of alkenes and metal mediated
carbonylation of alkynes is extensively used to generate the
carbonyl compounds including the ketones, esters, lactone, and
melamide.4,5 The hydration of alkynes had developed a
paramount interest worldwide among various research groups,
and it is a well-established and more advanced method for the
production of ketones. Due to their diversified applications,
ketones are the linchpins for various organic syntheses.
Moreover, they also serve as versatile intermediates in a wide
range of chemical syntheses such as natural products, drugs and
other valuable industrial products.6 The vast diversity of alkyne
In the year 2004, Vasudevan and co-workers20 reported a
catalyst-free methodology which exclusively works for terminal
alkynes. The alkynes in superheated water were heated at 200 ˚C
in a microwave reactor for 20 minutes to produces the ketones.
Although the catalyst-free alkyne hydration was reported for the
first time, but, due to the harsh reaction conditions, the high

2
Tetrahedron
temperature, unknown pressure, cannot be implemented for
phenylacetylene is a volatile and low boiling liquid, at low
pressure and high temperature; it vaporizes, and in the gaseous
phase, it is quite rare to react with the liquid water present in the
solvent mixture. While in present reaction conditions, the
moderate pressure and high temperature restricted the
vaporization of alkynes which make unable to convert it in its
vapor form, hence, it can undergo a hydration reaction. In our
opinion, it could be the best possible effect of pressure on to the
reaction. The optimised value of pressure for to get the highest
yield of desired product is 11 bar, while the higher pressure of
inert gas does not affect the product yield and supports our
proposed hypothesis. Another reason for this reaction may be the
higher ionisation of water molecules at higher pressure. In the
earlier reports related to the studies of ionisation of water at
various pressure and temperatures21 suggested that ionisation of
water molecules increases at higher pressure and the ionization of
water increases with the increasing temperature. Here, both the
facts again support the present hypothesis of the high yield of
hydrated product at a relatively high temperature and moderate to
high pressure.
large scale synthesis etc. Moreover, this method was not worked
for internal alkynes. All these shortfalls made this method
inappropriate for the metal-free bulk synthesis of ketones.
Earlier Methodologies
Metal Catalyst or Acid Catalyst: Au, Pd, Pt, Rh, Ru or
CF3SO3H
In Recent Past
The Present Work
Using water as a solvent reaction does not undergo any
transformation. (Table 1, entry 10). Hence, a mixture of water
and methanol was used as a solvent. Gratifyingly, the 1:1 ratio of
water and methanol as solvent enormously increases the yield of
desired product (table 1, entry 11). The presence of methanol in
reaction mixture enhances the solubility of the acetylenes in
water. Moreover, it also help in the ionisation of water which
directly favours the hydration reactions.22a,22b As it is reported
earlier that ionisation in water can be increased by increasing
temperature, pressure or both and by adding alcohols.22c Also by
increasing these parameters viscosity and surface tension of
water decreases and dielectric constant increases which improves
the solubility of organic compounds in water.22d Decreasing the
amount of water in solvent mixture produces the moderate
product yield (Table 1, entry 12). Inversely, the increasing the
amount of water in the solvent mixture improves the product
yield and the maximum recorded yield of 79% was obtained with
1:2 ratio of methanol and water (Table 1, entry 13). Use of other
alcohols, ethanol, isopropyl alcohol and tert-butanol showed a
substantial decrease in the yield.
Reaction carried out in Autoclave, without any catalyst
Herein, we investigated a catalyst-free methodology for
hydration of terminal and internal alkyne without using any metal
or acid catalyst. The present reaction is carried out in an
autoclave at high temperature and pressure. Apart from the
reactants, the present methodology needs only water/methanol
mixture as solvent. The present method has excellent functional
group compatibility and also works for both the terminal and
internal alkynes and do not produce any unwanted by-product.
