1,3-Dipolar cycloaddition reactions of acyl phosphonates with nitrile oxides: synthesis of phosphonate-containing dioxazole derivatives

Article abstract of DOI:10.1080/10426507.2020.1854259

New phosphonate-containing five-membered heterocyclic dioxazole derivatives are synthesized via 1,3-dipolar cycloaddition reactions of nitrile oxides used as dipole with acyl phosphonates under basic conditions. Herein, acyl phosphonates take part in the

Full text of DOI:10.1080/10426507.2020.1854259

Phosphorus, Sulfur, and Silicon and the Related Elements
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1,3-Dipolar cycloaddition reactions of acyl
phosphonates with nitrile oxides: synthesis of
phosphonate-containing dioxazole derivatives
Sidika Polat-Cakir
To cite this article: Sidika Polat-Cakir (2020): 1,3-Dipolar cycloaddition reactions of acyl
phosphonates with nitrile oxides: synthesis of phosphonate-containing dioxazole derivatives,
Phosphorus, Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2020.1854259
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2020.1854259
1,3-Dipolar cycloaddition reactions of acyl phosphonates with nitrile oxides:
synthesis of phosphonate-containing dioxazole derivatives
Sidika Polat-Cakir
Department of Chemical Engineering, Canakkale Onsekiz Mart University, Canakkale, Turkey
ABSTRACT
ARTICLE HISTORY
Received 5 October 2020
Accepted 18 November 2020
New phosphonate-containing five-membered heterocyclic dioxazole derivatives are synthesized via
1,3-dipolar cycloaddition reactions of nitrile oxides used as dipole with acyl phosphonates under
basic conditions. Herein, acyl phosphonates take part in the cyclization process as a dipolarophile
to afford the related dioxazole compounds in moderate-to-good yields (49–84%). Substituted aryl
nitrile oxides and aroyl phosphonates were employed in the 1,3-dipolar cycloaddition reactions
where triethylamine was the effective tertiary base. Alkyl version of acyl phosphonate also
afforded the expected cycloadduct, that is, dimethyl 5-isopropyl-3-phenyl-1,4,2-dioxazol-5-yl-5-
phosphonate. Diethyl/dimethyl 3,5-aryl-1,4,2-dioxazol-5-yl-5-phosphonate derivatives are fully char-
acterized by using 1H NMR, 13C NMR, 31P-NMR, and FT along with high-resolution mass
spectroscopy.
KEYWORDS
1,3-Dipolar cycloaddition;
acyl phosphonate;
dioxazole; heterocyclic;
dipole and dipolarophile
GRAPHICAL ABSTRACT
Introduction
formed nitrile oxides react immediately with a variety of
dipolarophiles, because they are unstable and are very react-
ive intermediates.[9] Commercially available aldehydes are
the precursor of corresponding nitrile oxides. Oxazoles and
isoxazole structures are important structures in the field of
medicinal chemistry, because they exhibit a wide range of
biological activity.[10] Isoxazole-based drug called valdecoxib
is used in the market to treat osteoarthritis and rheumatoid
arthritis.[11]
The 1,3-DC reactions of nitrile oxides with alkenes as a
dipolarophile are well documented.[12] Vinylphosphonate as
dipolarophile was used in the 1,3-DC with nitrile oxides for
the synthesis of phosphonate-containing isoxazole deriva-
tives. This work was reported by Ye et al. where the phos-
phonyl isoxazolines were isolated in 47–69% yields.[13] In
the literature, there are many examples of 1,3-DC reactions
of nitrile oxides with alkenes for the synthesis of five-mem-
bered N-heterocycles, but the cyclization reactions with alde-
hydes as dipolarophiles are very limited. Huisgen et al. have
reported the 1,3-DC reaction between nitrile oxide and ben-
zaldehyde in the presence of a base where the corresponding
dioxazole product was formed with 55% yield.[14] Azam
1,3-Dipolar cycloaddition (DC) reactions between dipoles
and dipolarophiles are one of the fundamental reactions of
organic chemistry for the synthesis of five-membered het-
erocycles.[1,2] There are two types of 1,3-dipoles, that is, allyl
anion and propargyl–allenyl anion.[1,2] Allyl anions are clas-
sified as having N-atom- and O-atom-centered dipoles.
Some examples for the N-atom-centered allyl anions are
azomethine ylides, nitro compounds, and nitrones. Carbonyl
ylides and carbonyl imines are the examples for the O-
atom-centered allyl anions. Alkenes and alkynes are the
most common dipolarophiles used in the 1,3-DC reactions.
The N-atom-centered dipole such as nitrile oxide (R
̶
CꢀNþ
̶
O-), which is a propargyl–allenyl type dipole, has
been utilized in the 1,3-DC reactions to construct five-mem-
bered N-heterocyclic compounds. Isoxazolidines are easily
synthesized via 1,3-dipolar cycloaddition of nitrile oxides to
alkenes.[3] Cycloaddition of nitrile oxides with alkynes offers
a direct synthesis of isoxazoles. This type of dipole is easily
obtained from readily available starting materials such as
dehydrogenation of aldoximes[4] or dehydration of nitroal-
kanes.[5,6] A more practical way to form nitrile oxide is the
addition of a base to hydroximoyl chloride.[7,8] The in situ et al. have also reported the synthesis of new dioxazole
CONTACT Sidika Polat-Cakir
spcakir@comu.edu.tr
Department of Chemical Engineering, Canakkale Onsekiz Mart University, Canakkale 17100, Turkey.
Supplemental data for this article can be accessed here.
