Synthesis and Catalytic Activity of Quaternary Ammonium Salts Containing gem-Dichlorocyclopropane and 1,3-Dioxolane Fragments

Article abstract of DOI:10.1134/S1070427220070046

Abstract: Quaternary ammonium salts containing gem-dichlorocyclopropane and 1,3-dioxolane groups were synthesized in high yield. The reactions of dichlorocarbonation of styrene and O-alkylation of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane in the presence of quaternary ammonium salts were studied. It was established that in the O-alkylation reaction, compounds containing cycloacetal and allyl moieties have the maximum efficiency in the series of catalysts studied. The structures of the isolated salts were proved by ¹H and ¹³C NMR spectroscopy.

Full text of DOI:10.1134/S1070427220070046

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2020, Vol. 93, No. 7, pp. 967–972. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Prikladnoi Khimii, 2020, Vol. 93, No. 7, pp. 952–957.
CATALYSIS
Synthesis and Catalytic Activity of Quaternary Ammonium Salts
Containing gem-Dichlorocyclopropane
and 1,3-Dioxolane Fragments
G. N. Sakhabutdinovaa, E. A. Yakovenkoa, G. Z. Raskil’dinaa,*,
and S. S. Zlotskiia
a Ufa State Petroleum Technological University, Ufa, 450062 Russia
*e-mail: graskildina444@mail.ru
Received September 22, 2019; revised March 17, 2020; accepted April 5, 2020
Abstract—Quaternary ammonium salts containing gem-dichlorocyclopropane and 1,3-dioxolane groups were
synthesized in high yield. The reactions of dichlorocarbonation of styrene and O-alkylation of 2,2-dimethyl-4-
hydroxymethyl-1,3-dioxolane in the presence of quaternary ammonium salts were studied. It was established that
in the O-alkylation reaction, compounds containing cycloacetal and allyl moieties have the maximum efficiency in
the series of catalysts studied. The structures of the isolated salts were proved by 1H and 13C NMR spectroscopy.
Keywords: quaternary ammonium salt, gem-dichlorocyclopropane and 1,3-dioxolane fragments,
hexamethylenetetramine, 4-[(allyloxy)methyl]-2,2-dimethyl-1,3-dioxolane
DOI: 10.1134/S1070427220070046
Quaternary ammonium salts are one of the most
commonly used classes of disinfectants in medicine,
textile, paint and varnish and food industries due to their
relatively low toxicity to humans and animals [1–3]. This
determines the importance and relevance of the synthesis
of new quaternary ammonium salts and the assessment
of their catalytic activity in reactions.
structure of molecules increases their biological activity
[5]. The aim of the present work was to synthesize
new quaternary ammonium salts containing gem-
dichlorocyclopropane and 1,3-dioxolane fragments,
and to evaluate their catalytic activity in the reactions
of dichlorocarbonation of styrene and O-alkylation of
2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane.
In [4], a method was proposed for preparing quaternary
salts from readily available pyridine compounds as initial
reagents. The disadvantages of this method are the multi-
stage synthesis and the duration of the reaction.
EXPERIMENTAL
Chromatographic analysis of the reaction products
was performed on a Carlo-Erba HRGC 5300 Mega Series
gas chromatograph with a flame ionization detector,
carrier gas helium, flow rate 30 mL min–1, capillary
column 25 m long, phase SE-30. Analysis conditions:
temperature programming from 50 to 280°С with a rise
rate of 8 deg min–1, temperature of the detector 250°С,
evaporator 300°С, carrier gas helium, 30 mL min–1.
Product identification was carried out using known
retention times. Mass spectra were recorded on a Crystal-
5000M instrument (30 m long capillary column, column
temperature from 80 to 280°C, transition line temperature
300°C, ion source temperature 300°C). The temperature
We have previously shown that the presence of
gem-dichlorocyclopropane and cycloacetal fragments
in the structure of molecules increases their biological
activity [5]. The aim of the present work was to obtain
new quaternary ammonium salts containing gem-
dichlorocyclopropane and 1,3-dioxolane fragments,
and to evaluate their catalytic activity in the reactions
of styrene dichlorocarbonation and O-alkylation of
2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane .
We have previously shown that the presence of gem-
dichlorocyclopropane and cycloacetal fragments in the
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SAKHABUTDINOVA et al.
increased at a rate of 20 deg min–1. The carrier gas
is helium. NMR spectra were recorded on a Bruker
AVANCE-500 spectrometer (1H 500.13 MHz) in CDCl3.
