Efficient synthesis of ether phosphonates using trichloroacetimidate and acetate coupling methods

Article abstract of DOI:10.1039/c8ra00702k

A series of ether phosphonates have been prepared by trichloroacetimidate and acetate coupling methods. Trichloroacetimidates or acetates were treated with primary and secondary alcohols as O-nucleophiles in the presence of catalytic TMSOTf to afford 21 examples of diethyl alkyloxy(substitutedphenyl)methyl phosphonates via C-O bond formation in 55-90% yields and short reaction time.

Full text of DOI:10.1039/c8ra00702k

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Efficient synthesis of ether phosphonates using
trichloroacetimidate and acetate coupling methods
Cite this: RSC Adv., 2018, 8, 7385
a
Ibrahim. A. I. Alib and Pavel. Pazderac
*
Walid. Fathalla,
Received 23rd January 2018
Accepted 9th February 2018
A series of ether phosphonates have been prepared by trichloroacetimidate and acetate coupling methods.
Trichloroacetimidates or acetates were treated with primary and secondary alcohols as O-nucleophiles in
the presence of catalytic TMSOTf to afford 21 examples of diethyl alkyloxy(substitutedphenyl)methyl
phosphonates via C–O bond formation in 55–90% yields and short reaction time.
DOI: 10.1039/c8ra00702k
rsc.li/rsc-advances
phthalimides,20 and benzhydryl derivatives.21 Also, we showed
the preparation of a number of N-protected non proteinogenic
Introduction
a-amino acid esters using trichloroacetimidate or acetate
coupling methods via C–C bond formation from the corre-
sponding methyl 2-benzamido-2-hydroxyacetate and benzyl(-
methoxycarbonyl)(hydroxy)methylcarbamate substrates and C-
nucleophiles.22
The strategies of both trichloroacetimidate and acetate
methods involve the transformation of the substrate hydroxyl
group into an excellent leaving group, such as tri-
chloroacetimidate or acetate by the reaction with tri-
chloroacetonitrile or acetic anhydride, respectively. The
successive addition of poor nucleophiles (alcohols) to these
active intermediates in the presence of Lewis acid give inter-
esting products via C–O bond formations, Fig. 1.
Phosphonates are an important class of organic compounds
showing remarkable applications as isosteric analogs of natural
phosphate esters.1,2 Phosphonates are key intermediates in
a variety of synthetically important reactions. The reaction of
stabilized phosphonate carbanions (ylides) with aldehydes or
ketones to afford E-selective alkenes is known as Horner–
Wadsworth–Emmons reaction (a modied Wittig reaction).3–5
A
number of methods have been reported for the preparation of
phosphonates. The Michaelis–Arbuzov reaction6,7 is an abun-
dant method for the preparation of phosphonates via P–C bond
formation. It involves the reaction of an aryl/alkyl halide with
trialkyl phosphite to give alkyl phosphonate. Hirao method8,9
shows the palladium-catalyzed cross-coupling of dia-
lkylphosphite with aromatic electrophiles for the synthesis of
arylphosphonates via aryl C–P bond formation. Recently, a-
functional phosphonates, a-aminophosphonates,10 a-acetox-
yphosphonates11 and a-hydroxyphosphonates12–15 showed
interesting medicinal applications as antiviral agents and
attracted the attention of many research groups. Abramov and
Pudovik method16,17 described the reaction of aldehydes with di
and trialkyl phosphite in the presence of a base to afford a-
hydroxyphosphonates. An efficient use of a-hydroxy phospho-
nates enables a mild process for the preparation of a-
substituted methyl phosphonates with promising biological
activities.
These ndings motivated the development of a series of
diethyl alkyloxy(substitutedphenyl)methyl phosphonate 6–8(a–
f), 10 and 12 using trichloroacetimidate and acetate coupling
methods via C–O bond formation.
Results and discussion
Nucleophilic addition of diethyl phosphite to benzaldehydes 1a–d
in 1 : 1 molar ratio using triethylamine as a base gave the dieth-
yl(hydroxy)arylmethyl phosphonates 2a–d in good yields (Scheme
1). The base-catalyzed addition reaction of trichloroacetonitrile to
a-hydroxyphosphonates 2a–d hydroxyl group in the presence of
DBU gave the desired diethyl 2-(2,2,2-trichloro-1-iminoethoxy)(3,4-
dimethoxyphenyl)methylphosphonates 3a–d, in 80–94% yield,
Scheme 1. The reactions of a-hydroxyphosphonates 2b–d with
acetic anhydride in the presence of DMAP (N,N-dimethyl amino-
pyridine) at room temperature afforded diethylmethylcarbonyloxy-
(4-methoxyphenyl)methylphosphonates 4b–d, Scheme 1.
The structure assignment of a-hydroxyphosphonates 2a–d,
active intermediates trichloroacetimidate derivatives 3a–d and
acetate derivatives 4b–d were based on 1H, 13C and 31P NMR
spectroscopic and elemental analysis are shown in the experi-
mental part.
The use of trichloroacetimidate and acetate methods are well
recognized in organic and carbohydrate synthesis via C–O or
C–C bond formations.18–21 Earlier we described the reaction of
O-phthalimidomethyl trichloroacetimidate and O-diphe-
nylmethyl trichloroacetimidate with C-nucleophiles in the
presence of TMSOTf to afford a series of N-substituted
aPhysics and Math. Engineering Dept., Faculty of Engineering, Port-Said University,
Port Said, Egypt. E-mail: walid3369@yahoo.com
bDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt
cCentre for Syntheses at Sustainable Conditions and Their Management, Chemistry
Dept., Faculty of Science, Masaryk University, Brno, Czech Republic
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Fig. 1 The trichloroacetimidate and acetate coupling methods from functionalized alcohol substrates.
Both active intermediates trichloroacetimidates 3a–d and
According to the presumed mechanism, the TMSOTf is used
acetates 4b–d are excellent precursors for the structure modica- to eliminate the trichloroacetimidate and acetate leaving
tion of the diethyl phosphonate residue via trichloroacetimidate groups with the subsequent formation of carbocation. This
and acetate coupling methods. However, our early results con- carbocation could be stabilized by an efficient electron donor
cerning this synthetic method applying diethyl 2-(2,2,2-trichloro-1- and a phenyl group but it is insufficient. In contrast there was
iminoethoxy)(phenyl)methyl phosphonate (3a) failed to give us the good stabilization in the case of a phenyl residue bearing an
desired products. Thus the reaction of trichloroacetimidate 3a with electron-donating –OR group at the 4-position. The nal step is
isobutyl alcohol in the presence of a catalytic amount of TMSOTf at the nucleophilic attack of the weak alcohol nucleophiles at the
room temperature did not give diethyl 2-methylpropyloxy(phenyl) stabilized carbocation to form the desired products 6–8(a–f) via
methyl phosphonate (5a) and instead decomposition was observed an overall SN1 mechanism. The attempted reaction of diethyl 2-
and a complex mixture was obtained, Scheme 2. On the other methylpropyloxy(4-methoxyphenyl)methyl phosphonate (6a)
hand, trichloroacetimidates 3b–d reacted with a variety of O- with isopropyl alcohol under the same reaction conditions, in
nucleophile acceptors (alcohols) in the presence of catalytic the presence of a catalytic amount of TMSOTf at room
amount of TMSOTf at room temperature and readily gave a series temperature in dichloromethane, failed to give the corre-
of functionalized ether phosphonates 6–8(a–f), Scheme 2, Table 1. sponding isopropyl ether phosphonate derivative 6b via trans-
Similarly, the acetate derivatives 4b–d reacted with a variety of O- etherication, Scheme 2.
nucleophile acceptors (alcohols) in the presence of a catalytic
Structure assignment of ether derivatives 6–8(a–f) were based
1
amount of TMSOTf at room temperature in dichloromethane and on H, 13C and 31P-NMR spectral and physicochemical analysis.
readily gave a series of functionalized ether phosphonates 6–8(a–f), The 1H-NMR spectrum of 6a shows an interesting doublet signal at
Scheme 2, Table 1.