ß 2020 Taylor & Francis Group, LLC

2
S. POLAT-CAKIR
Table 1. Investigation of bases in 1,3-DC reactions of benzohydroximoyl chloride 2a and phenyl acyl phosphonate 1a.
Entry
Basea
NEt3
NEt3
NEt3
NEt3
NEt3
NaHCO3
NaHCO3
Na2CO3
DABCO
DBU
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
DCM
40
76
Toluene
CH3CN
MeOH
DMF
Toluene
DCM
CH3CN
CH3CN
CH3CN
38
NDc
23
NRd
NRd
67
9
10
NDc
50
aThe reactions were carried out with hydroximoyl chloride 2a (2.0 equiv.), benzoyl acyl phosphonate 1a (1 equiv.), and base (2.5 equiv.) at the specified tempera-
ture until the disappearance of benzoyl acyl phosphonate indicated by TLC.
bIsolated chemical yield.
cND: not determined decomposed.
dNR: no reaction.
derivatives while testing them for potential antiviral activ- compound 3a was carried out in different solvents such as
ity.[15] In the latter work, various aldehydes were simply DCM, toluene, and acetonitrile. In the case of triethylamine
reacted with oxime under basic conditions to synthesize in toluene, the 1,3-DC reaction between nitrile oxide 1a and
the dioxazoles.
phenyl substituted acyl phosphonate 2a proceeded smoothly
at room temperature and offered the expected compound 3a
in 76% yield within 5–6 h. We have found that triethylamine
was the most effective tertiary base for the cycloaddition
reactions of acyl phosphonate with nitrile oxides.
Acyl phosphonates are one of the useful members of the
organophosphorous compounds, and they could be used as
a reagent to access P-atom-containing organic structures.
Having a phosphonate group in the structure may enhance
the biological activity of a parent structure.[16] Acyl phos-
phonates are used in many reactions and even in hetero
Diels–Alder reactions to synthesize glycosyl-type phospho-
nates where they act as a dienophile and easily react with
electron-rich dienes.[17] Herein, acyl phosphonates are uti-
lized in the 1,3-dipolar cyclization reaction of nitrile oxide
under basic condition to synthesize phosphonate-containing
new dioxazole five-membered heterocyclic compounds. In
the 1,3-DC reactions, acyl phosphonates take part as a dipo-
larophile, which leads to the formation of the dioxazole
cycloadducts possessing a phosphonate group.
The structure of 3a was elucidated by spectral analyses of
both proton and carbon NMRs along with DEPT and
HSQC. In the proton NMR, the triplet was observed at
1.19 ppm corresponding to the protons -CH3 of the
phosphonate group. The protons of –OCH2 in the phospho-
nate group appeared as multiples integrating for four hydro-
gens in the range 4.24 ꢁ 4.00 ppm. These two signals clearly
indicated the existence of diethyl phosphonate group in the
structure. The aryl group signals in the dioxazole structure
3a were observed at 7.81 ꢁ 7.30 ppm range integrating for
ten hydrogens. The carbon NMR spectra revealed ten signals
for the phenyl groups where the four of them were assigned
as quaternary C-atom by using DEPT-135 NMR. The qua-
ternary carbon atom of –C ¼ N (C-3) was observed at
158.2 ppm. The quaternary C-atom corresponding to
–OCO– (C-5) resonated at 118 ppm with a large coupling
constant value (JC-P ¼ 199.1 Hz) due to the neighboring P-
atom.[17,19] This characteristic signal (C-5) has been
observed in all synthesized phosphonate-containing dioxa-
zole structures 3a–3o in the range 109.2 ꢁ 116.0 ppm
obtained from carbon NMR. In the carbon NMR of 3a, the
signals at 64.7 and 64.5 ppm were assigned as -OCH2 corre-
sponding to the diethyl phosphonate group (PO(O
Results and discussion
To optimize the 1,3-dipolar cycloaddition reaction, benzohy-
droximoyl chloride 1a precursor of nitrile oxide acting as
dipole, and benzoyl acyl phosphonate 2a acting as dipolaro-
phile were chosen as the model substrates. Dechlorination of
benzohydroximoyl chloride with a base led to the formation
of nitrile oxide in situ. Benzoyl acyl phosphonate 2a was
easily prepared according to a literature procedure reported
by Taylor et al.[18] Tertiary bases (i.e., NEt3, DBU, and
DABCO) and inorganic bases (i.e., Na2CO3 and NaHCO3)
in different solvent systems were tested as shown in Table 1. CH2CH3)2) while the methyl group of the diethyl phospho-
The dechlorination reaction of benzohydroximoyl chloride nate resonated at 16.2 ppm. 31P NMR clearly indicated the
1a to synthesize the phosphonate-containing dioxazole existence of phosphonate group in the corresponding

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Table 2. Substrate scope of 1,3-DC reactions of nitrile oxides 1 with acyl phosphonates 2.
Entry
R1
R2
R3
Dioxazolea
Yield (%)b
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
Ph
Ph
OEt
OMe
OEt
OEt
OEt
OEt
OMe
OMe
OMe
OEt
OEt
OEt
OEt
OEt
OEt
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
76
74
74
49
78
60
69
77
59
4-MeC6H4-
4-MeOC6H4-
4-ClC6H4-
4-FC6H4-
2-ClC6H4-
3-ClC6H4-
CH(CH3)2
Ph
9
10
11
12
13
14
15
4-Me
4-Br
4-Cl
4-NO2
4-MeO
61
84
70
Ph
Ph
Ph
Ph
66
58/60c
84
Ph
aReaction is monitored by TLC, and the reaction mixture subjected to purification until the disappearance of acyl phosphonates indicated by TLC.
c
bIsolated chemical yield. Both NEt3 (toluene) and Na2CO3 (acetonitrile) were used as a base.
dioxazole structure. In the cycloaddition reaction, benzoyl corresponding dioxazole cycloadduct 3i was obtained in
acyl phosphonate 2a took part as a dipolarophile where the
in situ formed planar nitrile oxide appeared as a dipole.
