- Selective hydrolysis of phosphorus(v) compounds to form organophosphorus monoacids
-
An azide and transition metal-free method for the synthesis of elusive phosphonic, phosphinic, and phosphoric monoacids has been developed. Inert pentavalent P(v)-compounds (phosphonate, phosphinate, and phosphate) are activated by triflate anhydride (Tf2O)/pyridine system to form a highly reactive phosphoryl pyridinium intermediate that undergoes nucleophilic substitution with H2O to selectively deprotect one alkoxy group and form organophosphorus monoacids.
- Ash, Jeffrey,Cordero, Paula,Huang, Hai,Kang, Jun Yong
-
p. 6007 - 6014
(2021/07/21)
-
- Selective esterification of phosphonic acids
-
Here, we report straightforward and selective synthetic procedures for mono-and diesteri-fication of phosphonic acids. A series of alkoxy group donors were studied and triethyl orthoacetate was found to be the best reagent as well as a solvent for the performed transformations. An important temperature effect on the reaction course was discovered. Depending on the reaction temperature, mono-or diethyl esters of phosphonic acid were obtained exclusively with decent yields. The sub-strate scope of the proposed methodology was verified on aromatic as well as aliphatic phosphonic acids. The designed method can be successfully applied for small-and large-scale experiments without significant loss of selectivity or reaction yield. Several devoted experiments were performed to give insight into the reaction mechanism. At 30?C, monoesters are formed via an intermediate (1,1-diethoxyethyl ester of phosphonic acid). At higher temperatures, similar intermediate forms give diesters or stable and detectable pyrophosphonates which were also consumed to give diesters.31P NMR spectroscopy was used to assign the structure of pyrophosphonate as well as to monitor the reaction course. No need for additional reagents and good accessibility and straightforward purification are the important aspects of the developed protocols.
- Brodzka, Anna,Koszelewski, Dominik,Ostaszewski, Ryszard,Trzepizur, Damian
-
-
- Optimization and a Kinetic Study on the Acidic Hydrolysis of Dialkyl α-Hydroxybenzylphosphonates
-
The two-step acidic hydrolysis of α-hydroxybenzylphosphonates and a few related derivatives was monitored in order to determine the kinetics and to map the reactivity of the differently substituted phosphonates in hydrolysis. Electron-withdrawing substituents increased the rate, while electron-releasing ones slowed down the reaction. Both hydrolysis steps were characterized by pseudo-first-order rate constants. The fission of the second P-O-C bond was found to be the rate-determining step.
- Harsági, Nikoletta,Rádai, Zita,Szigetvári, áron,Kóti, János,Keglevich, Gy?rgy
-
-
- Transition metal-free access to 3,4-dihydro-1,2-oxaphosphinine-2-oxides from phosphonochloridates and chalcones through tandem Michael addition and nucleophilic substitution
-
A novel and transition metal-free synthesis of 3,4-dihydro-1,2-oxaphosphinine 2-oxides was developed. LiHMDS-mediated tandem Michael addition and nucleophilic substitution of readily available phosphonochloridates and chalcones afforded a variety of valuable 3,4-dihydro-1,2-oxaphosphinine 2-oxides bearing diverse functionalities in excellent yields and satisfactory to good diastereoselectivity (up to 99% yield and up to 99?:?1 dr).
- Fu, Zhicheng,Sun, Simin,Yang, Anjian,Sun, Fang,Xu, Jiaxi
-
supporting information
p. 13124 - 13127
(2019/11/11)
-
- Investigation of reactive intermediates and reaction pathways in the coupling agent mediated phosphonamidation reaction
-
The preparation of carboxamides through the coupling agent mediated reaction of carboxylic acids and amines is one of the most frequently employed reaction types of modern organic synthesis and has largely replaced older methods of amide formation based on reactive acyl chloride intermediates. However, the preparations of analogous phosphonamidates still rely on the use of phosphonochloridate intermediates - a method that is incompatible with sensitive functional groups. Herein, we present a comprehensive study in which different coupling agents are tested in the phosphonamidation reaction. The procedures, parallel to those typically applied to the preparation of carboxamides, were generally unsuccessful with regard to the coupling reactions of monoesters of phosphonic acids and amines, with the exception of those mediated by (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP). The implementation of a preactivation period in the absence of the amine coupling partner allowed for efficient phosphonamidate formation with coupling agents such as (1-cyano-2-ethyoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), [ethyl cyano(hydroxyimino)acetato-O2]tri-1-pyrrolidinylphosphonium hexafluorophosphate (PyOxim), dicyclohexyl carbodiimide (DCC), N,N′-diisopropylcarbodiimide (DIC), and N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU). The reactive intermediates observed by 31P NMR analysis were individually synthesized and examined to understand their influence on the reaction. A phosphonamidation reaction that uses (1-cyano-2-ethyoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU) to mediate the coupling of monoalkyl esters of phosphonic acids and amines was developed. A preactivation period without the amine was needed to obtain the product. Using this step allowed for other coupling agents to be successfully used in the reaction.
