An unexpected reaction of diethyl phosphite with electron-deficient dialkyl dicyanofumarates

Article abstract of DOI:10.1080/10426507.2015.1085045

Diethyl phosphite reacts with both dimethyl dicyanofumarate and dicyanomaleate in boiling 1,2-dichloroethane to yield, after chromatographic workup, a 1:1-mixture of the corresponding meso- and dl-dicyanosuccinates. The analogous transformation was observed in the cases of diethyl and diisopropyl dicyanofumarates. A reaction pathway via initial formation of a P-C bond followed by its hydrolytic cleavage is proposed.

Full text of DOI:10.1080/10426507.2015.1085045

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
An unexpected reaction of diethyl phosphite with
electron-deficient dialkyl dicyanofumarates
Grzegorz Mlostoń, Małgorzata Celeda & Heinz Heimgartner
To cite this article: Grzegorz Mlostoń, Małgorzata Celeda & Heinz Heimgartner
(
2015): An unexpected reaction of diethyl phosphite with electron-deficient dialkyl
dicyanofumarates, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
0.1080/10426507.2015.1085045
1
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Date: 14 January 2016, At: 05:39

PHOSPHORUS, SULFUR, AND SILICON
016, VOL. 191, NO. 2, 1–4
2
http://dx.doi.org/10.1080/10426507.2015.1085045
An unexpected reaction of diethyl phosphite with electron-deficient dialkyl
dicyanofumarates
a
a
b
Grzegorz Mlosto nꢀ , Ma»gorzata Celeda , and Heinz Heimgartner
a
b
Department of Organic and Applied Chemistry, University of º ꢀo d ꢀz , Tamka 12, PL 91-403 º ꢀo d ꢀz , Poland; Department of Chemistry, University of Zurich,
Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
ABSTRACT
ARTICLE HISTORY
Diethyl phosphite reacts with both dimethyl dicyanofumarate and dicyanomaleate in boiling 1,2-
dichloroethane to yield, after chromatographic workup, a 1:1-mixture of the corresponding meso- and dl-
dicyanosuccinates. The analogous transformation was observed in the cases of diethyl and diisopropyl
dicyanofumarates. A reaction pathway via initial formation of a P–C bond followed by its hydrolytic
cleavage is proposed.
Received 28 May 2015
Accepted 6 August 2015
KEYWORDS
Addition reactions; reaction
mechanisms; electron
deficient alkenes; dialkyl
phosphites; Michael addition
GRAPHICAL ABSTRACT
Introduction
terminal olefins in the presence of Mn(III) occurs via radical
intermediates. Interestingly, treatment of gem-dibromoalkenes
9
The electron-deficient dialkyl dicyanofumarates (E)-1 and
dicyanomaleates (Z)-1 are well known as a pair of isomeric ole-
fins, which can be used as prone dienophiles, dipolarophiles,
with diethylphosphite and triethylamine affords a mixture of
10
(E/Z)-monobromoalkenes.
1
2
The aim of the present study was to examine the reactiv-
3
and Michael acceptors. In the latter case, the reactions with N-
nucleophiles such as primary and secondary amines occur via
an addition/elimination mechanism leading to enamines of
ity of diethyl phosphite with dialkyl dicyanofumarates (E)-1
as activated alkenes and the potential use of this reaction
for the synthesis of hitherto unknown, polyfunctionalized
alkylphosphonates.
3
b
type 2 (Scheme 1). On the other hand, similar reactions with
strained 1-aza[1.1.0]bicyclobutanes 3 led to 1-azabicyclo[2.1.1]
3
a
hexanes 4. In the case of 3-amino-5-aryl-1H-pyrazoles 5, two
competitive additions onto (E)-1 via the nucleophilic C(4) and
4
NH , respectively, leading to 6 and 7 were observed. Reactions
2
of (E)-1 with b-amino alcohols were shown to occur via initial
N-nucleophilic attack, followed by cyclization, to give morpho-
5
lin-2-one derivatives 8 as final products. In addition, reactions
5
of (E)-1 with other N-nucleophiles such as hydrazine hydrate
and carbohydrazides were also studied.
6
Dialkyl and diarylphosphites constitute an important class of
P-nucleophiles. For example, the nucleophilic additions to the
7
CHN group of Schiff bases (Kabachnik-Fields reaction) is
widely applied for the synthesis of a-aminoalkylphosphonates.
Their reactions with activated and non-activated olefins are also
known. Whereas the addition onto nitroalkenes follows the typi-
8
cal Michael addition course, the hydro-phosphorylation of
Scheme 1
CONTACT Grzegorz Mlostoꢀn
gmloston@uni.lodz.pl
Department of Organic and Applied Chemistry, University of º ꢀo d ꢀz , Tamka 12, 91-403 º ꢀo d ꢀz , Poland
G. M. thanks the Rector of the University of º ꢀo d ꢀz for financial support (Basic Research Support). All authors thank Dr. K. Urbaniak for her help in preparation of the final
version of the manuscript.
©
2016 Taylor & Francis Group, LLC