Result and discussion
To follow the principles of green chemistry, we were
interested in developing a metal-free reaction method for
hydration of alkynes. Phenylacetylene was chosen as a model
substrate for all the optimisation. After some reactions under
different conditions with no results, our series of the trail is
interrupted by a trace product obtained in a reaction carried out in
an autoclave. Desired product acetophenone was obtained
through a reaction of phenylacetylene in an autoclave at 150 ˚C
and 11 bar of argon gas pressure in 14 hr. Here, methanol was
used as a solvent in the reaction. Scheme 1 represents the
parameters where the desired alkyne hydration product was
obtained. (Table 1, entry 9)
Further optimisation of temperature and time was carried out.
Temperature up to 110 ˚C does not produce even a trace of
desired product. Increasing the temperature to 120 ˚C a low yield
of the phenylacetylene obtained. Amount of product was
consistently increased with increasing the temperature up to 150
˚C (Table 1, entry 14-17), furthermore increase of temperature up
to 180 ˚C does not show any changes in the yield of product
(Table 1, entry 18-20). Duration of reaction up to 14 hr or more
produces a consistent yield (Table 1, entry 21-25), while the least
4-8 hr reaction produces below to average yield. However, it
further increases up to 14 hr and then become consistent (Table
1, entry 26-28).
Scheme 1: Temperature and pressure controlled the formation of
ketones
Present methodology was also found compatible with wide
variety functionalities. The substrate scope of this reaction is
represented in Table 2. Phenyl acetylenes substituted with
electron-donating or withdrawing groups produces excellent
yield of their corresponding methyl ketones. Besides the phenyl
acetylene, other aromatic alkynes (both terminal and internal),
including the functional groups like fluoro, chloro, bromo,
amino, alkyl, alkoxy also proceed hydration and affords excellent
yields. The ferrocenyl acetylene yield acetylferrocene in 83%
(Table 2, entries 2). ortho-, meta- and para- methyl-phenyl
acetylene reacted smoothly, forming the corresponding methyl
ketones in 84 %, 82 % and 83 % respectively (Table 2, entries 3-
5). Halo-substituted phenyl acetylenes such as 4-fluoro-, 4-
In the reaction, the inert gas pressure plays an important role.
During the pressure optimisation, it was found that product yield
was proportionally increased with continuously increasing
pressure from 0 to 11 bar (table 1, entry 1-6). Pressure below 9
bar does not initiate the reaction, while a small quantity of
product was obtained at 9 bar pressure of inert gas. Increasing the
pressure up to 11 bar increases the product yield. However, the
further increase in pressure does not produce any change in the
yield (Table 1, entry 7-9). We investigated argon, nitrogen and
CO2 gas for to generate the desired pressure but irrespective of
the nature of gas the product formation was consistent and hardly
brings any changes in the yield of transformed product. Since, the

3
chloro-, 4-bromo and 2-chlorophenyl acetylene yielded 78 %, 76
%, 73 % and 72 % respectively (Table 2, entries 6-9). ortho- and
para- methoxyphenylacetylene gave the corresponding products
in 84 % and 83 % yield (Table 2, entries 10, 11). 4-
ethylphenylacetylene reacted easily and formed the
corresponding ketones in 85% yields (Table 2, entries 12). The 4-
tert-butylphenylacetylene gave the corresponding ketones in 89
% (Table 2, entries 13); while the 3-aminophenylacetylene
yielded 80 % of the hydrated product (Table 2, entries 14).
Table 2 Substrate scope of hydration reaction in an autoclave
Yielda
(%)
Entry
Reactant
Product
1.
79
Table 1 Optimization of reaction parameters with
phenylacetylene
2.
3.
4.
5.
6.
7.
8.
9.
83
84
82
83
72
76
73
78
Ar
Pressure
(Bar)
Solvent Ratio
(MeOH: Water)
Temp Time
(˚C)
Yielda
(%)
Entry
(h)
1.
2.
