α-thiocyanatocarbonyl compounds. 2*. Condensation of phosphorylated α-phenyl-α-thiocyanatoacetaldehyde with phosphorus nucleophilic reagents

Article abstract of DOI:10.1007/s10593-009-0190-1

We are the first to report a study of the reaction of phosphorylated α-phenyl-α-thiocyanatoacetaldehyde with triphenylphosphine, dimethylphenylphosphine, and diethylphosphorous acid, which yields bisphosphorylated 4,5-thioazolidines.

Full text of DOI:10.1007/s10593-009-0190-1

Chemistry of Heterocyclic Compounds, Vol. 44, No. 11, 2008
α-THIOCYANATOCARBONYL COMPOUNDS.
2.* CONDENSATION OF PHOSPHORYLATED
α-PHENYL-α-THIOCYANATOACETALDEHYDE
WITH PHOSPHORUS NUCLEOPHILIC REAGENTS
Kh. A. Asadov1, G. G. Mikailov2, S. N. Guseinova2, R. N. Burangulova1,
R. J. Valiullina1, A. M. Magerramov2, and F. I. Guseinov1
We are the first to report a study of the reaction of phosphorylated α-phenyl-α-thiocyanatoacetaldehyde
with triphenylphosphine, dimethylphenylphosphine, and diethylphosphorous acid, which yields
bisphosphorylated 4,5-thioazolidines.
Keywords: dimethylphenylphosphine, diethylphosphorous acid, thiazolidine 4,5-bisphosphonate,
triphenylphosphine, phosphorylated α-thiocyanatoaldehydes.
The properties of alkyl and aryl thiocyanates have been studied rather extensively in light of the
insecticidal activity of some of these compounds [2]. The synthetic methods for various thiocyanate derivatives
are based, as a rule, on the reaction of the corresponding halides, sulfates, or sulfonates with ammonium or alkali
metal thiocyanates [3-5]. Phosphorylated α-thiocyanatoaldehydes, whose synthesis was reported in our previous
work [1], have considerable synthetic possibilities. These compounds are reagents for the preparation of a broad
range of linear and cyclic N-, P-, and S-containing derivatives, which may also contain other heteroatoms. As a
result of these synthetic uses and other practical applications, α-thiocyanatoacetaldehydes have attracted
considerable interest.
The direction of the reactions of organic thiocyanates with P(III) derivatives is largely a function of the
nature of the phosphorus reagent. The reaction may take place either heterolytically or homolytically.
Thiocyanates may enter both substitution reactions (due to the pseudohalide properties of the cyano group) and
addition or cycloaddition (due to the presence of a polarized triple bond) [6].
The adducts formed as the result of the addition of phosphines to nonconjugated carbonyl compounds
are unstable due to the lack of possibility of delocalization of the negative charge. Thus, such addition reactions,
which theoretically might proceed either at the oxygen atom or carbon atom of the carbonyl group, are
reversible and the equilibrium is strongly shifted toward the starting compounds. However, the formation of
stable compounds is possible when there is a subsequent reaction of the intermediate betaine with a second
molecule of the carbonyl compound or some conjugated group.
_______
* For Communication 1, see [1].
__________________________________________________________________________________________
2
1Kazan State Technological University, Kazan 420015, Russia; e-mail: esedoglu@mail.ru. Baku State
University, Baku AZ-1148, Azerbaijan; e-mail: mikail05@mail.ru. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 11, pp. 1707-1711, November, 2008. Original article submitted November
6, 2007.
0009-3122/08/4411-1391©2008 Springer Science+Business Media, Inc.
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We have found that the reaction of thiocyanatoacetaldehyde 1 with triphenylphosphine proceeds over
18-25 h at reflux in an inert solvent such as benzene or toluene to give intermediates 2 and 3. Subsequent
cyclization of compound 3 occurs with the participation of the strongly polarized C≡N bond of the SCN group.
The use of xylene as the solvent leads to tar formation.
A combined physicochemical and spectral study has shown that heterocyclization occurs in this reaction
with the formation of a heterocyclic product 4.
