Synthesis and aminomethylation of 2-isobutyl-3-and 4- diethoxyphosphorylmethylfurans

Article abstract of DOI:10.1134/S1070363206070103

Synthetic procedure for preparing 2-isobutyl-3-and 4-furancarboxylic acyl chlorides is developed. Reduction of these compounds with lithium alumohydride leads to corresponding alcohols which under treating with thionyl chloride in the presence of pyridine form chloromethyl derivatives. The latter compounds are phosphorylated with sodium diethyl phosphite under the Michaelis-Becker reaction conditions to give corresponding phosphonates. Reaction of compounds obtained with dimethyl(chloromethyl)amine proceeds at the free α-position of the furan ring and delivers aminophosphonates. These substances do not evolve dimethylamine even under the conditions of vacuum distillation (145-150°C, 1 mm Hg). Pleiades Publishing, Inc., 2006.

Full text of DOI:10.1134/S1070363206070103

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 7, pp. 1063 1068.
Pleiades Publishing, Inc., 2006.
Original Russian Text L.M. Pevzner, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 7, pp. 1111 1117.
Synthesis and Aminomethylation of 2-Isobutyl-3-
and 4-Diethoxyphosphorylmethylfurans
L. M. Pevzner
All-Russian Research Institute of Hydrolysis of Plant Material,
ul. Kalinina 13, St. Petersburg, 198099 Russia
Received December 7, 2005
Abstract Synthetic procedure for preparing 2-isobutyl-3- and 4-furancarboxylic acyl chlorides is developed.
Reduction of these compounds with lithium alumohydride leads to corresponding alcohols which under
treating with thionyl chloride in the presence of pyridine form chloromethyl derivatives. The latter compounds
are phosphorylated with sodium diethyl phosphite under the Michaelis Becker reaction conditions to give
corresponding phosphonates. Reaction of compounds obtained with dimethyl(chloromethyl)amine proceeds at
the free -position of the furan ring and delivers aminophosphonates. These substances do not evolve di-
methylamine even under the conditions of vacuum distillation (145 150 C,
1
mm Hg).
DOI: 10.1134/S1070363206070103
We have found previously [1,2] that 2-isobutyl-
furan halomethyl derivatives can eliminate hydrogen
chloride to give furylalkenes as is shown below.
At the same time synthetic approaches to these
compounds were not developed so far. We propose to
use alkyl 2-isobutylfurancarboxylates I and II as the
starting compounds.
Y
H3C
Synthesis of compound I was assumed to carry
out according to the following typical procedure.
CH2X
CH CH2
H3C
O
Y
COOC2H5
H3C
H3C
CH2X
CH
CH CH2
HX
H3C
O
H3C
O
I
Developing the studies of this unusual reaction we
decided to look for some other functional groups
which are capable of furylalkene formation by eli-
mination of a volatile products. Investigation of
2-aminomethylated diethoxyphosphorylmethylfurans
[3] showed that on handling or during the vacuum
distillation these compounds eliminate dimethylamine
in a noticeable amount. Therefore we assumed that in
the case of 2-isobutyl-5-dimethylaminomethylfurans
the conditions can be found which are favorable for
dimethylamine elimination leading to the phosphonates
with unsaturated side chain. Compounds of such
structure are valuable synthons for constructing the
carbon frame of furan-containing terpenes for instance
using the Wittig Horner reaction.
C2H5OOC
H3C
H3C
CH
O
II
Reaction of isopropylmagnesium chloride with 2-fur-
aldehyde leads to secondary alcohol III which by
means of the Markwald rearrangement can be con-
verted to ketoester IV [4]. The latter product is ke-
talyzed for protecting the ketone carbonyl group and
then is formylated with ethyl formate under the condi-
tions of the Claisen reaction [5]. Aldehyde V thus
obtained could be involved in cyclization in acidic
medium delivering furan I.