We used freshly distilled methylene chloride, chloroform,
petroleum ether, benzene, and toluene solvents (all
chemically pure grade, Tekhresurs LLC, Russia);
freshly calcined K2CO3 and MgSO4 (both pure
grade, Steklopribor LLC, Russia), tertiary amines—
4-[(2,2-dichlorocyclopropyl)methyl]morpholine,
4-(1,3-dioxolan-2-ylmethyl)morpholine, 4-(1,3-dioxolan-
4-ylmethyl)morpholine, prepared as described in [6].
(1Н, 2С8,12Н2), 3.67 d (2H, C6H2, J 4.3 Hz), 3.86 t (2H,
C5H2, J 7.0 Hz), 3.93–3.96 m (4H, 2C9,11H2), 3.98 t (2H,
t, C4H2, J 7.0 Hz), 4.34 d (2H, C13H2, J 7.1 Hz), 5.50 t
(1H, C2H, J 4.2 Hz), 5.64 d (1H, C15H2a, J 10.3 Hz),
5.72 d (1H, C15H2b, J 10.3 Hz), 5.99–6.09 m (1H,
C14H). 13C NMR spectrum, δ, ppm (J, Hz): 58.62
(2С8,12Н2), 59.01 (C13H2), 59.93 (2C9,11H2), 62.23
(C6H2), 65.13 (2C4,5H2), 97.52 (C2H), 125.52 (C14H),
128.70 (C15H2).
4-(1,3-Dioxolan-4-ylmethyl)-4-propen-2-ylmor-
pholinium-4 bromide (1c) or chloride (2c). White
powder, yield 50% (1c), 40% (2c); Тm = 65 (1c) and 61°С
(2c). 1Н NMR spectrum, δ, ppm (J, Hz): 3.43–3.55 m (1Н,
2С8,12Н2), 3.62 d (2H, C6H2, J 4.3 Hz), 3.66–4.10 m (2H,
C4H2), 3.90–3.98 m (4H, 2C9,11H2), 4.33 d (2H, C13H2,
J 7.1 Hz), 4.57 q (1H, C5H, J 7.0 Hz), 4.93 s (2H, C2H2),
5.62 d (1H, C15H2a, J 10.3 Hz), 5.70 d (1H, C15H2b,
J 10.3 Hz), 5.96–6.00 m (1H, C14H). 13C NMR spectrum,
δ, ppm (J, Hz): 60.52 (2C8,12H2), 61.50 (C13H2), 61.60
(2C9,11H2), 63.53 (C6H2), 75.03 (C4H2), 75.74 (C5H),
93.83 (C2H2), 125.52 (C15H2), 131.80 (C14H).
Synthesis of quaternary ammonium salts of
(4-[(2,2-dichlorocyclopropyl)methyl]-4-propen-2-yl-
morpholinium-4 bromide or chloride, 4-(1,3-diox-
olan-2-ylmethyl)-4-propene-2-ylmorpholinium-4
bromide or chloride, 4-(1,3-dioxolan-4-ylmethyl)-
4-propen-2-ylmorpholinium-4 bromide or chloride,
4-benzyl-4-(1,3-dioxolan-2-ylmethyl)morpholinium-4
bromide or chloride) (general procedure). In a 100 mL
round bottom flask 0.5 g (0.002 mol) of 4-[(2,2-dichlo-
rocyclopropyl) methyl]morpholine, or 0.3 g (0.002 mol)
of 4-(1,3-dioxolan-2-ylmethyl)morpholine, or 0.3 g
(0.002 mol) of 4-(1,3-dioxolan-4-ylmethyl)morpholine
and 0.3 g (0.002 mol) of allyl bromide (or chloride) or
0.3 g (0.002 mol) of benzyl bromide (or chloride) were
placed. The reaction mixture was kept for 2 h at room
temperature. The product, initially precipitated in the form
of oil, crystallized completely. The mixture was filtered,
the filter residue was washed with benzene (2 × 100 mL)
and dried in vacuum.
4-Benzyl-4-(1,3-dioxolan-2-ylmethyl)morpho-
linium-4 bromide (1d) or chloride (2d). White powder,
yield 83% (1d), 79% (2d); Тm = 56 (1d) and 53°С (2d).
