2-(1-Chloroalkyl)furans in the reaction with sodium diethyl phosphite

Article abstract of DOI:10.1134/S1070363206040207

2-(1-Chloroethyl) and 2-(1-chloro-2-methylpropyl)furans react with sodium diethyl phosphite to give two products, 2-(1-diethoxyphosphorylmethyl)furan and 2-alkyl-5-(diethoxyphosphoryloxy)furan. The fraction of the latter product increases with increasing size of the alkyl radical. 2-Methyl substitution in the substrate completely suppresses phosphate formation. 2-(1-Chloroethyl)-5-(2- methylpropyl)furan under the action of sodium diethyl phosphite eliminates hydrogen chloride to give the corresponding alkene. Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206040207

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 4, pp. 621 625.
Pleiades Publishing, Inc., 2006.
Original Russian Text
L.M. Pevzner, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 4, pp. 654 659.
2-(1-Chloroalkyl)furans in the Reaction
with Sodium Diethyl Phosphite
L. M. Pevzner
Russian Research Institute of Hydrolysis of Plant Materials, ul. Kalinina 13, St. Petersburg, 198099 Russia
Received June 10, 2005
Abstract 2-(1-Chloroethyl) and 2-(1-chloro-2-methylpropyl)furans react with sodium diethyl phosphite to
give two products, 2-(1-diethoxyphosphorylmethyl)furan and 2-alkyl-5- (diethoxyphosphoryloxy)furan. The
fraction of the latter product increases with increasing size of the alkyl radical. 2-Methyl substitution in the
substrate completely suppresses phosphate formation. 2-(1-Chloroethyl)-5-(2-methylpropyl)furan under the
action of sodium diethyl phosphite eliminates hydrogen chloride to give the corresponding alkene.
DOI: 10.1134/S1070363206040207
2-Hydroxyalkylfurans easily prepared from 2-fur-
aldehyde and its homologs are traditionally considered
to be extremely acidophobic compounds [1]. Evi-
dently, for this reason no attempts to convert these
alcohols to the corresponding chlorides have been
reported. At the same time, such secondary chlorides
present great interest as substrates for phosphorylation,
because in this case phosphorus is attached to an
asymmetric carbon atom, and further transformations
of the phosphorus-containing function may lead to
optically active phosphines. In this connection we
prepared 2-(1-chloroalkyl)furans and made an attempt
to react them with sodium diethyl phosphite.
quality, because its solutions in CDCl3 quickly
gelatinized.
Compound IIa was phosphorylated with sodium
diethyl phosphite in benzene at 80 C for 4 h. The
resulting products were isolated by vacuum distilla-
tion. A mixture of compounds boiling in the range
1
96 98 C (1 mm Hg) was obtained. Its H NMR spec-
trum contained two well-resolved sets of signals.
The main product gave a doublet of doublets at
1.26 ppm (JHH 7 Hz, JHP 16 Hz) assignable to the
side-chain methyl group, a doublet of distorted quar-
tets at 3.16 ppm (JHH 7 Hz, JHP 21 Hz) belonging to
the CH group on phosphorus, two broadened singlets
at 6.25 ppm and 7.29 ppm, and a broadened doublet
We chose as substrates a series of furans of general
formula I.
at 6.18 ppm (JHP 2 Hz). The
of this product was
23.8 ppm. The presented spectrPal data well describe
SOCl2
phosphonate III.
CH R2
OH
CH R2
Cl
R1
R1
C5H5N
O
O
The other set of signals comprised a quartet at
2.66 ppm characteristic of the methylene group of
ethyl at the furan ring and two broadened singlets at
6.03 and 6.96 ppm belonging to furan ring protons.
Ia Ie
IIa IIe
R1 = H, R2 = CH3 (a); R1 = R2 = CH3 (b); R1 = H, R2 =
CH(CH3)2 (c); R1 = CH3, R2 = CH(CH3)2 (d); R1
CH2CH(CH3)2, R2 = CH3 (e).