- Fredriksen, Kim Alex,Amedjkouh, Mohamed
-
p. 474 - 482
(2016/02/18)
-
- HIV-1 non-nucleoside reverse transcriptase inhibitors: Incorporation of benzylphosphonate moiety for solubility improvement
-
Benzylphosphonates of 5'-norcarbocyclic analogue of 2',3'-dideoxy-2',3'-didehydrouridine and its N3-benzyl derivatives with different substituents at the phosphorus atom were designed and synthesized in attempt to improve solubility of potentia
- Matyugina, Elena S.,Valuev-Elliston, Vladimir T.,Chizhov, Alexander O.,Kochetkov, Sergei N.,Khandazhinskaya, Anastasia L.
-
p. 114 - 116
(2016/04/10)
-
- Synthetic Strategy and Performances of a UV-Curable Poly Acryloyl Phosphinate Flame Retardant by Carbene Polymerization
-
A route to synthesize poly ethyl (4-acrylamidebenzyl) phosphinate (PPAC) was discussed and the optimal route was determined. Diethyl benzylphosphonate was synthesized by Arbuzov reaction, then, a nitryl was introduced onto the aromatic ring by the nitration reaction of ethyl benzylphosphonate. Subsequently the carbene polymerization of the product was carried out. Finally, the nitryls were reduced and amidated to introduce the acryloyl group into the prepolymer to obtain the target product (PPAC). PPAC can rapidly photopolymerize under UV light irradiation. The addition of PPAC decreased the smoke production rate (SPR), CO2 production (CO2P), and CO production (COP) of the UV-cured resin.
- Yu, Jia,Li, Minglei,Yu, Yong,Gao, Yanjing,Liu, Jiancheng,Sun, Fang
-
p. 1958 - 1970
(2015/12/12)
-
- Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides
-
Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H2N(CH2)2OP(OH)R, 4], a little-ex
- Chowdhury, Sarwat,Muni, Niraj J.,Greenwood, Nicholas P.,Pepperberg, David R.,Standaert, Robert F.
-
p. 3745 - 3748
(2008/02/13)
-
- Ionic-liquid-promoted Michaelis-Arbuzov rearrangement
-
Room-temperature imidazolium ionic liquids, [Rmim][X], proved to be environmentally benign recyclable solvents promoting the Michaelis-Arbuzov rearrangement, which can be performed even at room temperature in a short period of time. The best ionic liquid of choice depended on the starting phosphorus(III) ester, namely, for triethyl phosphite [bmim][NTf2] demonstrated better results while for ethyl diphenylphosphinite it was [hmim][Br].
- Matveeva,Odinets,Kozlov,Shaplov,Mastryukova
-
p. 7645 - 7648
(2007/10/03)
-
- Inhibitors of protein isoprenyl transferases
-
Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2 is selected from(a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16,(e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and(g) —C(O)NH—CH(R14)—C(O)NR17R18; R3 is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, ?and —P(W)RR3RR3′; R4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1 is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5—(d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
- -
-
-
- Reactions of phosphonates with organohaloboranes: New route to molecular borophosphonates
-
Phosphonates RPO(OR′)2 (R = Me, R′ = Et (1); R = CH2Ph, R′ = Et (2); R = CH double bond CH2, R′ = Et (3); R = CH2-CH double bond CH2, R′ = Me (4); R = CH2N3, R′ = Et (5)) react with CyBCl2 (6; Cy = C6H11) in a 1:1 molar ratio in toluene at -30 °C to form the primary adducts CyBCl2·O double bond PR(OR′)2 (7-11). These products undergo a thermally induced bis-chlorodealkylation with the formation of mixtures of oligomers [-O-PR(O-)-O-BCy(O-)]n (22-26) having isovalent P-O-B groupings. Under electron impact mass spectral conditions, the ions [RPO3BCy]4-Cy, which may be attributed to tetramers [RPO3BCy]4 (22′-26′), are detected. Compounds 22′-26′ presumably possess a central cubic M4O12P4 framework that is analogous to those found in alumino- and gallophosphate materials. NMR monitoring shows that [CyBCl(μ2-O)2PR(OR′)]2 (12-16) are formed as intermediates in these reactions. These unstable dimers 12-16 possess a cyclic core analogous to the single-four-ring (4R) secondary building units (SBUs) found in zeolites and phosphate molecular sieves. Hydrolysis of 12-16 and 22-26 with methanol at 30 °C gave respectively RPO(OH)(OR′) (17-21) and RPO(OH)2 (27-31). NMR monitoring reveals that the cyclic dimer [Me2B(μ2-O)2P(CH2Ph)(OEt)]2 (35a) is the primary adduct in the reaction of PhCH2PO(OEt)2 (2) with Me2BBr (34). Heating or prolonged storage at room temperature leads to a mixture of 35a, cyclic borophosphonate Me2BC(μ2-O)2P(CH2Ph)(OEt) (35b), and the mixed anhydride of benzylphosphonic acid and dimethylborinic acid (35c).