(CH3)2CHMgCl
C2H5OH
H+
H3C
H3C
CH CH2CO(CH2)2CO
CH CH
CHO
H3C
H3C
O
O
OC2H5
OH
III
IV
1063

1064
PEVZNER
CH(OC2H5)3 H3C
CHCH2(OC2H5)2(CH2)2COOC2H5
IV
C2H5OH, H+
H3C
HCOOC2H5
Na
H+
H3C
H3C
CHCH2(OC2H5)2CH2 CH COOC2H5
CHO
I
However it occured that two last steps of this syn-
thesis proceed with a complication. The aldehyde V
sodium derivative is a strong emulgator, and at
working up the reaction mixture for separation a large
amount of unreacted ketal is transfered into the water
phase. After acidification the target product V is
formed but its purification by vacuum distillation can
not provide removing of this admixture. The ester I
obtained is therefore substantially contaminated with
aliphatic compounds. Separation of pure furan can be
achieved olny by alkaline hydrolysis, isolation of the
mixture of acids, and treating it with thionyl chloride
in presence of DMF. The acyl chloride VI obtained
data was free from noticeable amounts of admixtures.
The acyl chloride VI reduction was carried out with
lithium alumohydride in ether at 36 C. The alcohol
VII obtained (yield 65%) is a stable compound with
no tendency of polymerization. Treating the alcohol
VII with thionyl chloride in ether in the presence of
pyridine was carried out at 17 25 C for 5 h. Vacuum
distillation afforded stable chloride VIII in 65% yield.
This product can be distilled in a vacuum without tar-
ring and does not darken on air at room temperature.
The chloride VIII phosphorylation was carried out
with sodium diethyl phosphite at 80 C in benzene for
14 h. Phosphonate IX was isolated by vacuum distilla-
tion in 71% yield.
1
after distillation in a vacuum according to H NMR
CH2OH
COCl
H3C
LiAlH4
H3C
CH CH2
CH CH2
H3C
O
H3C
O
VI
VII
CH2PO(OC2H5)2
CH2Cl
NaPO(OC2H5)2
H3C
H3C
SOCl2 H3C
CH CH2
CH CH2
C5H5N
O
H3C
O
VIII
IX
CH2PO(OC2H5)2
CH2N(CH3)2
(CH3)2NCH2Cl H3C
HCl.
IX
CH CH2
H3C
O
X
Aminomethylation of compound IX was carried
out with dimethyl(chloromethyl)amine analogously to
[3] in acetonitrile at 80 C for 6 h. We failed to isolate
obtained aminophosphonate hydrochloride X in the
crystalline form. The syrup-like salt X was prepared
nate Xa was isolated by vacuum distillation, bp
145 C (1 mm Hg). The product yield was 48% only,
nevertheles, we could not detect formation of the
deamination product with the expected boiling point
about 120 C (1 mm Hg) or dimethylamine in a
significant amount which should be condensed in a
trap cooled with liqiud nitrogen. That means that di-
methylamine elimination does not take place. De-
crease in the aminophosphonate yield may be prob-
ably caused by dealkylation of the phosphorus-con-
taining group in the presence of traces of sodium
ethoxide. This is confirmed indirectly by the fact that
1
in 83% yield and characterized by the H and 31P
NMR spectra.
For the isolation of free amine Xa the product ob-
tained was dissolved in ethanol and treated with the
equivalent amount of sodium ethylate in ethanol.
After removing sodium chloride the aminophospho-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

SYNTHESIS AND AMINOMETHYLATION OF 2-ISOBUTYL-3-
1065
only the mechanical losses were observed at the
repeated distillation of phosphonate Xa.
a thionyl chloride excess. This procedure delivered the
acyl chloride XI with bp 62 C (1 mm Hg) whose H
1
NMR spectrum did not contain signals of admixture.
Synthesis of the isomeric phosphonate with iso-
butyl and diethoxyphosphorylmethyl groups located
at the same side of the furan ring was started with the
preparation of the ester II by the modified Feist
Benary procedure [6] including condensation of chlo-
roacetaldehyde with ethyl isobutyrylacetate in water
pyridine medium. But it occured that the isolated
compound II was significantly contaminated with
aliphatic compounds. They could be removed only by
alkaline hydrolysis, extraction of nonhydrolyzed
material, and treating the acid mixture obtained with
The acyl chloride XI reduction was carried out
with lithium alumohydride in ether at 36 C. The
stable alcohol XII obtained was isolated by vacuum
distillation in 62% yield. Chloride XIII was prepared
by treating compound XII with thionyl chloride in
ether in the presence of pyridine at 15-20 C for 3 h.
Reaction product was isolated in 64% yield. It is a
stable compound which can be distilled in a vacuum
without decomposition and does not darken at room
temperature.
