|Year : 2012 | Volume
| Issue : 2 | Page : 109-115
Regioselective addition of alkyl phosphites on 6-(aryliminomethyl)-furobenzopyran-5-one derivatives
Nabila M. Ibrahim1, Asmaa A. Magd-El-Din2, Amira S. Abd El-All2, Eman F. Al-Amrousi1, Hisham Abdallah A. Yosef1
1 Department of Organometallic and Organometalloid Chemistry, Division of Organic Chemistry, National Research Centre, Dokki, Cairo, Egypt
2 Department of Natural and Microbial Products Chemistry, Division of Pharmaceutical and Drug Industries Research, National Research Centre, Dokki, Cairo, Egypt
|Date of Submission||01-Mar-2012|
|Date of Acceptance||13-May-2012|
|Date of Web Publication||18-Jul-2014|
Hisham Abdallah A. Yosef
Department of Organometallic and Organometalloid Chemistry, National Research Centre, Dokki, Cairo, 12622
Source of Support: None, Conflict of Interest: None
Trialkyl phosphites 2a,b attack 6-(aryliminomethyl)furobenzopyran-5-ones 1a–e regiospecifically at the carbon–carbon double bond of the γ-pyrone ring to yield new 1,2-addition phosphonate products for which structures 3a–e have been respectively assigned.
The alkyl phosphites 2a,b attacked the monoanils 1a–e at the azomethine carbon of the C=N bond to yield corresponding phosphonate adducts 5a–e when reactions were carried out in the presence of a controlled amount of acetic acid. Phosphonates 5a–e could also be obtained by the reaction of dialkyl phosphites 4a,b with anils 1a–e. Structures of the new phosphonates 3a–e were elucidated by elemental analyses as well as spectroscopic methods. The 1H and 13C nuclear magnetic resonance and infrared measurements were helpful tools in confirming the structures of the new products.
Results and conclusion
The insecticidal activities of phosphonates 3a–e and their respective regioisomers 5a–e against adult Aphis gossypii (Glover), which infest cotton crops, were determined. The structure–activity relationship has been discussed.
Keywords: 6-(aryliminomethyl)furobenzopyran-5-ones, 13C nuclear magnetic resonance, insecticidal activities, phosphorylation, regioselectivity, spectroscopic evidences, structural elucidation
|How to cite this article:|
Ibrahim NM, Magd-El-Din AA, El-All AA, Al-Amrousi EF, Yosef HA. Regioselective addition of alkyl phosphites on 6-(aryliminomethyl)-furobenzopyran-5-one derivatives. Egypt Pharmaceut J 2012;11:109-15
|How to cite this URL:|
Ibrahim NM, Magd-El-Din AA, El-All AA, Al-Amrousi EF, Yosef HA. Regioselective addition of alkyl phosphites on 6-(aryliminomethyl)-furobenzopyran-5-one derivatives. Egypt Pharmaceut J [serial online] 2012 [cited 2022 Aug 10];11:109-15. Available from: http://www.epj.eg.net/text.asp?2012/11/2/109/136958
| Introduction|| |
It is evident that compounds of phosphorus play vital roles in the living process. Our interest in the field of organophosphorus chemistry led us to study the preparation of organophosphorus compounds because of their increasing importance in industry and biology 1–3. Aldehydes 4–6, ketones 7, 8, aldimines 9–11 and ketimines 12–14 are suitable substrates for the preparation of members of this class of compounds. Recently, we have reported on the reaction of monoarylimines 1a–e, derived from 4-methoxy-5-oxo-5H-furo [2,3-g]benzopyran-6-carboxaldehyde and 4,9-dimethoxy-5-oxo-5H-furo [2,3-g]benzopyran-6-carboxaldehyde, with dialkyl phosphites 4a,b 1. Now, with our growing interest in the field of organophosphorus chemistry of arylimines derived from carbonyl compounds 9,12–14, we have studied the behaviour of trialkyl phosphites 2a,b towards the monoarylimines 1a–e under different reaction conditions.
| Subjects and methods|| |
Solvents were purified and dried according to usual procedures. Trialkyl phosphites are commercially available from Aldrich Chem. Co. (New Jersey, USA) and were freshly distilled immediately before use. The starting compounds 1a 1 , 1b 1, 1c 15, 1d 1 and 1e 1 were prepared according to the given procedures. Melting points were recorded on an electrothermal melting point apparatus and were uncorrected. The infrared spectra were obtained from KBr disks using a Brüker Vector 22 infrared spectrophotometer (Germany) and/or a JASCO FT/IR-300E fourier transform infrared spectrophotometer (Japan) and reported in cm−1. 1H-nuclear magnetic resonance (NMR) spectra were recorded on a Varian Mercury VX-300 spectrometer (Japan) (at 300 MHz) and/or a JEOL JNM-EX 270 FT spectrometer (Japan) (at 270 MHz). Proton chemical shifts (δ) are reported in ppm downfield from tetramethylsilane. 13C NMR spectra were recorded on a JEOL JNM-EX 270 FT (at 68 MHz) and/or a JOEL 500 AS (at 125 MHz) spectrometer. Mass spectra were recorded on a Finnigan SSQ 7000 spectrometer (Japan) and/or a Shimadzu GC MS-Q 1000 EX spectrometer at 70 eV (Electron Impact, Japan). Microanalyses were carried out at the Microanalytical Unit, Cairo University (Cairo, Egypt).