=
The
of this product was 1.4 ppm. The absence of
the thPird ring proton signal below 7 ppm provide
evidence to show that the product is a 2,5-disubsti-
tuted furan with a strong electron-acceptor substituent
Substitution of the hydroxy group by chlorine in
compounds Ia Ie was carried out by means of thionyl
chloride in the presence of pyridine at 20 25 C. The
resulting products were isolated by vacuum distilla-
tion.
CH CH3
O
PO(OC2H5)2
III
NaPO(OC5H5)2
IIa
2-(1-Chloroethyl)furan (IIa) occurred to be suf-
ficiently stable. It can be distilled in a vacuum without
noticeable decomposition, bp 23 24 C (1 mm Hg),
but it quickly becomes dark brown in air. We failed
(C2H5O)2P O
O
CH2 CH3
O
1
the H NMR spectrum of compound IIa of reasonable
IV
621

622
PEVZNER
in the 2 position, which follows from the different
chemical shifts of protons in the 3 and 4 positions of
the ring. The absence of noticeable splitting of the
furan proton signal from phosphorus and the P of this
product suggest that it is diethyl heteryl phosphate.
Its structure can be described by formula IV.
6 h. Vacuum distillation gave a fraction [bp 30 40 C
(1 mm Hg)] that comprised diethyl hydrogen phos-
phite and chloride IIc, and a fraction boiling at 110 C
(1 mm Hg).
1
The H NMR spectrum of the high-boiling fraction
contained two well-resolved sets of signals. The first
included a doublet of doublets at 3.00 ppm (CH-P,
JHH 7 Hz, JHP 23 Hz), a broadened signal at 6.26 ppm
(furan H3 and H4), and a signal at 7.29 ppm (furan
From the integral intensity ratio of the ring proton
signals the molar ratio of compounds III and IV was
estimated at 4:1.
H5). The
of this product was 22.7 ppm. This set of
P
signals characterizes phosphonate VI.
CH CH3
NaPO(OC5H5)2
CH3
IIb
O
The second set of signals included a distorted
doublet at 2.50 ppm characteristic of the methylene
fragment of the isobutyl group at the furan ring and
two doublets at 6.02 ppm and 6.93 ppm characteristic
of ring protons (furan H3 and H4, JHH 2 Hz). The
of this product is 1.28 ppm. The presented spectraPl
data characterize phosphate VII. The VI: VII ratio in
the obtained material was estimated at 1:1.4.
PO(OC2H5)2
V
Chloride IIb is much more labile than its analog
IIa. In the course of vacuum distillation [bp 32 33 C
(1 mm Hg)] it gets strongly colored, and a brown film
deposits on walls of the distillation system. Im-
mediately after distillation product IIb was dissolved
in benzene and involved in reaction with sodium
diethyl phosphite.
CH CH(CH3)2
PO(OC2H5)2
NaPO(OC5H5)2
CH3
IId
O
Phosphorylation of chloride IIb was carried out in
benzene at 80 C for 6.5 h. The only phosphorus-
containing product was phosphonate V. The H NMR
VIII
1
spectrum of this compound showed two doublets of
distorted quartets at 2.79 and 3.06 ppm (JHH 7 Hz,
JHP 21 Hz) related to the CH P fragment. The inten-
sity ratio of the upfield and downfield signals was 1:3.
The presented data show that phosphonate V exists as
a mixture of two conformers. The yield of the product
was 45%.
Chloride IId occurred to be less stable than its
analog IIc. It can also be distilled in a vacuum [bp
38 C (0.8 mm Hg)] but immediately darkens in air,
and a suspension of polymeric products quickly forms
in it. We failed to obtain a well-resolved spectrum of
this compound.