1Н NMR spectrum, δ, ppm (J, Hz): 1.56 t (1H, C10H2a,
J 7.6 Hz), 1.64 t (1H, C10H2b, J 7.6 Hz), 1.78–2.12 m
(1H, C8H), 3.35 t (4H, 2C3,5H2, J 8.6 Hz), 3.710–3.77 m
(2H, C7H2), 4.07 t (4H, 2C2,6H2, J 8.6 Hz,), 4.84 s (1H,
C11H2), 7.30 t (2H, 2C14,16H, J 9.7 Hz), 7.33 t (1H, C15H,
J 9.7 Hz), 7.45 t (2H, 2C13,17H, J 9.7 Hz). 13C NMR
spectrum, δ, ppm (J, Hz): 27.32 (C10H2), 29.05 (C8H),
58.51 (C7H2), 61.66 (С9), 62.27 (2C2,6H2), 63.50 (C11H2),
63.53 (2C3,5H2), 127.04 (C12), 129.44 (2C14,16H), 130.34
(C15H), 134.69 (2C13,17H2).
4-[(2,2-Dichlorocyclopropyl)methyl]-4-propen-
2-yl-morpholinium-4 bromide (1a) or chloride (2a).
White powder, yield 87% (1а), 70% (2а); Тm = 60°С (1а)
and 53°С (2а). 1Н NMR spectrum, δ, ppm (J, Hz): 1.67 t
(1H, C10H2a, J 7.7 Hz), 2.03 t (1H, C10H2b, J 7.7 Hz),
2.30–2.41 m (1H, C8H), 3.76 t (4H, 2C3,5H2, J 8.6 Hz),
3.83–3.89 m (2H, C7H2), 4.03–4.09 m (2H, C13H2),
4.19 t (4H, 2C2,6H2, J 8.6 Hz), 5.75 d (1H, C15H2a,
J 9.7 Hz), 5.95 d (1H, C15H2b, J 9.7 Hz), 6.10–6.14 m
(1H, C14H). 13C NMR spectrum, δ, ppm (J, Hz): 23.33
(C8H), 26.32 (C10H2), 56.84 (2C3,5H2), 57.27 (C7H2),
60.51 (2C2,6H2), 60.58 (C9), 61.24 (C13H2), 123.54
(C14H), 130.83 (C15H2).
Synthesis of 1-[(2,2-Dichlorocyclopropyl)methyl]-
3,5,7-triaza-1-azoniatricyclo[3,3,1,1]decane bromide
and chloride (general procedure). In a 100 mL round
bottom flask equipped with a reflux condenser with a
calcium chloride tube, a solution of 1 g (0.007 mol)
of hexamethylenetetramine (urotropine) in 10 mL of
chloroform was placed and a solution of 1.4 g (0.007 mol)
of 2- (bromomethyl)-1,1-dichlorocyclopropane or
2-(chloromethyl)-1,1-dichlorocyclopropane in 10 mL of
chloroform was added with stirring. The reaction mixture
was boiled in a water bath at 60°C for 4 h, then it was
cooled and an equal volume of dry petroleum ether was
added. The precipitate was filtered off, washed thoroughly
4-(1,3-Dioxolan-2-ylmethyl)-4-propen-2-
ylmorpholinium-4 bromide (1b) orchloride (2b). White
powder, yield 81 (1b), 66% (2b); Тm = 63 (1b) and 60°С
1
(2b). Н NMR spectrum, δ, ppm (J, Hz): 3.47–3.59 m
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SYNTHESIS AND CATALYTIC ACTIVITY OF QUATERNARY AMMONIUM SALTS
969
with dry ether and dried in vacuum at a temperature of
35–40°C.
1.40 s (3Н, С2′Н3), 3.43 d.d (1Н, С6Hа, J 9.9 Hz,
J 5.5 Hz), 3.50 d.d (1Н, С6Hb, J 9.8 Hz, J 5.8 Hz), 3.71 t
(1Н, С5Hа, J 8.3 Hz, J 6.5 Hz), 3.97–4.06 m (3Н, С5Hb,
С8Н2), 4.26 t (1Н, С4H, J 5.9 Hz), 5.16 d (1Н, С10Hа,
J 1.3 Hz, J 10.4 Hz), 5.26 d (1Н, С10Hb, J 1.4 Hz,
J 15.6 Hz), 5.83–5.93 m (1Н, С9H). 13C NMR spectrum,
δ, ppm (J, Hz): 25.34 (С2″), 26.70 (C2′), 66.77 (С5), 71.02
(С6), 72.44 (С8), 74.65 (С4), 109.35 (С2), 117.31 (С10),
134.41 (С9). Mass spectrum, m/e (Irel, %): 172 (none),
157 (100), 101(81), 73 (9), 55 (16), 43 (45).