| Experimental|| |
Reactions of 1a–e with trialkyl phosphites 2a,b
A mixture of the appropriate anil 1a–e (0.005 mol) and trialkyl phosphite (TAP) 2a (or 2b; 0.01 mol) was heated in the absence of a solvent at 100°C until the starting anil could no longer be detected (TLC) [TLC silica gel aluminum sheet (type 60 F254, Merk, Damstadt, Germany)]. After removal of the volatile materials in vacuo, the residual substance was washed with cold diethyl ether and then recrystallized from petroleum ether at 60–80°C to yield the respective phosphonates 3a–e in yellow crystalline forms.
Diisopropyl 6-((4-fluorophenylimino)methyl)-4-methoxy-5-oxo-6,7-dihydro-5H-furo [3,2-g]chromen-7-ylphosphonate (3a, C25H27FNO7P)
Yield 81%, melting point (MP) 128–130°C; IR (KBr, cm−1): 3096, 3064 (C–H aromatic), 2982 (C–H aliphatic, asymmetric), 2936 (C–H aliphatic, symmetric), 1713 (exocyclic C=O of a saturated 4-pyranone ring), 1647 (C=N), 1611, 1552 (C=C), 1247 (P=O), 1135 (C−O) and 1015 (P−O−C). 1H NMR (DMSO-d6): 1.00, 1.05, 1.10, 1.14 (12, O–CH–(C H 3)2, 4d, J HH=6.0 Hz), 4.03 (1H, CH–C H –CH=N, dd, J HH=8.0 Hz, J HP=10.8 Hz), 4.08 (3H, –OC H 3, s), 4.51 (2H, O–C H –CH3, dsp, J HH=6.0 Hz, J HP=10.8 Hz), 5.43 (1H, O–C H –P, dd, J HH=8.0 Hz, J HP=18.0 Hz), 6.90 (1H, O−CH−C H , furan ring d, J HH=7.17 (2H, aromatic meta to F atom, d, AB system, J HH=9 Hz); 7.26 (2H, aromatics ortho to F atom, d, AB system, J HH=9 Hz), 7.40 (1H, aromatic, s), 7.82 (1H, C H =N, d, 3 J HH=10.8 Hz), 7.91 (1H, O–C H , furan, d, J HH=2.0 Hz).
13C NMR (DMSO-d6): 21.02 (P–O–CH– C H3), 23.67 (P–C– C H–CH=N, 2 J CP=28.0 Hz), 60.84 (O– C H3), 70.71 (P–O– C H–CH3, d, 2 J CP=25.0 Hz), 74.45 (O– C H–P, d, 1 J CP=146.4 Hz), 94.88 ( C –H aromatic), 98.37 (quaternary aromatic carbon), 106.05 (O–CH– C H, furan), 112.25 (quaternary aromatic carbon), 116.80 (carbons ortho to fluorine atom, d,2 J CF=22.62 Hz), 118.36 (carbons meta to fluorine atom, d, 3 J CF=8.3 Hz), 137.26 (C=N– C ), 143.48 (O– C H furan), 145.27 ( C H=N), 154.92 ( C –OCH3), 157.81, 158.56 (quaternary aromatic carbons), 171.97 ( C –F) and 181.25 ( C =O). MS m/z (%): 503 [M]+ (3%). Anal. calcd (%) for C25H27FNO7P (503.46): C, 59.64; H, 5.41; F, 3.77; N, 2.78; P, 6.15. Found (%): C 59.76; H, 5.28; 2.61; P, 5.22.
Diisopropyl 6-((4-chlorophenylimino)methyl)-4-methoxy-5-oxo-6,7-dihydro-5H-furo [3,2-g]chromen-7-ylphosphonate (3b, C25H27ClNO7P)
Yield 80%; MP 118–120°C. IR (KBr, cm−1): 3110, 3066 (C–H aromatic), 2980 (C–H aliphatic, asymmetric), 2934 (C–H aliphatic, symmetric), 1717 (exocyclic C=O of a saturated 4-pyranone ring), 1645 (C=N), 1601, 1553 (C=C); 1246 (P=O); 1129 (C−O), and 983 (C−Cl aromatic). 1H NMR (DMSO-d6): 0.966, 1.04, 1.11, 1.18 (6H, O–CH(C H 3)2, 4d, J HH=8.1 Hz), 4.03 (1H, CH–C H –CH=N, d, J HH=10.8 Hz), 4.06 (3H, OC H 3, s), 5.41 (1H, P–C H –CH, dd, J HH=10.8 Hz, J HP=15.5 Hz), 6.87 (1H, O–CH–C H furan, d, J HH=3 Hz), 7.12 (2H, aromatic meta to chlorine, AB system, d, J HH=8.1 Hz), 7.25 (2H, aromatics ortho to chlorine, AB system, d, J HH=8.1 Hz), 7.41 (1H, s, aromatic), 7.80 (1H, –C H =N, d, J HH=10.8 Hz), 7.88 (1H, O–C H furan, d, J HH=3.0 Hz). MS m/z (%): [M]+• at 519 and 521 (2.7% and 0.83%). Anal. calcd (%) for C25H27ClNO7P (519.92): C, 57.75; H, 5.23; Cl, 6.82; N, 2.69; P, 5.96. Found (%): C, 57. 86; H, 5.02; Cl, 6.57; N, 2.61; P, 6.12.