A
comparative study of both tri- d ¼ 4.52 ppm with coupling constant 15.0 Hz typically associated
chloroacetimidate and acetate methodologies was carried out to with CHP. This chemical shi is common for all isolated phos-
examine the efficiency of reaction time and % of yield in both phonate derivatives 6–8(a–f) with chemical shis ranging from
methods. The results showed that, although all compounds were 4.37–4.93 ppm and with coupling constant ranging from 12–18 Hz.
prepared in good yields, there was a slight improvement in the % The 1H-NMR spectrum exhibit signals at d 0.90, 0.93, 1.84–1.97 and
of yield and in the reaction time (monitored by TLC) using the 3.16–3.28 ppm due to two CH3, CH and CH2 groups, respectively of
trichloroacetimidate method, see Experimental section.
the isobutyl-residue and signals at d 1.24–1.28 and 4.02–4.12 ppm
Scheme 1 Synthetic pathway of phosphonates trichloroacetimidates and acetates 3a–d and 4b–d.
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Scheme 2 Synthetic pathway of phosphonates 6–8(a–f) via C–O bond formation.
due to two OCH2CH3 residue. The 13C NMR spectrum of 6a shows Trichloroacetimidates 3a–d or acetates 4b–d were treated with
interesting doublet signals at d 16.3, 16.4, 62.7, 63.0, 76.9 and Lewis acid followed by reaction with O-nucleophiles to afford
77.5 ppm having coupling constants JCP 6.0, 6.0, 6.8, 6.8, 32.4 and the desired products via C–O bond formation. Both methods
169.6 Hz corresponding to CH3, CH3, OCH2P, OCH2P, CH2OCHP gave good yields of desired products in short reaction times,
and CHP groups, respectively. These signals are common for all and generally slightly better results were obtained using the
isolated products, which conrm the C–O bond formation. The trichloroacetimidate method. Applications of this methodology
previously mentioned signals are good evidences for either the C–P to synthesize various phosphonate analogues of alcohols con-
coupling, the diastereotopic nature or both for these individual taining primary and secondary hydroxy groups as O-nucleo-
groups. The 31P-NMR spectrum of 6a showed a single signal at d ¼ philes are under progress in our laboratory.
19.5 ppm corresponding to phosphonate phosphorus and was
used as an indicator for the purity of the products.
Experimental
The trichloroacetimidate method proved to be an excellent
method for the structure modication of diethyl hydroxy(sub-
stituted phenyl)methylphosphonate 2a–d. Next, the use of an
interesting derivatized alcohols was explored: (5-methyl-2-phenyl-
Solvents were puried and dried in the usual way. The boiling
range of the petroleum ether used was 40–60 ꢀC. Thin-layer
chromatography (TLC) utilized silica gel 60 F254 plastic plates
(E. Merck, layer thickness 0.2 mm). Detection was by UV
absorption. Melting points were determined on a Buchi 510
melting point apparatus. The 1H, 13C and 31P NMR spectra were
recorded at 300 MHz, 75.5 and 194.4 MHz, respectively (Bruker
AC 300) in CDCl3 with tetramethylsilane as an internal stan-
dard. The NMR analysis were performed at Organic Chemistry
Department Masaryk University, Brno, Czech Republic.
Elemental analyses were performed on a Flash EA-1112 instru-
ment at the Microanalytical Laboratory, Faculty of Science, Suez
Canal University, Ismailia, Egypt. 3,4-Dimethoxybenzaldehyde
1c and 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde 1d was
prepared by alkylation of vaniline as described in the
literature.24
1,3-dioxan-5-yl)methanol
9
and 2-(N-methyl-N-phenylamino)
ethanol 11. The dioxane derivative 9 was prepared by heating 1,1,1-
tris(hydroxymethyl)ethane with benzaldehyde in the presence of
toluene-p-sulfonic acid in benzene and this compound is known to
possess potential medicinal chemistry relevance.23 Thus the reac-
tion of trichloroacetimidate 3a–b with dioxane derivative 9 in the
presence of a catalytic amount of TMSOTf at room temperature in
dichloromethane and gave diethyl((5-methyl-2-phenyl-1,3-dioxan-
5-yl)methoxy)(substitutedphenyl)methyl phosphonate 10a–b in
62–70% yields, Scheme 3. Also trichloroacetimidate 3a reacted
with 2-(N-methyl-N-phenylamino)ethanol (11) in the presence of
a catalytic amount of TMSOTf at room temperature in dichloro-
methane and gave diethyl 2-(N-methyl-N-phenylamino)ethyloxy(4-
methoxyphenyl)methyl phosphonate 12 in 29% yield, Scheme 3.
Diethyl hydroxy(substitutedphenyl)methyl phosphonate 2a–d25
To a mixture of (20.7 g, 0.15 mol) of diethyl phosphonate and
1.09 g (0.011 mol) of triethylamine was added (0.15 mol) of
Conclusion
In conclusion, an efficient and very simple method for the aldehydes 1a–d portion wise during a period of 1 h at 50–70 ꢀC.
synthesis of various ether phosphonates by tri- The reaction mixture was subsequently stirred at 70 ꢀC for 2 h.
chloroacetimidate and acetate coupling methods is described. Aer cooling it was le over night to give white crystals, lter
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Table 1 Synthesis of ether phosphonate derivatives 6–8(a–f) and the comparative results between trichloroacetimidate and acetate coupling
methodsa
No.
Structure
TCI and Ac yield (time)
No.
Structure
TCI and Ac yield (time)
6a
81% (2 h), 76% (4 h)
7d
78% (3 h), 59% (4 h)
6b
72% (2 h), 64% (5 h)
7e
79% (1 h), 73% (5 h)
6c
75% (3 h), 71% (5 h)
7f
86% (2 h), 79% (4 h)
6d
82% (2 h), 76% (5 h)
8a
79% (2 h), 75% (2 h)
6e
67% (2 h), 71% (3 h)
8b
74% (1 h), 66% (3 h)
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Table 1 (Contd.)
No.
Structure
TCI and Ac yield (time)
No.
Structure
TCI and Ac yield (time)
6f
71% (3 h), 56% (4 h)
8c
80% (2 h), 78% (4 h)
7a
86% (1 h), 77% (4 h)
8d
81% (3 h), 72% (3 h)
7b
78% (1 h), 68% (4 h)
8e
71% (2 h), 63% (3 h)
7c
86% (2 h), 74% (4 h)
8f
79% (2 h), 69% (4 h)
a
Abbrev. TCI: trichloroacetimidate method, Ac: acetate method.
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Scheme 3 Synthesis of phosphonates 10a–b and 12 via C–O bond formation.
and wash with cold toluene and then recrystallized from
toluene to give pure crystals.
Diethyl hydroxy(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)
methyl phosphonate (2d)
1
36.9 g, yield 75% white crystals. Mp 87–88 ꢀC. H-NMR spec-
trum, (300 MHz, CDCl3), d, ppm (J, Hz): 1.19–1.37 (m, 6H,
2CH3), 2.50 (t, J ¼ 3.0 Hz, 1H, CH), 3.86 (s, 3H, OCH3), 3.92–4.17
(m, 4H, 2CH2), 4.39 (bs, 1H, OH), 4.74 (d, J ¼ 3.0 Hz, 2H, OCH2),
4.93 (d, JHP ¼ 9.0 Hz, 1H, CHP), 6.99–7.12 (m, 3H, H-Ar). 13C-
NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 4.0, CH3), 16.4
(d, JCP ¼ 4.0, CH3), 55.9 (OCH3), 56.8 (OCH2), 63.0 (d, JCP ¼ 7.6,
CH2OP), 63.2 (d, JCP ¼ 7.6, CH2OP), 70.5 (d, JCP ¼ 160.8, CHP),
75.8 (C^CH), 78.5 (C^CH), 110.9, 114.0, 119.5, 130.7, 146.6,
149.6 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 21.5 (P).
