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According to literature, the synthesis of dronic acid derivatives from the corresponding carboxylic acids using phosphorus trichloride and phosphorous acid as the P-reactants is controversial, due to the wide range of molar ratios and diverse conditions. In this minireview, we summarize our results on the clarification of these problems. For example, with zoledronic acid and risedronic acid, we found that, using methanesulfonic acid (MSA) as the solvent, 3.2 equivalents of phosphorus trichloride was enough. Generalizing this optimized method, etidronate, fenidronate, ibandronate and alendronate were obtained in yields of 38%–57%, which is reasonable for valuable dronates, and in most cases, with high purities. Mechanistic aspects are also discussed.

Recent results on the synthesis of substituted hydroxymethylenebisphosphonic acids (A and B), as well as acylated ethoxycarbonyl-methylphosphonate derivatives (C and D) are summarized. In the first part, solvent mixtures were applied in the preparation of known dronic acids, while in the second series of experiments, new acyl species were synthesized. [ABSTRACT FROM AUTHOR]

The possible combinations and connections of microwave (MW) and catalysts are discussed. MW-assisted reactions, such as the direct esterification or the alkylating esterification of phosphinic acids may be enhanced by an ionic liquid additive or a phase transfer catalyst (PTC), respectively. It is also possible that a catalytic transformation, like the Arbuzov reaction with aryl halides is promoted by MW irradiation. Moreover, it is also an option exemplified by the Kabachnik–Fields reaction, by the deoxygenation of phosphine oxides, or by the PTC alkylation of P = O functionalized active methylene containing substrates that MW irradiation substitutes the catalysts. Last but not least, as it is in the Hirao reaction, MWs may make possible the simplification of the catalyst system possible. [ABSTRACT FROM AUTHOR]

Two new pyridine-based asymmetric bifunctional organocatalysts containing one or two camphorsulfonamide units were synthesized. Asymmetric Michael addition of pentane-2,4-dione to β-nitrostyrene was catalyzed by these organocatalysts. During our experiments, influence of the solvent and temperature on the yield and enantioselectivity was studied. Using monocamphorsulfonamide derivative the S enantiomer of the corresponding Michael adduct was gained with moderate yield (up to 51 %) and low enantiomeric excess (up to 18 %). Organic solvent nanofiltration was successfully applied for the recovery of these organocatalysts. Furthermore, pyridine camphorsulfonamide was reduced to its piperidine derivative. Using piperidine monosulfonamide derivative racemic Michael adduct was obtained with excellent yield (up to 89 %). Beside its organocatalytic relevance, piperidine monosulfonamide derivative may also possess biological activity. [ABSTRACT FROM AUTHOR]

Abstract: A few new d‐mannitol‐based monoaza‐15‐crown‐5 type chiral lariat ethers and 18‐crown‐6 type macrocycles were synthesized. These crown compounds were used as phase transfer catalysts in asymmetric Michael addititons and in a Darzens condensation under mild conditions to afford the corresponding products in a few cases in good to excellent enantioselectivities. In the Michael addition of diethyl acetoxymalonate to trans‐chalcone, in the addition of diethyl acetamidomalonate to ß‐nitrostyrene, in the reaction of diethyl bromomalonate with benzylidene malononitriles, in the cyclopropanation reaction of diethyl bromomalonate and 2‐benzylidene‐1,3‐indandione, and in the Darzens condensation of α‐chloroacetophenone with benzaldehyde, maximum enantioselectivities of 39%, 65%, 99%, 56%, and 62%, respectively, were obtained in the presence of the d‐mannitol‐based macrocycles as the catalysts. [ABSTRACT FROM AUTHOR]

The reaction of 1H-imidazol-1-ylacetic acid and two equivalents of phosphorus trichloride/phosphorous acid at 75 °C in sulfolane, or in the presence of catalytic amounts of [bmim][BF4] afforded zoledronic acid in yields up to 75%. The joint use of the ionic liquid additive and sulfolane as the solvent was synergetic affording highly valuable zoledronic acid in a record yield of 93%. [ABSTRACT FROM AUTHOR]

Several new trans-dihydronarciclasine analogues were stereoselectively synthesised by applying our feasible and efficient process developed recently. These new phenanthridone alkaloid derivatives were obtained in both racemic and optically active forms. During their enantioselective syntheses, high selectivities (up to 99% ee) were achieved by using (8S,9S)-9-amino(9-deoxy)epiquinine as an organocatalyst. The modifications, the introduction of ethoxy or methoxy groups, were made in ring A of the phenanthridone scaffold. [ABSTRACT FROM AUTHOR]

The microwave (MW) technique has become an important tool also in the organophosphorus field of organic chemistry. On the one hand, otherwise reluctant reactions, such as the esterification of Pacids, may be enhanced by the effect of MW, while on the other hand, catalysts may be omitted, or catalyst systems may be simplified on MW irradiation. This later group includes the Kabachnik-Fields reactions, alkylation of active methylene-containing compounds, O-alkylations, deoxygenations, as well as the Hirao reaction. It is also the purpose of this review to elucidate the scope and limitations of the MW tool, to interpret the MW effects, and to model the distribution of local overheatings and their beneficial effect. [ABSTRACT FROM AUTHOR]