Diisopropyl 6-((4-bromophenylimino)methyl)-4-methoxy-5-oxo-6,7-dihydro-5H-furo [3,2-g]chromen-7-ylphosphonate (3c, C25H27BrNO7P)
Yield 83%, MP 150–152°C. IR (KBr, cm−1): 3066 (C–H, aromatic), 2979 (C–H aliphatic, asymmetric), 2933 (C–H aliphatic, symmetric), 1717 (exocyclic C=O of a saturated 4-pyranone ring), 1645 (C=N), 1601, 1553 (C=C), 1246 (P=O) and 1127 (P–O–C).
1H NMR (DMSO-d6): 0.09, 1.04, 1.11, 1.17 (12H, CH–(C H 3)2, four doublets, each of 1,3 J HH=5.4 Hz), 4.04 (1H, CH–C H –CH=N, d, J HH=10.8 Hz), 4.06 (3H, O–C H 3), 4.48 (2H, O–C H –(CH3)2, m), 5.41 (1H, O–C H –CH, dsp, J HH=10.8 Hz, J HP=19.3 Hz), 6.87 (1H, O–CH–C H , furan ring, d, J HH=2 Hz), 7.15 (2H, aromatic meta to bromine, AB system, d, J HH=8.1 Hz), 7.33 (2H, aromatic para to bromine, AB system, d, J HH=8.1 Hz), 7.56 (1H, aromatic, s), 7.82 (1H, C H =N, d, J HH=10.8 Hz),7.88 (1H, O–C H , furan, d, J HH=2.0 Hz). MS m/z (%): [M]+• at 564 and 566 (2.3 and 2.4%). Anal. calcd (%) for C25H27BrNO7P (564.37): C, 53.21; H, 4.82; Br, 14.16; N, 2.48; P, 5.49. Found (%): C, 53.58; H, 4.57; Br, 14.00; N, 2.24; P, 5.62.
Diisopropyl 6-((4-fluorophenylimino)methyl)-4,9-dimethoxy-5-oxo-6,7-dihydro-5H-furo [3,2-g]chromen-7-ylphosphonate (3d, C26H29FNO8P)
Yield 79%; MP 98–100°C. IR (KBr, cm−1): 3135, 3072 (C–H aromatic), 2983, 2935 (C–H aliphatic), 1714 (exocyclic C=O of a saturated 4-pyranone ring), 1644 (C=N), 1605, 1553 (C=C aromatic), 1240 (P=O) and 1197 (P–O–C). 1H NMR (DMSO-d6): 1.05, 1.11, 1.15, 1.16 (12H, CH(CH3), four doublets each with J HH=6.0 Hz), 3.86 (1H, CH–C H –CH=N, dd, 3 J HH=6.8 Hz, 3 J HH=8.3 Hz), 3.88 (3H, OC H 3,s), 3.92 (3H,OC H 3,s), 4.47 (2H, C H (CH3)2,dsp, J HH=6.3 Hz, J HP=11.5 Hz), 5.46 (1H, O–C H –P, dd, 3 J HH=6.8 Hz, 2 J HP=15 Hz), 7.07 (1H, O–CH–C H , furan ring, d, J HH=2.0 Hz), 7.21 (2H, aromatics meta to fluorine, AB system, 3d, J HH=8.1 Hz), 7.36 (2H, aromatics ortho to fluorine, AB system, d, 3 J HH=8.1 Hz). 7.77 (1H, CH–C H =N, d, J HH=9.3 Hz), 7.88 (1H, O–C H , furan ring, d, J HH=2.0 Hz). 13C NMR (DMSO-d6): 21.56 (O–CH–( C H3)2), 24.25 ( C H–CH=N), d, 2 J CP=14.31), 61.42 (O C H3), 61.75 (O C H3), 71.41 (O– C H–(CH3)2, d, 2 J CP=7.2 Hz), 74.41 (O– C H–P, d, 1 J CP=156.3 Hz), 98.79 (quaternary aromatic carbon), 105.99 (CH– C H furan), 113.79 (quaternary fused aromatic carbon), 116.92 (two carbons ortho to fluorine, d, 2 J CF=13.6 Hz), 118.52 (two carbons meta to fluorine, d, 3 J CF=5.4 Hz), 129.91 (C=N– C ), 143.97 (O– C H furan), 145.86 ( C H=N), 148.99, 149.49, 150.84, 159.02 (quaternary aromatic carbons), 172.67 ( C –F), 181.25 ( C =O). MS m/z (%): 533 (5%). Anal. Calcd. (%) for C26H29FNO8P (533.49): C, 58.54; H, 5.48; F, 3.56; N, 2.63; P, 5.81. Found (%): C, 58.28; H, 5.20; F, 3.31; N, 2.59; P, 5.95.