Found, %: C, 54.68; H, 6.43. For C15H21O6P (328.1). Calculated,
%: C, 54.88; H, 6.45.
Diethyl hydroxy(phenyl)methyl phosphonate (2a)
1
27.5 g, yield 76% white crystals. Mp 80–81 ꢀC. H NMR spec-
trum, (300 MHz, CDCl3), d, ppm (J, Hz): 1.19–1.34 (m, 6H,
2CH3), 3.82 (s, 3H, OCH3), 3.91–4.10 (m, 4H, 2CH2), 3.54 (bs, 1H,
OH), 5.00 (d, JHP ¼ 8.0 Hz, 1H, CHP), 7.24–7.46 (m, 5H, H-Ar).
13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 4.0, CH3),
16.4 (d, JCP ¼ 4.0, CH3), 55.3 (OCH3), 62.7 (d, JCP ¼ 7.6, CH2OP),
63.4 (d, JCP ¼ 7.6, CH2OP), 70.2 (d, JCP ¼ 158.4, CHP), 127.1,
127.2, 128.1, 128.3, 136.8 (C-Ar). 31P-NMR (194.4 MHz, CDCl3),
d, ppm: 21.6 (P). Found, %: C, 53.89; H, 6.94. For C11H17O4P
(244.1). Calculated, %: C, 54.10; H, 7.02.
Preparation of diethyl 2-(2,2,2-trichloro-1-
Diethyl hydroxy(4-methoxyphenyl)methyl phosphonate (2b)
iminoethoxy)(substitutedphenyl) methyl phosphonate 3a–d
1
34.4 g, yield 84% white crystals. Mp 90–91 ꢀC. H-NMR spec-
A stirred solution of diethyl hydroxy(substitutedphenyl)meth-
ylphosphonate 2a–d (10.0 mmol) in dry dichloromethane
(30 mL) was treated with trichloroacetonitrile (2.9 mL, 20 mmol)
and DBU (0.8 mL, 5.0 mmol). The reaction mixture was stirred
at room temperature for 2 h. The solvent was evaporated under
reduced pressure and the product was puried by column
chromatography 5% triethylamine in dichloromethane, to give
3a–d as whitish oil.
trum, (300 MHz, CDCl3), d, ppm (J, Hz): 1.19–1.29 (m, 6H,
2CH3), 3.80 (s, 3H, OCH3), 3.89–4.10 (m, 4H, 2CH2), 4.33 (bs, 1H,
OH), 4.95 (d, JHP ¼ 9.0 Hz, 1H, CHP), 6.87 (d, J ¼ 9.0 Hz, 2H, H-
Ar), 7.39–7.43 (m, 2H, H-Ar). 13C-NMR (75.0 MHz, CDCl3),
d, ppm: 16.3 (d, JCP ¼ 4.0, CH3), 16.4 (d, JCP ¼ 4.0, CH3), 55.2
(OCH3), 62.9 (d, JCP ¼ 7.6, CH2OP), 63.2 (d, JCP ¼ 7.6, CH2OP),
70.3 (d, JCP ¼ 161.6, CHP), 113.0, 113.7, 128.4, 128.5, 128.8,
159.5 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 21.7 (P).
Found, %: C, 52.39; H, 6.81. For C12H19O5P (274.1). Calculated,
%: C, 52.55; H, 6.98.
Diethyl 2-(2,2,2-trichloro-1-iminoethoxy)(phenyl)methyl
phosphonate (3a)
1
1.92 g, yield 91% brownish oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.16–1.29 (m, 6H, 2CH3), 3.78 (s, 3H,
OCH3), 3.94–4.17 (m, 4H, 2CH2), 6.22 (d, JHP ¼ 15.0 Hz, 1H,
CHP), 6.95–7.53 (m, 5H, H-Ar), 8.55 (brs, 1H, NH). 31P-NMR
(194.4 MHz, CDCl3), d, ppm: 16.4 (P). Found, %: C, 40.04; H,
4.32; N, 3.48. For C13H17Cl3NO4P (387.1). Calculated, %: C,
40.18; H, 4.41; N, 3.60.
Diethyl hydroxy(3,4-dimethoxyphenyl)methyl phosphonate
(2c)
40.6 g, yield 89% white crystals. Mp 101–103 ꢀC. 1H-NMR
spectrum, (300 MHz, CDCl3), d, ppm (J, Hz): 1.16–1.26 (m, 6H,
2CH3), 3.83 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 3.92–4.07 (m, 4H,
2CH2), 4.62 (bs, 1H, OH), 4.89 (d, JHP ¼ 9.0 Hz, 1H, CHP), 6.81
(d, J ¼ 9.0 Hz, 1H, H-Ar), 6.95–7.07 (m, 1H, H-Ar), 7.08 (s, 1H, H-
Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 4.0,
CH3), 16.4 (d, JCP ¼ 4.0, CH3), 55.8 (OCH3), 55.9 (OCH3), 62.9 (d,
Diethyl(2,2,2-trichloro-1-iminoethoxy)(4-methoxyphenyl)
methyl phosphonate (3b)
3.6 g, yield 87% brownish oil. 1H-NMR spectrum, (300 MHz,
JCP ¼ 7.6, CH2OP), 63.2 (d, JCP ¼ 7.6, CH2OP), 70.4 (d, JCP
¼
161.6, CHP), 110.5, 110.8, 110.9, 129.3, 148.7, 148.8 (C-Ar). 31P- CDCl3), d, ppm (J, Hz): 1.20–1.27 (m, 6H, 2CH3), 3.76 (s, 3H,
NMR (194.4 MHz, CDCl3), d, ppm: 21.7 (P). Found, %: C, 51.12; OCH3), 3.97–4.16 (m, 4H, 2CH2), 6.20 (d, JHP ¼ 15.0 Hz, 1H,
H, 6.89. For C13H21O6P (304.1). Calculated, %: C, 51.31; H, 6.96. CHP), 6.86 (d, J ¼ 9.0 Hz, 2H, H-Ar), 7.44 (d, J ¼ 6.0 Hz, 2H, H-
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Ar), 8.51 (brs, 1H, NH). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 20.9 (CH3), 55.2 (OCH3), 63.1 (d, JCP ¼ 6.8, CH2OP), 63.6 (d, JCP
¼
16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 55.2 (OCH3), 6.8, CH2OP), 70.1 (d, JCP ¼ 172.9, CHP), 113.9, 125.5, 129.5,
63.3 (d, JCP ¼ 6.0, CH2OP), 63.5 (d, JCP ¼ 6.0, CH2OP), 74.8 (d, 129.6, 159.9 (C-Ar), 169.3 (CO). 31P-NMR (194.4 MHz, CDCl3),
JCP ¼ 172.1, CHP), 90.9 (CCl3), 113.8, 113.9, 124.7, 124.7, 129.2, d, ppm: 18.0 (P). Found, %: C, 53.13; H, 6.57. For C14H21O6P
129.3 (C-Ar), 161.1 (C]N). 31P-NMR (194.4 MHz, CDCl3), (316.1). Calculated, %: C, 53.16; H, 6.69.
d, ppm: 16.5 (P). Found, %: C, 39.96; H, 4.42; N, 3.29. For C14
-
H19Cl3NO5P (417.0). Calculated, %: C, 40.17; H, 4.57; N, 3.35.
