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Vilsmeier Haack reaction of phosphonic dihydrazide: synthesis of 4 - {[(dimethyl) azaacyl ammonium chloride] methyl} amino-2,3-dihydro-3-oxo-4h-1,2,4,3-triazaphosphine

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  • Save International Journal of M aterials and Chemistry 2012, 2(5): 192-196 DOI: 10.5923/j.ijmc.20120205.02 Vilsmeier-Haack Reaction of Phosphonic Dihydrazide: Synthesis of 4- {[(Dimethyl)azanylidenonium Chloride] Methyl} Amino-2,3-Dihydro-3-Oxo-4H-1,2,4, 3-Triazaphosphole Tarik E. Ali*, Somaia M. Abde l-Karie m Synthetic Organic Labor atory, Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711, Cairo, Egypt Abstract A simp le method for the synthesis of 4-{[(dimethyl)azanylidenonium ch loride] methyl}amino-2,3-dihydro- 3-o xo -4H-1,2,4,3-t riazaphosphole (2) is described. Treat ment of phosphonic dihydrazide (1 ) with Vilsmeier-Haack reagent led direct ly to the title co mpound in high yield. Keywords Phosphonic Dihydrazide, Vils meier Reagent, 1,2,4,3-Triazaphosphole 1. Introduction A Literature search of the last decade revealed sustained interest in the application of the Vils meier Haack reagent in organic synthesis. The versatility of the reagent had been extended to activating agents as oxygen and nitrogen nucleophiles to yield the corresponding iminiu m salts[1-5]. On the other hand, phosphorus heterocycles containing nitrogen heteroatoms adjacent to phosphorus atom exh ibited interesting biological properties[6,7]. As a part of our search for new expected biologically active phosphorus heterocycles[8-11], we are interested in introducing such N−P−N pattern into heterocyclic structure by applying the Vils meier Haack reaction on phosphonic dihydrazide. To the best of our knowledge, the synthesis of phosphorus heterocycles by the Vilsmeier reagent has not been reported in literature. 2. Experimental 2.1. General The melt ing point was determined in an open capillary tube on a digital Stuart SM P-3 apparatus. Infrared spectrum was measu red on Perkin -Elmer 293 spect rophot o meter (cm-1), using KBr disks. 1H NM R spectrum was measured on Gemini-200 spectrometer (200 M Hz), using DMSO-d6 as a solvent and TM S (δ ) as th e internal stand ard . 13 C and Corresponding author: (Tarik E. Ali) Published online at Copyright © 2012 Scientific & Academic Publishing. All Rights Reserved 31P NMR spectra were registered on a Varian Inova 500 MHz spectrometer at room temperature using DMSO-d6 as a solvent and TMS as internal standard and 85% H3PO4 as external reference. Elemental microanalysis was performed at microanalysis center in National Research Center, Giza. The purity of the synthesized co mpound was checked by thin layer chro matography (TLC). Phosphonic dihydrazide was prepared according to the reported method[12]. 2.2. Synthesis of {[(di methyl)azanyli denonium chlori de]methyl}ami no-2,3-dihydro-3-oxo-4 H-1,2,4, 3-triazaphos phole (2) The Vils meier reagent was prepared by adding dimethylformamide (3.86 mL, 50 mmo l) in an ice -cold condition (0-5 ℃ ) under constant stirring. To this, phosphorus oxychloride (1.304 mL, 14 mmo l) was added dropwise over a period of 30 minutes and the resulting mixtu re was stirred for a further 30 minutes. Phosphonic dihydrazide (1) (550 mg, 5 mmol) was added to the Vils meier reagent and stirred for 4 hours at 50-60℃. The reaction mixture was cooled and poured crushed ice (30 g) under constant manual stirring. The reaction mixture was kept aside overnight. After adding acetone, the precipitate obtained was washed well with acetone. The product was filtered off and crystallized fro m acetone/water affording white crystals in 86% yield, m.p. 230−232 ℃. IR (νmax, cm-1): 3474−3150 (H-bonded, OH and NH), 2778 (P−H), 1713 (C=N+), 1661 (C=N), 1291 (P=O). 