After determining the optimized reaction conditions, dif-
ferent aromatic hydroximoyl chlorides and acyl phospho-
nates were subsequently tested to examine the substrate
scopes of those [3 þ 2] 1,3-DC reactions. Both electron
donating (ED) and electron withdrawing substituents (EW)
for both dipole and dipolarophile were used. The required
hydroximoyl chlorides were easily prepared according to a
procedure given in the literature.[20,21] Acyl phosphonate
derivatives were prepared via Arbuzov reaction by simply
treating the parent chlorides with both triethyl and trimethyl
phosphites.[18] As shown in Table 2, all of the tested sub-
strates in 1,3-DC reactions gave the expected dioxazole
cycloadducts 3a–3p. Aroyl phosphonates having different
positions on the phenyl ring and electronic properties were
used in cycloaddition reactions (Table 2, entries 1–8). They
all offered the corresponding phosphonate-containing dioxa-
zole derivatives 3a-3j in moderate yields. Methyl ester of
benzoyl phosphonate 2b used in the 1,3-DC reaction
afforded the expected cycloadduct 3b in similar yield of 3a
(entry 2). The electronic properties of aroyl phosphonates
did not notably affect the chemical yields except dioxazole
3d (Table 2, entry 4). The aroyl phosphonate 2d having a
strong electron donating group (MeO) on the phenyl group
at the para position afforded the cycloadduct 3d albeit in
low yield. Electron withdrawing groups such as Cl and F on
the phenyl ring also afforded the phosphonate-containing
dioxazole compounds 3e–3h in good yields (Table 2, entries
5-8). The alkyl version of acyl phosphonate 2a was also uti-
59% yield (Table 2, entry 9). Different substituted aromatic
N-hydroximoyl chlorides with either ED (CH3, MeO, naph-
thyl) or EW (Br, Cl, NO2) substituent were used as sub-
strates. The corresponding 1,3-DC reactions proceeded
smoothly giving the expected products 3j–3o in good yields
(Table 2, entries 10-14). The reaction between the nitrile
oxide 1n having the strong ED group-MeO on the phenyl
ring and the aroyl phosphonate 2a proceeded well where the
corresponding dioxazole 3n was attained in moderate yield
(Table 2, entry 14, 58% by using NEt3 in toluene). When
Na2CO3 was used as a base in acetonitrile, the yield of
cycloadduct 3n was improved slightly to 60%. Electron-defi-
cient N-hydroximoyl chloride 1 m furnished the dioxazole
product 3 m in 66% yield (entry 13). In addition, 1-naphthyl
substituted N-hydroximoyl chloride 1o was also used as a
substrate and then the dioxazole cycloadduct 3o was
obtained in high yield (entry 15, 84%).
Conclusions
The nitriles oxides were generated in situ and were reacted
with acyl phosphonate derivatives via 1,3-dipolar cycloadd-
ition reactions. Acyl phosphonates served as a dipolarophile
in the cyclization reaction, and the nitrile oxides were used
as 1,3-dipole. Nitrile oxides having either electron donating
or withdrawing substituent in the 1,3-DC reaction were eas-
ily prepared by using the corresponding hydroximoyl chlor-
ides. The dehalogenation process was easily carried out by
using triethylamine as a base. Both reactants in the 1,3-DC
lized in the 1,3-DC reaction of nitrile oxide 1a and reaction could be synthesized from readily available starting

4
S. POLAT-CAKIR
materials. A variety of substituted nitrile oxides and acyl the synthesis of hydroximoyl chloride derivatives were all
phosphonates was employed to understand the effect of the readily available starting materials, and all of them were pur-
substituent at different positions and the reactivity of the chased from the suppliers. Both the derivatives of acyl phos-
phonates and hydroximoyl chlorides were easily synthesized
according to the literature procedures.[18,20,21] The
Supplemental Materials contain sample 1H, 13C, and 31P
NMR spectra of products 3 (Figures S1–S47).
cycloadditions. In all cases, the expected phosphonate-con-
taining dioxazole compounds 3a-3o were obtained in mod-
erate to good yields. Alkyl version of the acyl phosphonate
was also tested as a dipolarophile in the 1,3-DC reaction.
The related phosphonate-containing dioxazole compound 3i
was obtained in 59% isolated chemical yield.
Electron-rich and electron-poor N-hydroximoyl chlorides
were also examined in the 1,3-DC reaction of acyl phospho-
nate, which furnished the dioxazole cycloadducts 3j-3o in
good yields. The electronic features of the aromatic moieties
in the 1,3-dipole did not significantly affect the product
yield. For example, both electron-rich arylhydroximoyl
chloride with an electron-donating 4-CH3O- (entry 14) and
electron-poor arylhydroximoyl chloride with an electron-
withdrawing group 4-NO2- (entry 13) both gave similar
yields (entry 13 with 66% yield and entry 14 with 60%
yield). In the case of dipolarophile, the electron-rich aroyl
phosphonate gave the dioxazole compound 3d in low yield
(entry 4, 49% yield) while the unsubstituted aroyl phospho-
nate 3a was isolated in 76% yield (entry 1).
Herein, a practical method is described for the synthesis
of phosphonate-containing dioxazole compounds via 1,3-
dipolar cycloaddition of nitrile oxides to acyl phosphonates
by using readily available starting materials. This work has
also demonstrated that acyl phosphonates could serve as a
dipolarophile in the 1,3-DC reactions with a dipole-nitrile
oxide. To that end, the investigations for the biological
activity of the newly synthesized phosphonate-containing
dioxazoles are in progress.
