Microwave-assisted alkylation of diethyl ethoxycarbonylmethylphosphonate under solventless conditions

Article abstract of DOI:10.1002/hc.21009

The reaction of diethyl ethoxycarbonylmethylphosphonate with a series of alkyl halides, under microwave (MW) and solventless conditions at 120°C, in the presence of Cs₂CO₃ and in the absence of a phase transfer catalyst afforded the corresponding monoalkylated products in yields of >70%. The thermal variant carried out in boiling acetonitrile was slow and led to incomplete conversions. In the MW method, the phase transfer catalyst is substituted by MW irradiation and there is no need for a solvent.

Full text of DOI:10.1002/hc.21009

Heteroatom Chemistry
Volume 23, Number 3, 2012
Microwave-Assisted Alkylation of Diethyl
Ethoxycarbonylmethylphosphonate under
Solventless Conditions
Alajos Gru¨n,1,2 Zso´fia Blastik,1 La´szlo´ Drahos,3 and
Gyo¨rgy Keglevich1
1Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
2Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemistry
and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary
3Chemical Research Center, Hungarian Academy of Sciences, 1525 Budapest, Hungary
Received 25 November 2011
ysis (PTC) [1,2]. A combination of PTC with mi-
ABSTRACT: The reaction of diethyl ethoxycarbonyl-
crowave (MW) irradiation, which is another power-
methylphosphonate with a series of alkyl halides, un-
ful technique [3–5], may offer additional advantages
der microwave (MW) and solventless conditions at
in general [6]. This was also demonstrated within the
120◦C, in the presence of Cs2CO3 and in the absence
alkylation of CH acidic compounds [7,8]. In these
of a phase transfer catalyst afforded the corresponding
cases, typically the solvent-free, solid–liquid phase
monoalkylated products in yields of >70%. The ther-
reactions were irradiated in the presence of a phase
mal variant carried out in boiling acetonitrile was slow
transfer catalyst. Tetraalkyl methylenebisphospho-
and led to incomplete conversions. In the MW method,
nates and methylenebis(phosphine oxides) form a
the phase transfer catalyst is substituted by MW irra-
special class of CH acidic compounds. Among these
ꢀ
C
diation and there is no need for a solvent. 2012 Wi-
substrates, the tetraethyl methylenebisphosphonate
ley Periodicals, Inc. Heteroatom Chem 23:241–246, 2012;
and, especially, bis(diphenylphosphinyl)methane
View this article online at wileyonlinelibrary.com. DOI
are not too reactive in C-alkylations. Consequently,
10.1002/hc.21009
the C-alkylation of these species requires harsher
conditions than for malonic esters, acetoacetic es-
ters, and analogues. Accordingly, [(EtO)2P(O)]2CH2
INTRODUCTION
and [Ph2P(O)]2CH2 were alkylated via salt formation
with potassium [9,10], or sodium hydride [11–14].
In these cases, the alkylated species were obtained
in variable (in most cases in poor) yields. The CH
acidic compounds with mixed functionalities, for
example, ethyl cyanomethylphosphonate are more
reactive and were converted to the alkylated deriva-
tives via salt formation with sodium hydride [15], or
by liquid–liquid PTC [16].
Substituted CH acidic compounds, such as mal-
onates and cyanomethylacetic esters, that are in-
termediates in the preparation of barbiturates may
be synthesized efficiently by phase transfer catal-
Correspondence
gkeglevich@mail.bme.hu.
Contract grant sponsor: Hungarian Scientific and Research
Fund.
to:
Gyo¨rgy
Keglevich;
e-mail:
The benzylation of diethyl ethoxycarbonyl-
methylphosphonate was carried out using potas-
sium [17], sodium hydride (in tetrahydrofuran
Contract grant number: OTKA K83118.