1H NM R (DM SO): δ 3.01 (s, 6H, 2 CH3), 6.00 (br, 1H, NH exchangeable with D2O), 8.35 (d, 1H, JPH=328 Hz, P−H), 8.05, 8.17 (dd, 1H, J=14 Hz, CH=Nexocyclic), 8.40 (s, 1H, CH=Nendocyclic), 11.32 (br, 1H, NH exchangeable with D2O). 13C NMR (DM SO): 45.2 (CH3), 47.3 (CH3), 158.1 (C=Nexocyclic), 166.3 193 International Journal of M aterials and Chemistry 2012, 2(5): 192-196 (C=Nendocyclic). 31P NMR (DM SO): δ 7.58 pp m. MS (I %): 226 (M+1, 7%), 225 (M+, 8%), 99 (3), 98 (17), 71 (42), 70 (24), 57 (100). Anal. Calcd for C4H11ClN5OP. 3/4H2O (225.10): C, 21.32; H, 5.55; N, 31.09. Found: C, 21.43; H, 5.62; N, 30.74%. 3. Results and Discussion Th e Vils meier-Haack react io n [13] was ap p lied t o phosphonic dihydrazide (1) to give 4- {[(dimethyl) azany lidenon iu m ch lo ride]methy l}amin o -2,3-d ih yd ro 3-o xo- 4H- 1,2, 4, 3-t r ia zaphos phole (2). A pos s ible mechan is m fo r th is react ion cou ld involve attack of the ch lo ro methy len imin iu m species o btained in situ fro m phosphorus oxychloride and dimethylformamide to react with the terminal amino groups of 1 leading to the iminiu m intermediate A. The intramo lecular cyclizat ion of A through addition of NH group adjacent to phosphorus atom to C=N+ group afforded the cyclic intermed iate B, which underwent removal of one mo lecule of dimethylamine to give the isolated product 2. Unfortunately, our attempts to hydrolyze of 2 were unsuccessful under different basic condition which resulted in the formation of a tarry material instead of the expected aldehyde 3, and we failed to isolate indiv idual compound[14]. Elemental analysis and mass spectrometry indicated a formu la with co mposition C4H11ClN5OP. 3/4H2O (225.10). This is explained by the presence of a water in the crystallized form, i.e. the mo lecular formu la of the proposed structure is the hydrated form of C4H11ClN5OP. Its IR spectrum displayed OH, NH, C=N+ and C=N functions at 3474−3150, 1713 and 1661 cm-1, respectively[15] (Figure 1). Also, its 1H NMR spectrum exh ibited two characteristic signals at δ 8.35 and δ 8.40 pp m corresponding to P−H and CH=Nendocyclic, respectively. Moreover, the proton of CH=N+exocyclic appeared as doublet doublet at δ 8.05 and 8.17 ppm with coupling constant around 14 Hz[16], along with the signals of NH protons which appeared at δ 6.00 and 11.32 pp m wh ich are rep laceable with deuterium on addition of D2O (Figure 2). Furthermore, its 13C NM R spectrum supported the suggested structure which showed the methyl carbon atoms at δ 45.2 and 47.3 pp m, wh ile the exocyclic and endocyclic C=N atoms appeared at δ 158.1 and 166.3 ppm, respectively (Figure 3). Finally, 31P NM R spectrum displayed a signal at δ 7.58 pp m. S cheme 1. The synthet ic pathway and it s mechanism for formation 2 via applying Vilsmeier-Haack react ion on phosphonic dihydrazide 1 Tarik E. Ali et al.: Vilsmeier-Haack Reaction of Phosphonic Dihydrazide: Synthesis of 4- {[(Dimethyl)azanylide 194 nonium Chloride] M ethyl} Amino-2,3-Dihydro-3-Oxo-4H-1,2,4,3- Triazaphosphole Figure 1. The IR spectrum of compound 2 Figure 2. The 1H-NMR spectrum of compound 2 195 International Journal of M aterials and Chemistry 2012, 2(5): 192-196 Figure 3. The 13C-NMR spectrum