Unusual behavior of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one towards some phosphorus reagents: Synthesis of novel diethyl 2-phosphonochromone, diethyl 3-phosphonopyrone and 1,3,2-oxathiaphosphinines

Article abstract of DOI:10.1080/00397911.2018.1560874

The chemical reactivity of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) towards some phosphorus reagents was studied. The enaminone 1 was cyclized into diethyl 2-phosphonochromone 2 via its treatment with diethyl phosphite in basic medium. However, its reaction with triethoxy phosphonoacetate gave the substituted pyrone phosphonate 3. In addition, two novel examples of 4-(dimethylamino)-6-(2-hydroxyphenyl)-2-sulfido-4H-1,3,2-oxathia-phosphinines 6 and 7 were obtained from treatment of enaminone 1 with O,O-diethyl dithiophosphoric acid and Lawesson’s reagent. When enaminone 1 was also treated with phosphorus decasulfide, it was turned into 4H-thiochromene-4-thione while its treatment with phosphorus tribromide, phosphorus oxychloride, or phenylphosphonic dichloride, 4H-4-oxo-chromene was isolated in all cases. The possible reaction mechanisms of the formation of these products were discussed. The structures of newly isolated products were established by elemental analysis and spectral tools.

Full text of DOI:10.1080/00397911.2018.1560874

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Unusual behavior of 3-(dimethylamino)-1-(2-
hydroxyphenyl)prop-2-en-1-one towards some
phosphorus reagents: Synthesis of novel diethyl 2-
phosphonochromone, diethyl 3-phosphonopyrone
and 1,3,2-oxathiaphosphinines
Tarik E. Ali, Mohammed A. Assiri, Ibrahim S. Yahia & Heba Y. Zahran
To cite this article: Tarik E. Ali, Mohammed A. Assiri, Ibrahim S. Yahia & Heba Y. Zahran
(2019): Unusual behavior of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one towards
some phosphorus reagents: Synthesis of novel diethyl 2-phosphonochromone, diethyl
3
1
-phosphonopyrone and 1,3,2-oxathiaphosphinines, Synthetic Communications, DOI:
0.1080/00397911.2018.1560874
To link to this article: https://doi.org/10.1080/00397911.2018.1560874
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SYNTHETIC COMMUNICATIONS
https://doi.org/10.1080/00397911.2018.1560874
Unusual behavior of 3-(dimethylamino)-1-(2-
hydroxyphenyl)prop-2-en-1-one towards some phosphorus
reagents: Synthesis of novel diethyl 2-phosphonochromone,
diethyl 3-phosphonopyrone and 1,3,2-oxathiaphosphinines
a,b
a,c
c,d,e
c,d,e
Tarik E. Ali , Mohammed A. Assiri , Ibrahim S. Yahia , and Heba Y. Zahran
a
b
Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia; Department of
c
Chemistry, Faculty of Education, Ain Shams University, Cairo, Egypt; Research Center for Advanced
Materials Science, King Khalid University, Abha, Saudi Arabia; Advanced Functional Materials and
d
Optoelectronic Laboratory, Department of Physics, Faculty of Science, King Khalid University, Abha,
e
Saudi Arabia; Nanoscience Laboratory for Environmental and Bio-medical Applications, Semiconductor
Lab., Department of Physics, Faculty of Education, Ain Shams University, Cairo, Egypt
ABSTRACT
ARTICLE HISTORY
The chemical reactivity of 3-(dimethylamino)-1-(2-hydroxyphenyl)-
prop-2-en-1-one (1) towards some phosphorus reagents was studied.
The enaminone 1 was cyclized into diethyl 2-phosphonochromone 2
via its treatment with diethyl phosphite in basic medium. However,
its reaction with triethoxy phosphonoacetate gave the substituted
pyrone phosphonate 3. In addition, two novel examples of 4-(dime-
thylamino)-6-(2-hydroxyphenyl)-2-sulfido-4H-1,3,2-oxathia-phosphi-
nines 6 and 7 were obtained from treatment of enaminone 1 with
O,O-diethyl dithiophosphoric acid and Lawesson’s reagent. When
enaminone 1 was also treated with phosphorus decasulfide, it was
turned into 4H-thiochromene-4-thione while its treatment with phos-
phorus tribromide, phosphorus oxychloride, or phenylphosphonic
