Russian Chemical Bulletin Vol. 48, No.

~,
~ February, 1999 367

Transformations of electrophilic reagents in a

diethyl phosphite--potassium carbonate--ethanol system
A. Yu. Platonov,* A. A. Sivakov, K N. Chistokletov, and. E. D. Maiorova

St. Petersbug State Technological University of Plant Polymers,

4 ul. [vana Chernykh, 198095 St. Petersburg, Russian Federation.
Fax: +7(095) 186 8600

Transformations of alkyl hatides, aldehydes, and activated alkenes in a (EtO)~PHO--

K2CO3--EtOH heterophase system were studied. The reactions are catalyzed by EtOK that
formed and follow the known schemes of the interaction of hydrophosphoryl compounds
with electrophiles.
Key words: diethyl phosphite, potassium carbonate, ethanol, alkali metal alkoxides,
deprotonation.

D e p r o t o n a t i o n o f t a u t o m e r s in r e a c t i o n s o f previously been described, 9 according to which dimethyl

hydrophosphoryl com- and diethyl phosphites are methylated with methyl io-
pomads, for example, ~P(O)H _. "- ~ P - O H dide in the presence of potash without catalysts and
dialkyl p h o s p h i t e s , with solvents. The reaction occurs under mild conditions
electrophiles occurs in the with high yields of alkylalion products.
presence of bases, in particular, alkali metal alkoxides, The effect of K~CO 3 as a deprotonating reagent
in the reaction mixture. Dialkyl phosphites are close in depends, in many aspects, not only on the substrate
acidity to aliphatic alcohols ~-3 and, as a rule, readily structure, but also on the reaction conditions. For the
tbrm anions trader the action of these bases. However, d i f h i o r o m e t h y l a t i o n o f phenols with c h l o r o d i f l u o -
the use in synthetic practice of alkoxides prepared from romethane, we observed l~ that chlorodifluoromethane
the corresponding alcohol and alkali metal is often reacts rather readily with phenol in the presence of
complicated by side processes, because the reaction K2CO 3 in ethanol, and the reaction rate decreases sharply
proceeds too vigorously. 4 when ethanol is replaced by dioxane. Such strong bases
Many works are known in which reactions of dialkyl as alkali metal alkoxides or 30--50% solutions of N a O H
phosphites with various electrophilic reagents were stud- are usually used for the d e h y d r o c h l o r i n a t i o n of
ied under conditions of phase-transfer catalysis (PTC), CHCIF2.U
inclnding a liquid--solid base system. 5 Special attention In this work, we estimated the efficiency of the
was given to the effect of phase-transfer catalysts, and action of K2CO 3 in an ethanolic medium in reactions of
the transformations in the system were considered from diethyl phosphites with various electrophiles, considered
the viewpoint of classical concepts of PTC. F o r ex- the mechanism of interaction of all components of the
a m p l e , a n h y d r o u s K2CO 3 in the p r e s e n c e o f (EtO)2PHO--K2CO3--EtOH system, and extended the
tetrabutylammonium bromide or 18-crown-6 was used 6,7 series of electrophiles reacting with dialkyl phosphites
for the Michaelis--Beeker alkylation of dialkyl phos- under these conditions.
phites and the addition to electrophilic alkenes accord- It has been shown that mixing of K2CO 3 with EtOH
ing to Pudovik. The reactions were carried out without a results in the formation of EtOK and K H C O j and the
solvent at 80--100 ~ for 2--8 h with a considerable establishment of the chemical and phase equilibrium
excess of K2COy For the alkylation of dialkyl phos- between the components of the system (Scheme 1).
phites and diarylphosphine oxides, a mixture of KOH
and K2CO 3 was used 8 as the solid phase, a solution o f an
alkylating reagent in benzene, T H F , or methoxyethane Scheme 1
was used as the liquid phases, and IS-crown-6 was the
catalyst. It has been shown, in particular, that the EtOH + K2CO3 ~ KHCO 3 + EtOK (sol)
alkylation in benzene does not proceed in the presence
of potash only, and the addition of phosphine oxide and
phosphites to ethyl cinnamate occurs in the presence of
1L 1L
catalytic quantities of KOH and K2CO 3. The phase- K2CO3 KHCO~ (s)
transfer version of the Michaelis--Becker reaction has
Translated from lzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 369--372, February, 1999.
1066-5285/99/4802-0367 $22.00 9 1999 Kluwer Academic/Plenum Publishers
368 Russ. Chem.BulL, Vol. 4S, No. 2, February, 1999 Platonov et al.