Diethyl 6-((4-chlorophenylimino)methyl)-4,9-dimethoxy-5-oxo-6,7-dihydro-5H-furo [3,2-g]chromen-7-ylphosphonate (3e, C24H25ClNO8P)
Yield 86%; MP 198–200°C. IR (KBr, cm−1): 3131, 3083 (C−H aromatic); 2975 (C−H aliphatic, asymmetric); 2930 (C−H aliphatic, symmetric); 1715 (exocyclic C=O of a saturated 4-pyranone ring); 1645 (C=N), 1600, 1552 (C=C); 1246 (P=O); 1129 (P–O–C); 984 (C−Cl aromatic). 1H NMR (DMSO-d6): 1.08 (6H, CH2–C H 3, t, J HH=7.1 Hz), 3.92 (3H, OC H 3, s), 3.71 (1H, C H –CH=N, dd, 3 J HH=6.7 Hz, 3 J HH=8.3 Hz) 3.97 (3H, OC H 3, s), 3.93–4.00 (4H, OC H 2CH3, m), 5.58 (1H, O–C H –P, dd, 3 J HH=10.0 Hz, 2 J HP=15.0 Hz), 7.15 (1H, O–C–C H , furan, d, 3 J HH=3.2 Hz), 7.40–7.45 (4H, aromatic, m), 7.85 (1H, C H =N, d, 3 J HH=10.2 Hz), 7.96 (1H, O–C H furan, d, J HH=3.2 Hz). 13C NMR (DMSO-d6): 16.18 (OCH2– C H3, d, 3 J CP=5.4 Hz), 38.72 (P–CH– C H, d, 2 J CP=20.9 Hz), 60.92 (O C H3), 61.34 (O C H3), 62.28 (P–O– C H2–CH3, d, 2 J CP=16.3 Hz), 74.20 (O– C H–P, d, 1 J CP=162.0 Hz), 98.95 (quaternary aromatic carbon), 105.34 (O–CH– C H, furan), 113.13 (quaternary aromatic carbon), 117.61 (carbons meta to chlorine), 127.25 (carbons ortho to chlorine), 129.39, 129.54 (quaternary aromatic carbons), 139.17 (C=N– C ), 142.47 (O– C H, furan), 145.51 ( C H=N), 148.36, 149.10, 150.39 (quaternary aromatic carbons) and 180.79 ( C =O). MS: m/ z (%): 521and 523 (3 and 0.92%). Anal. calcd (%) for C24H25ClNO8P (521.89): C, 55.23; H, 4.83; Cl, 6.79; N, 2.68; O, 24.53; P, 5.93. Found (%): C, 55.01; H, 4.69; Cl, 6.51; N, 2.50; P, 6.19.
Reactions of 1a–e with trialkyl phosphites 2a,b in the presence of acetic acid
A mixture of the appropriate anil 1a–e (0.005 mol), trialkyl phosphite 2a (or 2b; 0.01 mol) and a few drops of acetic acid was heated in the absence of a solvent at 100°C until the starting anil could no longer be detected (TLC). After removal of the volatile materials in vacuo, the residual substance was washed with cold diethyl ether and then recrystallized from ethanol to yield the respective phosphonates as yellow crystalline products, which were identified to be the corresponding phosphonates 5a–e (MP, mixed MP, comparative TLC and comparative IR) 1.
Toxicity of the tested compounds was studied under laboratory conditions using the slide-dip method 16 at the Central Agricultural Laboratory of Pesticides, Cairo, Egypt. Concentrations were prepared by dissolving each compound (0.05 g) in 5 ml of acetone and then diluting it with water in a ratio of 2 : 3 (this dilution did not cause any mortality in insects). Aphis gossypii was transferred onto a slide using a fine brush and then adults were affixed to a double-face scotch tape and fixed tightly onto the slide on their dorsal side. The slides were then dipped into the toxicant solution for 10 s and the excess toxicant was blotted off with filter paper. Mortality counts were carried out 2 h after treatment. A mortality of 50% for each compound was determined from the corresponding average mortality percentage that was corrected, if necessary, using Abbott’s formula 17.
| Results and discussion|| |
On performing the reaction of monoanils 1a–e with trialkyl phophites 2a,b in the absence of a solvent at 100 °C, yellow crystalline products were obtained. They were assigned the phosphonate structures 3a–e [Scheme 1].