dichloride, 4H-4-oxo-chromene was isolated in all cases. The possible
reaction mechanisms of the formation of these products were dis-
cussed. The structures of newly isolated products were established
by elemental analysis and spectral tools.
Received 17 October 2018
KEYWORDS
Chromone; enaminone;
1
,3,2-oxathiaphosphinines;
phosphonate; thiochromone
GRAPHICAL ABSTRACT
O
EtO
O
O
O
P
O
OEt
OEt
P
O
O
Me
EtO
OH
S
N
OMe
Phosphorus reagents
Me
S
OEt
S
OH
P
P
O
O
S
Me
Me
N
N
H
H
Me
Me
OH
OH
CONTACT Tarik E. Ali
tarik_elsayed1975@yahoo.com, tismail@kku.edu.sa
Department of Chemistry, Faculty of
Science, King Khalid University, Abha, Saudi Arabia.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
T. E. ALI ET AL.
Introduction
Organophosphorus compounds are an important class of chemical substances with a
[
1–4]
variety of applications in biology, agriculture, and chemistry.
Phosphorus-containing
heterocycles have been known since the late 19th century. However, a rapid develop-
ment of studies, related to a variety of functionalized phosphorus heterocycles, especially
[
5–7]
structures having P–O, P–N, and P–S bonds,
began only in the middle of the last
century, when the importance of phosphorus-containing substances in biological proc-
[
8–10]
esses was fully recognized.
are usually more reactive and more toxic than the phosphate derivatives.
biological properties, which reflect many different aspects of their chemical structure.
In addition, the phosphonate and thio-analog derivatives
[
11]
They have
[
12]
Some recently discovered naturally-occurring phosphonates and thiophosphonates are
described, together with some synthetic analogs. These synthetic analogs were utilized
[
13]
as tools for probing enzymic reaction
and inhibition of HIV virus by antisense oligo-
[
14]
nucleotides in patients suffering from AIDS.
On the other hand, enaminones are
chemical compounds consisting of an amino group linked through a C=C to a carbonyl
group. They are versatile synthetic intermediates that combine the ambident nucleophi-
[
15]
licity of enamines with the ambident electrophilicity of enones.
chemical reactivities of the enaminones facilitated their reactions with a variety
of electrophilic and nucleophilic reagents forming series of the variable
The different
a
[
16,17]
heterocycles.
In this investigation, because of the importance of phosphonate and thio-analog
derivatives, we studied the reactions of (2E)-3-(dimethylamino)-1-(2-hydroxyphenyl)-
prop-2-en-1-one (1) towards some variable phosphorus reagents aiming to synthesize
novel phosphonate or thiophosphonate containing heterocycles, which may be expected
to be biologically active.
Results and discussion
[
18]
The chemical reactivity of the enaminone 1
towards diethyl phosphite and triethoxy
phosphonoacetate as two examples of phosphorus esters was investigated. When com-
pound 1 was allowed to react with diethyl phosphite in toluene containing a few drops
of DBU as a basic catalyst, the reaction took place under the thermal condition and
gave the novel diethyl (4-oxo-4H-chromen-2-yl)phosphonate (2) in low yield 30%
3
1
[19]
(
Scheme 1). The P-NMR spectrum of product 2 had a singlet at d 21.2 ppm.
Its
1
H-NMR spectrum exhibited a quartet at d 4.18 (4 H, J = 7.2 Hz) and a triplet at d 1.14
6H, J = 7.2 Hz) assigned to the diethoxyphosphoryl group linked to the chromone
(
ring. Moreover, the H–3 proton linked to the pyran ring appeared as a singlet at d 6.51
ppm. The IR spectrum of 2 exhibited strong absorption bands at 1650 (C=Opyrone),
ꢀ
1
1
615 (C=C), 1228 (P=O), and 1026 (P–O–C) cm . The chromonyl phosphonate 2
probably originated in a concerted nucleophilic addition of the diethyl phosphite to the
enaminone via phospha-Michael addition reaction and removal of dimethylamine moi-
ety to give the non-isolable intermediate A. The latter intermediate spontaneously
underwent an intramolecular cycloaddition, followed by hydrogen elimination easily by
air (Scheme 1).