ClCH2
HOCH2
CH CH2
ClCO
H3C
H3C
LiAlH4
SOCl2
H3C
H3C
H3C
H3C
CH CH2
C5H5N
CH CH2
O
O
O
XI
XII
XIII
The chloride XIII phosphorylation was carried out
under the Michaelis Becker reaction conditions with
sodium diethyl phosphite in benzene at 80 C for 13 h.
Phosphonate XIV was isolated by vacuum distilla-
tion as a viscous oil with bp 118 C (1 mm Hg) in
72% yield.
CH2PO(OC2H5)2
CH2PO(OC2H5)2
NaPO(OC2H5)2
(CH3)2NCH2Cl
CH3 HCl
CH3
XIII
(CH3)2NCH2
CH2CH
CH2CH
CH3
CH3
O
O
XIV
XV
Phosphonate XIV was aminomethylated with di-
methyl(chloromethyl)amine in acetonitrile for 6 h.
Aminophosphonate hydrochloride XV was obtained
as a glass-like mass which did not give well formed
Thus, 3- and 4-substituted 2-isobutylfuran deriva-
tives show quite close chemical behavior in the con-
sidered reaction sequence. Yields of corresponding
isomeric alcohols, chlorides, and phosphonates are
similar and the products are equally stable. Amino-
methylation of phosphonates IX and XIV proceeds
under the similar conditions. The products obtained
have no tendency to eliminate dimethylamine. At the
same time in presence of the ethoxide traces dealkyla-
tion of phosphonates to esterosalts evidently takes
place causing decrease in the yield of free amino-
phosphonates at their isolation from the salts.
1
crystals. It was characterized by H amd 31P NMR
spectra. The yield of the product was 95%.
For isolation of the free aminophosphonate XVa
the hydrochloride XV was dissolved in ethanol and
treated with an equivalent amount of a sodium
ethoxide ethanolic solution. Sodium chloride was
removed, and the residue was distilled in a vacuum.
Aminophosphonate XVa was obtained as a viscous
oil with bp 151 153 C (1 mm Hg) in 59% yield. The
products of dimethylamine elimination or dimethyl-
amine itself were not found. Evidently the reason of
the moderate yield similarly to the previous case was
the dealkylation of phosphonate group in the presence
of sodium ethoxide traces. At repeated distillation of
phosphonate XVa the mechanical losses were only
observed.
EXPERIMENTAL
1
The H and 31P NMR spectra of compounds ob-
tained were taken on a Bruker AC-200 spectrometer
1
(200.13 MHz H; 80.014 MHz 31P) in CDCl3 and in
DMSO-d6 in the case of aminophosphonate hydro-
chlorides, with internal TMS (1H) and external 85%
H3PO4 (31P) as references.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1066
PEVZNER
2-Isobutyl-4-clhoroformylfuran (VI). a. To a
distilled in a vacuum. A fraction boiling in the range
73 79 C (1 mm Hg) was collected, yield 2.5 g.
Grignard reagent solution prepared from 55 ml of
isopropyl chloride and 14.5 g of magnesium in 150 ml
of ether 40.6 ml of 2-furaldehyde was added drop-
wise with stirring and cooling at 25 30 C. Resulting
mixture was stirred for 3 h and left overnight. Next
day the reaction mixture was treated with saturated
water solution of ammonium chloride until separation
of organic and inorganic phases was achieved, and
diluted with 150 ml of petroleum ether. Organic layer
was decanted, and the inorganic salt gel was treated
with stirring with 100 ml of petroleum ether. Joined
organic extracts were washed with water and dried
over sodium sulfate. Solvent was removed, and the
residue was distilled in a vacuum to give 45.7 g of the
product III with bp 46 46 C (1 mm Hg), n2D0 1.4680.