Diethyl methylcarbonyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (4c)
2.94 g, yield 85% whitish oil. 1H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.15 (t, J ¼ 6 Hz, 3H, CH3), 1.24 (t, J ¼
Diethyl(2,2,2-trichloro-1-iminoethoxy)(3,4-dimethoxyphenyl)
methyl phosphonate (3c)
4.2 g, yield 94% brownish oil. 1H-NMR spectrum, (300 MHz, 6.0 Hz, 3H, CH3), 2.10 (s, 3H, CH3), 3.82 (s, 3H, OCH3), 3.88 (s,
CDCl3), d, ppm (J, Hz): 1.25–1.32 (m, 6H, 2CH3), 3.89 (s, 6H, 2 3H, OCH3), 3.91–4.11 (m, 4H, 2CH2), 6.02 (d, JHP ¼ 12.0 Hz, 1H,
OCH3), 4.02–4.23 (m, 4H, 2CH2), 6.23 (d, JHP ¼ 12.0 Hz, 1H, CHP), 6.79 (d, J ¼ 6.0 Hz, 1H, H-Ar), 6.98–7.02 (m, 2H, H-Ar).
CHP), 6.86 (d, J ¼ 9.0 Hz, 1H, H-Ar), 7.09 (d, J ¼ 9.0 Hz, 2H, H- 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3),
Ar), 8.53 (brs, 1H, NH). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.4 (d, JCP ¼ 6.0, CH3), 20.8 (CH3), 55.8 (CH3), 55.9 (CH3), 63.1
16.4 (d, JCP ¼ 6.0, CH3), 16.5 (d, JCP ¼ 6.0, CH3), 55.8 (OCH3), (d, JCP ¼ 6.8, CH2OP), 63.7 (d, JCP ¼ 6.8, CH2OP), 70.3 (d, JCP
¼
63.3 (d, JCP ¼ 6.0, CH2OP), 63.7 (d, JCP ¼ 6.0, CH2OP), 74.9 (d, 172.9, CHP), 110.9, 120.9, 121.0, 125.7, 148.9, 149.4 (C-Ar), 169.2
JCP ¼ 172.1, CHP), 91.0 (CCl3), 110.8, 120.6, 120.7, 125.2, 148.9, (CO). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 17.9 (P). Found, %:
149.5 (C-Ar), 161.2 (C]N). 31P-NMR (194.4 MHz, CDCl3), C, 51.85; H, 6.54. For C15H23O7P (346.1). Calculated, %: C, 52.02;
d, ppm: 16.5 (P). Found, %: 40.02; H, 4.67; N, 3.05. For C15
-
H, 6.69.
H21Cl3NO6P (447.0). Calculated, %: C, 40.15; H, 4.72; N, 3.12.
Diethyl methylcarbonyloxy(3-methoxy-4-propargyloxyphenyl)
methyl phosphonate (4d)
2.44 g, yield 66% whitish oil. 1H NMR spectrum, (300 MHz,
Diethyl(2,2,2-trichloro-1-iminoethoxy)(3-methoxy-4-(prop-2-
yn-1-yloxy)phenyl)methyl phosphonate (3d)
3.8 g, yield 80% brownish oil. 1H-NMR spectrum, (300 MHz, CDCl3), d, ppm (J, Hz): 1.13 (t, J ¼ 6.0 Hz, 3H, CH3), 1.31 (t, J ¼
CDCl3), d, ppm (J, Hz): 1.22 (m, 6H, 2CH3), 2.50 (s, 1H, CH), 3.85 6.0 Hz, 3H, CH3), 2.21 (s, 3H, COCH3), 2.51 (s, 1H, CH), 3.87 (s,
(s, 3H, OCH3), 3.99–4.16 (m, 4H, CH, 2CH2), 4.73 (d, J ¼ 3.0 Hz, 3H, OCH3), 3.92–4.13 (m, 4H, CH, 2CH2), 4.74 (d, J ¼ 3.0 Hz, 2H,
2H, OCH2), 6.20 (d, JHP ¼ 12.0 Hz, 1H, CHP), 6.99–7.28 (m, 3H, CH2), 6.07 (d, JHP ¼ 12.0 Hz, 1H, CHP), 6.98–7.08 (m, 3H, H-Ar).
H-Ar), 8.53 (brs, 1H, NH). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3),
16.4 (d, JCP ¼ 6.0, CH3), 16.5 (d, JCP ¼ 6.0, CH3), 55.9 (OCH3), 16.4 (d, JCP ¼ 6.0, CH3), 20.9 (CH3), 56.0 (OCH3), 56.7 (OCH2),
56.7 (OCH2), 63.3 (d, JCP ¼ 6.8, CH2OP), 63.6 (d, JCP ¼ 6.8, 63.2 (d, JCP ¼ 6.0, CH2OP), 63.3 (d, JCP ¼ 6.0, CH2OP), 70.1 (d, JCP
CH2OP), 74.1 (d, JCP ¼ 171.4, CHP), 75.9 (C^CH), 78.4 (C^CH), ¼ 172.9, CHP), 75.9 (C^CH), 78.4 (C^CH), 111.9, 114.0, 120.7,
90.9 (CCl3), 111.2, 113.9, 120.3, 126.6, 147.3, 149.6 (C-Ar), 161.1 127.2, 147.3, 149.6 (C-Ar), 169.2 (CO). 31P-NMR (194.4 MHz,
(C]N). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 16.3 (P). Found, CDCl3), d, ppm: 17.9 (P). Found, %: C, 55.04; H, 6.19. For
%: C, 43.11; H, 4.36; N, 2.82. For C17H21Cl3NO6P (471.0).
Calculated, %: C, 43.20; H, 4.48; N, 2.96.
C17H23O7P (370.1). Calculated, %: C, 55.13; H, 6.26.
General procedure for the preparation of diethyl
alkyloxy(substitutedphenyl)methyl phosphonate 6–8(a–f), 10
and 12
Preparation of diethyl methylcarbonyloxy(substitutedphenyl)
methyl phosphonate 4b–d
A
solution of diethyl hydroxy(substitutedphenyl)methyl- A solution of trichloroacetimidate 3a–d or acetate 4b–d
phosphonate 2a–c (10.0 mmol) in acetic anhydride (1.2 mL, (1.0 mmol) in dichloromethane (40 mL) was added O-nucleo-
12.0 mmol) and DMAP (0.61 g, 5.0 mmol) and NEt3 (1.1 mL, philes (alcohols) (1.0 mmol) and TMSOTf (0.1 mmol). The
12.0 mmol) was stirred at room temperature for 4 h. The reac- reaction mixture was stirred at room temperature till comple-
tion mixture was evaporated under reduced pressure. The tion of the reaction (TLC monitored and the time was recorded).
residue was puried by column chromatography 4 : 1 pet. ether/ The reaction mixture was neutralized with solid sodium bicar-
ethyl-acetate, to give 4a–c as white oil.
bonate, ltered and concentrated in vacuo. The residue was
puried by ash chromatography 1 : 2 pet. ether/ethyl-acetate
to give the pure alkyloxy phosphonates 6–8(a–f), 10 and 12 as
colorless oil.
Diethyl methylcarbonyloxy(4-methoxyphenyl)methyl
phosphonate (4b)
2.94 g, yield 93% whitish oil. 1H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.19 (t, J ¼ 6.0 Hz, 3H, CH3), 1.28 (t, J ¼
6.0 Hz, 3H, CH3), 2.13 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 3.87–4.13
(m, 4H, 2CH2), 6.07 (d, JHP ¼ 12.0 Hz, 1H, CHP), 6.87 (d, J ¼ 0.26 g, yield 78% colorless oil. H NMR spectrum, (300 MHz,
6.0 Hz, 2H, H-Ar), 7.40–7.44 (m, 2H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm (J, Hz): 0.90 (d, J ¼ 3.0 Hz, 3H, CH3), 0.93 (d, J ¼
CDCl3), d, ppm: 16.2 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 3.0 Hz, 3H, CH3), 1.24–1.28 (m, 6H, 2CH3), 1.84–1.97 (m, 1H,
Diethyl 2-methylpropyloxy(4-methoxyphenyl)methyl
phosphonate (6a)
1
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CH), 3.16–3.28 (m, 2H, CH2), 3.82 (s, 3H, OCH3), 4.02–4.12 (m,
4H, 2CH2), 4.52 (d, JHP ¼ 15.0 Hz, 1H, CHP), 6.90 (d, J ¼ 6.0 Hz,
2H, H-Ar), 7.28–7.39 (m, 2H, H-Ar). 13C-NMR (75.0 MHz, CDCl3),
d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 19.2
(CH3), 19.3 (CH3), 28.4 (CH), 55.2 (OCH3), 62.7 (d, JCP ¼ 6.8,
CH2OP), 63.0 (d, JCP ¼ 6.8, CH2OP), 76.9 (d, JCP ¼ 32.4, CH2-
OCHP), 77.5 (d, JCP ¼ 169.6, CHP), 113.7, 113.8, 127.0, 129.2,
129.3, 159.7 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.5
(P). Found, %: C, 58.04; H, 8.16. For C16H27O5P (330.2). Calcu-
lated, %: C, 58.17; H, 8.24.