General procedure for the synthesis of
phosphonate-containing dioxazole
derivatives 3a–3p
To a solution of hydroximoyl chloride (2.5 equiv.) in tolu-
ene (10 mL) at 0 ꢂC under a nitrogen atmosphere was added
triethylamine (2.5 equiv) dropwise to generate in situ-related
nitrile oxide. Then, the dipolarophile acyl phosphonate (1
equiv.) was added to this mixture under vigorous stirring.
The resulting mixture was continued to stir vigorously at
room temperature until the completion of reaction con-
trolled by TLC usually for 5–6 h. The crude mixture was fil-
trated, evaporated, and subjected to column chromatography
for purification by using hexane:EtOAc mixtures. The syn-
thesized phosphonate-containing dioxazole derivatives were
obtained as oil after the column chromatography.
Diethyl 3,5-diphenyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3a
Oily compound, Rf ¼ 0.42 (3:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.81 ꢁ 7.74 (m, 2H), 7.70 ꢁ 7.65 (m,
2H), 7.44 ꢁ 7.38 (m, 1H), 7.39 ꢁ 7.30 (m, 5H), 4.24 ꢁ 4.00
(m, 4H, PO(OCH2CH3)2), 1.19 (q, J ¼ 6.9 Hz, 6H,
PO(OCH2CH3)2). 13C NMR (CDCl3, 100 MHz): d 158.2 (d,
JC-P ¼ 5.4 Hz, C ¼ N), 134.8 (d, JC-P ¼ 19.4 Hz, C), 131.8
(CH), 129.8 (CH), 128.6 (CH), 128.2 (CH), 126.9 (CH),
Experimental
126.1 (d, JC-P ¼ 2.6 Hz, CH), 121.9 (C), 110.8 (d, JC-P
¼
The chemical shift values for proton and carbon NMR were
reported in parts per million (ppm) relative to residual solv-
ent signal of CDCl3 unless otherwise stated (7.26 ppm in
proton NMR and 77.0 ppm in carbon NMR). JEOL NMR-
500 MHz was used for 31P analyses (202 MHz), and the
chemical shift (d) is reported in ppm relative to diethyl
phosphite (%3) as external reference. Bruker AVANCE III
400 MHz NMR was used for proton and carbon NMR
(400 MHz for proton and 100 MHz for carbon, respectively).
HRMS analyses were performed by using Agilent 6224 High
Resolution Mass at METU-Central Laboratory. Bruker
Platinum ATR-IR instrument was used for IR spectra, and
the data were reported in cmꢁ1. Silica gel 230-400-mesh was
used for the column chromatography to purify cycloadducts.
Ethyl acetate/hexane mixture was used as eluting solvent in
column chromatography. All cycloaddition reactions were
performed under nitrogen atmosphere. The progress of
cycloaddition reactions was monitored by TLC using silica
gel plates with fluorescent indicator. Phosphomolybdic acid
in ethanol (PMA) solution was used as a dying solution to
visualize the spots. Toluene was distilled from Na/benzophe-
199.1 Hz, –OCO–), 64.7 (d, JC-P ¼ 7.7 Hz, PO(OCH2CH3)2),
64.5 (d, JC-P ¼ 6.9 Hz, PO(OCH2CH3)2), 16.2 (t, JC-P
¼
5.9 Hz, PO(OCH2CH3)2). 31P NMR (CDCl3, 202 MHz): d
9.25. IR (cmꢁ1): 2983, 1348, 1258, 1223, 1016, 969, 689.
HRMS-EI (m/z): calculated for C18H21NO5P [M þ H]:
362.1157 and found: 362.1158.
Dimethyl 3,5-diphenyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3 b
Oily compound, Rf ¼ 0.58 (1:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.87 (d, J ¼ 7.1 Hz, 2H), 7.80 ꢁ 7.73