However, phosphonates 3a–e were found to be isomeric (microanalyses and mass spectrometry) but not identical (comparative MPs, TLC, IR and 1H NMR spectra) to phosphonates 5a–e 1 that were obtained from the reaction of anils 1a–e with dialkyl phosphites 4a,b [Scheme 2].
In contrast, the reaction of anils 1a–e with phosphites 2a,b, in the presence of a few drops of acetic acid, was found to yield phosphonates 5a–e 1 (MP, mixed MP, TLC and IR, Scheme 2].
Thus, it is clear that anils 1a–e behave differently towards alkyl phosphites depending on the nature of the reagent and/or the reaction conditions.
The spectroscopic measurements, particularly decoupled and distortionless enhancement by polarization transfer 13C NMR experiments, IR and 1H NMR, have provided valuable evidence in confirming the structure of phosphonates 3a–e. The assigned structure 3a is established by analytical and spectral data:
The IR spectrum (KBr) showed intense bands at 1247, 1135 and 1015 cm−1, corresponding to P=O, C–O and P–O–C alkyl stretching vibrations 18, 19, respectively. Absorption bands of the carbonyl group appeared at 1650 cm−1 in anil 1a and at 1647 cm−1 in phosphonate 5a 1, whereas in phosphonate 3a, it appeared at 1713 cm−1, a value that is typical for exocyclic C=O of a saturated six-membered ring 19. Moreover, the spectrum of 3a indicated the presence of C=N absorption at 1647 cm−1 (which appeared in the IR spectrum of 1a at 1616 cm−1) 1 and the absence of any absorption band because of the NH group, which generally appears in the region of 3350–3300 cm−1 18,19 (which appeared in the spectrum of 5a at 3303 cm−1) 1.
The 1H NMR spectrum of 3a (DMSO-d6, δ ppm) showed four doublets at 1.00, 1.05, 1.10 and 1.14 ppm, each with J HH=6.0 Hz, because of protons of the four methyl groups of the two isopropoxy groups attached to phosphorus. Apparently, the asymmetry of the molecule because of the presence of a stereocenter would render the four methyl groups diastereotopic, and hence anisochronous, thus resulting in the observed splitting pattern 20,21. Moreover, the isopropoxy-C H protons attached to phosphorus (2H) appeared as a doublet of septet at 4.51 ppm (with 3 J HH=6.0 Hz and 3 J PH=10.8 Hz) because of coupling with the methyl groups and the phosphorus atom, respectively. Signals were also recorded at 4.03 ppm (1H, CH–C H –CH=N, dd, 1,3 J HH=8.0 Hz, 1,3 J HH=10.8 Hz) and 5.43 ppm (1H, O−C H −P, dd, 1,3 J HH=8.0 Hz and 1,2 J HP=18.0 Hz) 22,23. Moreover, the doublet (1,3 J HH=10.8 Hz) that appeared at δ of 7.82 ppm could be attributed to the azomethine C H =N proton. The spectrum also lacked absorption due to D2O-exchangeable protons (N H or O H ).
The 13C NMR spectrum of 3a showed signals at 181.25 and 145.27 ppm because of carbon atoms of C =O and C H=N groups, whose signals appeared at 180.48 and 144.48 ppm, respectively, in the spectrum of 1a. The signals present at 111.31 and 154.17 ppm in the 13C NMR spectrum of 1a because of carbon-6 and carbon-7, respectively, disappeared in the spectrum of phosphonate 3a. Instead, two doublets centred at 23.67 ppm (2 J CP=28.0 Hz) and 74.45 ppm (1 J CP=146.4 Hz) appeared in the spectrum of 3a, assignable to carbon-6 and carbon-7, respectively. The last doublet was in the region of ter-carbon–oxygen chemical shifts and its large J-value was typical for spin–spin coupling between directly bonded carbon and phosphorus atoms 24,25. Meanwhile, in phosphonate 5a, the signal because of the carbon attached to phosphorus appeared at δ of 42.22 ppm (1 J CP=147.0 Hz) 1, cf. Experimental.
In the mass spectrum of 3a, the molecular ion peak (M+•; the cation radical a) appeared at m/z 503 (3%), showing its relative instability under electron bombardment. Cleavage of [M]+•at axis x produced the base peak cation b at m/z 338 (100%), which released a neutral CH2O molecule from the methoxy group to yield cation c at m/z 308 (2%). Radical (cation a) [M]+• was also cleaved at axis y to yield cation d at m/z 381 (1%), which in turn lost a neutral 1-propene molecule to yield cation e at m/z 339 (20% Scheme 3].
Thus, in their reactions with anils 1a–e, phosphites 3a and 3b undergo a Michael-type addition reaction 26,27 in which the phosphite–phosphorus atom regiospecifically attacks carbon-7 of the C=C bond in the γ-pyrone ring to yield 1,2-addition phosphonate products 3a–e exclusively [Scheme 4].