Diethyl benzyloxy(4-methoxyphenyl)methylphosphonate (6e)
1
0.33 g, yield 90% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.20 (t, J ¼ 6.0 Hz, 3H, CH3), 1.27 (t, J ¼
6.0 Hz, 3H, CH3), 3.82 (s, 3H, OCH3), 3.92–4.13 (m, 4H, 2CH2),
4.37 (d, JHP ¼ 12.0 Hz, 1H, CHP), 4.60–4.71 (m, 2H, CH2), 6.92 (d,
J ¼ 6.0 Hz, 2H, H-Ar), 7.31–40 (m, 7H, H-Ar). 13C-NMR (75.0
MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0,
CH3), 55.3 (OCH3), 62.9 (d, JCP ¼ 6.0, CH2OP), 63.2 (d, JCP ¼ 6.0,
CH2OP), 71.4 (d, JCP ¼ 15.1, CH2OCHP), 76.4 (d, JCP ¼ 172.9,
CHP), 113.9, 114.0, 126.2, 128.0, 128.2, 128.4, 129.6, 129.7,
137.1, 159.9 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.6
(P). Found, %: C, 62.48; H, 6.76. For C19H25O5P (364.1). Calcu-
lated, %: C, 62.63; H, 6.92.
Diethyl 1-methylethyloxy(4-methoxyphenyl)methyl
phosphonate (6b)
1
0.26 g, yield 83% colorless oil. H NMR spectrum, (300 MHz,
Diethyl 2-phenylethyloxy(4-methoxyphenyl)methyl
phosphonate (6f)
CDCl3), d, ppm (J, Hz): 1.08 (d, J ¼ 6.0 Hz, 3H, CH3), 1.14 (d, J ¼
6.0 Hz, 3H, CH3), 1.19–1.25 (m, 6H, 2CH3), 3.57–3.76 (m, 1H,
1
CH), 3.87 (s, 3H, OCH3), 3.92–4.09 (m, 4H, 2CH2), 4.64 (d, JHP
18.0 Hz, 1H, CHP), 6.84 (d, J ¼ 9.0 Hz, 2H, H-Ar), 7.33–7.36 (m,
2H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP
6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 20.9 (CH3), 23.0 (CH3), 55.1
(OCH3), 62.7 (d, JCP ¼ 8.0, CH2OP), 63.1 (d, JCP ¼ 8.0, CH2OP),
71.3 (d, JCP ¼ 13.6, CHOCHP), 75.5 (d, JCP ¼ 171.4, CHP), 113.6,
113.7, 117.6, 129.3, 159.5, 159.6 (C-Ar). 31P-NMR (194.4 MHz,
CDCl3), d, ppm: 20.0 (P). Found, %: C, 56.78; H, 7.83. For
¼
0.15 g, yield 39% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.13–1.21 (m, 6H, 2CH3), 2.84–2.89 (m,
2H, CH2), 3.59–3.69 (m, 2H, CH2), 3.73 (s, 3H, OCH3), 3.89–4.01
(m, 4H, 2CH2), 4.56 (d, JHP ¼ 15.0 Hz, 1H, CHP), 6.83 (d, J ¼
9.0 Hz, 2H, H-Ar), 7.14–7.28 (m, 7H, H-Ar). 13C-NMR (75.0 MHz,
CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3),
¼
36.2 (CH2), 55.7 (OCH3), 62.8 (d, JCP ¼ 8.0, CH2OP), 63.2 (d, JCP
8.0, CH2OP), 71.3 (CH2) (d, JCP ¼ 13.6, CH2OCHP), 78.4 (d, JCP
¼
¼
C
15H25O5P (316.1). Calculated, %: C, 56.95; H, 7.97.
170.6, CHP), 113.7, 113.8, 126.2, 126.5, 128.2, 128.9, 129.3,
129.4, 138.6, 159.7, 159.8, 163.6 (C-Ar). 31P-NMR (194.4 MHz,
CDCl3), d, ppm: 19.1 (P). Found, %: C, 63.26; H, 7.13. For
Diethyl propargyloxy(4-methoxyphenyl)methyl phosphonate
(6c)
C
20H27O5P (378.2). Calculated, %: C, 63.48; H, 7.19.
1
0.19 g, yield 62% colorless oil. H NMR spectrum, (300 MHz,
Diethyl 2-methylpropyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (7a)
CDCl3), d, ppm (J, Hz): 1.21 (t, J ¼ 6.0 Hz, 3H, CH3), 1.30 (t, J ¼
6.0 Hz, 3H, CH3), 2.46 (s, 1H, CH), 3.81 (s, 3H, OCH3), 3.89–3.95
(m, 2H, CH2), 4.01–4.08 (m, 4H, 2CH2), 4.93 (d, JHP ¼ 15.0 Hz,
1H, CHP), 6.70–6.91 (m, 4H, H-Ar). 13C-NMR (75.0 MHz, CDCl3),
d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 55.2
(OCH3), 56.4 (d, JCP ¼ 15.9, CH2OCHP), 62.8 (d, JCP ¼ 7.6,
1
0.23 g, yield 65% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 0.86 (d, J ¼ 3.0 Hz, 3H, CH3), 0.89 (d, J ¼
3.0 Hz, 3H, CH3), 1.19–1.23 (m, 6H, 2CH3), 1.80–1.91 (m, 1H,
CH), 3.12–3.24 (m, 2H, CH2), 3.83 (s, 3H, OCH3), 3.85 (s, 3H,
OCH3), 4.01–4.07 (m, 4H, 2CH2), 4.48 (d, JHP ¼ 18.0 Hz, 1H,
CHP), 6.79–6.92 (m, 2H, H-Ar), 7.00 (s, 1H, H-Ar). 13C-NMR (75.0
MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 5.3, CH3), 16.4 (d, JCP ¼ 5.3,
CH3), 19.1 (CH3), 19.2 (CH3), 28.4 (CH), 55.8 (2 OCH3), 62.7 (d,
CH2OP), 63.1 (d, JCP ¼ 7.6, CH2OP), 75.5 (C^CH), 75.6 (d, JCP
¼
172.1, CHP), 78.6 (C^CH), 113.9, 114.0, 125.2, 129.8, 129.9,
160.0 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.2 (P).
Found, %: C, 57.57; H, 6.63. For C15H21O5P (312.1). Calculated,
%: C, 57.69; H, 6.78.
JCP ¼ 6.8, CH2OP), 63.0 (d, JCP ¼ 6.8, CH2OP), 78.7 (d, JCP
¼
160.0, CHP), 76.9 (d, JCP ¼ 32.5, CH2OCHP), 110.7, 110.8, 111.0,
120.6, 127.4, 149.0 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm:
19.4 (P). Found, %: C, 56.64; H, 8.07. For C17H29O6P (360.2).
Calculated, %: C, 56.66; H, 8.11.
