Condensation of 1,2,4-Butanetriol with Carbonyl Compounds and Reactions of Hydroxyalkyl-1,3-dioxacyclanes

Article abstract of DOI:10.1134/S107036321808008X

A mixture of isomers of 2-(1,3-dioxolan-4-yl)ethanol and 1,3-dioxan-4-ylmethanol was prepared by reaction of 1,2,4-butanetriol with paraformaldehyde. This mixture was subjected to O-alkylation, O-acylation, condensation with phenyl isocyanate, and substitution of OH groups for Cl. The relative activity of acetone derivatives of glycerol and 1,2,4-butanetriol in reactions with allyl chloride and benzyl chloride was estimated.

Full text of DOI:10.1134/S107036321808008X

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 8, pp. 1601–1605. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © G.Z. Raskil’dina, Yu.G. Borisova, S.S. Zlotskii, 2018, published in Zhurnal Obshchei Khimii, 2018, Vol. 88, No. 8, pp. 1280–1284.
Condensation of 1,2,4-Butanetriol with Carbonyl Compounds
and Reactions of Hydroxyalkyl-1,3-dioxacyclanes
a
a
a
G. Z. Raskil’dina *, Yu. G. Borisova , and S. S. Zlotskii
a
Ufa State Petroleum Technological University, ul. Kosmonavtov 1, Ufa, Bashkortostan, 450062 Russia
*
e-mail: graskildina444@mail.ru
Received April 5, 2018
Abstract––A mixture of isomers of 2-(1,3-dioxolan-4-yl)ethanol and 1,3-dioxan-4-ylmethanol was prepared by
reaction of 1,2,4-butanetriol with paraformaldehyde. This mixture was subjected to O-alkylation, O-acylation,
condensation with phenyl isocyanate, and substitution of OH groups for Cl. The relative activity of acetone
derivatives of glycerol and 1,2,4-butanetriol in reactions with allyl chloride and benzyl chloride was estimated.
Keywords: 1,2,4-butanetriol, O-alkylation, O-acylation, acetone derivatives of glycerol
DOI: 10.1134/S107036321808008X
Condensation of glycerol with aldehydes is known
to give a mixture of isomeric 5- and 6-membered
cyclic acetals where 1,3-dioxolanes slightly dominate.
With acetone and other ketones, glycerol forms only
Condensation of triol 1 with formaldehyde 2 in
benzene at 80°C in the presence of cation-exchange
resin KU-2 gave rise to a mixture enriched with a
6-membered product (4a : 4b = 1 : 4). The reaction of
1 with acetone 3 carried out under the same conditions
resulted in a single product, specifically 2,2-dimethyl-4-
hydroxyethyl-1,3-dioxolane 5 (Scheme 1). Chromato-
graphic and spectral studies showed the absence of the
5
-membered derivatives [1, 2]. These compounds are
used as components of motor fuels, additives in the
food and perfume industries, and reactants in the
synthesis of pharmaceuticals [3].
6
-membered isomer in the reaction mass. In the
Data on acetals and ketals of 1,2,4-butanetriol 1 are
few and the ratio of 5- to 6-membered isomers is
determined by temperature, duration of synthesis,
structure of carbonyl compounds, solvent, etc. [4, 5].
reaction with ketones, therefore, triol 1 behaves
completely similarly to glycerol.
The mixture of formals 4a and 4b (1 : 4) was
In the present work, heterogeneous catalytic condensa-
tion of triol 1 with formaldehyde 2 and acetone 3 has
been studied and certain transformations of the hetero-
cyclic alcohols obtained have been performed.
subjected to a reaction with thionyl chloride (benzene,
4
h) to form the corresponding chlorides 6a and 6b
1 : 4). The presence of 4-chloromethyl-1,3-dioxane 6b
in the isomer mixture (6a, 6b) was additionally
(
Scheme 1.