2012 Wiley Periodicals, Inc.
c
ꢀ
241

242 Gru¨n et al.
TABLE 1 Alkylation of CH Acidic Compounds in Solid–Liquid Phase, in the Presence of Alkali Carbonate
T/t
M2CO3
Y CH2 Z + RX
Y CH
R
Z
Y
Z
RX M2CO3 Solvent Mode of heating T/p (◦C/bar)
t
Yield of Y–CHR–Z Ref Entry
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
C(O)Me
C(O)Me
CN
EtI
K2CO3
–
–
–
MW
MW
MW
ꢀ
160/12
185/12
185/12
56
45 min
45 min
45 min
20 h
30 min
30 min
45 min
45 min
1.5 h
4 h
4 h
4 h
3 h
24 h
93
92
81
78
85
87
75
78
80
[29,30]
[29,30]
[29,30]
[29,30]
[29,30]
[29,30]
[29,30]
[29,30]
[31]
[31]
[32]
[32]
[32]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
nPrBr K2CO3
nBuBr K2CO3
EtI
EtI
K2COa Acetone
K2CO33
–
–
–
–
–
–
MW
MW
MW
MW
MW
MW
MW
MW
MW
ꢀ
140/11
140/11
120/9
120/9
140/11
120/6
180/13.5
180/13.5
120/9
82
nPrBr K2CO3
EtI
nPrBr K2CO3
Cs2CO3
P(O)(OEt)2 P(O)(OEt)2 nPrBr Cs2CO3
K2CO3
CN
P(O)(OEt)2 P(O)(OEt)2 EtI
57b,c
40d
46e
45f
44g
64
59
75
82
Ph2P(O)
PhP(O)
nPrBr Cs2COa MeCN
nPrBr Cs2CO33 MeCN
BnBr Cs2CO3 MeCN
BnBr Cs2CO3 MeCN
[32]
[32]
[32]
[32]
P(O)(OEt)2 CN
nPrBr K2CO3
nBuBr K2CO3
–
–
MW
MW
ꢀ
100/2.5
120/3
82
2 h
2 h
24 h
24 h
nPrBr Cs2CO3 MeCN
nBuBr Cs2CO3 MeCN
ꢀ
82
[32]
ꢀ = traditional heating.
aIn the presence of 10% of TEBAC.
bProportion in the mixture on the basis of GC.
cThe mixed esters with one or two PrO groups were also present in 33% and 10%, respectively.
dAt a conversion of 64%.
eAt a conversion of 74%.
f At a conversion of 57%.
gAt a conversion of 60%.
[18,19], N,N-dimethylformamide (DMF) [20,21]), or
potassium carbonate [22,23] as the deprotonating
agent generating the anion in a separate step, or in
the presence of the benzyl halide. In most cases, the
benzylation required prolonged reaction times and
the yields were variable.
The alkylation of diethyl ethoxycarbonylmethyl-
phosphonate was also described using sodium hy-
dride in DMF [24] or ethylene glycol dimethyl ether
[25], or using potassium tert-butylate in dimethyl
sulfoxide [26–28]. At the same time, the butylation
was also accomplished using K2CO3/NaI [23].
Recently, we have systematically studied the
effect of MW and PTC on the alkylation of a variety
of CH acidic compounds. It was found by us that
diethyl malonate, ethyl acetoacetate, and ethyl
cyanoacetate could be efficiently alkylated under
MW and solventless conditions in the presence of
K2CO3 and in the absence of a phase transfer cat-
alyst (triethylbenzylammonium chloride, TEBAC).
It means that MW irradiation substituted the phase
transfer catalyst (Table 1, entries 1–8) [29,30].
The same was experienced for the ethylation of
tetraethyl methylenebisphosphonate using Cs2CO3
(Table 1, entry 9) [31]. Applying n-propyl bromide
as the alkylating agent, the ester with one or two
PrO groups also appeared in the mixture (Table 1,
entry 10) [31]. Tetraphenylmethylene(bisphosphine
oxide) was a very hindered model. The alkylations
were best carried out in the presence of 5% of
TEBAC and in an acetonitrile solution using Cs2CO3
as the base. The conversions were far from com-
plete, and the yields of the alkylated products were
only 40–46% (Table 1, entries 11–13) [32]. In this
instance, the preparation under traditional thermal
conditions led to similar results (Table 1, entry 14)
[32]. Finally, the MW-assisted solventless alkylation
of diethyl cyanomethylphosphonate provided the
alkylated products in a 59–64% yield (Table 1,
entries 15 and 16). The application of TEBAC was
harmful, as it promoted the formation of phos-
phonates with mixed ester functionalities [32]. The
alkylation carried out in the presence of Cs2CO3 in
boiling acetonitrile furnished the C-alkyl derivatives
in a 75–82% yield after a 24-h reaction time (Table 1,
entries 17, 18).