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SYNTHETIC COMMUNICATIONS
3
O
P
H
O
EtO
OEt
O
OEt
O
Me
N
P
Toluene
DBU
Me
OEt
OH
OH
-
HNMe2
A
1
O
O
-
H2
0%
H
OEt
OEt
3
O
P
O
P
O
O
EtO
EtO
2
B
Scheme 1. Reaction of the enaminone 1 with diethyl phosphite.
OEt OEt
O
EtO
O
O
P
O
O
Me EtO
P
H
N
OEt
Me
Dioxane
DBU
OH
OH
O
OEt
1
- HNMe2
C
1
,5-shift proton
EtO
EtO
O
O
P
OH
OH
O
O
OEt
-
EtOH
5%
P
OEt
5
O
OEt
OH
3
D
Scheme 2. Reaction of the enaminone 1 with triethoxy phosphonoacetate.
In the same manner, the enaminone 1 reacted with triethoxy phosphonoacetate in
toluene under the basic condition. On the basis of spectral data, the structure of the iso-
lated product was identified as diethyl [6-(2-hydroxyphenyl)-2-oxo-2H-pyran-3-
yl]phosphonate (3) in moderate yield (Scheme 2). Compound 3 showed the absorption
31
bands at 1679 (C=Opyrone), 1252 (P=O), and 1036 (P–O–C). Furthermore, the P-NMR
spectrum of compound 3 recorded a singlet at d 22.8 ppm due to a phosphonate group.
1
In its H-NMR, the diethoxy moiety was displayed at d 1.06 and 1.37 (t, J = 7.2 Hz,
6
H, CH ) and 3.76–3.82, 4.13–4.19 (m, 4H, CH ) ppm, while the H–5 proton of pyrone
3
2
ring was exhibited as a doublet at d 6.66 ppm, with coupling constant 5.6 Hz.
1
3
Moreover, the C-NMR spectrum of 3 showed among others a doublet (JPC = 174 Hz)
at d 119.6 ppm due to the C–P, whereas the C=Opyrone appeared at d 167.7 ppm.

4
T. E. ALI ET AL.
O
S
Me
N
P S
Me
4
10
N
Me
OH
Me
SH
1
E
S
S
S
-
HNMe2
8%
Me
8
S
N
H
Me
4
F
Scheme 3. Reaction of the enaminone 1 with P4S10 in toluene.
Compound 3 was properly formed through an initial attack of the carbanion C–atom of
P-reagent on the b-carbon atom of allylic system of enaminone 1 in tandem loss of
dimethylamine moiety forming the intermediate C. This intermediate underwent 1,5-
proton shift, followed by further elimination of the ethyl alcohol molecule via an intra-
[
20]
molecular cyclization (Scheme 2).
Next, we studied the behavior of the enaminone 1 towards some phosphorus sul-
fides. The interaction of phosphorus decasulfide with compound 1 in dry toluene
resulted in the formation of red crystals of the known 4H-thiochromene-4-thione (4)
[
21–23]
in high yield 88% yield (Scheme 3).
The reaction mechanism that outlined in
Scheme 3 showed that compound 4 was formed through the thionation of carbonyl
and hydroxyl groups, followed by an intramolecular cyclization and removal of
dimethylamine molecule.
In addition, the interesting novel 1,3,2-oxathiaphosphinine derivative 6 was smoothly
obtained in 62% yield from the reaction of enaminone 1 with O,O-diethyl dithiophos-
phoric acid (formed in situ) in absolute ethanol under thermal condition (Scheme 4).
Obviously, the initial nucleophile attacks the thiol group of phosphorus reagent on
b-carbon atom of the allylic system, forming the intermediate G without the elimination
[
24]
of dimethylamine molecule as an unusual behavior.
This latter intermediate under-
went 1,3-proton shift, followed by elimination of ethanol molecule through the attack of
enolic OH at the phosphonate moiety (Scheme 4). The structure of 1,3,2-oxathiaphos-
1
phinine 6 was supported by elemental analysis and spectral tools. The H-NMR spec-
trum of 6 showed the OH proton at d 10.10 ppm and two types of the methyl protons
at d 1.14 (3H, t, EtO) and 2.91, 2.94 (6H, s, NMe ). In addition, the two protons of
2
1
,3,2-oxathiaphosphinine ring appeared as two doublets at d 6.02 and 6.68 ppm with
13
coupling constant 7.2 Hz that indicated to their presence in cis-form. Besides, its C-
NMR spectrum displayed the characteristic carbon atoms of NMe (43.2 and 44.2) and
2
EtO (12.8 and 60.9) ppm, whereas the carbon atoms of 1,3,2-oxathiaphosphinine
appeared at d 68.3 (C–4), 93.6 (C–5), and 153.0 (C–6) ppm.