The negative charge, formed on carbon-6 in phosphonium betaine intermediate 6, is resonance stabilized through conjugation with the carbonyl and/or imine groups. This conjugation reduces the activation energy for addition. Thereafter, the betaine 6 undergoes solvation to yield intermediate 7 with pentacovalent phosphorus similar to that in many phosphobetaine structures 28. Collapse of 7 through the release of an alcohol molecule yielded the respective phosphonates 3a–e.
However, when the reactions were performed in acetic acid, trialkyl phosphites 2a,b were hydrolysed first to the corresponding dialkyl analogous 4a,b, which in turn reacted with anils 1a–e to yield phosphonates 5a–e. Apparently, the regiochemistry of the nucleophilic addition of alkyl phosphites 2 and 4 to anils 1a–e may be attributed to the steric and electronic nature of both reactants. Thus, in terms of the hard–soft acid–base principle 29, 30, alkyl phosphites are considered to be soft bases. However, trialkyl phosphites are softer bases than dialkyl phosphites because of the tautomerism shown by the latter [Scheme 2]. However, because of the +R effect exerted by the adjacent oxygen atom, carbon-7 may be relatively less positively polarized (softer acid) than the azomethine carbon of the C=N bond. Therefore, it may be energetically more favourable for alkyl phosphites 2a,b (softer base) with their relatively bulky size to add to carbon-7 (softer acid), rather than to the azomethine carbon, to avoid the steric crowding 31 exerted by the substituted phenyl group on nitrogen in the transition states, leading to intermediates 6 and 7. However, phosphites 4 (harder base), with their relatively smaller size, tend to add preferentially at the more electrophilic azomethine carbon atom (harder acid) of the polarized C=N bond to yield 5. In this case, delocalization of the negative charge that developed on nitrogen over the substituted phenyl group stabilized the intermediate transition state.
Pesticidal activities are associated with a variety of organophosphorus compounds 32, 33, which may become less effective as a result of development of crossresistance in pests. Therefore, continuous efforts are being made towards developing a new generation of these pesticides. This led us to study the effect of phosphonates 3a–e and 5a–e on A. gossypii (Glover) using actillic (O-[2-(diethylamino0–6-methyl-4-pyridiminyl]O,O-dimethylphosphorothioate) as a standard reference (cf. Experimental). This sucking aphid pest infests cotton crops worldwide. It affects cotton yield by direct feeding and fibre quality by excreting honeydew, which supports the growth of harmful microorganisms. The results for the insecticidal activity of phosphonates 5a–e have been reported 1. However, as the biological and pharmaceutical activities of many organic compounds 34, 35, including phosphonate derivatives 36–38, strongly depend on the position of a given group in a certain class of compounds, it will be interesting to report the insecticidal activity for phosphonates 3a–e and compare it with the activity of their regioisomers 5a–e [Table 1].
|Table 1: Effect of treatment with phosphonates 3a–e and 5a–e on adults of Aphis gossypii (Glover)|
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From the results in [Table 1], it is evident that:
The LC50 values indicated that all of the tested compounds showed insecticidal activity against adult A. gossypii (Glover).
Among phosphonates 3 and 5, compound 3a was found to be the most effective, with a toxicity index (TI) value of 83.28% (LC50=1489.71), when compared with the reference insecticide actillic (TI=100%, LC50=1240.67). Compound 3e was found to be the least effective (TI=8.43%, LC50=14714.36). The order of decreasing activity was as follows: 3a>3c>5c>5a>3b>5d>5b>3d>5e>3e.
Among phosphonates 3, the order of decreasing activity was 3a>3c>3b>3d>3e, whereas for phosphonates 5, the order was 5c>5a>5d>5b>5e.
For the phosphonates that were derived from compound 1a (R=H), 3a–c, in which the phosphorus atom is linked to carbon-7, were found to be more active than their respective regioisomers 5a–c, in which the phosphorus atom is linked to the azomethine carbon. However, for the derivatives of 1b (R=OCH3), phosphonates 5d and 5e (phosphorus–azomethine carbon bond) were found to be more active than phosphonates 3d and 3e (phosphorus–carbon-7 bond), respectively.
Phosphonates 3e and 5e that have the diethylphosphoryl moiety (Rº=C2H5) are less effective than the other derivatives that have the diisopropylphosphoryl moiety (Rº=i-C3H7).