of compound 2 4. Conclusions [6] He LN, Zhuo RX, Chen RY, Li K, Zhang YJ. Synthesis of biologically active phosphorus heterocycles via cyclization 4-{[(Dimethyl)azanylidenoniu mch loride]methyl} ami no-2,3-dihydro-3-o xo-4H-1,2,4,3-triazaphosphole (2) is reactions of Lawesson's reagent. Heteroatom Chem 1999; 10; 105-111. achieved in high y ield via treat ment of phosphonic [7] Wan L, Alkorta I, Elguero J, Sun J, Zheng W. The structural and dihydrazide (1) with Vils meier-Haack reagent. theoretical study of 1H-3,5-diphenyl- 1,2,4-diazaphosphole in the solid state. Tetrahedron 2007; 63; 9129-9135. REFERENCES [8] Ali TE, Halacheva SS. Synthetic approach of novel bis (α-aminophosphonic acid) derivatives of chromone containing 1,2,4,3-triazaphosphole moieties. Heteroatom Chem 2009; 20; 117-122. [1] Katritzky AR, C. M . M arson. Synthesis of a [9] Ali TE. Synthesis and antibacterial activity of some new dodecahydro-18,21-dioxoniakekulene. J Am Chem Soc thiadiaza/triazaphospholes, thiadiaza/triaza/tetraza- phosphinine 1983; 105; 3279-3284. s and thiadiaza/tetrazaphosphepines containing 1,2,4-triazinone moiety. Eur J M ed Chem 2009; 44; 4539-4546. [2] Horvath A, Hermecz I, Podanyi B, M eszaros Z. Nitrogen bridgehead compounds. Vilsmeier Haack acylation of 6,7,8,9-tetrahydro-4h-pyrido[1,2-a] pyrimidin-4-ones. J Heterocycl Chem 1985; 22; 593-598. [10] Ali TE. Synthesis of some new 1,3,2-oxazaphosphinine, 1,3,2-diazaphosphinine, acyclic and/or cyclic α-aminophosphon ate derivatives containing chromone moiety. Posphorus Sulfur Silicon and Relat Elem 2010; 185; 88-96. [3] Balasundaram B, Venugopal M , Perumal PT. Synthetic studies on N-acetyl derivatives of amino acids and [11] Abdel-Aziz SA, Ali TE, El-M ahdy KM , Abdel-Karim SM . thiolactone using Vils meier-haack reagent. Tetrahedron Synthesis and antimicrobial activities of some novel bis-pyrazole Lett 1993; 34; 4249-4254. derivatives containinga hydrophosphoryl unit. Eur J Chem 2011; 2, 25-35. [4] Becker C, Roshchupkina G, Rybalova T, Gatilov Y, Reznikov V. Transformations of 2,2-dimethyl-2,4dihydro-3H-pyrrol-3-on-1-oxide derivatives in the Vilsmeier–Haack reaction conditions. Tetrahedron 2008; [12] Shukla JS, Zaidi M GH. Synthesis of some newer polyhydrazides containing hydrazinophosphite linkage. Asian J Chem 1993; 5; 253-258. 64; 9191-9199. [13] Nohara A, Umetani T, Sanno A. Studies on antianaphylactic [5] Ali Tasneem M M , Rajanna KC, Prakash PK. An efficient and facile synthesis of 2-chloro- 3-formyl-quinolines from acetanilides in micellar media by vilsmeier-haack agents-I : A facile synthesis of 4-oxo-4H-1-benzopyran-3-carbo xaldehydes by Vilsmeier reagents. Tetrahedron 1974; 30; 3553-3559. cyclisation. Synlett 2001; 2; 251-257. [14] Golyanskaya OM , Voloshin NA, Chernyshev AV, Dubonosov Tarik E. Ali et al.: Vilsmeier-Haack Reaction of Phosphonic Dihydrazide: Synthesis of 4- {[(Dimethyl)azanylide 196 nonium Chloride] M ethyl} Amino-2,3-Dihydro-3-Oxo-4H-1,2,4,3- Triazaphosphole AD, M etelitsa AV, M ezheritskii VV, Bern VA. Synthesis and reactions of 2-(dimethyl-aminomethylidene) -6-methoxyn aphto[1,8-bc]pyran-3-one. Russ J Org Chem 2008; 44; 602-607. [15] Elguero J, Gil R, Jacquier R. Sur l'identification par infrarouge des groupes immonium. Spectrochim Acta, 1967; 23A; 383-385. [16] Kira M A, Aboul-Enien MN, Korkor M I. The Vilsmeier-Haack reaction. IV. Reaction of phosphorus oxychloride-dimethylform amide with semicarbazones. J Heterocycl Chem 1970; 7; 25-28.

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