ꢀ
G. MLOSTON ET AL.
2
Results and discussion
respectively, yielded, after chromatographic purification, 1:1-
The reaction of diethyl phosphite with dimethyl dicyanofuma- mixtures of the corresponding meso- and dl-succinates 9b and
rate ((E)-1a) in boiling 1,2-dichloroethane was complete after 9c, respectively, in good yields.
1
7
h and the H NMR spectrum of the crude mixture, prelim-
In order to check the scope of this unexpected hydrogena-
inarily purified by filtration through a short silica gel layer, tion of electron-deficient ethylenes of type 1, additional experi-
showed the presence of two singlets of equal intensity at 4.27 ments with fumarodinitrile, dimethyl fumarate, as well as
and 4.21 ppm as well as two equally intense singlets at 3.93 and tetracyanoethylene and diethyl phosphite were performed
3
1
.92 ppm. The integration of these signals revealed a ratio of under the same conditions. In the first two cases, starting mate-
:3 corresponding to two CH and two MeO groups. Unexpect- rials were recovered, whereas in the third case decomposition
edly, the spectrum did not show signals, which could be attrib- was observed.
uted to EtO groups expected for the 1:1 adduct. On the other
The conversion of (E)-1b into the corresponding succinates
hand, the P NMR spectrum of the crude mixture showed two 9b was reported previously to occur upon hydrogenation over
3
1
1
2
signals located at 7.4 and ¡13.2 ppm. Whereas the first signal PtO in ethanol. On the other hand, a mixture of isomers 9a
2
is typical for diethyl phosphite, the second one may be corre- was obtained by treatment of (E)-1a with dimethoxycarbene
1
11
lated with diethyl phosphate. In the H NMR spectrum of the and subsequent hydrolytic cleavage.
crude mixture, measured without preliminary filtration
The mechanistic explanation of the reaction shown in
through silica layer, two signals at 4.27 and 4.21 ppm were Scheme 3 is based on the assumption that the nucleophilic
accompanied by another two singlets of a major product attack of the diethyl phosphite via the P-atom
located at 4.60 and 4.58 ppm, respectively.
zwitterionic intermediate A, which may exist in equilibrium
7
a,13a
leads to the
After chromatographic workup, a non-separable 1:1 mixture with the oxaphosphol derivative B (Scheme 3). The intramolec-
1
of two products was obtained as colorless oil. The H NMR ular proton transfer in A affords intermediate C, which reacts
spectrum displayed the same signals of CH and MeO groups with water yielding adduct D, which undergoes a dissociation
observed in the reaction mixture (after filtration through SiO ). to give the succinates 9 and diethyl phosphate.
2
1
3
In addition, the C NMR data evidenced two sets of signals
located at 36.88/36.96, 54.76/54.82, 112.22/112.40, and 162.75/ dimethyl dicyanosuccinate (9a) was confirmed via additional
62.87 ppm. Based on these data and by comparison with test experiments in which the reaction of (E)-1a with diethyl
The role of water and silica gel in the final formation of
1
11
reported data, the products were identified as meso- and dl- phosphite was performed in dry (experiment A) and wet
dimethyl succinates 9a (Scheme 2). The optimized yield of the (experiment B) 1,2-dichloroethane. The experiment in wet 1,2-
products was 55%.
dichloroethane was also performed in the presence of a sus-
The analogous reaction of diethyl phosphite with dimethyl pended small portion of silica gel (experiment C). Thus, in the
1
dicyanomaleate ((Z)-1a) gave the same mixture of products in
H NMR spectrum of the crude mixture of experiments B and
comparable yield. Similarly, the experiments performed with C, the isomers of 9 were formed as sole products. The presence
diethyl and diisopropyl dicyanofumarates ((E)-1b and (E)-1c), of diethyl phosphate formed as the second product of the
Scheme 2
Scheme 3