- Mortier, Jacques
-
p. 4266 - 4275
(2008/10/08)
-
- Toward synthetic adrenaline receptors: Strong, selective, and biomimetic recognition of biologically active amino alcohols by bisphosphonate receptor molecules
-
Xylylene bisphosphonates represent a new class of artificial receptor molecules for alkylammonium ions (Schrader, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 2649-2651). Molecular recognition takes place in a 1:1 chelate- binding mode, and an almost ideal array of short, linear hydrogen bonds is created that guarantees maximum electrostatic and hydrogen-bond interactions. The host molecule, which was designed to imitate the natural adrenergic receptor, is selective for 1,2- and 1,3-amino alcohols due to formation of an additional cooperative hydrogen bond between the phosphonate anion and the hydroxyl groups. Biologically important amino alcohols such as glucosamine, 1-aminosorbitol, ephedrine, and the β-blocker propranolol are bound in DMSO with K(a) values between 60 000 and 130 000 M-1. Secondary amines are complexed at least as strongly as their primary counterparts. The phosphonate ester groups allow lateral recognition of the substate. This could be demonstrated for adrenaline model compounds that were recognized by phosphonates carrying extended aromatic ester groups for Π,Π-interactions.
- Schrader, Thomas
-
p. 264 - 272
(2007/10/03)
-
- Strong binding of alkylguanidinium ions by molecular tweezers: An artificial selective arginine receptor molecule with a biomimetic recognition pattern
-
Bisphosphonates 2 and 3 represent the first artificial receptor molecules for alkylguanidinium ions. They bind to the guanidinium moiety by forming a 1:l chelate complex, stabilized by a planar network of electrostatic interactions and hydrogen bonds. Thi
- Schrader, Thomas
-
p. 1537 - 1541
(2007/10/03)
-
- Kinetic Study on the Alkaline Hydrolysis of Some Tetracoordinate PV Esters of 2,4-Dinitrophenol
-
The alkaline hydrolysis of 2,4-dinitrophenyl esters of benzylphosphinic, benzylphosphonic and benzylphosphonamidic acid does not proceed through a carbanion-promoted dissociative mechanism, a possible alternative pathway to the usual SN2(P) process; this is a further indication of the clear preference for associative displacement at phosphorous.
- Cevasco, Giorgio,Thea, Sergio
-
p. 1103 - 1106
(2007/10/02)
-
- Photochemical C-P Bond Cleavage of Nitrobenzylphosphonate Ions
-
Upon UV-irradiation, the C-P bond of p-nitrobenzylphosphonate ions cleaved with a quantum yield of about 0.7 in an aqueous alcohol solution to give 1,2-bis(4-nitrophenyl)ethane, p-nitrotoluene, orthophosphate, and alkyl dihydrogenphosphate.Whereas in an aqueous solution 1,2-bis(4-nitrophenyl)ethane was produced as a main product, in an alcohol solution only p-nitrotoluene was produced.This photolysis may proceed via intramolecular electron tranfer from PO32- group to nitro aromatic moiety to form an excited state, which undergoes C-P bond cleavage to give p-nitrobenzyl anion and monomeric metaphosphate anion as intermediates.The C-P bond cleavage of p-nitrobenzylphosphonate ion occurred more readily than those of o- and m-nitrobenzylphosphonate ions.
- Okamoto, Yoshiki,Iwamoto, Narimasa,Toki, Susumu,Takamuku, Setsuo
-
p. 277 - 282
(2007/10/02)
-
- PHOSPHONAMIDATE COMPOUNDS
-
Phosphonamidates of the formula STR1 wherein X is a substituted or unsubstituted imino or amino acid or ester. These compounds possess angiotensin converting enzyme activity and are thus useful as hypotensive agents.
- -
-
-
- Phosphonamidate compounds
-
Phosphonamidates of the formula STR1 wherein X is an amino acid or ester. These compounds possess angiotensin converting enzyme inhibition activity and enkephalinase inhibition activity. Thus they are useful as hypotensive and analgesic agents.
- -
-
-