Chloride IId was phosphorylated with sodium di-
ethyl phosphite in benzene at 80 C for 9.5 h. Phos-
phonate VIII was isolated by vacuum distillation in
CH CH(CH3)2
1
O
48% yield. The H NMR spectrum of this product
PO(OC2H5)2
IIcNaPO(OC H )
5
5 2
contained two doublets of doublets at 2.60 (JHH 7 Hz,
JHP 21 Hz) and 2.88 ppm (JHH 7 Hz, JHP 21 Hz),
related to the CHP fragment. The intensity ratio of
these signals was 1:2. This fact provides evidence to
show that phosphonate VIII, like V, exists as a
mixture of two conformers. In both cases, the con-
former giving the downfield signal is preferred.
VI
CH2 CH(CH3)2
(C2H5O)2P O
O
O
VII
Chloride IIc occurred to be so stable that we
managed not only to distill it in a vacuum [bp 39
40 C (1 mm Hg)], but also to obtain its well-resolved
1H NMR spectrum. Methyl groups of the isobutyl
fragment in this compound give two doublets at 0.91
and 1.04 ppm (JHH 7 Hz) in a 1:1 ratio. Most prob-
ably, this observable points to nonequivalence of these
groups, rather than to the fact that chloride IIc exists
as a mixture of two conformers.
The isobutyl fragment of phosphonate VIII has
1
nonequivalent methyl groups. In the H NMR spec-
trum, they give doublets of equal intensity at 0.91
(JHH 7 Hz) and 1.05 ppm (JHH 7 Hz).
H1
H2
NaPO(OC5H5)2 H3C
IIe
CH CH2
C=C
H
H3C
O
IX
Phosphorylation of compound IIc with sodium di-
ethyl phosphite was carried out in benzene at 80 C for
Chloride IIe is thermally unstable. Even during
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2-(1-CHLOROALKYL)FURANS IN THE REACTION
623
vacuum distillation (bp 40 C) a black polymeric film
deposits on the internal surface of the distillation
system. For this reason, we failed to obtain a well-
phosphites with air oxygen at elevated temperatures.
Hence, phosphites XII and XIII should appear on a
certain stage of the process.
1
resolved H NMR spectrum of this compound. Im-
mediately after distillation chloride IIe was involved
in reaction with sodium diethyl phosphite. The pro-
cess was carried out at 80 C in benzene for 5 h.
Vacuum distillation of the reaction mixture gave a
mixture of alkene IX and diethyl hydrogen phosphite.
No formation of phosphorus-containing furans was
observed in this case.
R
(C2H5O)2P O
XII, XIII
O
R = C2H5 (XII), CH2CH(CH3)2 (XIII).
It is known [3] that sodium diethyl phosphite is
alkylated by its oxygen atom in polar solvents only.
Therefore, in the process under study, certain condi-
tions arise that favor increased polarity of the medium.
As already noted, compounds II lose chloride ion
fairly easily. If this process is accompanied by fast
deprotonation, alkene formation takes place. Other-
wise, formation of an ion pair would be expected. It
is this case that conditions for local increase of the
dielectric permittivity of the medium are created. This
increase is very significant, because the charges of ion
centers rather than effective charges arise on the
dipole poles. The structure of such an ion pair can
conventionally be presented by formula XIV.
Hence, whether the reaction of 2-(1-chloroalkyl)-
furans with sodium diethyl phosphite takes one or
another pathway depends significantly on the structure
of the chloroalkyl radical and on the substituent in the
5 position of the ring.
The formation of phosphonates most probably
proceeds by a usual Michaelis Becker scheme and
only slightly depends on the structure of the chloro-
alkyl radical (the yields of phosphonates V and VIII
are 45 and 48%, respectively). It should be em-
phasized that the reaction proceeds in a nonpolar
solvent with an unionized substrate. The formation of
alkene IX on dehydrohalogenation of chloride IIe
may well occur thermally, which is indirectly evi-
denced by the facility of its polymerization on
vacuum distillation. Performing the reaction in a di-
lute solution and binding hydrogen chloride with
sodium diethyl phosphite favors stabilization of the
final product. Note that dehydrohalogenation involves
no isomerization to form compound X, whereas with
bis(chloromethyl)furan XI this isomerization is the
main reaction pathway [2].