1H NMR spectrum, , ppm: 0.725 d (CH3-isopropyl,
JHH 7 Hz), 0.875 d (CH3-isopropyl, JHH 7 Hz), 1.925
m (CH-isopropyl), 4.000 s (OH), 4.100 d.d (CH-OH);
6.050 s (H4-furan), 6.150 s (H3-furan), 6.670 s (H5-
furan).
e. The sample with bp 73 79 C (1 mm Hg), 5.0 g,
obtained according to the prceeding procedure was
refluxed with stirring with a solution of 3.4 g of
potassium hydroxide in 25 ml of water for 3 h. The
reaction mixture obtained was extracted with 10 ml of
ether to remove nonhydrolized material, and then
acidified to pH 1. Obtained oil was extracted 3 times
with ether, the extract was dried over calcium chloride,
ether was distilled off, and the residue was kept in a
vacuum (1 mm Hg) for 1 h at room temperature to
give 3.3 g of crude 2-isobutylfuran-4-carboxylic acid
as a dark red viscous oil.
f. The sample obtained in the preceeding stage,
3.3 g, was dissolved in 15 ml of benzene, and 2.8 ml
of thionyl chloride and 3 drops of DMF were added
to it. The mixture obtained was refluxed with stirring
for 4 h, benzene was removed at reduced pressure, and
the residue was distilled in a vacuum to give 2.8 g of
1
acyl chloride VI, bp 67 C (1 mm Hg). H NMR
b. A mixture of 38.8 g of alcohol III and 156 ml
of ethanol containing 0.5 g of hydrogen chloride was
refluxed with stirring for 9 h, ethanol was distilled off
at reduced pressure, and the residue was distilled in a
vacuum to give 34.1 g of ketoester IV, bp 79 C
(1 mm Hg), n2D0 1.4260.
spectrum, (CDCl3), , ppm: 0.910 d (CH3-isobutyl,
JHH 7 Hz), 1.992 m (CH-isobutyl); 2.440 d.d
(CH2-isobutyl, JHH 7 Hz); 6.210 s (H3-furan); 7.720 s
(H5-furan).
2-Isobutyl-4-hydroxymethylfuran (VII). To a
suspension of 0.7 g of lithium alumohydride in 60 ml
of ether a solution of 2.8 g of the acyl chloride VI in
10 ml of ether was added dropwise with stirring at a
rate providing slight boiling of reaction mixture. After
the addition was complete the reaction mixture was
stirred for 1 h and left overnight. On the next day it
was treated with 5 ml of ethyl acetate and then with
the ammonium chloride saturated solution until the
phase separation. Clear etheral solution was decanted,
dried over calcium chloride and distilled in a vacuum
to give 1.5 g (65%) of alcohol VII with bp 62 63 C
c. A mixture of 34.4 g of ketoester IV, 29 ml of
triethyl orthoformate, 10 ml of absolute ethanol and
0.3 ml of concentrated sulfuric acid was refluxed with
stirring for 12 h, the volatile products were distilled
off at reduced pressure, and the residue was distilled
in a vacuum to give 29.2 g of ketal with bp 78 C
(1 mm Hg), n2D0 1.4280.
d. To the vigorously stirred suspension of 2.8 g of
sodium foil in 100 ml of toluene 28 g of ketal and
17.4 g of ethyl formate were added dropwise from
two different dropping funnels. The component addi-
tion rate was regulated to provide simultaneous com-
pletion of loading. During the addition the reaction
mixture was cooled with water. After the addition was
complete the mixture obtained was stirred for 3 4 h
to complete disappearance of sodium pieces and then
left overnight. On the next day it was treated with
50 ml of water, organic layer was separated and once
more extracted with 50 ml of water. Joined water ex-
tracts were acidified with hydrochloric acid to pH 1
and stirred at room temperature for 1 h. Then the re-
action mixture was extracted with benzene (3 40 ml),
the extract was treated with 0.3 ml of perchloric acid,
and resulting mixture was refluxed with the Dean
Stark trap until complete separation of water. Toluene
was removed at reduced pressure, and the residue was
1
(1 mm Hg). H NMR spectrum (CDCl3), , ppm: 0.86
d (CH3-isobutyl, JHH 7 Hz); 1.83 m (CH- isobutyl,
JHH 7 Hz); 2.36 d.d (CH2-isobutyl, JHH 7 Hz);
3.11 s (OH); 4.21 s (CH2OH); 5.83 s (H3-furan); 7.04
s (H5-furan).