(m, 2H), 7.55 ꢁ 7.49 (m, 1H), 7.48 ꢁ 7.42 (m, 5H), 3.84 (d,
J ¼ 9.2 Hz, 3H, PO(OCH3)2), 3.82 (d, J ¼ 9.2 Hz, 3H,
PO(OCH3)2). 13C NMR (CDCl3, 100 MHz): d 158.3 (d, JC-P
¼ 5.1 Hz, C ¼ N), 134.7 (d, JC-P ¼ 19.5 Hz), 132.0, 130.0,
128.7, 128.4, 127.0, 126.0, 121.8, 110.9 (d, JC-P ¼ 199.3 Hz,
–OCO–), 55.0 (d, JC-P ¼ 7.0 Hz, PO(OCH3)2), 54.8 (d, JC-P
¼ 7.1 Hz, PO(OCH3)2). 31P NMR (CDCl3, 202 MHz): d
11.55. IR (cmꢁ1): 2963, 1349, 1262, 1021, 962, 837, 752, 688.
none and was used freshly in 1,3-DC reactions. Acyl chlor- HRMS-EI (m/z): calculated for C16H16NNaO5P [M þ Na]:
ides, the precursor of acyl phosphonates, and aldehydes for 356.0664 and found: 356.0666.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Diethyl 3-phenyl-5-p-tolyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3c
Diethyl 5-(4-fluorophenyl)-3-phenyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3f
Oily compound, Rf ¼ 0.44 (3:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.90 ꢁ 7.83 (m, 2H), 7.77 (ddt, J ¼ 6.9,
5.3, 1.7 Hz, 2H), 7.58 ꢁ 7.49 (m, 1H), 7.51 ꢁ 7.40 (m, 2H),
7.13 (t, J ¼ 8.8 Hz, 2H), 4.34 ꢁ 4.11 (m, 4H, PO(O
CH2CH3)2), 1.32 (t, J ¼ 7.0 Hz, 3H, PO(OCH2CH3)2), 1.28
(t, J ¼ 7.0 Hz, 3H, PO(OCH2CH3)2). 13C NMR (CDCl3,
100 MHz): d 163.4 (dd, JC-F ¼ 249.4 Hz, JC-P ¼ 2.1 Hz, CF),
Oily compound, Rf ¼ 0.44 (3:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.78 (d, J ¼ 7.0 Hz, 2H), 7.57 (dd,
J ¼ 8.3, 1.7 Hz, 2H), 7.37 (d, J ¼ 7.7 Hz, 2H), 7.16 (d,
J ¼ 7.6 Hz, 3H), 4.19 ꢁ 4.01 (m, 4H, PO(OCH2CH3)2), 2.29
(s, 3H, CH3), 1.20 (td, J ¼ 7.0, 5.7 Hz, 6H,
PO(OCH2CH3)2). 13C NMR (CDCl3, 100 MHz): d 157.9 (d,
JC-P ¼ 5.2 Hz, C ¼ N), 139.6 (d, JC-P ¼ 2.2 Hz), 132.0 (d,
158.0 (d, JC-P ¼ 5.4 Hz, C ¼ N), 131.8, 130.7 (dd, JC-P
¼
JC-P ¼ 18.8 Hz), 131.5, 128.6, 128.4, 126.6, 125.8 (d, JC-P
¼
19.8 Hz and JC-F ¼ 3.1 Hz), 128.5, 128.2 (dd, JC-F ¼ 8.7 Hz
and JC-P ¼ 2.6 Hz), 126.4, 121.5, 115.1 (d, JC-F ¼ 21.9 Hz),
110.2 (d, JC-P ¼ 200.8 Hz, –OCO–), 64.6 (d, JC-P ¼ 7.4 Hz,
PO(OCH2CH3)2), 64.5 (d, JC-P ¼ 7.2 Hz, PO(OCH2CH3)2),
16.1 (t, JC-P ¼ 5.8 Hz, PO(OCH2CH3)2). 31P NMR (CDCl3,
202 MHz): d 8.98. IR (cmꢁ1): 2983, 1347, 1260, 1228, 1095,
1015, 971, 837, 688. HRMS-EI (m/z): calculated for
C18H20FNO5P [M þ H]: 380.1063 and found: 380.1061.
2.6 Hz), 121.7, 110.7 (d, JC-P ¼ 199.4 Hz, –OCO–), 64.3 (d,
JC-P ¼ 7.0 Hz, PO(OCH2CH3)2), 64.2 (d, JC-P ¼ 7.3 Hz,
PO(OCH2CH3)2), 20.8 (CH3), 16.0 (t, JC-P ¼ 5.9 Hz,
PO(OCH2CH3)2). 31P NMR (CDCl3, 202 MHz): d 9.39. IR
(cmꢁ1): 2983, 1348, 1258, 1098, 1015, 970, 818, 689.
HRMS-EI (m/z): calculated for C19H23NO5P [M þ H]:
376.1314 and found: 376.1315.
Dimethyl 5-(2-chlorophenyl)-3-phenyl-1,4,2-dioxazol-5-
yl-5-phosphonate 3 g
Dimethyl 5-(4-methoxyphenyl)-3-phenyl-1,4,2-dioxazol-
5-yl-5-phosphonate 3d
1
Oily compound, Rf ¼ 0.50 (3:1 hexane:EtOAc). H NMR (d-
1
Oily compound, Rf ¼ 0.50 ((1:1) hexane:EtOAc). H NMR
acetone, 400 MHz): d 7.80 ꢁ 7.71 (m, 3H), 7.54 ꢁ 7.29 (m,
6H), 3.74 (d, J ¼ 4.1 Hz, 3H, PO(OCH3)2), 3.72 (d,
J ¼ 4.2 Hz, 3H, PO(OCH3)2). 13C NMR (CDCl3, 100 MHz): d
(CDCl3, 400 MHz): d 7.87 (d, J ¼ 7.0 Hz, 2H), 7. 70 (dd,
J ¼ 8.9, 1.7 Hz, 2H), 7.52 (d, J ¼ 7.4 Hz, 1H)), 7.46 (t,
J ¼ 7.5 Hz, 2H), 6.97 (d, J ¼ 8.8 Hz, 2H), 3.85 (d,
J ¼ 10.5 Hz, 3H, PO(OCH3)2), 3.84 (d, J ¼ 10.2 Hz, 3H,
PO(OCH3)2), 3.83 (s, 3H, OCH3). 13C NMR (CDCl3,
100 MHz): d 160.7, 158.0 (d, JC-P ¼ 5.2 Hz, C ¼ N), 128.4,
127.31, 127.29, 126.7, 126.2 (d, J JC-P ¼ 19.8 Hz), 121.5,
113.5, 110.7 (d, JC-P ¼ 201.0 Hz, –OCO–), 54.9 (OCH3),
54.6 (d, JC-P ¼ 7.0 Hz, PO(OCH3)2), 54.5 (d, JC-P ¼ 7.1 Hz,
PO(OCH3)2). 31P NMR (CDCl3, 202 MHz): d 11.73. IR
(cmꢁ1): 2958, 1348, 1252, 1010, 837, 757, 689. HRMS-EI
(m/z): calculated for C17H18NNaO6P [M þ Na]: 386.0769
and found: 386.0769.