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5
OEt
OEt
S
S
P
O
P
O
S
OEt
O
S
OEt
Me
Me (EtO) P(S)SH
- HNMe2
2
N
H
N
EtOH
Me
H
H
OH
Me
OH
OH
G
1
5
1
,3-shift proton
OEt
S
OEt
S
S
P
P
O
OH
OH
S
OEt
Me
-
EtOH
62%
Me
N
N
H
H
Me
Me
OH
6
H
Scheme 4. Reaction of the enaminone 1 with P4S10 in absolute ethanol.
OMe
P
S
+ S
O
O
Me
LR
+
N
Me
N
Me
Toluene
H
OH
Me
OH
1
I
OMe
57%
S
OMe
LR = 2
P
O
S
P
Me
S
+ S
N
H
Me
OH
7
Scheme 5. Reaction of the enaminone 1 with LR in toluene.
Interestingly, the reaction of enaminone 1 with Lawesson’s reagent (LR) in dry tolu-
ene, did not give the product 4 but it afforded 4-(dimethylamino)-6-(2-hydroxy-
phenyl)2-(4-methoxyphenyl)-2-sulfido-4H-1,3,2-oxathiaphosphinine (7) advantageously
in 57% yield (Scheme 5). Compound 7 was regarded to be formed via one-step [4 þ 2]
1
cycloaddition mechanism as shown in Scheme 5. The H-NMR spectrum of 7 showed
that the protons of methyl groups at d 2.94, 3.00 (NMe ), and 3.89 (OMe) ppm.
2