It can be seen that the MW-assisted solventless
and catalyst-free accomplishment, in most of the
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Alkylation of Diethyl Ethoxycarbonylmethylphosphonate under Solventless Conditions 243
TABLE 2 Solid–Liquid Phase Alkylation of Diethyl Ethoxycarbonylmethylphosphonate 1 under MW Conditions (See the
Experimental Section)
Composition (%)a
RX
M2CO3
TEBAC (10%)
T (◦C)
t(h)
1
2
Other
Yield of 2
Entry
EtI
EtI
EtI
EtI
EtI
EtI
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
–
–
–
120
120
130
120
120
120
130
130
120
120
120
120
120
130
130
120
2
3
2
2
2
2
2
3
2
2
2
2
2
3
3
3
13
11
5
30
5
12
28
25
31
10
34
7
18
16
17
27
82 (2a)
85 (2a)
85 (2a)
57 (2a)
86 (2a)
75 (2a)
57 (2b)
59 (2b)
34 (2b)
79 (2b)
22 (2b)
83 (2c)
63 (2d)
63 (2d)
32 (2d)
59 (2d)
5
4
10
13
9
13
15
16
35
11
44
10
19b
21c
51d
14e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
72 (2a)
70 (2a)
+
–
+
–
–
nPrBr
nPrBr
nPrBr
nPrBr
nPrBr
nBuBr
BnBr
BnBr
BnBr
BnBr
+
–
71 (2b)
+
–
–
70 (2c)
53 (2d)
–
+
–
aOn the basis of GC.
bIncluding 7% of the dibenzylated product.
cIncluding 8% of the dibenzylated product.
dIncluding 6% of the dibenzylated product.
eIncluding 11% of the dibenzylated product.
cases, is a good alternative to other variations, for ex-
ample, to the solid–liquid phase, typically the phase
transfer catalyzed method applying alkali carbonate
in acetonitrile at the boiling point.
As the MW-assisted method elaborated by us
seemed to be of general value, we wished to try
it out in the alkylation of diethyl ethoxycarbonyl-
methylphosphonate and we wished to find the opti-
mum conditions.
Using ethyl iodide and K2CO3 at 120◦C, the pro-
portion of the ethyl-substituted product (2a) was
82% and 85%, respectively, after a 2-h reaction time
(Table 2, entries 1 and 2). Almost similar results
were obtained at 130◦C for 3 h (Table 2, entry 3).
It is noteworthy that the use of 10% TEBAC as the
phase transfer catalyst led to a decreased conver-
sion of 70% and an increase in the proportion of the
by-products (Table 2, entry 4). Performing the ethy-
lation in the presence of Cs2CO3 at 120◦C for 2 h, the
outcome was similar to that with K2CO3 at 120◦C for
3 h or at 130◦C for 2 h (Table 2, entries 5 vs. 2 and 3).
The presence of TEBAC was again harmful (Table 2,
entry 6).
Changing for n-propyl bromide, a similar trend
was experienced as with ethyl iodide. At the same
time, K2CO3 was not as effective as Cs2CO3. Using
K2CO3, the maximum proportion of the propylated
compound 2b was 57–59%, and this was even lower
(34%) in the presence of TEBAC (Table 2, entries
7–9). The application of Cs2CO3 led to better re-
sults; the proportion of the desired product (2b) was
79% at 120◦C after a 2-h reaction time (Table 2, en-
try 10). It is a noteworthy observation that in this
case the phase transfer catalyst had a dramatic im-
pact on the conversion and proportion of product
2b. Instead of 96%, the conversion was only 66%
and the proportion of the propylated substrate was
only 22% instead of 75%. At the same time, the
by-products represented as much as 44% in-
stead of 21% (Table 2, entry 11 vs. 10). Among
RESULTS AND DISCUSSION
We wished to try out the MW-assisted solventless
and catalyst-free alkylation of diethyl ethoxycar-
bonylmethylphosphonate in the presence of K2CO3
and Cs2CO3 applying ethyl iodide, n-propyl bromide,
n-butyl bromide, and benzyl bromide as simple alky-
lating agents (Scheme 1). The mixtures were ana-
lyzed by gas chromatography (GC).
MW
T, t
M2CO3
O
O
O
O
P(OEt)2
OEt
P(OEt)2
C OEt
+
RX
(1.2 equiv.)