2-Isobutyl-4-chloromethylfuran (VIII). To a so-
lution of compound VII, 1.5 g, in 15 ml of ether
0.8 ml of pyridine was added, and then a solution of
0.7 ml of thionyl chloride in 5 ml of ether was added
dropwise with stirring at 17 25 C. Obtained mixture
was stirred for 5 h at room temperature, pyridinium
chloride was filtered off, ether was removed, and the
residue was distilled in a vacuum to give 1.6 g (65%)
1
of chloride VIII with bp 56 C (1 mm Hg). H NMR
spectrum (CDCl3), , ppm: 0.869 d (CH3-isobutyl,
JHH 7 Hz), 1.910 m (CH-isobutyl), 2.400 distotred d
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

SYNTHESIS AND AMINOMETHYLATION OF 2-ISOBUTYL-3-
1067
(CH2-isobutyl, JHH 7 Hz); 4.400 s (CH2Cl); 6.012 s
2-Isobutyl-3-chloroformylfuran (XI). a. To a so-
lution of 25.8 g of ethyl isobutyrylacetate in 30 ml of
pyridine 20 ml of 50% water solution of chloroacetal-
dehyde was added in one portion. The mixture ob-
tained was stirred for 9 h at 45 C, poured into 200 ml
of water, acidified with hydrochloric acid to pH 1,
saturated with salt and extracted with toluene (3
80 ml). The extract was washed with water and dried
over calcium chloride. Solvent was removed at re-
duced pressure and the residue was distilled in a
vacuum to give 20.7 g of the fraction with bp 53
(H3-furan); 7.281 s (H5-furan).
2-Isobutyl-4-(diethoxyphosphorylmethyl)furan
(IX). To a solution of sodium diethyl phosphite pre-
pared from 0.2 g of sodium and 1.0 ml of diethyl
hydrogen phosphite in 15 ml of benzene, 0.8 g of
chloride VIII was added in one portion and obtained
mixture was refluxed with stirring for 15 h. Sodium
chloride was removed on a centrifuge, solvent was
evaporated at reduced pressure, and the residue was
distilled in a vacuum to give 0.9 g (71%) of phos-
phonate IX with bp 123 125 C (1 mm Hg), nD20
65 C (1 mm Hg), n2D0 1.4430.
1
1.4550. H NMR spectrum (CDCl3), , ppm: 0.869 d
b. The sample obtained in the preceeding stage,
20.8 g, was refluxed with stirring for 4 h with a solu-
tion of 20 g of potassium hydroxide in a mixture of
20 ml of water and 30 ml of ethanol. Then ethanol
was distilled off, the residue was diluted with 50 ml
of water and extracted with petroleum ether. Water
layer was acidified with hydrochloric acid to pH 1 and
evolved product was extracted with ether. Etherial
extract was dried over calcium chloride, ether was
distilled off, and the residue was kept in a vacuum
(1 mm) at 25 C for 1 h. Crude 1-isobutylfuran-3-
carboxylic acid, 7.1 g, was obtained as a mixture of
crystals and oil.
(CH3-isobutyl, JHH 7 Hz); 1.241 t (CH2-ethyl, JHH
7
Hz); 1.993 m (CH-isobutyl, JHH 7 Hz), 2.400 d.d
(CH2-isobutyl, JHH 7 Hz); 2.870 d (CH2P, JHP 21 Hz);
4.029 m (CH2OP, JHH 7 Hz, JHP 11 Hz); 5.980 s (H3-
furan); 7.180 d (H5-furan, JHP 4 Hz). 31P NMR spec-
trum (CDCl3):
26.534 ppm.
P
2-Isobutyl-4-(diethoxyphosphorylmethyl)-5-
(dimethylaminomethyl)furan hydrochloride (X).
To a solution of 1.7 g of phosphonate IX in 15 ml of
anhydrous acetonitrile 0.6 g of dimethyl(chlorome-
thyl)amine was added in one portion and resulting
mixture was refluxed with stirring at 80 C for 6 h.