PHOSPHORUS, SULFUR, AND SILICON
3
hydrolytic cleavage of C was evidenced by the presence of two for 9b, and 8:2 for 9c) as the eluent. Product 9c was addi-
signals registered at d 1.34 (t, J
D 7 Hz, CH ), and 4.10–4.15 tionally crystallized from hexane containing a small amount
H,H
3
1
3b
(
m, CH ), respectively. On the other hand, in experiment A, of dichloromethane.
2
the isomers of 9 were formed side by side with an unstable
intermediate product with two, mentioned above, characteristic
singlets located at 4.60 and 4.58 ppm, respectively. Very likely,
they corresponded to a mixture of the water sensitive dl- and
Dimethyl 2,3-Dicyanobutanedioate (ca. 1:1 Mixture of
meso-9a and dl-9a)
1
1
1
meso-isomers of the intermediate compound C, i.e. the initially Colorless thick oil; yield: 55 % (108 mg). H NMR (CDCl ): d D
3
formed Michael adduct (Scheme 3).
3.92 (s, 6H, CH ); 3.93 (s, 6H, CH ); 4.21 (s, 2H, CH); 4.27 (s,
3 3
1
3
2
(
1
H, CH). C NMR (CDCl ): d D 36.8 (CH ), 36.9 (CH ); 54.7
3
3
3
CHCN), 54.8 (CHCN); 112.2 (CN), 112.4 (CN), 162.7 (CHO),
Conclusions
62.9 (CHO). IR (film): 3020m, 2963vs, 2919vs, 2259s (n ),
CꢀN
The presented study showed that the electron-deficient 1770vs (n
dicyanofumarates and dicyanomaleates react with diethyl 1098s, 1009s, 985s, 932m, 874m, 840m, 798m, 776m.
phosphite in the absence of any catalyst in boiling 1,2-
), 1743vs (n
), 1653m, 1440vs, 1270vs, 1184s,
CHO
CHO
dichloroethane to give after chromatographic work-up the
corresponding succinates as a 1:1 mixture of diastereoisom-
ers. The control experiments with other electron-deficient
Diethy l 2,3-Dicyanobutanedioate (ca. 1:1 Mixture of
meso-9b and dl-9b)
1
6
1
ethylenes demonstrated that both CN and CO R groups are
2
Colorless thick oil; yield: 72 % (161 mg). H NMR (CDCl ): d D
3
required for a successful reaction. To the best of our knowl-
edge, this is first case of a hydrogenation of an ethylene
derivative upon treatment with a dialkyl phosphite and sub-
sequent hydrolytic cleavage of the in situ formed Michael
adduct. The importance of the presence of both electron-
withdrawing groups is reflected by the smooth bond cleavage
in the proposed intermediate D.
1
.38 (t, J
D 7.1 Hz, 6H, CH ); 1.39 (t, J
D 7.1 Hz, 6H,
H,H
3
H,H
CH ); 4.23 (s, 2H, CH), 4.28 (s, 2H, CH); 4.36¡4.41 (m, 8H,
3
1
3
CH ). C NMR (CDCl ): d D 13.7 (CH ); 13.8 (CH ); 37.1
2
3
3
3
(CHCN); 37.2 (CHCN); 64.4 (CH CH ); 64.5 (CH CH ); 112.4
2 3 2 3
(
CN); 112.6 (CN); 162.2 (CHO), 162.4 (CHO). IR (film): 2988s,
2
1
8
916s, 2259m (n
), 1750vs (n
), 1647m, 1471m, 1447m,
CHO
CꢀN
371s, 1301s, 1258s, 1224s, 1097s, 1098s, 1019s, 931m, 854s,
40m, 786m.
Experimental
Diisopropyl 2,3-Dicyanobutanedioate (ca. 1:1 Mixture of
meso-9c and dl-9c)
Melting points were determined in a capillary using a Melt-
Temp. II (Aldrich) apparatus and are uncorrected. The IR spec-