R
no solvent
M = K, Cs
C
1
2
RX = EtI, nPrBr, nBuBr, BnBr
R = Et (a), nPr (b), nBu (c), Bn (d)
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

244 Gru¨n et al.
the by-products, the propylated ethoxycarbonyl-
methylphosphonate with ethyl n-propyl and di-n-
propyl ester functions (3b [δP (CDCl3) 23.05, (M +
H)+found = 281.1519, C12H26O5P requires 281.1518]
and 4b [δP (CDCl3) 23.00, (M + H)+found = 295.1676,
C13H28O5P requires 295.1674], respectively) could be
identified.
O
O
P(OEt)2
Bn
Bn
C
OEt
5d
From the best experiments, the alkylated deriva-
tives were prepared by column chromatography.
Hence, product 2a was obtained in 72–70% yields
from the experiments covered by Table 2 (entries 3
and 5). Similarly compounds 2b, 2c, and 2d were
obtained in 71%, 70%, and 53% yields, respectively,
based on experiments outlined by entries 10, 12, and
14 of Table 2.
O
O
OEt
OnPr
OEt
OnPr
OnPr
OEt
P
C
P
C
Pr
Pr
O
O
3b
4b
The alkylated ethoxycarbonylmethylphospho-
nates 2a–d were described in the literature [33–38],
but they were characterized only partially. All the
products synthesized have now been subjected to
The butylation with n-butyl bromide was carried
out under the best conditions found in the case of
the n-propyl analogue. Hence, applying 120◦C for 2
h in the presence of Cs2CO3 and in the absence of a
catalyst, the proportion of the n-butyl product (2c)
was 83% (Table 2, entry 12).
1
spectral characterization by 31P, 13C, and H NMR,
as well as mass spectrometry (MS) methods.
For comparative purposes, the alkylations were
also carried out under traditional thermal condi-
tions in acetonitrile at the boiling point for 24 h.
On the one hand, the ethoxycarbonylmethylphos-
phonate (1) was alkylated in the presence of K2CO3
and TEBAC at the boiling point of acetonitrile. On
the other hand, Cs2CO3 was used without a cata-
lyst. This was possible due to the better liphophility
of Cs2CO3. All these reactions were reluctant and
stopped at incomplete conversions. In the presence
of K2CO3 and TEBAC, the maximum proportion of
alkylated products 2a–c was 11–28% with 72–80%
unreacted starting material 1 present. Using Cs2CO3
without a catalyst, the reaction mixture contained
45–74% of product 2 (Table 3). In the presence of
TEBAC, side reactions could be observed. The ben-
eficial effect of the application of MW irradiation in
the alkylation reactions under discussion is obvious.
The benzylation of CH acidic compound 1 was
also studied. It was found that in the presence of
K2CO3 as the base, the proportion of the benzy-
lated product 2d was 63% working at 120◦C for
2 h or 130◦C for 3 h, showing that no complete
conversion could be achieved under such condi-
tions (Table 2, entries 13 and 14). The effect of
the phase transfer catalyst was the same as in the
previous cases: The relative proportion of the by-
products increased to 51% (Table 2, entry 15). Re-
placing K2CO3 with Cs2CO3, the outcome of the
benzylation remained practically unchanged (Table
2, entry 16). It was observed that the by-products
included the dibenzylated product, diethyl 1,1-
dibenzyl(ethoxycarbonyl)methylphosphonate (5d).
In the aforementioned cases, its proportion
amounted to 7–11%.
TABLE 3 Solid–Liquid Phase Alkylation of Diethyl Ethoxycarbonylmethylphosphonate 1 under Thermal Conditions in Boiling
Acetonitrile for 24 h
Composition (%)a
RX
M2CO3
TEBAC (10%)
1
2
Other
Entry
EtI
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
+
+
+
–
–
–
79
80
72
24
55
31
11 (2a)
14 (2b)
28 (2c)
74 (2a)
45 (2b)
69 (2c)
10
6
1
2
3
4
5
6
nPrBr
nBuBr
EtI
–
2b
nPrBr
nBuBr
–
–
c
d
aOn the basis of GC.
b−dNo change on prolonged heating.