Then solvent was distilled off at reduced pressure and
the residue was kept in a vacuum (1 mm) for 1 h at
25 C. The salt X was obtained as a very viscous syrup,
c. The compound prepared by the above procedure,
7.1 g, was dissolved in 30 ml of benzene and refluxed
with 7 ml of thionyl chloride and 0.2 ml of DMF for
5 h. Distillation of reaction mixture in a vacuum gave
6.6 g of acyl chloride XI, bp 62 C (1 mm Hg), nD20
1
yield 1.9 g (83%). H NMR spectrum (DMSO-d6), ,
ppm: 0.758 d (CH3-isobutyl, JHH 7 Hz); 1.158 t (CH3-
ethyl, JHH 7 Hz); 1.780 m (CH-isobutyl, JHH 7 Hz);
2.307 d (CH2-isobutyl, JHH 7 Hz); 2.730 s (CH3 N);
3.099 d (CH2P, JHP 20.6 Hz); 3.959 m (CH2OP, JHH
7 Hz, JHP 11 Hz); 4.284 s (CH2N-furan); 5.939 s (H3-
furan); 9.50 br.s (NH). 31P NMR spectrum (DMSO-
1
1.4860. H NMR spectrum (CDCl3), , ppm: 0.927 d
(CH3-isobutyl, JHH 7 Hz); 2.081 m (CH-isobutyl, JHH
7 Hz); 2.841 d.d (CH2-isobutyl, JHH 7 Hz);
6.748 s (H4-furan); 7.278 s (H5-furan).
d6):
25.967 ppm.
2-Isobutyl-3-hydroxymethylfuran (XII). To a
suspension of 1.7 g of lithium alumohydride in 50 ml
of ether a solution of 8.4 g of acyl chloride in 15 ml
of ether was added dropwise with stirring and cooling
at a rate providing slight boiling of reaction mixture.
After the addition was complete the reaction mixture
was stirred for 3 h at room temperature and left over-
night. On the next day the mixture obtained was
treated with 10 ml of ethyl acetate and then with the
saturated water solution of ammonium chloride until
the phase separation. Organic phase was decanted and
the gel-like mixture of inorganic compounds and
water was stirred for 10 min with 30 ml of ether.
Joined etheral solutions were dried over calcium
chloride, ether was removed and the residue was dis-
tilled in a vacuum to give 4.3 g (62%) of the alcohol
P
2-Isobutyl-4-(diethoxyphosphorylmethyl)-5-
(dimethylaminomethyl)furan (Xa). To a solution of
1.9 g of the salt X in 25 ml of ethanol a solution of
sodium ethylate obtained from 0.12 g of sodium and
10 ml of ethanol was added with stirring. After keep-
ing for 20 min at room temperature the sodium chlo-
ride formed was removed on a centrifuge, solvent was
evaporated at reduced pressure, and the residue was
distilled in a vacuun to give 0.8 g (48%) of amino-
1
phosphonate Xa, bp 145 C (1 mm Hg). H NMR
spectrum(CDCl3), , ppm: 0.867 d (CH3-isobutyl, JHH
7 Hz); 1.249 t (CH3-ethyl, JHH 7 Hz); 1.913 m (CH-
isobutyl, JHH 7 Hz); 2.200 s (CH3 N); 2.406 distorted
d (CH2-isobutyl, JHH 7 Hz); 2.882 d (CH2P, JHP
20.6 Hz); 3.368 s (CH2N); 4.029 m (CH2OP, JHH
7 Hz, JHP 11 Hz); 5.982 s (H-furan).
1
XII, bp 61 62 C (1 mm Hg). H NMR spectrum
(CDCl3), , ppm: 0.883 d (CH3-isobutyl, JHH 7 Hz);
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1068
PEVZNER
1.940 m (CH-isobutyl, JHH 7 Hz); 2.467 d (CH2-iso-
butyl, JHH 7 Hz); 4.417 s (CH2OH), 6.350 s (H4-
furan), 7.246 s (H5-furan).
(95%) of the salt XV as a glassy mass. 1H NMR spec-
trum (DMSO-d6), , ppm: 0.810 d (CH3-isobutyl, JHH
7 Hz); 1.192 t (CH3-ethyl, JHH 7 Hz); 1.926 m (CH-
isobutyl); 2.380 d.d (CH2-isobutyl, JHH 7 Hz);
2.679 s (CH3 N); 2.739 d (CH2P, JHP 22 Hz);
3.978 m (CH2OP, JHH 7 Hz, JHP 11 Hz); 4.127 s
(CH2N); 6.613 s (H4-furan). 13P NMR spectrum
2-Isobutyl-3-chloromethylfuran (XIII). To a so-
lution of 4.3 g of alcohol XII and 2.5 ml of pyridine
in 50 ml of ether a solution of 2 ml of thionyl chloride
in 5 ml of ether was added dropwise with stirring at
15 20 C. The mixture obtained was kept for 3 h at
room temperature, pyridine hydrochloride was filtered
off, ether was removed at reduced pressure and the
residue was distilled in a vacuum to give 3.1 g (64%)
(DMSO-d6):
25.592 ppm.
