A Practical Synthesis o f 2-Azidophenylisocyanide

El-Shihi, T.; Herrmann, R.

doi:10.1515/znb-1986-0127

Cited by 8 publications

(1 citation statement)

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“…To prove the above mentioned hypothesis, easily available ortho-azido benzoic acid 24 6 was selected as a model case. Thus, alkylative esterification of 6, via the corresponding cesium salt 25 , with high loaded Merrifield resin (3.4 mmol/g) resulted in polymer-bound ortho-azido Scheme 1 Scheme 2 ester 7.…”

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Solid-Phase Synthesis of 3H-Quinazolin-4-ones Based on an Aza Wittig-Mediated annulation Strategy

Villalgordo¹,

Obrecht²,

Chucholowsky³

1998

Synlett

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Aza Wittig-mediated annulation provides a highly efficient and straightforward strategy for the parallel synthesis of 3H-quinazolin-4-ones on solid support. The products were recovered in good yields and exhibited excellent purities.Combinatorial chemistry and related multiple synthesis technologies toward the synthesis of small organic molecules have recently emerged as powerful tools for lead structure identification. Thus, numerous protocols have already been disclosed for the construction of various heterocyclic and other compound libraries 1-8 . For most of these protocols, the use of solid phase methods has been the technique of choice 9-11 . As a part of our ongoing project devoted toward the development of efficient solid phase methodologies for the combinatorial and parallel synthesis of diverse heterocyclic systems 11,12 we have focused our attention on the benzopyrimidone (quinazoline) nucleus 1. (Figure 1) Figure 13H-Quinazolin-4-ones of type 1 represent an interesting pharmacophore that displays a wide rage of biological properties [13][14][15] . Therefore, an efficient strategy for the combinatorial and parallel synthesis of this interesting target, that allows the introduction of a high degree of molecular diversity, would be of interest.Herein, we report a highly versatile solid phase synthesis of quinazolinones 1, which efficiently combines the aza Wittig reaction with a multidirectional cleavage process. As recent literature has discussed in depth, [16][17][18][19][20][21][22] iminophosphoranes have been shown to be useful intermediates in organic synthesis, particularly for the preparation of different heterocyclic systems containing an endocyclic C,N double bond. In these cases, an aza Wittig-mediated annulation reaction was involved as the key step. Our working hypothesis began with the idea that a benzoic acid derivative containing an ortho-azido 2, or an ortho-amino group 3 would be tethered to the Merrifield resin and would provide the starting point for the formation of the corresponding phosphorylimine derivative 4 via a Kirsanov 19 or a Staudinger 23 reaction respectively.Division of the polymer bound iminophosphorane beds 4, followed by suitable manipulations and a cyclative cleavage process from the resin, would produce various heterocycles. We envisioned that this strategy could be applied efficiently to create compound libraries of diverse fused pyrimidones 5. (Scheme 1).To prove the above mentioned hypothesis, easily available ortho-azido benzoic acid 24 6 was selected as a model case. Thus, alkylative esterification of 6, via the corresponding cesium salt 25 , with high loaded Merrifield resin (3.4 mmol/g) resulted in polymer-bound ortho-azido Scheme 1 Scheme 2Downloaded by: National University of Singapore. Copyrighted material. 1406LETTERS SYNLETT ester 7. Treatment of 7 with a 5-fold excess PPh 3 in THF at room temperature produced the corresponding iminophosphorane 8 attached to the resin (evolution of N 2 clearly detected). Division of the resin beads and subsequent aza Witti...

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confidence: 99%

Solid-Phase Synthesis of 3H-Quinazolin-4-ones Based on an Aza Wittig-Mediated annulation Strategy

Villalgordo¹,

Obrecht²,

Chucholowsky³

1998

Synlett

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Template Synthesis of Benzannulated N‐Heterocyclic Carbene Ligands

Hahn

Langenhahn

Meier

et al. 2003

Chemistry A European J

186

103

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The reaction of 2-azidophenyl isocyanide (7) with [M(CO)(5)(thf)] (M=Cr, W) yields the isocyanide complexes [M(CO)(5)(7)] (M=Cr 8, M=W 9). Complexes 8 and 9 react with tertiary phosphines such as triphenylphosphane at the azido function of the isocyanide ligand to give the 2-triphenylphosphiniminophenyl isocyanide complexes 10 (M=Cr) and 11 (M=W). The polar triphenylphosphiniminophenyl function in complexes 10 and 11 can be hydrolyzed with H(2)O/HBr to afford triphenylphosphane oxide and the complexes containing the unstable 2-aminophenyl isocyanide ligand. This ligand spontaneously cyclizes by intramolecular nucleophilic attack of the primary amine at the isocyanide carbon atom to yield the 2,3-dihydro-1H-benzimidazol-2-ylidene complexes 12 (M=Cr) and 13 (M=W). Double deprotonation of the cyclic NH,NH-carbene ligands in 12 and 13 with KOtBu and reaction with two equivalents of allyl bromide yields the N,N'-dialkylated benzannulated N-heterocyclic carbene complexes 14 (M=Cr) and 15 (M=W). The molecular structures of complexes 9 and 11-15 were confirmed by X-ray diffraction studies.

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