Synthesis of cyclohexyl isovalerate by carbonylation of isobutylene with carbon monoxide and cyclohexanol in the presence of Pd(PPh3)4?PPh3?TsOH and its antimicrobial activity

Article abstract of DOI:10.1134/S1070428017100189

A procedure has been developed for the synthesis of cyclohexyl isovalerate by reaction of isobutylene with carbon monoxide and cyclohexanol in the presence of the three-component catalytic system Pd(PPh₃)₄?PPh₃?TsOH. Cyclohexyl isovalerate showed a pronounced antibacterial activity.

Full text of DOI:10.1134/S1070428017100189

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 10, pp. 1596–1597. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © N.O. Appazov, S.S. Seitzhanov, A.T. Zhunissov, R.A. Narmanova, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53,
No. 10, pp. 1560–1561.
SHORT
COMMUNICATIONS
Synthesis of Cyclohexyl Isovalerate by Carbonylation
of Isobutylene with Carbon Monoxide and Cyclohexanol
in the Presence of Pd(PPh3)4‒PPh3‒TsOH
and Its Antimicrobial Activity
N. O. Appazov,* S. S. Seitzhanov, A. T. Zhunissov, and R. A. Narmanova
Korkyt Ata Kyzylorda State University, ul. Aiteke bi 29A, Kyzylorda, 120014 Kazakhstan
*e-mail: nurasar.82@mail.ru
Received October 28, 2016
Abstract—A procedure has been developed for the synthesis of cyclohexyl isovalerate by reaction of
isobutylene with carbon monoxide and cyclohexanol in the presence of the three-component catalytic system
Pd(PPh3)4‒PPh3‒TsOH. Cyclohexyl isovalerate showed a pronounced antibacterial activity.
DOI: 10.1134/S1070428017100189
Isovaleric acid esters are used as components of
medicines (valerian root, corvalol, validol), perfumes,
and food flavoring agents (ethyl, propyl, isoamyl,
hexyl, decadienyl, geranyl, and 2-phenylethyl iso-
valerates) [1–3]. Industrial methods for the synthesis of
carboxylic acid esters are based on esterification of
carboxylic acids with the corresponding alcohols. The
technology is complicated and is environmentally
unsafe because of a number of secondary operations
(neutralization, washing, etc.), producing large
amounts of industrial wastes.
bonylation of isobutylene (1) with CO and cyclo-
hexanol in the presence of Pd(PPh3)4‒TsOH (1 :12) at
100°C and a pressure of 2.0 MPa for 4 h [15].
We have developed a procedure for the synthesis of
ester 2 by reaction of alkene 1 with carbon monoxide
and cyclohexanol under catalysis by the three-com-
ponent system Pd(PPh3)4‒PPh3‒TsOH (1 :3 :12) at
100°C (CO pressure 2.0 MPa, 4 h). Under these con-
ditions, ester 2 was formed in quantitative yield and
was isolated in up to 71% yield. The product structure
was confirmed by IR and mass spectra. The IR spec-
trum of 2 contained absorption bands at 3000–2872
(C–H) and 1294–1095 cm–1 (C–O–C) and a strong
band at 1736 cm–1 (C=O).
Preliminary tests revealed considerable antimicro-
bial and antifungal activity of compound 2 against
Staphylococcus aureus, Escherichia coli, Pseudo-
monas aeruginosa, and Candida albicans. The anti-
microbial and antifungal activity of 2 was assayed by
the agar diffusion method [16]. Ester 2 was dissolved
in 96% ethanol to a concentration of 1 mg/mL. The
bacterial and fungal cultures were grown by incubation
for 18–24 h at 37°C, dispersed in a 0.9% solution of
sodium chloride, and applied in 1-mL portions to Petri
A promising method for the manufacture of carbox-
ylic acid esters is alkoxycarbonylation of alkenes with
carbon monoxide and alcohols in the presence of
catalysts based on Group VIII transition metal com-
plexes [4–14]. Ethyl carboxylates can be obtained by
reaction of alkenes with carbon monoxide and ethanol
in the presence of the two-component catalytic system
Pd(PPh3)4‒TsOH (1 : 3 to 1 : 12) at 60‒100°C and
a pressure of 0.5‒3.0 MPa (reaction time 0.5‒4 h).
A significant drawback of this procedure is that it is
hardly suitable for the preparation of esters from
alicyclic alcohols. Cyclohexyl isovalerate (2) was
obtained in a low yield (46.6%) by hydroalkoxycar-
OH
CH2
Me
O
Pd(PPh3)4–PPh3–TsOH
+
CO +
Me
Me
Me
O
1
2
1596

SYNTHESIS OF CYCLOHEXYL ISOVALERATE
dished filled with beef extract agar to obtain a “con-
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Gas chromatographic–mass spectrometric analysis
was performed using an Agilent Technologies 7890A
chromatograph coupled with a 5975C mass-selective
detector; HP-5MS capillary column, 30 m×0.25 mm,
carrier gas helium; injector temperature 250°C; oven
temperature programming from 40°C (1 min) at a rate
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ratio 1000:1; electron impact; retention time of 2
19.4 min. The IR spectra were recorded on a Shimadzu
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 10 2017