158.4 (d, JC-P ¼ 5.5 Hz, C ¼ N), 132.3, 132.1 (d, JC-P
¼
19.9 Hz), 131.8, 131.3, 131.0, 129.1, 128.5, 126.9, 126.4,
121.5, 110.9 (d, JC-P ¼ 202.1 Hz, –OCO–), 54.9 (d, JC-P
¼
7.2 Hz, PO(OCH3)2), 54.7 (d, JC-P ¼ 7.2 Hz, PO(OCH3)2).
31P NMR (CDCl3, 202 MHz): d 10.89. IR (cmꢁ1): 2962,
1348, 1265, 1067, 1022, 762, 685. HRMS-EI (m/z): calculated
for C16H16ClNO5P [M þ H]: 368.0455 and found: 368.0455.
Dimethyl 5-(3-chlorophenyl)-3-phenyl-1,4,2-dioxazol-5-
yl-5-phosphonate 3 h
1
Oily compound, Rf ¼ 0.50 (3:1 hexane:EtOAc). H NMR (d-
acetone, 400 MHz):
d
7.93 (dd, J ¼ 7.2, 1.6 Hz, 2H),
7.78 ꢁ 7.71 (m, 2H), 7.69 ꢁ 7.63 (m, 1H), 7.62 ꢁ 7.54 (m,
4H), 3.88 (d, J ¼ 6.5 Hz, 3H, PO(OCH3)2), 3.85 (d,
J ¼ 6.5 Hz, 3H, PO(OCH3)2). 13C NMR (CDCl3, 100 MHz): d
158.0 (d, JC-P ¼ 5.2 Hz, C ¼ N), 136.6 (d, JC-P ¼ 19.9 Hz),
Diethyl 5-(4-chlorophenyl)-3-phenyl-1,4,2-dioxazol-5-yl-
5-phosphonate 3e
Oily compound, Rf ¼ 0.50 (3:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.77 (d, J ¼ 7.0 Hz, 2H), 7.62 (dd,
J ¼ 8.6, 1.7 Hz, 2H), 7.47 ꢁ 7.36 (m, 3H), 7.33 (d, J ¼ 8.0 Hz,
2H), 4.22 ꢁ 4.04 (m, 4H, PO(OCH2CH3)2), 2.29 (s, 3H,
CH3), 1.22 (t, J ¼ 7.0 Hz, 3H, PO(OCH2CH3)2), 1.20 (t,
J ¼ 7.1 Hz, 3H, PO(OCH2CH3)2). 13C NMR (CDCl3,
100 MHz): d 158.1 (d, JC-P ¼ 5.4 Hz, C ¼ N), 135.9 (d, JC-P
¼ 2.4 Hz), 133.4 (d, JC-P ¼ 19.8 Hz), 131.9, 128.6, 128.4,
134.2, 131.9, 130.0, 129.6, 128.6, 126.8, 126.0 (d, JC-P
2.8 Hz), 124.2 (d, JC-P ¼ 2.2 Hz), 121.2, 109.9 (d, JC-P
¼
¼
199.9 Hz, –OCO–), 54.9 (d, JC-P ¼ 6.9 Hz, PO(OCH3)2), 54.7
(d, JC-P
¼
7.2 Hz, PO(OCH3)2). 31P NMR (CDCl3,
202 MHz): d 10.98. IR (cmꢁ1): 2958, 1346, 1267, 1026, 1022,
765, 686. HRMS-EI (m/z): calculated for C16H16ClNO5P
[M þ H]: 368.0455 and found: 368.0457.
127.6 (d, JC-P ¼ 2.6 Hz), 126.8, 121.5, 110.2 (d, JC-P
¼
200.0 Hz, –OCO–), 64.7 (d, JC-P ¼ 7.2 Hz, PO(OCH2CH3)2),
Dimethyl 5-isopropyl-3-phenyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3j
64.5 (d, JC-P ¼ 7.4 Hz, PO(OCH2CH3)2), 16.2 (t, JC-P
¼
5.7 Hz, PO(OCH2CH3)2). 31P NMR (CDCl3, 202 MHz): d
8.81. IR (cmꢁ1): 2983, 1347, 1262, 1090, 1014, 968, 824, 687.
HRMS-EI (m/z): calculated for C18H20ClNO5P [M þ H]:
396.0768 and found: 396.0768.
Oily compound, Rf ¼ 0.34 ((1:1) hexane:EtOAc). NMR
(CDCl3, 400 MHz): d 7.80 (d, J ¼ 7.1 Hz, 2H), 7.54–7.41 (m,
3H), 3.89 (d, J ¼ 10.3 Hz, 3H, PO(OCH3)2), 3.83 (d,

6
S. POLAT-CAKIR
J ¼ 10.4 Hz, 3H, PO(OCH3)2), 2.50 (pd, J ¼ 6.9 and 5.0 Hz, –OCO–), 64.7 (d, JC-P ¼ 7.8 Hz, PO(OCH2CH3)2), 64.6 (d,
1H, CH(CH3)2), 1.15 (dd, J ¼ 6.9 and 2.6 Hz, 6H, JC-P ¼ 7.3 Hz, PO(OCH2CH3)2), 16.3 (t, JC-P ¼ 5.8 Hz,
CH(CH3)2). 13C NMR (CDCl3, 100 MHz): d 158.3 (C ¼ N), PO(OCH2CH3)2), 16.2 (t, JC-P ¼ 6.0 Hz, PO(OCH2CH3)2).