H
Cl
CH+R
+
CH R
O
O
XIV
Sodium diethyl phosphite that appears in the sphere
of its influence behaves as if it is placed in a polar
medium, i.e. it reacts by the oxygen atom. Therewith,
the phosphite formed by the -attack on the side chain
occurs to be affected by the same factors that favor
elimination of chloride ion. As a consequence, no
O-alkylation products by this site are found. Contrary
to that, phosphites XII and XIII are stable and un-
dergo oxidation of the phosphorus-containing group
only. The increase of the fraction of the phosphite as
compared to phosphonate (5.6-fold) is consistent with
the concept that the stability of the carbocation in ion
pair XIV increases due to the stronger electron-donor
effect of the isopropyl group compared to methyl and
due to the enhanced shielding of the carbocationic
center. 5-Methyl substitution in the furan suppresses
completely phosphite formation in spite of the ex-
pected enhanced stability of the carbocation. This
result provides further evidence for facile elimination
of the anion from the position of the side chain.
H3C
CH2CH3
C=CH
H3C
O
X
ClCH2
H3C
H3C
CH2Cl
CH CH2
O
XI
ClCH2
H3C
C=CH
HCl
CH3
H3C
O
The formation of unusual products IV and VII can
be explained as follows. While studying the reactions
of 2-(1-chloroalkyl)furans with sodium diethyl phos-
phite we never observed products formed by halogeno-
philic attack. Therefore, the formation of phosphates
should be explained by oxidation of the corresponding
The above reasoning allows us to conclude that the
main factor determining the pathway of the reaction
is ionization of haloalkylfuran. If it creates conditions
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 4 2006

624
PEVZNER
for O-alkylation of the phosphite salt, trialkyl phos-
phites are formed. Therewith, the phosphite ion can
be attacked both by the furan ring and by the side
chain, but in the last case no stable products are
formed. In principle, anion exchange with the ion pair
can only take place without P O C bond formation.
Deprotonation of the cation in such ion pair leads to
alkene formation. Unionized haloalkylfuran enters the
Michaelis Becker reaction with sodium diethyl
phosphite to form phosphonate.
at reduced pressure, and the residue was distilled in a
vacuum to give 3.0 g of a fraction with bp 96 98 C
(1 mm Hg). H NMR spectrum, , ppm: phosphonate
1
III: 1.21 m (ethyl CH3), 1.26 d.d (CH3 CHP, JHH
7 Hz, JHP 16 Hz); 3.16 d.q (CHP, JHH 7 Hz, JHP
21 Hz); 4.00 m (CH2OP); 6.18 br.d (furan H3, JHP
2 Hz); 6.25 br.s (furan H4); 7.29 br.s (furan H5);
P
23.8 ppm; phosphate IV: 1.21 m (ethyl CH3); 2.66 q
(CH2 furan, JHH 7 Hz); 4.00 m (CH2OP); 6.03 br.s
(furan H3); 6.96 br.s (furan H4),
1.4 ppm.
P
Phosphonate III/phosphate IV ratio 4:1.
EXPERIMENTAL
2-(1-Diethoxyphosphorylethyl)-5-methylfuran
(V). To a solution of sodium diethyl phosphite pre-
pared from 0.6 g of sodium and 4.2 ml of diethyl
hydrogen phosphite in 35 ml of benzene, a solution
of 3.4 g of cloride IIb in 5 ml of benzene was added
in one portion with stirring at 70 C. The reaction
mixture was refluxed with stirring for 6.5 h, sodium
chloride was removed by centrifugation, the solvent
was evaporated at reduced pressure, and the residue
was distilled in a vacuum to give 2.6 g (45%) of
1
The H NMR spectra were recorded on a Tesla BS-
497C (100 MHz) spectrometer in CDCl3 against
internal HMDS. The phosphorus chemical shifts were
calculated from INDOR spectra.