1-[(2,2-Dichlorocyclopropyl)methyl]-3,5,7-triaza-
1-azoniatricyclo[3,3,1,1]decane bromide (3a) or
chloride (3b). Yellow powder, yield 68 (3a) and 55%
(3b); Тm = 48°С (3а) and 39°С (3b). 1Н NMR spectrum,
δ, ppm (J, Hz): 0.89 t (1H, C14H2a, J 7.7 Hz), 1.06 t (1H,
C14H2, Hb, J 7.7 Hz), 1.56–1.68 m (1H, C12H), 2.31 d.d
(1H, C11H2a, J 13.8 Hz, J 8.7 Hz), 2.54 d.d (1H, C11H2b,
J 13.8 Hz, J 8.7 Hz), 3.70–3.79 m (6H, 3C2,8,10H2),
4.61–4.68 m (6H, 3C4,6,9H2). 13C NMR spectrum, δ, ppm
(J, Hz): 21.06 (C12H), 25.87 (C14H2), 55.18 (C3H2), 59.07
(C9), 69.64 (3C2,8,10H2), 78.10 (3C4,6,9H2).
RESULTS AND DISCUSSION
The corresponding quaternary ammonium salts were
synthesized in the reaction of tertiary amines based on
morpholine and halogen derivatives of allyl or benzyl
in quantitative yield. The best results [yield of salts
1a–1d 80–90%] were produced using allyl and benzyl
bromides. The yield of quaternary salts 2a–2d from the
corresponding chlorides did not exceed 10%. Amines
containing 1,3-dioxolane groups form salts 1b, 1c with a
close yield (84 and 88%, respectively) and are more active
than the gem-dichlorocyclopropane derivative [yield of
salts 1a and 1d 76 and 72%, respectively] (Scheme 1).
Synthesis of 4-[(allyloxy)methyl]-2,2-dimethyl-
1,3-dioxolane. To a solution of 4 g (0.03 mol) of
2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane in 30 mL
of toluene and 0.8 g (0.003 mol) of the catalyst 1b or 1c,
or triethylammonium bromide, either 0.9 g of catalyst 1a,
or 1 g of catalyst 1d or 3a, 50 g of a 50% NaOH solution
was added with vigorous stirring at 30°C. Then, after 2 h,
11.5 g (0.15 mol) of allyl chloride were added dropwise.
Sample were taken every hour. Upon completion of the
reaction, the mixture was washed with water, extracted
with methylene chloride (3 × 30 mL), dried over
anhydrous MgSO4, and the solvent was removed.
Under the same conditions, based on the well-known
hexamethylenetetramine (urotropin), we synthesized
bromide 3a and chloride 3b containing a gem-dichlo-
rocyclopropane fragment with a yield of 68 and 55%,
respectively:
4-[(Allyloxy)methyl]-2,2-dimethyl-1,3-dioxolane
(4). Yield 94%, colorless liquid, Тb = 74°С (5 mmHg).
1Н NMR spectrum, δ, ppm (J, Hz): 1.32 s (3Н, С2″Н3),
3b
3a
3a, 3b
The catalytic activity of the resulting bromides 1a–1c,
3a in the O-alkylation of the well-known heterocyclic
alcohol 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane
with allyl chloride was determined. Earlier, we found
that ether 4 has herbicidal properties [7] and based on it
multifunctional glycols, intermediates of drug synthesis,
can be produced [8, 9] (Scheme 2).
From the resulting data (Fig. 1), it follows that the
quaternary salts 1b, 1c, in which cycloacetal and allyl
groups similar to the reagents alcohol and olefin are
present, have the maximum efficiency in the series of the
studied catalysts. We can assume that 1a and 1b among
the salts studied, are better associated with oxymethyl
ketal and allyl chloride molecules, which increases the
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SAKHABUTDINOVA et al.
Scheme 1.
1a, 2a
1b, 2b
1c, 2c
X = Br (1a–1d), Cl (2a–2d)
1d, 2d
Scheme 2.
Cat.
4
efficiency of O-alkylation and contributes to an increase
triethylbenzylammonium bromide and the quaternary salt
in the yield of the target ether 4. The known catalyst
1a containing the gem-dichlorocyclopropane fragment
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SYNTHESIS AND CATALYTIC ACTIVITY OF QUATERNARY AMMONIUM SALTS
971
Time, h
Time, h
Fig. 1. The activity of quaternary ammonium salts in the
synthesis of 4-[(allyloxy)methyl]-2,2-dimethyl-1,3-dioxolane.