OH
OH
OH
K КU У- 2- 2
H C
2
O
O
O
O
O
HO
OH
2
2
44 аa
44 bб
1
1
OH
3 2
( )
3
(CС HH ) C2 CO O
O
O
CH3
H C
3
5
5
1
601

1
602
RASKIL’DINA et al.
a
Table 1. Conditions for synthesis of triol 1 formals and
compounds 6–9 based thereon
Table 2. Relative reactivity of alcohols 5 and 10 with
respect to allyl chloride and benzyl chloride (NaOH, 30°C, 2 h)
Reaction
conditions
Reaction Yield,
Molar ratio
5 : 10 : X
Reagents
Reagent X
=CHCH Cl
Reaction products
products
%
b
1
+ 2
Toluene,
KU-2, 100°C,
h
4a : 4b
60
CH
2
2
1 : 1 : 2B
11 : 12 = 10 : 1
11 : 12 = 10 : 1
(1 : 4)
c
1
.5 : 1.5 : 0.5
5
c
BnCl
1 : 1 : 2
13 : 14 = 12 : 1
4
4
4
4
a, 4b + SO
2
Cl
=CHCH
C(O)Cl Pyridine,
Pyridine,
6a : 6b
(1 : 4)
63
92
88
94
a
b
The relative reactivity was calculated by GLC. Conversion of
1
0°C, 4 h
c
alcohol was no more than 30%. Conversion of chloride was no
a,4 b + CH
2
2
Cl 50% NaOH,
5°C, 8 h
7a : 7b
(1 : 3)
more than 30%.
2
a, 4b + ClC
2
H
4
8a : 8b
(1 : 5)
means of competitive reaction method (Scheme 3,
Table 2). Judging from the yields of ethers 11 and 12,
3 and 14 in the initial stages (conversion up to 30%),
the glycerol derivative 5 is an order of magnitude more
reactive than ketal 10. Consequently, the farther the
OH group is from the cycloacetal moiety, the lower is
its activity in O-alkylation reactions.
3
0°C, 8 h
a, 4b + PhN=C=O
Hexane,
0°C, 6 h
9a : 9b
1
3
(1 : 3)
verified by an authentic synthesis of 6b through
condensation of allyl chloride with formaldehyde
according to a known method [6] (Scheme 2). Formals
The structure of the resulting five- and six-
membered heterocycles is confirmed by H and
1
13
4
a and 4b in their reactions with allyl chloride,
C
monochloroacetyl chloride, and phenyl isocyanate
form the corresponding derivatives 7–9. The yield of
the compounds obtained and the isomer ratio are
presented in Table 1.
NMR spectroscopy. The signals of triol formals 4a and
4b and substituted 1,3-dioxoacyclanes 6–9 were
assigned based on the analysis of the chemical shifts
and the spin-spin coupling constants of the hetero-
1
cyclic moiety’s protons. Specifically, in the H NMR
At the initial stage of O-alkylation of the formals
mixture (4a, 4b) by allyl chloride (1–2 8 h, 20–25%
conversion) the main product in the reaction mass is a
substituted 1,3-dioxane 7b, whose concentration is 8–
spectrum of the 6a–6b isomer mixture, the singlets at
2
4
.85 and 5.00 ppm correspond to the C methylene
group of 4-(2-chloroethyl)-1,3-dioxolane 6a, and the
4
C methine protons of the five-membered cycle appear
10 times greater than that of isomeric 1,3-dioxolane 7a.
as a multiplet at 4.20–4.25 ppm. The chloromethyl
group resonates as multiplets at 3.62–3.66 ppm. The
To assess the effect of the OH group position
1
remote from the heterocycle on the OH group’s
activity, the rate of ethers formation during the
reaction of ketals of glycerol 5 and triol 1 with allyl
chloride and benzyl chloride was investigated by
H NMR spectrum of chloride 6b is characterized with
doublets in the region of 5.01 and 4.73 ppm with the
coupling constant of 6.3 Hz, which correspond to the
2
4
C methylene group of 1,3-dioxane, with C methine
Scheme 2.