| Conclusion|| |
The present study clearly shows that anils 1a–e behave as ambident electrophiles, as they could be attacked by the phosphite reagents 2 and/or 4 either on carbon-7 or the azomethine carbon, yielding a variety of phosphonate regioisomers. The regioselectivity of attack depends on the steric and electronic nature of both the reagents and the substrates as well as the reaction conditions. Thus, although trialkyl phosphites 2 regiospecifically attack carbon-7 in anils 1a–e to yield phosphonates 3a–e exclusively, the dialkyl phosphites 4 attack the azomethine carbon regiospecifically to yield phosphonates 5a–e 1. However, the reaction of 2 with 1 in the presence of a few drops of acetic acid yielded phosphonates 5. The new phosphonates 3a–e which is derived from furochromones belong to many biologically active centers which can be used as drugs 39,40. They also belong to the pharmacologically interesting α-aminophosphonates 41–43. Insecticidal activity tests have confirmed that the phosphonate adduct 3a shows marked potency against adult A. gossypii (Glover), which infest cotton crops. Moreover, there is a marked difference in activity between the respective regioisomers, which confirms the structure–activity relationship principle.
| References|| |
|1.||Hafez TS, Yosef HAA, Abou Yousef HM, Al-Amrousi EF, Mahran MRH. Synthesis and insecticidal activities of some phosphonate adducts derived from 6-(aryliminomethyl)-furobenzopyran-5-ones. Phosphorus, sulfur and silicon and the related elements. 2010;185:2277–2285 |
|2.||Hafez TS, Essawy SA, Al-Amrousi EF, Mahran MRH. Reactions of furobenzopyran-6-carboxaldehydes with alkyl phosphites and ylidenetriphenyl phosphoranes (Wittig reagents). Egypt J Chem. 2007:45–58 |
|3.||Savignac P, Iogra B Modern phosphorus chemistry. 2003 Boca Raton CRC Press, Fl |
|4.||El Kaïm L, Gaultier L, Grimaud L, Dos Santos A. Formation of new phosphates from aldehydes by a DBU-catalysed phospha-brook rearrangement in a polar solvent. Synlett. 2005;15:2335–2336 |
|5.||Deron A, Milewska M, Barycki J, Sawka-Dobrowolska W, Gancarz R. NMR studies of the bishydroxy bisphosphonate synthesis from o-phthalic aldehyde and diethyl phosphate. Heteroatom Chem. 2002;13:157–164 |
|6.||Plazuk D, Zakrzewski J, Rybarczyk-Pirek A. Diastereoselective addition of dimethyl phosphite to 3,3º,4,4º-tetramethyl-1,1º-diphosphaferrocene-2-carbox aldehyde. J Organometal Chem. 2006;691:3098–3102 |
|7.||Mahran MR, Khidre MD, Abdou WM. The reaction of isatin, 5-methylisatin and their monoximes with alkyl phosphites, triphenylphosphine and phosphorus ylides. Phosphorus, sulfur and silicon. 1995;101:17–27 |
|8.||Borowitz IJ, Anschel M, Readio PD. Reactions of fluorenones and tetraphenyl cyclopentadienones with tricovalent phosphines and phosphites. J Org Chem. 1971;36:553–560 |
|9.||Khidre MD, Abou-Yousef HM, Mahran MRH. On the reaction of 3-(aryliminomethyl)chromones with alkyl phosphites and methylenetriphenylphosphoranes (Wittig reagents). Phosphorus, sulfur and silicon and related elements. 1998;140:147–157 |
|10.||Nazarski RB, Lewkowski JA, Skowroński R. Rationalization of the stereochemistry of an addition of dialkyl phosphites to certain chiral aldimines: the experimental and theoretical approach. Heteroatom Chem. 2002;13:120–125 |
|11.||Yuan C, Li S, Li C, Chen S, Huang W, Wang G, Pan C, Zhang Y. New strategy for the synthesis of functionalized phosphonic acids. Pure Appl Chem. 1996;68:907–912 |
|12.||Sidky MM, Mahran MR, Abdou WA, Hafez TS. Reaction of alkyl phosphites with mono-anils of benzil and o-naphthoquinone. Egypt J Chem. 1984;27:809–816 |
|13.||Abdou WM, Abd El-Rahman NM, Mahran MR. The behaviour of 3-aryliminoxindoles toward alkyl phosphites. J Prakt Chem. 1989;331:906–912 |
|14.||Boulos LS, Shabana R, Shaker YM. The behavior of 2-substituted-1,3-diphenylpropane-1,3-tione toward organophosphorus reagents. Heteroatom Chem. 2000;11:57–64 |
|15.||Fawzy NM, Swelam SA, Batran SA. Synthesis and pharmaceutical activity of new series of chromonyl derivatives. Boll Chim Farm. 2004;143:24–33 |
|16.||Dittrich J. A comparative study of toxicological test method on population of the two-spotted spider mits (Tetranychus telaricus). J Econ Entomol. 1962;55:633–648 |