Heteroatom Chemistry DOI 10.1002/hc

Microwave-Assisted Alkylation of Diethyl Ethoxycarbonylmethylphosphonate under Solventless Conditions 245
In summary, the MW-assisted and solventless
method was extended to the alkylation of an-
other CH acidic compound, diethyl ethoxycarbonyl-
methylphosphonate 1, where K2CO3 or Cs2CO3 is
the solid phase and the substrate, along with the
alkyl halide, forms the liquid phase. Regarding yields
and reaction times, the MW-assisted and solvent-
less procedure is more efficient as compared to the
thermal variant, when the CH acidic substrate is
alkylated using alkali carbonates in boiling ace-
tonitrile in the presence or absence of a phase
transfer catalyst leading to incomplete conversions.
Additional advantages are that the phase transfer
catalyst is substituted by MW irradiation, and there
is no need for a solvent.
Diethyl
1-(Ethoxycarbonyl)propylphosphonate
(2a) (Table 2, Entry 3). Yield: 72%; 31P NMR
(CDCl3) δ: 22.9, δP: [33] 22.1; 13C NMR [34] (CDCl3)
δ: 13.1 (d, J = 15.9, CH2), 14.4 (s, CH3), 16.4 (d,
J = 2.4, CH3), 16.5 (d, J = 2.0, CH3), 20.8 (d,
J = 5.0, CH3), 47.6 (d, J = 131.5, CH), 61.4 (s,
CH2O), 62.7 (d, J = 6.9, CH2O), 62.8 (d, J = 6.5,
1
CH2O), 169.3 (d, J = 4.7, C = O); H NMR [34]
(CDCl3) δ: 0.99 (t, 3H, J = 7.3, CH3), 1.38–1.27 (m,
9H, CH3), 2.07–1.86 (m, 2H, CH2), 2.92–2.79 (m,
1H, CH), 4.26–4.10 (m, 6H, CH2); HRMS, (M +
H)+ = 253.1207, C10H22O5P requires 253.1205, (M +
Na)+ = 275.1028, C10H21O5PNa requires 275.1019.
Diethyl
1-(Ethoxycarbonyl)butylphosphonate
(2b) (Table 2, Entry 10). Yield: 71%; 31P NMR
(CDCl3) δ: 23.10, δP: [35] 20.3; 13C NMR (CDCl3)
δ: 13.6 (s, CH3), 14.1 (s, CH3), 16.3 (d, J = 2.4,
CH3), 16.4 (d, J = 2.1, CH3), 21.6 (d, J = 15.4,
CH2), 29.0 (d, J = 5.1, CH2), 45.7 (d, J = 131.4,
CH), 61.3 (s, OCH2), 62.6 (d, J = 6.6, POCH2),
62.7 (d, J = 6.1, POCH2), 169.3 (d, J = 4.8, C O);
1H NMR (CDCl3) δ: 0.93 (t, 3H, J = 7.3, CH3),
1.48–1.27 (m, 2H + 3H + 6H, CH2, CH3), 1.88–1.74
(m, 1H, CH2), 2.07–1.90 (m, 1H, CH2), 3.01–2.89 (m,
1H, CH), 4.25–4.10 (m, 6H, OCH2); HRMS, (M +
H)+ = 267.1360, C11H24O5P requires 267.1361, (M +
Na)+ = 289.1181, C11H23O5PNa requires 289.1175.
EXPERIMENTAL
General
1
The 31P, 13C, and H NMR spectra were obtained
on a Bruker DRX-500 spectrometer operating at
202.4, 125.7, and 500 MHz, respectively. Chemi-
cal shifts are downfield relative to 85% H3PO4 or
tetramethylsilane (TMS). The couplings are given in
Hz. MS was performed on a ZAB-2SEQ instrument.
The MW-assisted reactions were carried out in a
CEM Discover microwave reactor (CEM Microwave
Technology Ltd., Buckingham, UK) equipped with a
pressure controller using ca. 30-W irradiation.