OH
OH
R
R
O
O
+ O
O
O
O
+ O
O
4a
4b
6a−9a
6b−9b
R = Cl H+
+
H C
O
Cl
2
2
2 2 2 6 5
R = Cl (6a, 6b), OCH CH=CH (7a, 7b), OCOCH Cl (8a, 8b), OCONHC H (9a, 9b).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 8 2018

CONDENSATION OF 1,2,4-BUTANETRIOL WITH CARBONYL COMPOUNDS
1603
Scheme 3.
O
O
O
Cl
H C
3
CH3
O
+
O
O
OH
H C
3
CH3
OH
12
O
O
+
O
O
H C
3
CH3
H C
3
CH3
1
1
3
5
10
O
O
O
Cl
H C
CH3
3
1
O
+
O
O
H C
CH3
3
14
protons of the six-membered cycle appearing as a
multiplet at 4.00–4.04 ppm. The chloromethyl group is
detected as a triplet in the region of 3.60 ppm with the
coupling constant of 3.2 Hz.
5.00 ppm and doublets of 1,3-dioxolane moiety (7a) at
4.70 and 5.02 ppm with the coupling constant of
7
6.3 Hz. It should be noted that the presence of a C
ether bond promotes an upfield shift of the proton
signal. For instance, while these protons resonate at
3.80 and 3.88 ppm in the mixture of 4a–4b triol
formals obtained, their signals appear at 3.70 and
1
3
In the C NMR spectra of the 6a–6b isomer
7
mixture the C signals observed in the 35 and 42 ppm
regions are characteristic of compounds 6a and 6b,
3
.75 ppm, respectively, in the 7a–7b ether mixture.
respectively. Note the difference between the signals
2
13
of the C atom adjacent to the two heteroatoms for a
The C NMR spectra of 7a–7b ether mixture show
2
five- (6a) and six-membered (6b) molecules: the C
the presence of terminal double bond signals at 117
7
signal for 1,3-dioxolane derivative 6a is downfield
and 135 ppm, as well as the appearance of C signals at
(
(
96 ppm) as compared with 1,3-dioxane derivative 6b
93 ppm).
72 ppm both for 4-[2-(allyloxy)ethyl]-1,3-dioxolane 7a
and for 4-[(allyloxy)methyl]-1,3-dioxane 7b.
1
For the ether mixture of 4-[2-(allyloxy)ethyl]-1,3-
The H NMR spectra of the ester mixture of 2-(1,3-
dioxolane 7a and 4-[(allyloxy)methyl]-1,3-dioxane 7b,
the H NMR spectral signals are confirmed by the
dioxolan-4-yl)ethylchloroacetate 8a and 1,3-dioxan-4-
ylmethylchloroacetate 8b are distinguished by the
1
presence of a terminal double bond. The CH group of
presence of a singlet of the chloromethylene (CH Cl)
2
7
a and 7b at a multiple bond resonates at 5.90 ppm as
a multiplet, and the protons of the methylene group
CH ) are detected as a doublet at 5.11–5.30 ppm with
group that appears in the region of 4.11 ppm. The
proton signals of C adjacent to the ester group
resonate between 4.13 and 4.19 ppm as a multiplet for
the 1,3-dioxolane derivative and at 4.22 ppm as a
doublet of doublets with the coupling constant of 5.1
and 6.6 Hz for the 1,3-dioxane derivative.
7
(
2
the coupling constant of 1.2 and 2.8 Hz. The presence
of a heterocyclic moiety is indicated by singlets of the
C atom of 1,3-dioxane moiety (7b) at 4.83 and
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 8 2018

1
604
RASKIL’DINA et al.
1
3
The common features of the C NMR spectrum for
were used. 4-[(Hydroxy)ethyl]-2,2-dimethyl-1,3-dioxolane,
4-[(allyloxy)methyl]-2,2-dimethyl-1,3-dioxolane, 4-[(benzyl-
oxy)methyl]-2,2-dimethyl-1,3-dioxolane, and 4-[(allyl-
oxy)ethyl]-2,2-dimethyl-1,3-dioxolane were prepared
according to known procedures [1–4].
the mixture of 8a and 8b are the presence of the
chlorine-containing CH Cl group, which has a
2
chemical shift at 41 ppm, and significantly more down-
field signals of the ester group at 167 ppm. The protons
of the methylene group bonded to two heteroatoms,
appear at 95 ppm for 2-(1,3-dioxolan-4-yl)ethylchloro-
acetate 8a and 94 ppm for 1,3-dioxane-4-ylmethyl-
chloroacetate 8b.