131.5, 128.5, 126.5, 121.6, 116.0 (d, JC-P ¼ 190.8 Hz, 31P NMR (CDCl3, 202 MHz): d 9.10. IR (cmꢁ1): 2983, 1343,
–OCO–), 54.3 (d, JC-P ¼ 7.1 Hz, PO(OCH3)2), 53.8 (d, JC-P 1259, 1014, 968, 797, 696. HRMS-EI (m/z): calculated for
¼ 7.3 Hz, PO(OCH3)2), 33.0 (d, JC-P ¼ 22.7 Hz, CH(CH3)2), C18H20ClNO5P [M þ H]: 396.0768 and found: 396.0769.
15.2 (d, JC-P ¼ 4.2 Hz, CH(CH3)2). 31P NMR (CDCl3,
202 MHz): 13.12. d IR (cmꢁ1): 2958, 1352, 1263, 1024, 832,
762, 689. HRMS-EI (m/z): calculated for C13H19NO5P
[M þ H]: 300.1001 and found: 300.1001.
Diethyl 3-(4-nitrophenyl)-5-phenyl-1,4,2-dioxazol-5-yl-5-
phosphonate 3n
1
Oily compound, Rf ¼ 0.49 ((1:1) hexane:EtOAc). H NMR
(CDCl3, 400 MHz): d 8.31 (d, J ¼ 8.9 Hz, 2H), 8.05 (d,
Diethyl 5-phenyl-3-p-tolyl-1,4,2-dioxazol-5-yl-5-
J ¼ 8.9 Hz, 2H), 7.71 ꢁ 7.79 (m, 2H), 7.49 ꢁ 7.44 (m, 3H),
phosphonate 3k
4.32 ꢁ 4.07 (m, 4H, PO(OCH2CH3)2), 1.31 (t, J ¼ 7.1 Hz, 3H,
Oily compound, Rf ¼ 0.35 (2:1 hexane:EtOAc). 1H NMR PO(OCH2CH3)2), 1.27 (t, J ¼ 7.1 Hz, 3H, PO(OCH2CH3)2).
(CDCl3, 400 MHz): d 7.71 ꢁ 7.64 (m, 4H), 7.38 ꢁ 7.32 (m, 13C NMR (CDCl3, 100 MHz): d 157.0 (d, JC-P ¼ 4.9 Hz,
3H), 7.17 (d, J ¼ 8.0 Hz, 2H), 4.20 ꢁ 4.01 (m, 4H, C ¼ N), 149.5, 134.1 (d, JC-P ¼ 18.7 Hz), 130.2, 128.3, 127.9,
PO(OCH2CH3)2), 2.32 (s, 3H, CH3), 1.19 (q, J ¼ 6.8, 6H, 125.9 (d, JC-P ¼ 2.9 Hz), 123.9, 118.4, 112.0 (d, JC-P
¼
PO(OCH2CH3)2). 13C NMR (CDCl3, 100 MHz): d 158.3 (d, 199.5 Hz, –OCO–), 64.9 (d, JC-P ¼ 7.6 Hz, PO(OCH2CH3)2),
JC-P ¼ 5.3 Hz, C ¼ N), 142.4, 134.9 (d, JC-P ¼ 19.6 Hz), 64.8 (d, JC-P ¼ 6.6 Hz, PO(OCH2CH3)2), 16.2 (t, JC-P
¼
129.8, 129.3, 128.1, 126.9, 126.1 (d, JC-P ¼ 2.6 Hz), 119.0, 6.2 Hz, PO(OCH2CH3)2). 31P NMR (CDCl3, 202 MHz): d
110.6 (d, JC-P ¼ 198.2 Hz, –OCO–), 64.6 (d, JC-P ¼ 7.3 Hz, 8.70. IR (cmꢁ1): 2983, 1525, 1341, 1221, 1015, 974, 846, 712,
PO(OCH2CH3)2), 64.5 (d, JC-P ¼ 7.1 Hz, PO(OCH2CH3)2), 692. HRMS-EI (m/z): calculated for C18H20N2O7P [M þ H]:
21.4 (CH3), 16.20 (d, JC-P ¼ 7.4 Hz, PO(OCH2CH3)2), 16.19 407.1008 and found: 407.1008.
(d, JC-P ¼ 7.1 Hz, PO(OCH2CH3)2). 31P NMR (CDCl3,
202 MHz): d 9.32. IR (cmꢁ1): 2982, 1344, 1261, 1016, 967,
Diethyl 3-(4-methoxyphenyl)-5-phenyl-1,4,2-dioxazol-5-
yl-5-phosphonate 3o
744, 696. HRMS-EI (m/z): calculated for C19H23NO5P
[M þ H]: 376.1314 and found: 376.1319.