O
O
(EtO)2P
Ph
(EtO)2P
Ph3P
SCN
CHO
SCN
+
HC PPh3
+
Ph
–
1
O
2
O
O
O
(EtO)2P
(EtO)2P
Ph
PPh3
NH
SCN
PPh3
(EtO)2P
SCN
Ph
_
S
+
PPh3
HO
C
Ph
3
O
4
OH
The IR spectrum of heterocycle 4 has a broad absorption band at 1177-1203 cm-1, which is assigned to
C=P bond stretching vibrations. The stretching band at 2120-2160 cm-1 characteristic for the SCN group and the
OH group band at 3100-3500 cm-1 are lacking. The IR spectrum also has a C=O group band at 1722 cm-1 and a
secondary amino group band at 2910 cm-1. The 1H NMR spectrum in acetone-d6 has signals for the CH3 group at
1.00 ppm and for the OCH2 group at 4.00 ppm as well as a multiplet at 7.30-7.80 ppm (Ph, 3JPH = 10 Hz) and a
broad singlet at 11.00 ppm for the NH proton with integral intensities 6:4:20:1.
All these data and the finding two resonance signals in the range 23.7 and 27.1 ppm in the 31P NMR
spectrum of the heterocycle 4 indicate that this reaction proceeds to give heterocyclic structure 4.
The reaction of 1 with dimethylphenylphosphine proceeds analogously to give dimethylphenyl
derivative 5.
The ease of the reaction of aldehyde 1 with triphenylphosphine led us to study the behavior of its
diacetal relative to Ph3P. These studies showed that weakly nucleophilic triphenylphosphine is inert toward this
acetal even upon prolonged heating at reflux.
An attempt to use BF3 etherate in order to obtain S-(triphenyl)quasiphosphonium tetrafluoroborate also
was unsuccessful even though the possible coordination of boron trifluoride at the –S–C≡N group might have
been expected to polarize this moiety and permit attack of triphenylphosphine at the sulfur atom, i.e., BF3 might
have been expected to facilitate the electrophilic activation of the nucleophilic substitution. This failure is
apparently due to steric factors of the sulfur atom itself and the three bulky substituents at the central carbon
atom.
There is no information in literature on the reactions of thiocyanatocarbonyl compounds with
diethylphosphorous acid. Hence, we tried to carry out the reaction of thiocyanate 1 with esters of trivalent
phosphorus acids since alkyl thiocyanates are known to undergo the Arbuzov reaction with alkyl phosphites to
give thiol phosphates [5, 7].
The reaction of aldehyde 1 with diethylphosphorous acid in the presence of sodium ethylate as catalyst
gives O,O-diethyl(2-oxo-5-phenyl-4H-1,3-thiazolidine-4,5) bisphosphonate (7) in high yield ( 70%).
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Addition of diethylphosphorous acid at the carbonyl group of compound 1 probably occurs in the first
step, yielding intermediate adduct 6, which undergoes intramolecular cyclization to form a thiazolidine ring 7.
1
The composition and structure of 7 were supported by elemental analysis and IR, H, and 31P NMR
spectroscopy.
Ph
C
Ph
P(O)(OEt)2
P(O)(OEt)2
OH
(EtO)2P(O)
(EtO)2P(O)
EtONa
1 + (EtO)2PHO
S
NH
7
O
6
N
1
The H NMR spectrum of heterocycle 7, in addition to characteristic signals of the ethoxyl and phenyl
3
fragments, has signals for the methine proton as a doublet of doublets at 5.20 ppm with JPH = 12.5 Hz and
31
3JPH = 20 Hz and a broad signal for the NH proton at 9.8 ppm. The P NMR spectrum has phosphorus nuclear
signals at 16.18 (br. s) and 23.52 ppm (d).
The IR spectrum of compound 7 has stretching bands for the following functional groups: 1017 (P–O–P),
1097 (P–O–P), 1261 (P=O), 1745 (C=O), 2962 cm-1 (NH). The reason for the shift of the P=O band (from
1280-1290 to 1261 cm-1) and the NH band (from 3200-3300 to 2962 cm-1) is attributed presumably to formation of a
hydrogen bond between the P=O and NH groups due to the orientation of the phosphoryl group relative to the plane
of the heterocycle.
The reaction schemes given above show that the reactions of phosphorylated thiocyanatoacet aldehyde 1
with phosphorus nucleophilic reagents, leading to heterocyclic products, have a common feature, namely, addition
of the nucleophile at the carbonyl group and subsequent intramolecular heterocyclization involving the SCN group.