6
T. E. ALI ET AL.
O
O
O
O
O
Me
- HNMe2
N
i-iii
Me
Me
OH
N
H
8
Me
1
J
i, PBr , Toluene, Et N
3
3
ii, POCl , Toluene, Et N
3
3
iii, PhP(O)Cl , Toluene , Et N
2
3
Scheme 6. Reaction of the enaminone 1 with phosphorus halides in toluene.
The presence of a methoxy group in 7 was also attested by a signal at d 54.9 ppm in its
1
3
C-NMR spectrum, whereas the dimethylamino group appeared at d 43.4 and 44.2
31
ppm. The product 7 also showed a signal at d 51.6 ppm in its P-NMR spectrum.
As an extension of this study, the behavior of enaminone 1 towards some phosphorus
halides was also investigated. Thus, the reaction of enaminone 1 with phosphorus tri-
bromide, phosphorus oxychloride, or phenylphosphonic dichloride in dry toluene con-
taining triethylamine did not give any phosphorylated product (Scheme 6). Instead the
[
18]
simple 4H-chromone (8) was formed in all cases.
The formation of compound 8
might be due to the preference of enaminone 2 to cyclize than to react with the phos-
phorus reagent that facilitated the cyclization process (Scheme 6).
Conclusion
In summary, we studied the interaction of 3-(dimethylamino)-1-(2-hydroxyphenyl)-
prop-2-en-1-one (1) with some examples of phosphorus esters and sulfides. These reac-
tions afforded novel phosphorus compounds such as chromonyl and pyranyl
phosphonates as well as 1,3,2-oxathiaphosphinine derivatives. However, 4H-chromone
and full thia analog were isolated when enaminone was treated with phosphorus halides
and phosphorus decasulfide, respectively.
Experimental
The melting points were determined in an open capillary tube on a digital Stuart SMP-
3
apparatus. Infrared spectra were measured on Perkin–Elmer 293 spectrophotometer
1
13
using KBr disks. H- and C-NMR spectra were measured on Gemini-300BB spectrom-
eter (400 and 100 MHz), using DMSO-d as a solvent and TMS (d) as an internal
6
3
1
standard. P-NMR spectra were measured on a Bruker (162 MHz) spectrophotometer
using DMSO-d as a solvent, TMS as an internal standard and 85% H PO as an exter-
6
3
4
nal reference. Mass spectra were recorded on direct probe controller inlet part to single
quadropole mass analyzer in (thermo scientific GCMS). Elemental microanalysis was
performed on Perkin–Elmer 2400II at the Chemical War department, Ministry of
Defense. The purity of the synthesized compounds was checked by thin layer chroma-
tography (TLC) and elemental microanalysis. 3-(Dimethylamino)-1-(2-hydroxyphenyl)-
prop-2-en-1-one (1) was prepared according to the reported method rported in the
[
18]
literature.

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7
Synthesis of diethyl (4-oxo-4H-chromen-2-yl)phosphonate (2)
A mixture of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) (0.95 g, 5
mmol) and diethyl phosphite (0.7 mL, 5 mmol) in dry toluene (30 mL) containing a
few drops of DBU as a catalyst, was heated under reflux for 10 hours. The solvent was
concentrated into one-third of the volume. After adding petroleum ether (15 ml), the
formed solid was filtered off, washed with ether and crystallized from diluted methanol
ꢁ
ꢀ1
to give pale yellow solid in 30% yield; mp 98 ꢀ 100 C. IR (KBr), (v max, cm ): 3055
CꢀH ), 2950 (CꢀH ), 1650 (C=O), 1615 (C=C), 1228 (P=O), 1026 (PꢀOꢀC).
(
arom
aliph
1
H-NMR (400 MHz, DMSO-d ): 1.14 (t, 6H, J = 7.2 Hz, CH ), 4.18 (q, 4H, J = 7.2 Hz,
6
3
OCH ), 6.51 (s, 1H, Hꢀ3), 7.19 (t, 1H, J = 8 Hz, Hꢀ6), 7.47 (t, 1H, J=7.6 Hz, Hꢀ8),
2
13
7
.59 (t, 1H, J=7.6 Hz, Hꢀ7), 7.89 (d, 1H, J=8.0 Hz, Hꢀ5). C-NMR (100 MHz,
DMSO-d ): 16.4 (CH ), 63.5 (OCH ), 114.0 (Cꢀ3), 118.9 (Cꢀ8), 123.8 (Cꢀ6), 125.2
6
3
2
(
(
Cꢀ4a), 129.6 (Cꢀ5), 134.8 (Cꢀ7), 156.9 (d, J=152 Hz, C ꢀ 2), 159.0 (Cꢀ8a), 177.5
31 þ
Cꢀ4). P-NMR (162 MHz, DMSO-d ): 21.8 ppm. MS (m/z, I%): 282 (M , 10%).
6
Anal. Calcd for C H O P (282.24): C, 55.32%; H, 5.36%. Found: C, 55.01%; H, 5.03%.
1
3
15 5
Funding
The authors express their appreciation to “The Research Center for Advanced Materials Science
RCAMS)” at King Khalid University for funding this work under [grant number RCAMS/KKU/
03-18].
(
0
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