The concentration of EtOK in the solution remains [EtOKl/mmol L-I

ahnost constant when the amount of K2CO 3 added is no
6 "S ....
less than 25--30 g per liter EtOH (Fig. 1), and the
concentration of the K2CO 3 dissolved is almost three
times lower than that of EtOK.
The transition of potassium hydrogencarbonate that
formed from the solution (sol) to the solid (s) phase is 4
most likely the driving force of the shift of equilibrium to
the right. This is confirmed by the introduction of KHCO 3
into the system, which results in a decrease in the con-
centration of potassium ethoxide to the level determined
2
by the solubility o f potassium hydrogencarbonate in etha-
nol (Fig. 2). Thus, the alkali metal carbonate--alcohol
system can be considered as a phase-transfer reaction
system for the generation of alkoxide ions.
z........ L i i
In the heterophase system described, diethyl phos-
phite shotdd be transformed into the diethyl phosphite 0" 0.4 0.8 1.2 1.6
anion, the reaction form active with respect to electro- [K2CO31(%)
philic reagents. F o r this purpose, various electrophiles Fig. 1. Dependence of the concentration of EtOK in the
were added to the diethyl phosphite--K2CO3--ethanol K2CO3--EtOH system on the amount o f K2CO 3 at 20 ~
system: alkyl halides, alkenes with electron-withdrawing
substiments at the donble bond, and aromatic aldehydes. [EtOK1/mmol L-I
It iaas been established that the interaction occurs in
accordance with the classical schemes of the Mieh-
aelis--Becker (a), Pudovik (b), and Abramov (c) reac-
tions (Scheme 2).

Scheme 2

0
II Q
(EtO)2P-CH--CH--R3

.3 9 i i i L
4~8
0 20 40 60 80
b TRIcH=CR2R 3 [KHCO3](%)
0 0
K2CO~/EtOH R4-Cu -H u Fig. 2. Dependence of the concentration of EtOK on the
(EtO)2P(O)H H+ (EtO)2PO- c ~ (EtO)2P-- CH--R4 content of KHCO 3 in the solid phase of the KHCO3--K?CO 3 -
I .

a ~RX OH
EtOH system at 20 ~
9--14
0
11 products, most likely, esters of carbonic acid, which is
(EtO)2P--R confirmed by the absorption band a t 1740 cm -I h~ the
1--3 IR spectra of the nonpurified products.
The structures of the known c o m p o u n d s 1, 3 - - 9 are
RX = CH2=CH---CH2Br (1), PhCH2Cl (2), CICH2COOEt (3); confirmed by the coincidence of t h e physicochemical
R ~ = Ph, R 2 = R 3 = CN (4); R 1 = R2 = CN, !:t3 = COOEt (7); constants with the published data lz,~7; the reaction prod-
R I = Pr i, R2 = R 3 = COOEr (5); R 1 = R3 = COOEr, R2 = H (6); ucts were characterized by 3ip N M R and IR spectros-
R 1 = R 2 = H, R 3 = ON (8);
copy. In addition, phosphonates 4 and 9 were synthe-
R4 = Ph (9); 4-FCaH 4 ( 1 0 ) ; 4-MeOC6H 4 (11);
sized by traditional procedures using EtONa. C o m -
3,4-(MeO)2C6H 3 (12); 4-01C6H 4 (13); 4-SrC6H 4 (14)
pounds obtained by different m e t h o d s were identical,
The reactions along directions b and c occur most which was confirmed by the absence of depression of
readily and in high yields (Table 1). The reaction along melting temperatures of the specimens alter mixing and
route (a) requires higher temperatures and a greater identical IR spectra.
amount o f K2CO 3. U n d e r these conditions, the reac- The use of the K2CO3--ethanol system has several
tions with allyl bromide and benzyl chlorides are ac- synthetic advantages over the generation of alkoxide
companied by the formation of minor quantities of by- from an alkali metal and alcohol: m i l d e r reaction condi-
Reactions ofelectrophilies with (EtO)2PHO--K2CO3--EtOH Russ.Chem.Bull., Vol. 48, No. 2, Febma~, 1999 369