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:0
0:1
1:1
2:1
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
150
150
150
150
150
150
150
150
150
150
150
150
150
120
130
140
150
160
170
180
150
150
150
150
150
150
150
150
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
4
nd
23
34
45
60
79
79
79
Trace
nd
69
45
79
20
50
60
79
79
79
79
nd
23
43
67
79
79
79
79
00
9.0
3.
4.
5.
9.5
10.0
10.5
11.0
11.5
12.0
11.0
11.5
12.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
11.0
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
8
10
12
14
16
18
20
10.
84
Condition: Solvent MeOH: Water (1:2), Temperature 150 ˚C,
11.0 bar argon, 14 hr, aIsolated yield, nd = not detected
The reaction was further extended to the internal alkynes with
maintaining the similar reaction parameters, a significant
transformation of 78 % was obtained with the symmetrical
diphenyl acetylene while 80 % yield of the hydrated product was
11.
12.
13.
83
85
89
recorded
with
the
unsymmetrical
1-methyl-4-
(phenylethynyl)benzene respectively (Table 2, entries 15 and 16).
Here, hydration of both the symmetrical and unsymmetrical
diarylacetylene regioselectively forms only one product and the
formation of carbonyl group is preferred at the position where
carbonyl is conjugated with a substituted phenyl group.23

4
Tetrahedron
References and notes
14.
15.
16.
80
78
80
1. Trost BM, Acc. Chem. Res. 2002; 35; 695-705.
2. Satrawala N, Sharma KN, Matsinha LC, Maqeda L,
Siangwata S, Smith GS, Joshi RK, Tetrahedron Lett. 2017;
58; 2761–2764.
3. Jagadeesh RV, Stemmler T, Surkus AE, Junge H, Junge K,
Beller M, Nature Protocols 2015; 10; 548-557.
4. Morandi B, Wickens ZK, Grubbs RH, Angew. Chem. 2013;
125; 3016 –3020.
5. a)Mitsudome T, Mizumoto K, Mizugaki T, Jitsukawa K,
Kaneda K, Angew. Chem. 2010; 122; 1260-1262. b)
DeLuca RJ, Edwards JL, Steffens LD, Michel BW, Qiao X,
Zhu C, Cook SP, Sigman MS, J. Org. Chem. 2013; 78;
1682-1683. c) Mathur P, Jha B, Raghuvanshi R, Joshi RK,
Mobin SM, J. Organomet. Chem. 2012; 712; 7-14. d) Jha
BN, Raghuvanshi R, Joshi RK, Mobin SM, Mathur P, Appl.
Organometal. Chem. 2017; 31; 1-6. e) Colquhoun HM,
Thompson DJ, Twigg MV, Carbonylation: Direct Synthesis
of Carbonyl Compounds. New York: Plenum; 1991. f)
Wender I, Pino P, Organic Synthesis via Metal Carbonyls,
vols. 1 and 2. New York: Wiley Interscience, 1977. g) Joshi
RK, Satrawala N, Tetrahedron Lett. 2017; 58; 2931–2935.
6. Wu X, Bezier D, Darcel C, Adv. Synth. Catal. 2009; 351;
367 – 370.
Condition: Solvent MeOH: Water (1:2), Temperature 150 ˚C,
11.0 bar argon, 14 hr, a isolated yield
To address the issue of scalability of the method which was
the limitation of the previous approach,20 in the present method 1
gm of phenyl acetylene was considered for the reaction with
adopting the optimised reaction parameters after the completion
of the reaction, a 70% of acetophenone was isolated. This
indicates the present method can be utilized for the bulk
production in relevant industries.
Conclusion
7. a) Alonso F, Beletskaya IP, Yus M, Chem. Rev. 2004; 104;
3079-3159. b) Beller M, Seayad J, Tillack A, Jiao H, Angew.
Chem. Int. Ed. 2004; 43; 3368 – 3398.