Diethyl 4-chlorobutyloxy(4-methoxyphenyl) methyl
phosphonate (6d)
1
0.17 g, yield 46% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.17 (t, J ¼ 6.0 Hz, 3H, CH3), 1.28 (t, J ¼
6.0 Hz, 3H, CH3), 1.56–1.92 (m, 4H, 2CH2), 3.38–3.64 (m, 4H,
2CH2), 3.83 (s, 3H, OCH3), 3.98–4.08 (m, 4H, 2CH2), 4.56 (d, JHP
Diethyl 1-methylethyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (7b)
1
¼ 12.0 Hz, 1H, CHP), 6.84 (d, J ¼ 9.0 Hz, 2H, H-Ar), 7.33–7.23 (m, 0.26 g, yield 74% colorless oil. H NMR spectrum, (300 MHz,
2H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP
6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 26.7 (CH2), 29.3 (CH2), 44.9 (m, 6H, 2CH3), 3.54–3.62 (m, 1H, CH), 3.80 (s, 3H, OCH3), 3.88
¼
CDCl3), d, ppm (J, Hz): 1.08 (d, J ¼ 6.0 Hz, 6H, 2CH3), 1.11–1.22
(ClCH2), 55.6 (OCH3), 62.6 (d, JCP ¼ 8.0, CH2OP), 63.1 (d, JCP
¼
(s, 3H, OCH3), 3.92–4.06 (m, 4H, 2CH2), 4.59 (d, JHP ¼ 18.0 Hz,
8.0, CH2OP), 71.6 (d, JCP ¼ 13.6, CH2OCHP), 77.5 (d, JCP ¼ 172.1, 1H, CHP), 6.76–6.91 (m, 2H, H-Ar), 6.99 (s, 1H, H-Ar). 13C-NMR
CHP), 113.6, 114.0, 125.1, 129.7, 129.9, 159.8 (C-Ar). 31P-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 5.3, CH3), 16.4 (d, JCP
¼
(194.4 MHz, CDCl3), d, ppm: 19.1 (P). Found, %: C, 52.56; H, 5.3, CH3), 21.0 (CH3), 23.0 (CH3), 55.7 (OCH3), 55.8 (OCH3), 62.8
7.03. For C16H26ClO5P (364.1). Calculated, %: C, 52.68; H, 7.18. (d, JCP ¼ 6.8, CH2OP), 63.1 (d, JCP ¼ 6.8, CH2OP), 71.5 (OCH) (d,
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JCP ¼ 13.6, CHOCHP), 75.6 (d, JCP ¼ 167.6, CHP), 110.7, 110.8,
111.0, 120.4, 128.1, 148.8 (C-Ar). 31P-NMR (194.4 MHz, CDCl3),
d, ppm: 19.8 (P). Found, %: C, 55.39; H, 7.67. For C16H27O6P
(346.2). Calculated, %: C, 55.48; H, 7.86.
Diethyl 2-phenylethyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (7f)
1
0.28 g, yield 69% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.21 (t, J ¼ 6.0 Hz, 3H, CH3), 1.26 (t, J ¼
6.0 Hz, 3H, CH3), 2.90 (t, J ¼ 9.0, 6.0 Hz, 2H, CH2), 3.63–3.79 (m,
2H, CH2), 3.85 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), 3.97–4.04 (s,
4H, 2CH2), 4.55 (d, JHP ¼ 15.0 Hz, 1H, CHP), 6.79–6.93 (m, 3H,
H-Ar), 7.14–7.28 (m, 5H, H-Ar). 13C-NMR (75.0 MHz, CDCl3)
d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 36.2
(CH2), 55.8 (OCH3), 55.9 (OCH3), 62.8 (d, JCP ¼ 6.8, CH2OP), 63.2
(d, JCP ¼ 6.8, CH2OP), 71.3 (d, JCP ¼ 14.3, CH2OCHP), 78.6 (d, JCP
¼ 169.9, CHP), 110.7, 110.8, 110.9, 120.7, 120.8, 126.2, 127.1,
128.2, 128.9, 138.7, 149.0, 149.2 (C-Ar). 31P-NMR (194.4 MHz,
CDCl3) d, ppm: 19.1 (P). Found, %: C, 61.52; H, 7.08. For
Diethyl propargyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (7c)
1
0.19 g, yield 56% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.05 (t, J ¼ 6.0 Hz, 3H, CH3), 1.15 (t, J ¼
6.0 Hz, 3H, CH3), 2.39 (s, 1H, CH), 3.72 (s, 3H, OCH3), 3.82 (s,
3H, OCH3), 3.87–3.94 (m, 2H, CH2), 3.99–4.17 (m, 4H, 2CH2),
4.75 (d, JHP ¼ 15.0 Hz, 1H, CHP), 6.70–6.91 (m, 3H, H-Ar). 13C-
NMR (75.0 MHz, CDCl3), d, ppm: 16.2 (d, JCP ¼ 6.0, CH3), 16.3
(d, JCP ¼ 6.0, CH3), 55.7 (OCH3), 55.8 (OCH3), 56.3 (d, JCP ¼ 15.9,
CH2OCHP), 62.8 (d, JCP ¼ 6.8, CH2OP), 63.2 (d, JCP ¼ 6.8,
CH2OP), 75.6 (C^CH), 75.7 (d, JCP ¼ 172.1, CHP), 78.4 (C^CH),
110.8, 111.2, 121.3, 125.6, 148.9, 149.4 (C-Ar). 31P-NMR (194.4
MHz, CDCl3), d, ppm: 19.0 (P). Found, %: C, 55.95; H, 6.60. For
C
21H29O6P (408.2). Calculated, %: C, 61.76; H, 7.16.
Diethyl 2-methylpropyloxy(3-methoxy-4-propargyloxyphenyl)
methyl phosphonate (8a)
1
0.25 g, yield 66% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 0.90 (t, J ¼ 3.0 Hz, 6H, 2CH3), 1.21–1.27
(m, 6H, 2CH3), 1.82–1.95 (m, 1H, CH), 2.50 (d, J ¼ 3.0 Hz, 1H,
CH), 3.15–3.27 (m, 2H, CH2), 3.86 (s, 3H, OCH3), 3.98–4.09 (m,
4H, 2CH2), 4.51 (d, JHP ¼ 15.0 Hz, 1H, CHP), 4.73 (d, J ¼ 3.0 Hz,
2H, CH2), 6.90–7.04 (m, 3H, H-Ar). 13C-NMR (75.0 MHz, CDCl3),
d, ppm: 16.3 (d, JCP ¼ 5.3, CH3), 16.4 (d, JCP ¼ 5.3, CH3), 19.2
(CH3), 19.3 (CH3), 28.4 (CH), 55.8 (OCH3), 56.8 (OCH2), 62.8 (d,
JCP ¼ 6.8, CH2OP), 63.1 (d, JCP ¼ 6.8, CH2OP), 75.8 (C^CH), 76.9
(d, JCP ¼ 31.7, CH2OCHP), 77.7 (C^CH), 78.6 (d, JCP ¼ 160.6,
CHP), 111.3, 113.9, 120.5, 128.9, 146.8, 149.6 (C-Ar). 31P-NMR
(194.4 MHz, CDCl3), d, ppm: 19.3 (P). Found, %: C, 59.23; H,
7.46. For C19H29O6P (384.2). Calculated, %: C, 59.37; H, 7.60.
C
16H23O6P (342.1). Calculated, %: C, 56.14; H, 6.77.