Table 1. Reaction conditions and yields of reaction products in ture (see Table I) in a flask equipped with a reflux condenser
the reactions of electrophiles with (EtO)2PHO in the K~CO 3 - and a CaCI 2 tube. The reaction course was monitored by G LC
EtOH system and TLC.
The reaction mixture was fltered through a glass filter, and
the precipitate was washed with an appropriate solvent. Then
Corn- K~CO3--(EtO)~PHO T t/h Yield the filtrate was neutralized with acetic acid, the solvents were
pound - /g tool -l~ /~ ('%) removed, and the residue was separated from potassium ac-
1 5.0 60 2 92 etate. The products were purified by distillation in vacuo or by
2 5.0 78 2 8* recrystaltization. The yields of the reaction products are pre-
3 5.0 78 2 33 sented in Table I.
4 0.5 25 1 80 Diethyl allylphosphonate (1), b.p. 98--99 ~ (12 Tort).
5 0.5 25 2 77 3tp NMR, ~5: 26.1. IR, v/era-l: 3070 ( H - - C = ) ; 1650 (C=C);
6 0.5 28 1 90 1245 (P=O).
7 0.5 25 1 84 Diethyl (ethoxyear~nylmethyl)pbosphonate (3), b.p. I01 ~
8 0.5 40 2 66 (0.4 Torr). 31p NMR, 5: 19.4. IR, v/era-l: 1715 (C=O); 1260
9 0.5 25 l 80 (P=O). The IR spectrum of 3 is identical with that of diethyl
10 0.5 20 1 82 (ethoxycarbonylmethyl)phosphonate cited in Ref. 12.
11 0.5 20 1 71 Diethyl (l-phenyl-2,2-dieyanoethyl)phosphonate (4), b.p.
12 0.5 40 1.5' 82 170--172 ~ (0.4 Torr). 31p NMR, 5: 18.6. IR, v / c m - t : 2200
13 0.5 20 1 66 (CN); 1240 (P=O).
14 0.5 20 1 73 Diethyl (2-methyl- 1-diethoxyea~onylmethyl)propylphospho-
nate (5), b.p. 150--152 ~ (1 Tort). 3tp NMR, 8: 27.9. IR,
* Determined from the GLC data. v/era-l: 1710 (C=O); 1240 (P=O).
Diethyl (l,2-diethoxyeartmnylethyl)phosphonate (6), b.p.
140--144 ~ (1 Ton). 31p NMR, ~5: 20.6. tR, v/era-l: 1740
tions, low c o n c e n t r a t i o n s of strong bases in the reaction (C=O); 1260 (P=O).
m e d i u m , simplicity o f performing syntheses, high yields Diethyl (2-eyano-2-ethoxyearbonyl- l-phenylethyl)phos-
o f products o f the addition of diethyl phosphite to phonate (7), b.p. 165--168 ~ (0.4 Tort). 3tp N M R , ~5: 22.1.
IR, v/cm-l: 2200 (CN); 1750 (C=O); 1250 (P=O).
electrophilic multiple bonds, and a possibility to exclude
Diethyl 2-cyanoethyiphosphonate (8), b.p. 121--123 ~
phase-transfer catalysts. (1 Tort). 31p NMR, 8: 26.9. IR, v/era-t: 2230 (CN); 1235
Thus, the heterophase diethyl p h o s p h i t e - - K ~ C O 3 - (P=O).
ethanol system is efficient for the preparation of diethyl Diethyl c~-hydroxybenzylphosphonate (9), m.p. 83--84 ~
p h o s p h o n a t e s with different structures. (from CC14). 31p NMR, ~5: 20.5. IR, v/era-I: 3250 (OH); 1240
(P=O).
Diethyl ct-hydroxy-4-fluorobenzylphosphonate (10), m.p.
Experimental 49--54 ~ (from benzene--heptane). 3tp N M R , 8: 21.2. IR,
v/cm-~: 3250 (OH); 1250 (P=O). Found (%): C, 49.86;