8. a) Nishizawa M, Skwarczynski M, Imagawa H, Sugihara T,
Chem. Lett. 2002; 31; 12-13. b) Wasacz JP, Badding VG, J.
Chem. Educ. 1982; 59; 694-695. c) Bach RD, Woodard RA,
Anderson TJ, Glick MD, J. Org. Chem. 1982; 47; 3107-
3712.
9. a) Kadota I, Lutete LM, Shibuyab A, Yamamotob Y,
Tetrahedron Lett. 2001; 42; 6207–6210. b) Fukuda Y,
Shiragami H, Utimota K, Nozaki H, J. Org. Chem. 1991; 56;
5816-5819. c) Kataoka Y, Matasumoto O, Ohashi M,
Yamagata T, Tani K, Chem. Lett. 1994; 1283-1284. d) Dasa
AK, Parka S, Muthaiahd S, Hong SH, Synlett. 2015; 26;
2517–2520. e) Alvarez MJR, Lombardia NR, Schumacher S,
Iglesias DP, Moris F, Cadierno V, Alvarez JG, Sabin JB,
ACS Catal., 2017; 11; 7753–7759.
In this note, we had devised a new metal/catalyst/reagent-free
methodology for hydration of alkynes at possible reaction
conditions. Transformation of acetylene to ketone was entirely
controlled by tuning the temperature and pressure of the reaction.
The reaction shows excellent functional group compatibility and
works smoothly for aryl containing either electron donating or
withdrawing functional groups. Moreover, significant yield of the
product was also obtained irrespective the position of functional
group attached with benzene. Hence, reaction indicates the
robustness nature towards all possible alkynes. Apart from
alkynes present method need the only mixture of water and
methanol as solvent and does not form any by-product. This
method offers high atom economy and successfully implemented
for the bulk synthesis of ketone in fine chemical industries.
The general procedure of the reaction
In a 100 mL capacity of autoclave vessel a 60 mL solution of
methanol and water (1:2) was added, further 1mmol alkynes were
added to this solution. The autoclave was three times purged with
the gas and then finally pressurized up to the 11 bar pressure. The
reaction mixture was vigorously stirred at 150 ˚C for continuous
14 hr. After the completion of the reaction, the reactor was
cooled to room temperature, and then the argon pressure was
carefully released to the atmospheric pressure. Methanol from the
reaction mixture is removed using rotatory evaporator. After that,
the reaction mixture was transferred in a separating funnel, and it
was worked up with ethyl acetate. The organic layer was
separated and dried over Na2SO4. Afterwards, it was filtered and
concentrated under reduced pressure. The resulted crude mixture
was purified by silica gel column chromatography using ethyl
acetate/n-hexane as eluent, and pure keto product was isolated.
10. a) Hiscox W, Jennings PW, Organometallics 1990; 9; 1997-
1999. b) Jennings PW, Hartman JW, Hiscox HC, Inorg.
Chim. Acta 1994; 222; 317-322.
11. a) Blum J, Huminer H, J. Mol.Catal. 1992; 75; 153-160. b)
Lumbroso A, Vautravers NR, Breit B, Org. Lett. 2010; 12;
5498-5501. c) Kwong F, Li Y, Lam W, Qiu L, Lee H,
Yeung C, Chan K, Chan ASC, Chem. Eur. J. 2005; 11; 3872
– 3880. d) Omae I, Appl. Organometal. Chem. 2008; 22;
149–166.