Substitution of hydroxyl with chlorine in 2-(1-
hydroxyalkyl)furans (I) (general procedure). To a
solution of 0.1 mol of 2-(1-hydroxyalkyl)furan and
0.105 mol of pyridine in 100 ml of ether, a solution of
0.1 mol of thionyl chloride in 50 ml of ether was
added dropwise with vigorous stirring at 10 15 C.
The reaction mixture was stirred at this temperature
for 4-5 h, pyridine hydrochloride was filtered off,
ether was distilled off at reduced pressure, and the
residue was distilled in a vacuum. The resulting com-
pounds were involved in further transformations as
soon as possible.
1
phosphonate V, bp 116 118 C (1 mm Hg). H NMR
spectrum, , ppm: 1.26 t (ethyl CH3, JHH 7 Hz);
1.40 d.d (CH3 CHP, JHH 7 Hz, JHP 16 Hz); 2.18 s
(CH3-furan), 2.79 d.q (CH P, JHH 7 Hz, JHP 21 Hz);
3.06 d.q (CH-P, JHH 7 Hz, JHP 21 Hz); 3.96 m
(CH2OP, JHH 7 Hz, JHP 11 Hz); 5.81 br.d (furan H4,
JHH 3 Hz); 6.98 d.d (furan H3), JHH 3 Hz, JHP 2 Hz);
26.8 ppm. The ratio of the conformers (form the
P
2-(1-Chloroethyl)furan (IIa). Yield 47%, bp 23
24 C (1 mm Hg).
intensities of the signals at 3.06 and 2.79 ppm) is 3:1.
Reaction of chloride IIc with sodium diethyl
phosphite. To a solution of sodium diethyl phosphite
prepared from 0.6 g of sodium and 4 ml of diethyl
hydrogen phosphite in 30 ml of benzene, a solution of
4.5 g of chloride IIc in 10 ml of benzene was added
with stirring in one portion at 70 C. The reaction mix-
ture was refluxed with stirring for 6 h, sodium chlo-
ride was removed by centrifugation, the solvent was
evaporated at reduced pressure, and the residue was
distilled in a vacuum to give a fraction (1.2 g) with bp
30 40 C (1 mm Hg) consisting of diethyl hydrogen
phosphite with a small admixture of chloride IIc and
a fraction (3.6 g) with bp 110 C (1 mm Hg). 1H NMR
2-(1-Chloroethyl)-5-methylfuran (IIb). Yield
42%, bp 32 33 C (1 mm Hg).
2-(1-Chloro-2-methylpropyl)furan (IIc). Yield
1
59%, bp 39 40 C (1 mm Hg). H NMR spectrum, ,
ppm: 0.91 d (isobutyl CH3, JHH 7 Hz); 1.04 d (iso-
butyl CH3, JHH 7 Hz); 2.30 m (isobutyl CH); 4.56 d
(CHCl, JHH 7 Hz); 6.19 br.s (furan H3 + H4); 7.25 s
(furan H5).
2-(1-Chloro-2-methylpropyl)-5-methylfuran
(IId). Yield 49%, bp 38 C (0.8 mm Hg).
2-(1-Chloroethyl)-5-(2-methylpropyl)furan (IIe).
Yield 23%, bp 40 C (1 mm Hg).
spectrum,
,
ppm: phosphonate VI: 0.90 m
[(CH3)2C]; 1.P20 m (ethyl CH3, JHH 7 Hz); 2.10 m (iso-
butyl CH, JHH 7 Hz); 3.00 d.d (CHP, JHH 7 Hz, JHP
23 Hz), 3.95 m (CH2OP, JHH 7 Hz, JHP 11 Hz);
Reaction of chloride (IIa) with sodium diethyl
phosphite. To a solution of sodium diethyl phosphite
prepared from 0.6 g of sodium and 4 ml of diethyl
hydrogen phosphite in 30 ml of benzene, a solution of
3.5 g of chloride IIa in 4 ml of benzene was added in
one portion at 70 C. The reaction mixture was re-
fluxed with stirring for 4 h, sodium chloride was
removed by centrifugation, the solvent was evaporated
6.26 br.s (furan H3 + H4); 7.29 br.s (furan H5);
P
22.7 ppm; phosphate VII: 0.90 m [(CH3)2C]; 1.20 m
(ethyl CH3); 1.90 m (isobutyl CH JHH 7 Hz); 2.50 d
(isobutyl CH2), JHH 7 Hz, JHP 11 Hz); 6.02 d (furan
H4, JHH 2 Hz); 6.93 d (furan H3, JHH 2 Hz),
P
1.28 ppm. Phosphonate VI:phosphate VII ratio 1:1.4.
