Applications Of H-phosphonates In Synthesis Of Phosphorus-containing Functional Compounds

H-phosphonates and their immediate derivatives have many applications in organic synthesis in recent years. The rich chemistry, low cost, stably maintained and easy availability of H-phosphonates make them an excellent choice synthone in a number of practically important organic reactions,H-phosphonates are intermediates in the synthesis of important classes of compounds such as α-aminophosphonic acids, heterocyclic α-aminophosphonates, α-hydroxyalkylphosphonates, phosphoramides, epoxyalkylphosphonates, alkynylphosphonates, bisphosphonates, nucleoside H-phosphonates, and poly (alkylene H-phosphonate)s. This is largely due to the versatility of H-phosphonates, which allow for their use as phosphorylation agents. The applications of H-phosphonates in the synthesis of phosphorus-containing functional compounds have become an important research field attracted by the scientists at home and abroad.In this thesis, some of the most important practical applications of the H-phosphonates in the synthesis of phosphorus-containing functional compounds and structural studies on the obtained compounds are shown in the following paragraphs:1. An efficient method to construct alkynylphosphonates using CuSo4·5H2O as the catalyst of the aerobic oxidative coupling of terminal alkynes with H-phosphonates is reported. CuSO4·5H2O, as a relatively benign and dirt cheap reagent, which can be stored and handled in the laboratory using normal laboratory methods, has not yet been seen as the catalyst employed for such air-induced C-P bond-forming reactions. And we have examined a variety of conditions for the reaction to find the optimal reaction conditions for this coupling reaction. Using the optimal reaction conditions, twenty two alkynylphosphonates were synthesized and their structures were confirmed by HRMS, NMR, ESI-MS, and IR. The tentative reaction mechanism was discussed. This method described in this thesis can be successfully used for the straightforward synthesis of alkynylphosphonates. 2. The methodology towards synthesis of these3-amino-2-hydroxy-2,3-dihydrobenzo[d][1,2]oxaphosphole2-oxides, a new kind of organophosphorus heterocycles, was accidentally found in the process of an intentional synthesis of a-aminophosphonate through Kabachnik-Fields reaction through a one-pot, three-component procedure using2-hydroxyacetophenones or2-hydroxybenzaldehyes, primary amines and H-phosphonates. Using diisopropyl H-phosphonate along with2-hydroxyacetophenone or any of the substituted2-hydroxyacetophenones and primary amines, a wide range of the corresponding heterocyclic a-aminophosphonates could be synthesized in relatively high yields. In the case of using2-hydroxybenzaldehye as the starting reactant, the chemical reactions, towards only in the cyclic-product favored direction, observably could be conducted by employing diphenyl H-phosphite as the phosphoryl reagent under the circumstances. Twenty seven heterocyclic a-aminophosphonates were synthesized and their structures were confirmed by HRMS, NMR, ESI-MS, and IR, and the tentative reaction mechanism was proposed. The approaches described here obviously have significant advantages in terms of experimental simplicity, mild reaction conditions and easy work-up, and would surely represent a convenient tool for the synthesis of a variety of this novel type of organophosphorus heterocycles.3. It is detoxified in the body by introduction of dialkylamion groups into the2-position of quinoline, and the derivatives of2-(Dialkylamino)quinolines have some biological activities, such as antioxidant activity and anticancer activity. A novel method has been developed for the synthesis of2-(Dialkylamino)quinolines which are prepared by assisted by H-phosphonates in this thesis. The optimum conditions were founded. A mechanism which trialkylamines assisted with H-phosphonates have a nucleophilic attack to the a-position of quinoline oxides to form a series of2-(Dialkylamino)quinolines was proposed by theoretical calculations and31P NMR profiles, and the structures of2-(Dialkylamino)quinolines were confirmed by NMR and ESI-MS. This novel method described in this thesis can be used for the synthesis of2-(Dialkylamino)quinolines.4. Using diethyl H-phosphonate as the reactant to synthesize tetraethyl ethenylidenebisphosphonates, and then tetraethyl ethenylidenebisphosphonates undergo facile Michael-type addition reaction with aryl amines to give eight nitrogen-containing bisphosphonates, and the reaction conditions of the addition reaction were optimized. The structures of nitrogen-containing bisphosphonates were confirmed by NMR, ESI-MS, and IR. To investigate the structures of the nitrogen-containing bisphosphonates, fragmentation pathways of einght nitrogen-containing bisphosphonates were investigated by electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry (ESI-MS"). The four-membered ring ions containing P-O-P-C were observed by successive loss several molecules of ethylene and one molecule of water from [M+H]+and [M+Na]+. And fragmentation pathways of eight fragmentation pathways of eight nitrogen-containing bisphosphonates (BPs), including Pamidronate, Alendronate, and five corresponding acylated derivatives, and Risedronate, were investigated by ESI-MSn in negative ion mode. The four-membered ring ions containing P-O-P-C which can hopefully be treated as a diagnostic ion of bisphosphonate group were observed by successive loss one or two molecules of water. Besides typical fragment ions of all the BPs, chloroacetyl Alendronate, chloroacetyl Pamidronate and Risedronate showed some additional fragmentation ions, containing triple bond ions owing to elimination of water from their enol anions. The hydrogen/deuterium (H/D) exchange experiment, theoretical calculations and the high-resolution mass spectrometry (Q-TOF) were appropriately employed to rationalize the proposed fragmentation pathways. These observations may have some potential applications in the structural elucidation and interpretation of mass spectra of nitrogen-containing bisphosphonate derivatives.5. A series of novel piperazine phosphoramide analogues of2-arylquinolones are synthesized through a facile phosphorylated reaction and their structures are elucidated by NMR, HR MS and ESI MS. Various2-arylquinolone linked by phosphoryl piperazine were synthesized to improve their undesirable physicochemical and biological properties.