12. Bruneau C, Dixneuf PH, Chem. Commun. 1997; 507-512
13. a) Li F, Wang N, Lu L, Zhu G, J. Org. Chem. 2015; 80;
−3546. b) Liang
3538
Org. Lett. 2015; 17; 162
S, Jasinski J, Hammond GB, Xu B,
−165. c) Wang
W, Hammond GB,
Xu B, J. Am. Chem. Soc. 2012; 134; 5697−5705. d) Marion
N, Ramon RS, Nolan SP, J. Am. Chem. Soc. 2009; 131;
448–449. e) Leyva A, Corma A, J. Org. Chem. 2009; 74;
2067–2074. f) Mizushima E, Sato K, Hayashi T, Tanaka T,
Angew. Chem. 2002; 114; 4745-4747. g) Teles JS, Brode S,
Chabanas M, Angew. Chem. Int. Ed. 1998; 37; 1415-1418.
h) Xu X, Kim SH, Zhang X, Das AK, Hirao H, Hong SH,
Organometallics 2013; 32; 164–171. i) Fukuda Y, Utimoto
K, J. Org. Chem. 1991; 56; 3731-3734. j) Casado R, Contel
M, Laguna M, Romero P, Sanz S, J. Am. Chem. Soc. 2003;
125; 11925-11935. k) Fremont P, Singh R, Stevens ED,
Acknowledgements
R.K. Joshi thanks to Department of Science and Technology
for financial assistance (INT/RUS/RFBR/P0222). M. Ali and
A.K. Srivastava thanks to MANF-UGC, New Delhi and MNIT
Jaipur respectively for providing research fellowships. Authors
acknowledge MRC, MNIT Jaipur for providing characterisation
facilities.

5
Petersen JL, Nolan SP, Organometallics 2007; 26; 1376-
1385.
14. a) Rao KTV, Prasad PSS, Lingaiah N, Green Chem. 2012;
14; 1507–1514. b) Thuong MBT, Mann A, Wagner A,
Chem. Commun. 2012; 48; 434–436.
15. Damiano JP, Postel M, J. Organomet. Chem. 1966; 522;
303-305.
16. Tachinami T, Nishimura T, Ushimaru R, Noyori R, Naka H,
J. Am. Chem. Soc. 2013; 135; 50–53.
17. Jin X, Oishi T, Yamaguchi K, Mizuno N, Chem. Eur. J.
2011; 17; 1261 – 1267.
18. a) Liu W, Wang H, Li C, Org. Lett. 2016; 18; 2184–2187. b)
Chen D, Guo C, Zhang H, Jin D, Li X, Gao P, Wu X, Liu
X, Liang Y, Green Chem. 2016; 18; 4176-4180. c) An J,
Bagnell L, Cablewski C, Strauss CR, Trainor RW J. Org.
Chem. 1997; 62; 2505-2511. d) Ye M, Wen Y, Li H, Fu Y,
Wang Q, Tetrahedron Lett. 2016; 57; 4983–4986.
19. Hu N, Aso Y, Otsubo T, Ogura F, Tetrahedron Lett. 1986;
27; 6099-6102.
20. Vasudevan A, Verzal MK, Synlett 2004; 4; 0631-0634.
21. Millero FJ, Hoff EV, Kahn L, J. Solution Chem. 1972; 1;
309-327.
22. a) Farajtabar, A, Gharib, F, Journal of Taibah University for
Science 2009; 2; 7-13. b) Rochesteran, CH, Wilson, DN, J.
Chem. Soc., Faraday Trans. 1 1976; 72; 2930 – 2938. c)
Gbashi, S, Njobeh, P, Steenkamp, P, Tutu, H, Madala, N,
Chem. Cent. J. 2016; 10; 37 – 49. d) Bandura, AV, Lvov,
SN, J. Phys. Chem. 2006; 35; 15 – 30.
23. a) Bras, G, Provot, O, Peyrat, J, Alami, M, Brion, J,
Tetrahedron Letters 2006; 47; 5497–5501. b) Israelsohn, O,
Vollhardt, KPC, Blum, J, J. Mol. Catal. A: Chem. 2002;
184; 1–10.

6
Tetrahedron
Highlights
• Autoclave assisted metal/reagent/catalyst
free hydration of terminal and internal
alkynes.
• Excellent functional group compatibility
with gram scale synthesis of ketones.
• No
by-product,
eco-friendly,
water
mediated, economic and sustainable
methodology.