Diethyl
1-(Ethoxycarbonyl)pentylphosphonate
(2c) (Table 2, Entry 12). Yield: 70%; 31P NMR
(CDCl3) δ: 23.8; 13C NMR [36] (CDCl3) δ: 13.8 (s,
CH3), 14.2 (s, CH3), 16.4 (d, J = 2.4, CH3), 16.4 (d,
J = 2.1, CH3), 22.2 (s, CH2), 26.8 (d, J = 5.0, CH2),
30.6 (d, J = 14.9, CH2), 45.9 (d, J = 131.2, CH), 61.3
(s, OCH2), 62.6 (d, J = 6.4, POCH2), 62.7 (d, J =
General Procedure for the MW-Assisted and
Solventless Alkylation of Diethyl
Ethoxycarbonylmethylphosphonate under MW
Conditions
1
6.1, POCH2), 169.2 (d, J = 4.7, C O); H NMR [36]
(CDCl3) δ: 0.90 (t, 3H, J = 6.6, CH3), 1.42–1.27 (m,
3H + 6H + 4H, CH2, CH3), 2.06–1.77 (m, 2H, CH2),
3.00–2.86 (m, 1H, CH), 4.25–4.10 (m, 6H, OCH2);
HRMS, (M + H)+ = 281.1519, C12H26O5P requires
281.1518, (M + Na)+ = 303.1343, C12H25O5PNa
requires 303.1332.
0.20 g (0.89 mmol) of triethyl phosphonoacetate,
1.07 mmol of alkyl halide (ethyl iodide: 0.09 mL,
n-propyl bromide: 0.10 mL, n-butyl bromide: 0.12
mL, benzyl bromide: 0.13 mL), 0.89 mmol of alkali
carbonate (K2CO3: 0.12 g, Cs2CO3: 0.32 g), and if nec-
essary 0.02 g (0.09 mmol) of TEBAC were measured
in a tube that was placed in the MW reactor and was
irradiated under pressure control at 30 W at the ap-
propriate temperature (T) for the appropriate time
(t). Then the mixture was taken up in 20 mL of ace-
tonitrile, and the resulting suspension filtered and
the filtrate concentrated in vacuum. The residue so
obtained was analyzed by GC and in certain cases
(indicated in Table 2 and below) purified by column
chromatography (3% methanol in dichloromethane,
silica gel) to afford products 2a–d.
Diethyl
2-Phenyl-1-(ethoxycarbonyl)ethylphos-
phonate (2d) (Table 2, Entry 13). Yield: 53%; 31P
NMR (CDCl3) δ: 22.0; 13C NMR [37] (CDCl3) δ: 14.1
(s, CH3), 16.4 (d, J = 2.3, CH3), 16.5 (d, J = 2.1,
CH3), 32.9 (d, J = 4.4, CH2), 47.8 (d, J = 129.2,
CH), 61.4 (s, CH2), 62.9 (d, J = 3.7, CH2), 63.0 (d,
J = 6.5, CH2), 126.8 (s, Ar), 128.6 (d, J = 7.3, Ar),
129.4 (d, J = 242.1, Ar), 138.5 (d, J = 16.0, Ar),
1
168.5 (d, J = 4.7, C O); H NMR [38] (CDCl3) δ:
1.14 (t, 3H, J = 7.1, CH3), 1.35 (t, 6H, J = 7.1,
CH3), 3.33–2.92 (m, 2H + 1H, CH2, CH), 4.23–4.06
The following products were thus prepared.
Heteroatom Chemistry DOI 10.1002/hc

246 Gru¨n et al.
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General Procedure for the Alkylation of Diethyl
Ethoxycarbonylmethylphosphonate (1) under
Traditional Thermal Conditions
A mixture of 0.40 g (1.78 mmol) of diethyl ethoxy-
carbonylmethylphosphonate (1), 2.14 mmol of the
alkylating agent (0.17 mL of EtI, 0.19 mL of n-propyl
bromide, 0.23 mL of n-butyl bromide, and 0.25 mL
of benzyl bromide), 0.25 g (1.78 mmol) of K2CO3
and 0.040 g (0.18 mmol) of TEBAC (variation A), or
0.63 g (1.78 mmol) of Cs2CO3 (instead of K2CO3 and
TEBAC) (variation B) in 10 mL of acetonitrile was
stirred at the boiling point for 24 h. Then, the mix-
ture was filtrated, the solid was washed with 3 mL
of acetonitrile, and the combined organic phase was
concentrated. The oil so obtained was taken up in 6
mL of dichloromethane and filtered through a small
silica gel layer. The residue was analyzed by GC. For
details, see Table 3.
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ACKNOWLEDGMENTS
This work is connected to the scientific program
of the “Development of quality-oriented and har-
monized R + D + I strategy and functional model
at BME” project. This project is supported by the
New Sze´chenyi Plan (Project ID: TAMOP-4.2.1/B-
09/1/KMR-2010-0002).
´
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Heteroatom Chemistry DOI 10.1002/hc