2
-(1,3-Dioxolan-4-yl)ethanol (4a) and 1,3-dioxan-
-ylmethanol (4b) (isomer mixture). A mixture of 5 g
0.04 mol) of 1,2,4-butanetriol, 1 g (0.03 mol) of
4
(
paraformaldehyde, 30 mL of anhydrous toluene, and
10% by weight of activated cation-exchange resin KU-
2 were boiled until the calculated amount of water
(0.7 mL) was obtained. Upon completion of the
reaction (5 8 h), the solution was cooled and the cation-
exchange resin was filtered off. The filtrate was
evaporated and the residue was distilled in vacuo
(80°C, 10 mmHg). Yield 3 g (60%).
1
The H NMR spectra of a mixture of substituted
isocyanates 9a and 9b are characterized by the benzene
ring’s doublets between 7.00 and 7.50 ppm and the NH
group’s singlet in a downfield position (8.53 ppm)
indicating the formation of the corresponding amides
9
a and 9b.
7
13
The C signals in the C NMR spectra of the
mixture of 2-(1,3-dioxolan-4-yl)ethylphenylcarbamate
a and 1,3-dioxan-4-ylmethylphenylcarbamate 9b
resonate at 65 ppm. The signals appearing at 118–
40 ppm are due to the presence of an aromatic moiety
linked to the amide group. As such, the chemical shifts
2-(1,3-Dioxolan-4-yl)ethanol (4a). Mass spectrum,
9
m/z (I , %): 117 (1), 87 (22), 73 (25), 57 (20), 44
rel
(100), 30 (30).
1
1
,3-Dioxan-4-ylmethanol (4b). Mass spectrum,
m/z (I , %): 117 (1), 87 (100), 57 (30), 45 (27), 31
2
4
5
rel
of the characteristic protons at the C , C , and C atoms
of heterocyclic structures did not change significantly.
(
48).
4-(2-Chloroethyl)-1,3-dioxolane (6a) and 4-chloro-
The obtained data indicate that ketones, in
particular acetone, are effective for selective protection
of vicinal hydroxyl groups in polyols, and that the 1,3-
dioxolane moiety does not interfere with the glycerol
methyl-1,3-dioxane (6b). 1.4 g (0.012 mol) of thionyl
chloride was added to a mixture of 1 g (0.008 mol) of
2
-(1,3-dioxolan-4-yl)ethanol and 1,3-dioxan-4-yl-
methanol and 0.7 g (0.008 mol) of pyridine, while
cooling to 0°C. The reaction mixture was stirred at 10–
reaction by free CH OH group.
2
1
2°C until sulfur dioxide ceased to evolve (5 h),
EXPERIMENTAL
followed by addition of chloroform (30 mL) and water
washing of the reaction mass, avoiding boiling up
The reaction products were analyzed on an HRGS
300 Mega Series Carlo Erba chromatograph equipped
(
violent decomposition of thionyl chloride). The
5
residue was distilled. Yield 0.42 g (43%), colorless
liquid with a pungent odor.
with a flame ionization detector, with helium as carrier
gas, flow rate 30 ml/min, 25 m column, temperature 50–
80°C, programmable heating at a rate 8 deg/min,
detector temperature 250°C, and vaporizer temperature
00°C. Chromato-mass spectra were recorded on a
Chromatec-crystal 5000.2 instrument (30 m capillary
quartz column, analysis duration 20 min, ion source
temperature 260°C, transfer line temperature 300°C,
scanning range 30–300 Da, pressure 37–43 mTorr,
helium as carrier gas, heating rate 20 deg/min). To
obtain the mass spectra of the compounds, the electron
impact ionization method was used. NMR spectra were
recorded on a Bruker AVANCE-400 (400.13 MHz)
spectrometer in CDCl3.