P
2-Isobutyl-3-(diethoxyphosphorylmethyl)-5-(di-
methylaminomethyl)furan (XVa). To a solution of
4.1 g of the salt XV in 100 ml of ethanol a solution of
sodium ethylate prepared from 0.26 g of sodium and
20 ml of ethanol was added with stirring. The mixture
obtained was stirred for 20 min, sodium chloride was
removed on a centrifuge, ethanol was distilled off at
reduced pressure, and the residue was distilled in a
vacuum to give 2.2 g (59%) of aminophosphonate
1
of chloride XIII with bp 45 C (1 mm Hg). H NMR
spectrum (CDCl3), , ppm: 0.930 d (CH3-isobutyl,
JHH 7 Hz); 2.000 m (CH-isobutyl, JHH 7 Hz);
2.505 d.d (CH2-usobutyl, JHH 7 Hz); 4.449 s (CH2Cl);
6.374 s (H4-furan); 7.274 s (H5-furan).
2-Isobutyl-3-(diethoxyphosphorylmethyl)furan
(XIV). To a solution of sodium diethyl phosphite
prepared from 0.5 g of sodium and 3.2 ml of diethyl
hydrogen phosphite in 40 ml of benzene 3.1 g of
chloride XIII was added with stirring in one portion
at 80 C. Reaction mixture was refluxed with stirring
for 14 h, sodium chloride precipitate was removed on
a centrifuge, benzene was distilled off at reduced
pressure and the residue was distilled in a vacuum to
give 3.5 g (72%) of phosphonate XIV with bp 118 C
1
XVa with bp 151 153 C (1 mm Hg). H NMR spec-
trum (CDCl3), , ppm: 0.840 d (CH3-isobutyl, JHH
7 Hz); 1.217 t (CH3-ethyl, JHH 7 Hz); 1.935 m (CH-
isobutyl); 2.100 s (CH3 N); 2.360 d.d (CH2-isobutyl,
JHH 7 Hz); 2.780 d (CH2P, JHH 20 Hz); 3.355 s
(CH2N); 3.395 m (CH2OP, JHH 7 Hz, JHP 11 Hz);
6.136 s (H4-furan).
REFERENCES
1
(1 mm Hg). H NMR spectrum (CDCl3), , ppm:
1. Pevzner, L.M., Zh. Obshch. Khim., 2003, vol. 73, no. 2,
0.863 d (CH3-isobutyl, JHH 7 Hz); 1.214 t (CH3-ethyl,
JHH 7 Hz); 1.922 m (CH-isobutyl); 2.389 d.d (CH2-
isobutyl, JHH 7 Hz); 2.806 d (CH2P, JHP 20 Hz);
3.994 m (CH2OP, JHH 7 Hz, JHP 11 Hz); 6.305 s (H4-
furan); 7.191 s (H5-furan). 31P NMR spectrum
p. 281.
2. Pevzner, L.M., Zh. Obshch, Khim., 2005, vol. 75, no. 6,
p. 991.
3. Pevzner, L.M., Zh. Obshch. Khim., 2004, vol. 74, no. 5,
p. 770.
(CDCl3):
26.524 ppm.
P
4. Ponomarev, A.A., Sintezy i reaktsii furanovykh ve-
shchestv (Syntheses and Reactions of Furan Com-
pounds), Saratov: Saratov Gos. Univers., 1960, p. 244.
2-Isobutyl-3-(diethoxyphosphorylmethyl)-5-(di-
methylaminomethyl)furan (XV). To a solution of
3.2 g of phosphonate XIV in 50 ml of dry acetonitrile
1.1 g of dimethyl(chloromethyl)amine was added in
one portion, and the mixture was refluxed with stir-
ring at 80 C for 6 h. The homogenic solution formed
was evaporated at reduced pressure and the resiue was
kept in a vacuum (1 mm) for 3 h at 30 C to give 4.1 g
5. Sintezy geterotsiklicheskikh soedinenii (Syntheses of
Heterocyclic Compounds), Midgonyan, A.L., Ed.,
Erevan: Akad. Nauk Arm. SSR, 1959, no. 4, p. 83.
6. Winberg, H.E., J. Am. Chem. Soc., 1960, vol. 82, no. 3,
p. 1428.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006