Diethyl 4-chlorobutyloxy(3,4-dimethoxyphenyl)methyl
phosphonate (7d)
1
0.27 g, yield 69% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.19 (t, J ¼ 6.0 Hz, 3H, CH3), 1.34 (t, J ¼
6.0 Hz, 3H, CH3), 1.50–1.72 (m, 4H, 2CH2), 3.51–3.70 (m, 2H,
CH2), 3.88 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), 4.02–4.10 (m, 2H,
CH2), 4.53 (d, JHP ¼ 15.0 Hz, 1H, CHP), 6.71–6.87 (m, 2H, H-Ar),
7.63 (s, 1H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d,
JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 27.3 (CH2), 29.3 (CH2),
44.7 (ClCH2), 55.4 (OCH3), 56.9 (OCH3), 62.6 (d, JCP ¼ 6.8,
CH2OP), 63.5 (d, JCP ¼ 6.8, CH2OP), 71.4 (d, JCP ¼ 13.6, CH2-
OCHP), 78.1 (d, JCP ¼ 170.6, CHP), 110.5, 112.0, 121.8, 126.4,
149.0, 149.7 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.2
(P). Found, %: C, 51.56; H, 7.01. For C17H28ClO6P (394.1).
Calculated, %: C, 51.71; H, 7.15.
Diethyl 1-methylethyloxy(3-methoxy-4-propargyloxyphenyl)
methyl phosphonate (8b)
1
0.34 g, yield 89% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.17–1.25 (m, 12H, 4CH3), 2.49 (d, J ¼
3.0 Hz, 1H, CH), 3.58–3.66 (m, 1H, CH), 3.84 (s, 3H, OCH3),
3.93–4.09 (m, 4H, 2CH2), 4.63 (d, JHP ¼ 18.0 Hz, 1H, CHP), 4.70
(d, J ¼ 3.0 Hz, 2H, CH2), 6.89–7.04 (m, 3H, H-Ar). 13C-NMR (75.0
MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0,
CH3), 21.0 (CH3), 23.1 (CH3), 55.9 (OCH3), 56.8 (OCH2), 62.8 (d,
JCP ¼ 7.8, CH2OP), 63.3 (d, JCP ¼ 7.8, CH2OP), 71.6 (d, JCP ¼ 13.6,
CHOCHP), 75.8 (C^CH), 75.6 (d, JCP ¼ 171.4, CHP), 78.5
(C^CH), 111.3, 111.5, 113.9, 120.4, 129.6, 146.8 (C-Ar). 31P-NMR
(194.4 MHz, CDCl3), d, ppm: 19.8 (P). Found, %: C, 59.22; H,
7.46. For C19H29O6P (384.2). Calculated, %: C, 59.37; H, 7.60.
Diethyl benzyloxy(3,4-dimethoxyphenyl)methyl phosphonate
(7e)
1
0.32 g, yield 81% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.17 (t, J ¼ 6.0 Hz, 3H, CH3), 1.25 (t, J ¼
6.0 Hz, 3H, CH3), 3.86 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 4.02–
4.12 (m, 4H, 2CH2), 4.37 (d, JHP ¼ 12.0 Hz, 1H, CHP), 4.61 (dd, J
¼ 9.0, 12.0 Hz, 2H, CH2), 6.83 (d, J ¼ 9.0 Hz, 1H, H-Ar), 6.94–6.96
(m, 1H, H-Ar), 7.05 (s, 1H, H-Ar), 7.29 (s, 5H, H-Ar). 13C-NMR
(75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d,
Diethyl propargyloxy(3-methoxy-4-propargyloxyphenyl)methyl
phosphonate (8c)
1
JCP ¼ 6.0, CH3), 55.8 (OCH3), 55.9 (OCH3), 62.7 (d, JCP ¼ 6.8, 0.27 g, yield 74% colorless oil. H NMR spectrum, (300 MHz,
CH2OP), 63.2 (d, JCP ¼ 6.8, CH2OP), 71.4 (d, JCP ¼ 14.3, CH2- CDCl3), d, ppm (J, Hz): 1.11 (t, J ¼ 6.0 Hz, 3H, CH3), 1.20 (t, J ¼
OCHP), 76.6 (d, JCP ¼ 171.4, CHP), 110.8, 110.9, 111.2, 111.3, 6.0 Hz, 3H, CH3), 2.42 (t, J ¼ 3.0 Hz, 1H, CH), 2.47 (t, J ¼ 3.0 Hz,
121.1, 121.2, 126.7, 127.9, 128.2, 128.3, 137.1, 149.1 (C-Ar). 31P- 1H, CH), 3.78 (s, 3H, OCH3), 3.82–3.94 (m, 2H, CH2), 3.98–4.08
NMR (194.4 MHz, CDCl3), d, ppm: 19.5 (P). Found, %: C, 60.87; (m, 4H, 2CH2), 4.65 (d, J ¼ 3.0 Hz, 2H, OCH2), 4.81 (d, JHP
¼
H, 6.74. For C20H27O6P (394.2). Calculated, %: C, 60.91; H, 6.90. 15.0 Hz, 1H, CHP), 6.86–6.98 (m, 3H, H-Ar). 13C-NMR (75.0
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MHz, CDCl3), d, ppm: 16.2 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, NMR (194.4 MHz, CDCl3), d, ppm: 18.9 (P). Found, %: C, 63.69;
CH3), 55.9 (OCH3), 56.5 (d, JCP ¼ 15.9, CH2OCHP), 56.9 (OCH2), H, 6.72. For C23H29O6P (432.2). Calculated, %: C, 63.88; H, 6.76.
62.9 (d, JCP ¼ 6.8, CH2OP), 63.2 (d, JCP ¼ 6.8, CH2OP), 75.7 (d, JCP
¼ 169.1, CHP), 75.7 (C^CH), 76.0 (C^CH), 78.3 (C^CH), 78.5
Diethyl((5-methyl-2-phenyl-1,3-dioxan-5-yl)methoxy)(4-
methoxyphenyl)methyl phosphonate (10a)
(C^CH), 111.6, 113.9, 121.1, 127.1, 147.2, 149.7 (C-Ar). 31P-NMR
(194.4 MHz, CDCl3), d, ppm: 18.9 (P). Found, %: C, 58.92; H,
6.29. For C18H23O6P (366.1). Calculated, %: C, 59.01; H, 6.33.
1
0.29 g, yield 62% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 0.87 (s, 3H, CH3), 1.20–1.33 (m, 6H,
2CH3), 3.59–3.73 (m, 4H, 2CH2), 3.81 (s, 3H, OCH3), 3.88–4.16
Diethyl 4-chlorobutyloxy(3-methoxy-4-propargyloxyphenyl)
methyl phosphonate (8d)
(m, 6H, 3CH2), 4.65 (d, JHP ¼ 15.0 Hz, 1H, CHP), 5.39 (s, IH, CH),
6.90 (d, J ¼ 9.0 Hz, 2H, H-Ar), 7.32–7.43 (m, 7H, H-Ar). 13C-NMR
1
(75.0 MHz, CDCl3), d, ppm: 16.4 (d, JCP ¼ 5.3, CH3), 16.5 (d, JCP
¼
0.26 g, yield 62% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.15–1.48 (m, 6H, 2CH3), 1.58–1.89 (m,
4H, 2CH2), 2.51 (t, J ¼ 3.0 Hz, 1H, CH), 3.41–3.61 (m, 4H, 2CH2),
5.3, CH3), 19.2 (CH3), 34.6 (C), 55.7 (OCH3), 62.6 (d, JCP ¼ 7.8,
CH2OP), 63.1 (d, JCP ¼ 7.8, CH2OP), 72.8 (OCH2), 73.0 (d, JCP
¼
14.3, CH2OCHP), 73.7 (OCH2), 79.0 (d, JCP ¼ 170.6, CHP), 101.7
(OCH), 113.9, 114.0, 126.1, 126.2, 128.2, 128.9, 129.5, 129.6,
138.3, 159.8 (C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.2
(P). Found, %: C, 61.95; H, 7.14. For C24H33O7P (464.2). Calcu-
lated, %: C, 62.06; H, 7.16.