Oily compound, Rf ¼ 0.36 (1:1 hexane:EtOAc). 1H NMR
(CDCl3, 400 MHz): d 7.80 (d, J ¼ 8.9 Hz, 2H), 7.78 ꢁ 7.71
Diethyl 3-(4-bromophenyl)-5-phenyl-1,4,2-dioxazol-5-yl-
(M, 3H), 7.49 ꢁ 7.38 (m, 3H), 6.94 (d, J ¼ 8.9 Hz, 2H),
5-phosphonate 3 l
4.29 ꢁ 4.08 (m, 4H, PO(OCH2CH3)2), 3.85 (s, 3H, OCH3),
Oily compound, Rf ¼ 0.29 (3:1 hexane:EtOAc). 1H NMR 1.29 (t, J ¼ 7.3 Hz, 3H, PO(OCH2CH3)2), 1.25 (t, J ¼ 7.2 Hz,
(CDCl3, 400 MHz): d 7.78 ꢁ 7.73 (m, 4H), 7.64 ꢁ 7.59 (m, 3H, PO(OCH2CH3)2). 13C NMR (CDCl3, 100 MHz): d 162.3,
2H), 7.49 ꢁ 7.44 (m, 3H), 4.30 ꢁ 4.09 (m, 4H, 158. 0 (d, JC-P ¼ 5.3 Hz, C ¼ N), 134.9 (d, J ¼ 19.5 Hz),
PO(OCH2CH3)2), 1.30 (t, J ¼ 7.3 Hz, 3H, PO(OCH2CH3)2), 129.7, 128.6, 128.0, 126.0 (d, J ¼ 2.9 Hz), 114.0, 110.3 (d,
1.28 (t, J ¼ 7.0 Hz, 3H, PO(OCH2CH3)2). 13C NMR (CDCl3, J ¼ 198.9 Hz, –OCO–), 64.5 (d, JC-P
¼
6.9 Hz,
100 MHz): d 157.5 (d, JC-P ¼ 5.1 Hz, C ¼ N), 134.4 (d, JC-P PO(OCH2CH3)2), 64.4 (d, JC-P ¼ 7.3 Hz, PO(OCH2CH3)2),
¼ 19.3 Hz), 131.9, 129.8, 128.2, 128.1, 126.3, 125.9 (d, JC-P
¼
55.1 (OCH3), 16.1 (t, JC-P ¼ 6.6 Hz, PO(OCH2CH3)2). 31P
2.9 Hz), 120.7, 111.0 (d, JC-P ¼ 199.0 Hz, –OCO–), 64.5 (d, NMR (CDCl3, 202 MHz): d 9.41. IR (cmꢁ1): 2981, 1607,
JC-P ¼ 7.4 Hz, PO(OCH2CH3)2), 64.4 (d, JC-P ¼ 6.9 Hz, 1514, 1346, 1256, 1016, 967, 837, 651. HRMS-EI (m/z): cal-
PO(OCH2CH3)2), 16.1 (t, JC-P ¼ 7.5 Hz, PO(OCH2CH3)2). culated for C19H23NO6P [M þ Na]: 414.1082 and
31P NMR (CDCl3, 202 MHz): d 9.08. IR (cmꢁ1): 2973, 1345, found: 414.1082.
1260, 1229, 1098, 1008, 976, 836, 700. HRMS-EI (m/z): cal-
culated for C18H20BrNO5P [M þ H]: 440.0262 and
Diethyl 3-(naphthalen-1-yl)-5-phenyl-1,4,2-dioxazol-5-yl-
5-phosphonate 3p
found: 440.0262.
Oily compound, Rf ¼ 0.48 ((1:1) hexane:EtOAc). 1H
Diethyl 3-(4-chlorophenyl)-5-phenyl-1,4,2-dioxazol-5-yl-
7.89 ꢁ 7.84 (m, 3H)NMR (CDCl3, 400 MHz): d 8.89 (d,
5-phosphonate 3 m
J ¼ 8.6 Hz, 1H), 8.09 (d, J ¼ 7.3 Hz, 3H), 7.76 (d, J ¼ 8.2 Hz,
1
Oily compound, Rf ¼ 0.50 ((2:1) hexane:EtOAc). H NMR 1H), 7.54 (t, J ¼ 7.7 Hz, 1H), 7.47 ꢁ 7.34 (m, 5H), 4.32 ꢁ 4.06
(d-acetone, 400 MHz): d 7.95 ꢁ 7.90 (m, 2H), 7. 78 ꢁ 7.75 (m, 4H, PO(OCH2CH3)2), 1.24 (t, J ¼ 7.1 Hz, 6H,
(m, 2H), 7.66 ꢁ 7.58 (m, 2H), 7.53 ꢁ 7.49 (m, 3H), PO(OCH2CH3)2). 13C NMR (CDCl3, 100 MHz): d 157.8 (d,
4.27 ꢁ 4.03 (m, 4H, PO(OCH2CH3)2), 1.26 (t, J ¼ 7.1 Hz, 3H, J ¼ 5.4 Hz, C ¼ N), 134.7 (d, J ¼ 19.7 Hz), 133.1, 132.5, 129.6,
PO(OCH2CH3)2), 1.25 (t, J ¼ 7.1 Hz, 3H, PO(OCH2CH3)2). 129.5, 128.3 (d, J ¼ 5.8 Hz), 128.0, 127.5, 126.2, 125.9 (d,
13C NMR (CDCl3, 100 MHz): d 157.7 (d, JC-P ¼ 5.5 Hz, J ¼ 2.7 Hz), 125.7, 124.3, 118.2, 109.2 (d, JC-P ¼ 199.0 Hz,
C ¼ N), 138.1, 134.7 (d, JC-P ¼ 19.0 Hz), 130.0, 129.1, 128.3, –OCO–), 64.3 (d, JC-P ¼ 7.0 Hz, PO(OCH2CH3)2), 64.2 (d,
126.1 (d, JC-P ¼ 2.8 Hz), 120.5, 111.2 (d, JC-P ¼ 199.6 Hz, JC-P ¼ 7.2 Hz, PO(OCH2CH3)2), 16.0 (t, JC-P ¼ 5.1 Hz,

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
PO(OCH2CH3)2). 31P NMR (CDCl3, 202 MHz): d 9.56. IR
(cmꢁ1): 2982, 1259, 1016, 974, 805, 773, 696. HRMS-EI (m/
z): calculated for C22H23NO5P [M þ H]: 412.1314 and found:
412.1313.
ꢀ
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Acknowledgment
The author thanks to Canakkale Onsekiz Mart University for financing
this research and also thanks to Middle East Technical University
(METU), Department of Chemistry.
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This work was supported by Canakkale Onsekiz Mart University, the
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