4
-(2-Chloroethyl)-1,3-dioxolane (6a). Mass spect-
2
rum, m/z (I , %): 135 (36), 137 (12), 106 (20), 108
rel
(
7), 89 (10), 91 (3), 73 (100), 53 (10).
-Chloromethyl-1,3-dioxane (6b). Mass spectrum,
m/z (I , %): 135 (7), 137 (2), 106 (3), 108 (1), 89 (15),
3
4
rel
9
1 (4), 87 (100), 57 (20).
-[2-(Allyloxy)ethyl]-1,3-dioxolane (7a) and 4-
(allyloxy)methyl]-1,3-dioxane (7b). A mixture of
4
[
0
1
.5 g (0.004 mol) of 2-(1,3-dioxolan-4-yl)ethanol and
,3-dioxan-4-ylmethanol, 30 mL of benzene, and 30 g
of 50% sodium hydroxide solution and 10 wt % of
catamine AB was stirred at 60–65°C for 2 8 h. The
mixture was cooled to room temperature and 1.6 g
(0.02 mol) of allyl chloride was added. The reaction
Commercially available reagents, like glycerol,
allyl chloride, benzyl chloride, acetone, and benzene,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 8 2018

CONDENSATION OF 1,2,4-BUTANETRIOL WITH CARBONYL COMPOUNDS
1605
was carried out until the initial alcohols were
completely converted (8 h) while heating to 30°C.
After cooling, 30 mL of dichloromethane was added
and the mixture was water washed until neutral, then
dried and evaporated. The desired product was
obtained by vacuum distillation. Yield 0.4 g (60%),
colorless liquid.
mixture of 0.5 g (0.004 mol) of 2-(1,3-dioxolan-4-yl)-
ethanol and 1,3-dioxan-4-ylmethanol in 10 mL of
hexane and 1.9 g (0.016 mol) of phenylisocyanate in
5 mL of hexane was stirred at 35°C. Upon completion
of the reaction (TLC control), the mixture was cooled
to room temperature and the crystals were filtered off,
water washed, air dried, and recrystallized from
hexane. Yield 0.4 g (40%), white powder.
4
-[2-(Allyloxy)ethyl]-1,3-dioxolane (7a). Mass
spectrum, m/z (I , %): 157 (1), 100 (11), 87 (16), 73
2-(1,3-Dioxolan-4-yl)ethylphenylcarbamate (9a).
rel
(
45), 71 (100), 57 (50).
-[(Allyloxy)methyl]-1,3-dioxane (7b). Mass
spectrum, m/z (I , %): 101 (13), 87 (100), 71 (55), 57
Mass spectrum, m/z (Irel, %): 237 (10), 137 (25), 119
(
100), 106 (24), 91 (40), 44 (46).
4
1,3-Dioxan-4-ylmethylphenylcarbamate (9b). Mass
rel
(
54).
spectrum, m/z (Irel, %): 237 (20), 137 (65), 119 (100),
1 (50), 87 (40), 43 (40).
9
2
-(1,3-Dioxolan-4-yl)ethylchloroacetate (8a) and
1
,3-dioxan-4-yl-methylchloroacetate (8b). A mixture
CONFLICT OF INTERESTS
of 1 g (0.008 mol) of 2-(1,3-dioxolan-4-yl)ethanol and
,3-dioxan-4-ylmethanol, 0.6 g (0.008 mol) of an-
1
No conflict of interest was declared by the authors.
hydrous pyridine, and 0.8 g (0.008 mol) of mono-
chloroacetyl chloride was heated to 30°C for 8 h. The
recovered oil crystallized within 24 8 h under cooling
and trituration. The reaction mixture was poured into a
mixture of 15 g of ice and 30 mL of 1N HCl and
stirred until a suspension was formed. The crude
product was filtered off, washed with ice water, dried,
and evaporated, the residue was distilled in vacuo.
Yield 0.5 g (30%), colorless liquid with a pungent
odor.
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(
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 8 2018