3.84 (s, 3H, OCH3), 3.99–4.06 (m, 4H, 2CH2), 4.48 (d, JHP
¼
12.0 Hz, 1H, CHP), 4.71 (d, J ¼ 3.0 Hz, 2H, OCH2), 6.89–7.13 (m,
3H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP
¼
6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 26.9 (CH2), 29.3 (CH2), 44.7
(CH2), 55.9 (OCH3), 56.0 (OCH3), 56.7 (OCH2), 62.9 (d, JCP ¼ 6.8,
CH2OP), 63.1 (d, JCP ¼ 6.8, CH2OP), 69.9 (d, JCP ¼ 13.6, CH2-
OCHP), 75.9 (C^CH), 78.4 (d, JCP ¼ 170.6, CHP), 78.6 (C^CH),
110.8, 112.0, 121.8, 126.4, 149.0, 149.7 (C-Ar). 31P-NMR (194.4
MHz, CDCl3), d, ppm: 19.2 (P). 31P-NMR (194.4 MHz, CDCl3),
d, ppm: 19.2 (P). Found, %: C, 54.34; H, 6.65. For C19H28ClO6P
(418.1). Calculated, %: C, 54.48; H, 6.74.
Diethyl((5-methyl-2-phenyl-1,3-dioxan-5-yl)methoxy)(3,4-
dimethoxyphenyl)-methyl phosphonate (10b)
1
0.35 g, yield 70% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 0.87 (s, 3H, CH3), 1.19 (t, J ¼ 6.0 Hz, 3H,
CH3), 1.26 (t, J ¼ 6.0 Hz, 3H, CH3), 3.63–3.75 (m, 4H, 2CH2),
3.59–3.79 (m, 2H, CH2), 3.88 (s, 3H, OCH3), 3.96 (s, 3H, OCH3),
4.01–4.15 (m, 4H, 2CH2), 4.63 (d, JHP ¼ 15.0 Hz, 1H, CHP), 5.38
(s, IH, CH), 6.84–7.00 (m, 2H, H-Ar), 7.05 (s, 1H, H-Ar), 7.28–7.37
(m, 5H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.4 (d, JCP
¼ 6.0, CH3), 16.5 (d, JCP ¼ 6.0, CH3), 19.1 (CH3), 35.0 (C), 55.8
Diethyl benzyloxy(3-methoxy-4-propargyloxyphenyl)methyl
phosphonate (8e)
1
0.36 g, yield 87% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.19 (d, J ¼ 6.0 Hz, 3H, CH3), 1.24 (d, J ¼
6.0 Hz, 3H, CH3), 2.52 (d, J ¼ 3.0 Hz, 1H, CH), 3.87 (s, 3H,
OCH3), 3.90–4.13 (m, 4H, 2CH2), 4.38 (d, J ¼ 12.0 Hz, 1H, CH),
4.40 (d, JHP ¼ 12.0 Hz, 1H, CHP), 4.67 (d, J ¼ 12.0 Hz, 1H, CH),
4.77 (d, J ¼ 3.0 Hz, 2H, CH2), 6.94–6.98 (m, 3H, H-Ar), 7.06–7.32
(m, 5H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm: 16.3 (d, JCP
¼ 6.0, CH3), 16.5 (d, JCP ¼ 6.0, CH3), 55.9 (OCH3), 56.8 (OCH2),
62.8 (d, JCP ¼ 6.8, CH2OP), 63.1 (d, JCP ¼ 6.8, CH2OP), 71.5 (d, JCP
¼ 14.3, CH2OCHP), 75.9 (C^CH), 76.6 (d, JCP ¼ 170.6, CHP),
78.5 (C^CH), 111.6, 111.7, 113.9, 120.8, 120.9, 127.9, 128.2,
128.4, 137.1, 147.1, 149.8 (C-Ar), 31P-NMR (194.4 MHz, CDCl3),
d, ppm: 19.4 (P). Found, %: C, 63.03; H, 6.48. For C22H27O6P
(418.2). Calculated, %: C, 63.15; H, 6.50.
(OCH3), 55.9 (OCH3), 62.8 (d, JCP ¼ 7.8, CH2OP), 63.1 (d, JCP
¼
7.8 CH2OP), 72.9 (d, JCP ¼ 14.3, CH2OCHP), 73.2 (OCH2), 73.3
(OCH2), 79.0 (d, JCP ¼ 170.6, CHP), 101.8 (OCH), 110.8, 111.1,
111.2, 120.8, 120.9, 126.1, 128.2, 128.3, 128.9, 138.3, 149.0, 149.3
(C-Ar). 31P-NMR (194.4 MHz, CDCl3), d, ppm: 19.2 (P). Found, %:
C, 60.62; H, 6.85. For C25H35O8P (494.2). Calculated, %: C, 60.72;
H, 7.13.
Diethyl 2-(N-methyl-N-phenylamino)ethyloxy(4-
methoxyphenyl)methyl phosphonate (12)
1
0.12 g, yield 29% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.21 (t, J ¼ 6.0 Hz, 3H, CH3), 1.26 (t, J ¼
6.0 Hz, 3H, CH3), 2.98 (s, 3H, CH3), 3.57–3.68 (m, 4H, 2CH2),
3.82 (s, 3H, OCH3), 3.93–4.11 (m, 4H, 2CH2), 4.58 (d, JHP
¼
Diethyl 2-phenylethyloxy(3-methoxy-4-propargyloxyphenyl)
methyl phosphonate (8f)
15.0 Hz, 1H, CHP), 6.68 (d, J ¼ 9.0 Hz, 2H, H-Ar), 6.87 (d, J ¼
9.0 Hz, 2H, H-Ar), 7.18–7.35 (m, 5H, H-Ar). 13C-NMR (75.0 MHz,
CDCl3), d, ppm: 16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3),
36.2 (CH3), 55.7 (OCH3), 55.8 (NCH2), 62.8 (d, JCP ¼ 7.8, CH2OP),
63.6 (d, JCP ¼ 7.8, CH2OP), 71.4 (d, JCP ¼ 14.3, CH2OCHP), 78.7
(d, JCP ¼ 163.1, CHP), 110.7, 110.8, 110.9, 120.7, 120.8, 126.1,
127.1, 128.2, 128.9, 138.7, 149.0 (C-Ar). 31P-NMR (194.4 MHz,
CDCl3) d, ppm: 19.1 (P). Found, %: C, 61.87; H, 7.38; N, 3.44. For
1
0.35 g, yield 82% colorless oil. H NMR spectrum, (300 MHz,
CDCl3), d, ppm (J, Hz): 1.16–1.24 (m, 6H, 2CH3), 2.51 (s, 1H, CH),
2.88–2.93 (m, 2H, CH2), 3.67–3.71 (m, 2H, CH2), 3.79 (s, 3H,
OCH3), 3.92–4.04 (m, 4H, 2CH2), 4.56 (d, JHP ¼ 15.0 Hz, 1H,
CHP), 4.73 (d, J ¼ 3.0 Hz, 2H, CH2), 6.86–6.98 (m, 3H, H-Ar),
7.17–7.38 (m, 5H, H-Ar). 13C-NMR (75.0 MHz, CDCl3), d, ppm:
16.3 (d, JCP ¼ 6.0, CH3), 16.4 (d, JCP ¼ 6.0, CH3), 36.2 (CH2), 55.8
C
21H30NO5P (407.2). Calculated, %: C, 61.90; H, 7.42; N, 3.44.
(OCH3), 56.8 (OCH2), 62.9 (d, JCP ¼ 6.8, CH2OP), 63.2 (d, JCP
¼
6.8, CH2OP), 71.5 (d, JCP ¼ 13.6, CH2OCHP), 75.8 (C^CH), 78.5
(C^CH), 78.6 (d, JCP ¼ 169.9, CHP), 111.2, 111.3, 113.9, 120.5,
Conflicts of interest
120.6, 126.2, 128.3, 128.6, 129.0, 138.7, 146.9, 149.7 (C-Ar); 31P- There are no conicts to declare.
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14 D. Q. Shi, Z. L. Sheng, X. P. Liu and H. Wu, Heteroat. Chem.,
2003, 14, 266–268.
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