ꢁ
tra were recorded on a NEXUS FT-IR spectrophotometer as Colorless crystals, yield: 66 % (166 mg), mp: 54–56 C (hexane/
¡1
1
13
31
1
film or KBr pellets; absorptions in cm . The H, C, and
P
CH Cl ). H NMR (CDCl ): d D 1.37 (dd, J
D 6.3, 1.7 Hz,
2
2
3
H,H
NMR spectra were measured on a Bruker Avance III instru- 12H, CH ); 1.38 (dd, J
D 6.3, 0.5 Hz, 12H, CH ); 4.17 (s, 2H,
3
H,H
3
1
3
ment (600, 150, and 243 MHz, resp.) using solvent signals as CHCN); 4.22 (s, 2H, CHCN); 5.14–5.21 (m, 4H, CH ).
C
i-Pr
reference. Chemical shifts (d) are given in ppm and coupling NMR (CDCl ): d D 21.3 (CH ); 21.4 (CH ); 37.3 (CHCN); 37.4
3
3
3
constants J in Hz. All crude mixtures were separated by prepar- (CHCN); 73.1 (CH ); 73.2 (CH ); 112.6 (CN); 112.8 (CN);
i-Pr
i-Pr
ative TLC.
161.7 (CHO); 161.9 (CHO). IR (KBr): 2987m, 291ms, 2935m,
2
1
263w (n
), 1743vs (n
), 1467m, 1377m, 1321m, 1296s,
CHO
CꢀN
283s, 1258s, 1227s, 1202m, 1102s, 9352m, 838m, 825m. EI-
Starting materials
C
C
MS: 251 [100, (M–1) ], 252 [14, (M) ]. Anal. calcd. for
Dialkyl dicyanofumarates 1a¡c were obtained from the cor- C H N O (252.27): C 57.13, H 6.39, N 11.10; found: C 57.15,
1
2
16
2
4
1
4
responding alkyl cyanoacetates by reaction with SOCl .
H 6.15, N 11.10 %.
2
The SOCl used for this reaction was freshly purified by dis-
2
1
5
tillation over quinoline and linseed oil. Diethyl phosphite
and 1,2-dichloroethane were used as commercially available
materials.
Reaction of Diethyl Phosphite with Dimethyl
Dicyanofumarate—Test Experiments
A solution of dimethyl dicyanofumarate (1a) (97 mg,
0
.5 mmol) and diethyl phosphite (104 mg, 0.75 mmol) in: (A)
Reactions of Diethyl Phosphite with Dialkyl
Dicyanofumarates
dry 1,2-dichloroethane (1 mL); (B) “wet” 1,2-dichloroethane,
or (C) “wet” 1,2-dichloroethane with a small portion (ca.
A solution of the corresponding dialkyl dicyanofumarates 100 mg) of silica gel, was placed in a 5 mL flask and heated in
ꢁ
1
a¡c (1 mmol) and diethyl phosphite (1.5 mmol) in 1,2- an oil bath at 85 C for 6 h. After this time, the solvent was
dichloroethane (2 mL) was heated to reflux. The progress of evaporated and the residues were obtained as viscous oils. In
the reaction was monitored by H NMR spectroscopy and in the case of experiment C, the solution was firstly filtered
1
all cases complete conversion of 1 was evidenced after 6 h. through silica gel and the separated silica gel was washed with a
After this time, the solvent was evaporated. The obtained portion of dichloromethane (10 mL) containing a few drops of
mixtures were purified by preparative TLC (SiO ), using a methanol. The obtained crude mixtures were dissolved in
2
1
mixture of petroleum ether and ethyl acetate (7:3 for 9a, 6:4 CDCl and immediately analyzed by H NMR spectroscopy.
3

ꢀ
G. MLOSTON ET AL.
4
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