|17.||Abbott WS. A method of computing the effectiveness of an insecticide. J Econ Entomol. 1925;18:265–267 |
|18.||Bellamy LJ The infra-red spectra of complex molecules. 1958;311 New York John Wiley and Sons Inc. |
|19.||Hediger HJ Methods of analysis in chemistry: infrared spectroscopy. 1971;Vol. 1 New York Academic publishing Company |
|20.||Rameriz F, Madan OP, Heller SR. A crystalline tetra alkoxyalkyl phosphorane from the reaction of trimethyl phosphite with an α,β-unsaturated ketone. 3-benzylidene-2,4-pentanedione P31 and H1 nuclear magnetic resonance spectra. J Am Chem Soc. 1965;87:731–734 |
|21.||Eliel EL, Wilen SH, Mander LN Stereochemistry of organic compounds. 1994 New York Wiley:488–492 |
|22.||Silverstein RM, Basler GC, Morrill TC Spectrometric identification of organic compounds. 19915th ed New York John Wiley & Sons |
|23.||Hesse M, Meier H, Zeeh B Spectroscopic methods in organic. 1991 4th ed. Stuttgart Thieme Chemistry |
|24.||Breitmeir E, Voelter W Carbon-13 NMR spectroscopy. 19873rd ed. Weinheim VCH Verlagsgesellschaft |
|25.||Kalinowski HO, Berger S Braun S 13C NMR spectroscopy. 1984 Stuttgart Thieme Verlag |
|26.||Bergmann ED, Ginsburg D, Pappo R. The Michael reaction. Org React . 1959;10:179–555 |
|27.||Oare DA, Heathcock CH. Stereochemistry of the base-promoted Michael addition reaction. Top Stereochem. 1989;19:227–407 |
|28.||Ramirez F, Bhatia SB, Smith CP, Ramirez F, Bhatia SB, Smith CP. Reaction of heterocyclic polycarbonyl compounds with phosphite esters. Alloxan and parabanic acid. J Org Chem. 1966;31:4105–4110 |
|29.||Pearson RG, Songstad J. Application of the principle of hard and soft acids and bases to organic chemistry. J Am Chem Soc. 1967;89:1827–1836 |
|30.||Saville B. The concept of hard and soft acids and bases as applied to multi-center chemical reactions. Angew Chem Int Ed Engl. 1967;6:928–939 |
|31.||Kornblum N, Seltzer R. Steric hindrance as a factor in the alkylation of ambident anions: the alkylation of potassium 2,6-di-t-butylphenoxide. J Am Chem Soc. 1961;83:3668–3671 |
|32.||Aizawa H Metabolic maps of pesticides. 1989;Vol. 2 San Diego, CA Academic Press |
|33.||Büchel KH Chemistry of pesticides. 1983 New York Wiley-Interscience:82 |
|34.||Legrand S, Nordlander G, Nordenhem H, Borg-Karlson A-K, Unelius CR. Hydroxy-methoxybenzoic methyl esters: synthesis and antifeedant activity on the pine weevil, Hylobius abietis. Z Naturforschung [B]. 2004;59:829–835 |
|35.||Valderrama JA, Benites J, Cortés M, Pessoa-Mahana H, Prina E, Fournet A. Studies on quinones. Part 38: synthesis and leishmanicidal activity of sesquiterpene 1,4-quinones. Bioorg Med Chem. 2003;11:4713–4718 |
|36.||Yuan C, Li C. Studies on organophosphorus compounds 59. Regioselective phosphorylation and formylation of propenylphosphonates – a novel and convenient route to propenylidenebisphosphonates and 1-methoxycarbonylpropenylphosphonates. Heteroatom Chem. 1992;3(5–6):637–646 |
|37.||Yao CYJ, Li S. Structural effect of electrophiles on the regioselectivity of carbanion derived from dialkyl allylphosphonates. Phosphorus, sulfur and silicon. 1990;53:21–27 |
|38.||Balakrishnan VK, Han X, VanLoon GW, Dust JM, Toullec J, Buncel E. Acceleration of nucleophilic attack on an organophosphorothioate neurotoxin, fenitrothion, by reactive counterion cationic micelles. Regioselectivity as a probe of substrate orientation within the micelle. Langmuir. 2004;20:6586–6593 |
|39.||Mustafa A Furopyrans and furopyrones. 1967 London Interscience Publishers:14–101 |
|40.|| An encyclopedia of chemicals, drugs and biologicals. 200113th ed. Whitehouse Stations, NJ Merck & Co. Inc. No. 5327, p. 950; No. 10071, p. 1784; No. 227, p. 44; No. 3894, 683:2001 |
|41.||Li Z-G, Huang R-Q, Shao R-L, Zhao Y, Long Y-X. The synthesis of α-(4-antipyryl)amino-(substituted) phenyl-methylphosphonic acid derivatives. Phosphorus, sulfur and silicon and related elements. 1999;Vol. 155:137–145 |
|42.||Hudson HR, Lee RJ, Matthews RW. 1-Amino-1-aryl- and 1-amino-1-heteroaryl-methanephosphonic acids and their n-benzhydryl-protected diethyl esters: preparation and characterization. Phosphorus, sulfur and silicon and the related elements. 2004;179:1691–1709 |
|43.||Sepúlveda-Arquesa J, González-Rosendeb ME. Synthetic and theoretical studies of novel ring closure and ring opening reactions. Arkivoc. 2005;2006:5–19 |