The molar ratio of 2,2-dimethyl-4-hydroxymethyl-1,3-
dioxolane : allyl chloride = 1 : 5, 50% NaOH solution, 10 wt %
catalyst, temperature 30°C. (1) Triethylbenzylammonium
bromide; (2) 4-[(2,2-dichlorocyclopropyl)methyl]-4-propen-2-
yl-morpholinium-4 bromide; (3) 4-(1,3-dioxolan-2-ylmethyl)-
4-propen-2-ylmorpholinium-4 bromide, 4-(1,3-dioxolan-
4-yl-methyl)-4-propen-2-ylmorpholinium-4 bromide;
(4) without catalyst; (5) 4-benzyl-4-(1,3-dioxolan-2-ylmethyl)-
morpholinium-4 bromide; (6) 1-[(2,2-dichlorocyclopropyl)-
methyl]-3,5,7-triaza-1-azoniatricyclo [3.3.1.1]decane bromide.
Fig. 2. The activity of quaternary ammonium salts in the
synthesis of (2,2-dichlorocyclopropyl)benzene. The molar ratio
of styrene : CHCl3 = 1 : 10, 50% NaOH solution, 10 wt % catalyst,
temperature 0°C. (1) 4-Benzyl-4-(1,3-dioxolan-2-ylmethyl)-
morpholinium-4 bromide, (2) triethylbenzylammonium
bromide, (3) 1-[(2,2-dichlorocyclopropyl)methyl]-3,5,7-triaza-
1-azoniatricyclo[3.3.1.1]decane bromide, (4) without catalyst.
CONCLUSIONS
are close in activity, and the urotropine derivative under
these conditions is the least active.
Based on tertiary amines containing gem-dichlorocy-
clopropane and cycloacetal fragments, new quaternary
ammonium salts were synthesized with a yield of 40–87%.
It was found that in the O-alkylation of 2,2-dimethyl-4-hy-
droxymethyl-1,3-dioxolane with the allyl chloride of the
4-(1,3-dioxolan-2-ylmethyl)-4-propen-2-ylmorpholinium-4
bromide and 4-(1,3-dioxolan-4-ylmethyl)-4-propen-2-yl-
morpholinium-4 bromide salts, in which cycloacetal and
allyl moieties are present, have the maximum efficiency
among the studied catalysts. The introduction of 4-benzyl-
4-(1,3-dioxolan-2-ylmethyl)morpholinium-4 bromide
containing gem-dichlorocyclopropane fragment into the
dichlorocarbenation reaction of styrene under interphase
catalysis increased the activity to 35%.
In the styrene dichlorocarbonation under interphase
catalysis [10] the best results were obtained using the salt
1g containing the gem-dichlorocyclopropane fragment
(Fig. 2).
Cat.
5
The activity of urotropine salt 3a is close to the
well-known triethylbenzylammonium bromide catalyst
(Fig. 2).
ACKNOWLEDGMENTS
The resulting data show that the presence of
substituents in the molecules of quaternary salts, the
structure of which coincides with the structure of the
reagents, increases their catalytic activity.
The authors are grateful to L.V. Spirikhin, head of the
laboratory of the Federal Institute of Physics and Chemistry of
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the UFIC RAS for their assistance in identifying the structure
of the compounds.
https://doi.org/10.1016/j.ejmech.2010.06.014
4. Ng, C.L.L., Singhal, V., Widmer, F., Wright, L.C.,
Sorell, T.C., and Jolliffe, K.A., Bioorg. Med. Chem.,
2007, vol. 15, no. 10, pp. 3422–3429.
FUNDING
https://doi.org/10.1016/j.bmc.2007.03.018
The studies were supported by the RFBR contest mol_ev_a
(Eureka! Idea) under the contract no. 19-33-80002/19 of
12/07/2018.
5. Valiev, V.F., Yakovenko, E.A., Bulatova, Yu.I.,
Mirakyan, M.S., Borisova, Yu.G., Mikhailova, N.N., and
Raskil’dina, G.Z., Bash. Khim. Zh., 2016, vol. 23, no. 4,
pp. 94–98.
CONFLICT OF INTEREST
6. Kazakova, A.N., Timofeeva, S.A., Yumakaeva, Yu.M.,
Khairullina, A.F., and Zlotskii, S.S., Bash. Khim. Zh.,
2010, vol. 17, no. 4, pp. 19–23.
The authors declare no conflict of interest requiring
disclosure in this article.
7. Valiev, V.F., Raskil’dina, G.Z., Mudrik, T.P.,
Bogomazova, A.A., and Zlotskii, S.S., Bash. Khim. Zh.,
2014, vol. 21, no. 3, pp. 25–27.
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