Thus, this first study of phosphorylated α-phenyl-α-thiocyanatoacetaldehyde with triphenylphosphine,
dimethylphenylphosphine, and diethylphosphorous acid has yielded a promising approach for the preparation of
new bisphosphorylated heterocycles with an unusual combination of substituents. These products hold promise
as new types of ligands in the synthesis of organophosphorus metal complexes.
EXPERIMENTAL
1
The IR spectra were taken in vaseline mull or KBr pellets on a UR-20 spectrometer. The H NMR
spectra were taken on a Tesla BS-567 spectrometer at 200 MHz with HMDS as the standard. The 31P NMR
spectra were taken on a Bruker MSL-400 spectrometer at 162 MHz in 85% H3PO4 as the standard.
O,O-Diethyl 2-Oxo-5-phenyl-4-triphenylphosphinothiazolidine-5-phosphonate (4). A mixture of
aldehyde 1 (3.13 g, 0.01 mol) and triphenylphosphine (2.62 g, 0.01 mol) was heated at reflux in toluene for
18 h. The solvent was removed in vacuum and the crystalline precipitate of heterocycle 4 was filtered off,
washed with ether, and dried to give 4.0 g (70%) compound 4, mp 157-158°C. IR spectrum, ν, cm-1: 1177-1203
1
(C=P), 1280 (P=O), 1722 (C=O), 2910 (NH). H NMR spectrum in acetone-d6, δ, ppm (J, Hz): 1.00 (6H, m,
2CH3); 4.00 (4H, m, 2OCH2); 7.30-7.80 (20H, m, 4C6H5); 11.00 (1H, br. s, NH). 31P NMR spectrum, δ, ppm:
23.7, 27.1. Found, %: N 2.48; P 10.69; S 5.63. C31H31NO4P2S. Calculated, %: N 2.43; P 10.78; S 5.57.
O,O-Diethyl 2-Oxo-4-dimethylphenylphosphino-5-phenylthiazolidine-5-phosphonate (5) was
obtained analogously to compound 4 in 72% yield, mp >330°C. IR spectrum, ν, cm-1: 1170-1195 (C=P), 1289
1
(P=O), 1710 (C=O), 2981 (NH). H NMR spectrum in C6D6, δ, ppm (J, Hz): 1.05 (6H, m, 2CH3); 1.4 (6H, d,
3JPH = 26, 2CH3); 4.00 (4H, m, 2OCH2); 7.3-7.5 (5H, m, C6H5); 8.2 (1H, br. s, NH). 31P NMR spectrum, δ, ppm:
23.42, 29.84. Found, %: N 3.14; P 13.81; S 7.15. C21H27NO4P2S. Calculated, %: N 3.1; P 13.75; S 7.1.
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O,O-Diethyl 2-Oxo-5-phenyl-4H-thiazolidine-4,5-bisphosphonate (7). A solution of diethyl
phosphite (1.38 g. 0.01 mol) in ether (10 ml) was added with stirring to a mixture of aldehyde 1 (3.13 g,
0.01 mol), EtONa (0.3 g, 0.01 mol), and absolute ether (30 ml) at room temperature. Stirring was continued for
2 h at room temperature and 1 h at reflux. Then, 10 ml water was added to the reaction mixture. The ethereal
layer was removed and the aqueous layer was extracted thrice with ether. The combined ethereal extracts were
dried over MgSO4. Removal of the solvent gave 3.16 g (70%) bisphosphonate 7 as an oil. IR spectrum, ν, cm-1:
1
1017 (P–O–C), 1097 (P–O–C), 1261 (P=O), 1745 (C=O), 2962 (NH). H NMR spectrum in acetone-d6, δ, ppm
3
3
(J, Hz): 1.00 (12H, m, 4CH3); 4.10 (8H, m, 4OCH2); 5.20 (1H, dd, JPH = 12.5, JPH = 20, CH); 7.10-7.50 (5H,
m, C6H5); 9.8 (1H, br. s, NH). 31P NMR spectrum, δ, ppm: 16.18, 23.52. Found, %: N 3.14; P 13.55; S 7.07.
C17H27NO7P2S. Calculated, %: N 3.10; P 13.75; S 7.10.
This work was carried out with the financial support of the Russian Basic Research Fund (Grant
No. 07-03-00316a) and the Russian Federation President's Grant MK-4043.2007.3.
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