IR spectra were recorded on an IKS-29 instrument (in H, 6.64; P, 11.76. CILHI6FO4P. Calculated (%): C, 50.39;
Nujol or thin films). 31p NMR spectra were recorded on an H, I6.15; P, 11.81.
RYa-2306 spectrometer (16.2 MHz) with 85"% H3PO ~ as the Diethyl ct-hydroxy-4-methoxylmnzylphosphonate (11), m.p.
external standard. The reaction course was monitored by TLC 123--125 ~ (from CC14). Found (%): C, 52.20; H, 6.53;
(Silufol UV-254, C1-|2C12, visualization by 1"% KMnO 4) and P, ll.47. CI~HI9OsP. Calculated (%): C, 52.55; H, 6.98;
GLC on a Chrom 4 chromatograph (a column 2500• P, 11.29. 31p-NMR, 8: 2t.4. IR, v/era-l: 3250 (OH); 1250
with 5% OV-225 on Chromaton N-Super (0.16--0.20 rain), a (P=O).
katharometer, helium as the carrier gas with a rate flow of 30 Diethyl a-hydroxy-3,4-dimethoxybenzylphosphonate (12),
mL min - t ) at 120 ~ The degree of conversion of diethyl m.p. 95--97 ~ (from benzene--heptane). Found (,%):
phosphonate was determined by the absolute calibration method. C, 51.56; H, 7.45; P, 9.79. CI3H~IO6P. Calculated (%):
The distribution of components in the K2CO3--EtOH C, 51.31; H, 6.96 P, 10.18. 3tp NM'R, ~: 21.2. IR, v/era-l:
heterophase system was determined by titrimetry. A weighed 3240 (OH); 1260 (P=O).
sample of anhydrous potassium carbonate (d _< 160 mesh) was Diethyl ~-hydroxy-4-ehlorobenzytphosphonate (13), m.p.
stirred with anhydrous ethanol (10 mL) at 20+0.2 ~ for 30 63--66 ~ (from benzene--heptane). Found (%): C, 46.77; H,
rain. In the study of the influence of potassium bicarbonate on 5.86; P, 10.57. CItHt6CIO4P. Calculated (%): C, 47.41; H.
the distribution of components in the K2CO3--EtOH system, 5.79; P, I1.11. 31p NMR, 5: 20.4. IR, v / c m - t : 3230 (OH)i
the weight of the solid sample was calculated from the condi- 1230 (P=O).
tion that the overall amount of carbonates was equal to 20 Diethyl ct-hydroxy-4-bromobenzylphosphonate (14), m.p.
mmol. The suspension obtained was filtered through a POR-16 62--72 ~ (from heptane--CCt4). Found (%): C, 40.54; H,
glass filter. The filtrate was weighed, and the alcohol removed. 5.47; P, 8.90. CttH16BrO4P. Calculated (%): C 40.89; H,
The residue was diluted with water and titrated with 0.1 N HCI 4.99; P, 9.59.31p NMR, 5: 20.1. IR, v/cm-l: 3250 (OH); 1260
using acid-base indicators. (P=O).
Reaction of diethyl phosphite with electrophiles (general
procedure). A mixture of diethyl phosphite (30.t5 retool), a References
substrate (30.15 retool) (alkyl halide, aldehyde, or activated
alkene), and anhydrous K2CO 3 (36.18 mmol for reaction (a)
or 3.6 mmol for reactions (b) and (c)) in I0 mL of anhydrous 1. E. N. Tsvetkov, M. I. Tcrekhova, E. S. Petrov, R. A.
ethanol was stirred vigorously at the corresponding tempera- Malevannaya, S. P. Mesets, A. 1. Shatenshtein, and M. I.
370 Russ. Chem.Bull., Vol. 48, No 2, February, 1999 Platonov et aL