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2-(1-CHLOROALKYL)FURANS IN THE REACTION
625
2-(1-Diethoxyphosphoryl-2-methylpropyl)-5-me-
thylfuran (VIII). To a solution of sodium diethyl
phosphite prepared from 0.9 g of sodium and 6 ml of
phosphite in 40 ml of benzene, a solution of 6.3 g of
chloride IId in 10 ml of benzene was added in one
portion with stirring at 70 C. The reaction mixture
was refluxed with stirring for 9.5 h, sodium chloride
was removed by centrifugation, the solvent was eva-
porated at reduced pressure, and the residue was distil-
led in a vacuum to give 4.9 g (48%) of phosphonate
in one portion with stirring at 70 C. The reaction mix-
ture was refluxed with stirring for 5 h, sodium chlo-
ride was removed by centrifugation, the solvent was
evaporated at reduced pressure, and the residue was
distilled in a vacuum to give 0.9 g of a fraction with
bp 42 46 C (1 mm Hg), consisting of alkene IX and
1
diethyl hydrogen phosphite. H NMR spectrum,
,
ppm: alkene IX: 0.82 d (isobutyl CH3, JHH 7 Hz);
1.95 m (isobutyl CH, JHH 7 Hz); 2.42 d (isobutyl
CH2, JHH 7 Hz); 4.99 d (trans-CH1=, JHH 12 Hz);
5.50 d (cis-CH2=, JHH 17 Hz); 5.91 d (furan H3, JHH
2 Hz); 6.07 d (furan H4, JHH 2 Hz); 6.36 d.d (CH=,
1
VIII, bp 103 C (0.8 mm Hg). H NMR spectrum, ,
ppm: 0.91 d (isobutyl CH3, JHH 7 Hz); 1.05 d (iso-
butyl CH3, JHH 7 Hz); 1.30 t (ethyl CH3, JHH 7 Hz);
1.80 2.20 m (isobutyl CH); 2.22 s (CH3 furan); 2.60
d.d (CHP, JHH 7 Hz, JHP 21 Hz); 2.88 d.d (CHP, JHH
7 Hz, JHP 21 Hz); 4.00 m (CH2OP, JHH 7 Hz, JHP
1
2
JH H 17 Hz, JH H 12 Hz). The yield of the alkene was
estimated at 70%.
REFERENCES
11 Hz); 5.83 br.d (furan H4, JHH 2 Hz); 6.11 br.d
(furan H3, JHH 2 Hz);
22.9 ppm. The ratio of the
conformers (from the intPensities of the signals at 2.60
and 2.88 ppm) is 1:2.
1. Ponomarev, A.A., Sintezy i reaktsii furanovykh ve-
shchestv (Syntheses and Reactions of Furan Com-
pounds), Saratov: Saratov Gos. Univ., 1960, p. 121.
Reaction of chloride IIe with sodium diethyl
phosphite. To a solution of sodium diethyl phosphite
prepared from 0.2 g of sodium and 2 ml of diethyl
hydrogen phosphite in 12 ml of benzene, a solution of
1.2 g of chloride IId in 5 ml of benzene was added
2. Pevzner, L.M., Russ. J. Gen. Chem., 2005, vol. 75,
no. 6, p. 936.
3. Benezza, C. and Bravet, H., Can. J. Chem., 1975,
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