Kabachnik, lzv. Akad. Naulr SSSR, Set. Khim., 1978, 1981 E. D. Maiorova, Zh. Org. Khim., 1994, 30, 947 [Russ.
[Bu//. Acad. Sci. USSR, Div. Chem. SeL, 1978, 27, 1743 J. Org. Chem., 1994, 30 (Engt. Transl.)].
(Engl. Transl.)]. 11. M. M. Yagupol'skii, Aromaticheskie i geterotsiklicheskie
2. J. P. Guthrie, Con. J. Chem., I979, 57, 236. soedineniya s ftorsoderzhashchimi zamestitelyami [Aromatic
3. P. R. Hammond, J. Chem. Soc., 1962, I365. and Heterocyclic Compounds with Fluorine-Containing Sab-
4. A. N. Pudovik, 1. V. Gur'yanova, and E. A. Ishmaeva, stituents], Naukova Dumka, Kiev, 1986 (in Russian).
Reaktsii i metody issledovaniya organicheskikh soedinenii [2. R. R. Shagidullin, F. S. Mukhametov, R. B. Nigmatullina,
]Reactions and Methods of the Study of Organic Com- V. S. Vinogradova, and A. V. Chernova, Atlas IK-spektrov
pounds], 1968, 19 (in Russian). fosforovganieheskikh soedinenii [Atlas of IR Spectra of Orga-
5. M. I. Kabachnik and T. A. Mastryukova, Phase-Transfer nophosphorus Compounds], Nauka, Moscow, 1977 (in Rus-
Catalysis in Organophosphon~s Chemistry, Chemistry Re- sian).
views, Ed. M. Vol'pin, 1966, 21, part 3. 13. B. A. Arbuzov and V. S. Vinogradova, Izv. Akad. Nauk
6. M. Fedorynski, K. Wojciechowski, and M. Makosza, SSSR, Ser. Khim., 1957, 54 [Bull. Aead. Sci. USSR, Div.
J. Org. Chem., 1978, 4682. Chem. Sci., 1957, 6 (Engl. Transl.)].
7. M. Makosza and K. Wojciechowski, Bull. PoL Acad. Sci., 14. B. A. Arbuzov and A. I. Razumov, Izv. Akad. Nauk SSSR,
1984, 32, 175. Ser. ](him., 1951, 714 (in Russian).
8. K. A. Petrov, L. 1. Sivova, 1. V. Smirnov, and L. Yu. 15. A. N. Pudovik, Izv. Akad. Nauk SSSR, Ser Khim., 1952,
Kryukova, Zh. Obshch. Khim., 1992, 62, 327 [J. Gen. 926 (in Russian).
Chem. USSR, 1992, 62 (Engl. Transl.)].. 16. A. N. Pudovik and B. A. Arbuzov, Zh. Obshch. Khim.,
9. N. A. Bondarenko, M. V. Rudomino, and E. N. Tsvetkov, 1951, 21, 1837 [J. Gen. Chem. USSR, 1951, 21 (Engl.
Izv. Akad. Nauk SSSR, Ser. Khim., 1990, 1196 [Bull. Aead. Transl.)].
Sci. USSR, Div. Chem. Sci., 1990, 39, 1077 (Engl. Transl.)]. 17. V. S. Abramov, Zh. Obshch. [(him., 1952, 22, 647 [J. Gen.
10 A. A. Sivakov, V. N Chistokletov, A. Yu. Platonov, and Chem. USSR, 1952, 22 (Engl. Transl.)].

Received March 24, 1998;

in revised form July 16, 1998