A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively). The substituents of chalcone had a significant impact on the yield and enantioselectivity in the reaction of diethyl acetoxymalonate. The highest enantiomeric excess ( ee) values (99% ee) were measured in the case of 4-chloro- and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of chalcone and benzylidene-malononitriles using diethyl bromomalonate as the nucleophile (MIRC reaction) was also developed. The corresponding chiral cyclopropane diesters were obtained in moderate to good (up to 99%) enantioselectivities in the presence of the threitol-based crown ethers. [ABSTRACT FROM AUTHOR]

The synthesis of the drug alendronate from γ-aminobutyric acid and phosphorus trichloride/phosphorous acid as the P-reagents is revisited using methanesulfonic acid and sulfolane as solvents and ionic liquids ( ILs) as additives according to a novel approach. Besides elaborating efficient synthetic methods with a record yield of up to 80%, the misleading literature data were also clarified. It is a novel trend to use ILs as only catalysts or additives and not as solvents. [ABSTRACT FROM AUTHOR]

The microwave (MW) technique become an important tool in organophosphorus chemistry. On the one hand, otherwise reluctant reactions, such as the Diels–Alder cycloadditions, inverse Wittig-type reactions, esterification of P-acids, alcoholysis of P-esters, may be promoted on the effect of MW, while on the other hand, catalysts may be omitted, or catalyst systems may be simplified on MW irradiation. This later group includes the Kabachnik–Fields and the Pudovik reactions, deoxygenation, as well as the Hirao- and the Arbuzov reactions. [ABSTRACT FROM PUBLISHER]

New chiral monoaza-15-crown-5 type macrocycles annelated to methyl 4,6-O-benzylidene-α-d-galactopyranoside have been synthesized. These crown ethers proved to be efficient catalysts in a few asymmetric reactions under mild phase transfer catalytic conditions. Michael adducts were formed with good to excellent enantioselectivities, so the addition of diethyl acetamidomalonate to β-nitrostyrene took place with up to 92% ee, while the reaction of diethyl acetoxymalonate with chalcones proceeded with up to 99% ee. Using diethyl bromomalonate as the nucleophile, the chiral cyclopropane derivatives were formed in up to 99% ee with the addition to chalcone, in up to 78% ee in the reaction with benzylidene malononitrile, and in up to 76% ee in the reaction with 2-benzylidene-1,3-diphenyl-1,3-propanedione applying α-d-galactoside-based crown ethers as the catalysts. In the Michael addition, the substituents of the chalcone had a considerable impact on the outcome of the reactions. Quantum chemical calculations have also been employed to evaluate the origin of the stereoselectivities. [ABSTRACT FROM AUTHOR]

The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the heterogeneity of the reaction mixtures. This review sheds light on the optimum choice and ratio of the P-reactants, and on the optimum conditions. [ABSTRACT FROM AUTHOR]

The basic method for the synthesis of dronic acid derivatives (etidronate, fenidronate, pamidronate, alendronate, ibandronate, zoledronic acid, and risedronic acid) starting from the corresponding carboxylic acid, phosphorus trichloride and phosphorous acid is surveyed. The focus is on the optimized syntheses elaborated by us using only 3.2 equivalents of phosphorus trichloride as the P-reagent in methanesulfonic acid as the solvent. [ABSTRACT FROM PUBLISHER]

The chiral monoaza-15-crown-5 lariat ether annelated to methyl-4,6-O-benzylidene-α-D-glucopyranoside has been applied as a phase-transfer catalyst in several Michael addition reactions under mild conditions affording the adducts with good to excellent enantioselectivities. In the addition of α-substituted diethyl malonates to trans-chalcones, the substituents of the reactants had a significant impact on the yield and enantioselectivity. Among the reactions of substituted diethyl malonates, that of diethyl-2-acetoxymalonate gave the best results (up to 97% ee). New phase-transfer-catalyzed cyclopropanation reactions (MIRC reactions) of a few enones were also developed using diethyl 2-bromomalonate as the nucleophile. The corresponding chiral cyclopropane derivatives were formed with enantioselectivities up to 92% from 2-benzylidenemalononitrile starting materials, in up to 60% enantiomeric excess using 2-benzylidene-1,3-diphenyl-1,3-propanediones, and in up to 88% optical purity applying trans-chalcones as the starting materials. [ABSTRACT FROM AUTHOR]

The solid-liquid phase C-alkylation of active methylene containing compounds with C=O or P=O functions under phase transfer catalysis or microwave conditions has been summarized in this minireview. The mono- and dialkylation of the methylene containing derivatives was investigated under microwave (MW) conditions. It was found that in many cases, there was no need to use phase transfer catalyst under MW conditions. Moreover, most of the reactions were carried out without any solvent. These results mean a serious green chemical advantage. [ABSTRACT FROM AUTHOR]

Our recent results on the synthesis of dronates/dronic acids have been summarized. [ABSTRACT FROM PUBLISHER]

ABSTRACT The synthesis of pamidronic acid and sodium pamidronate dihydrate from β-alanine and P-reagents (phosphorus trichloride and phosphorous acid) was investigated at 75°C in different solvents, and the preparation was optimized. In sulfolane, the use of 2 equiv of phosphorus trichloride and phosphorous acid was found the optimum to lead to pamidronic acid in a yield of 63%. In methanesulfonic acid, 3.2 equiv of phosphorus trichloride was necessary without any phosphorous acid to give pamidronate dihydrate in the best yield (57%) after hydrolysis and pH adjustment. In the first case, the P-nucleophile may be (HO)2P-O-PCl-O-P(OH)2 or (HO)2P-O-PCl2, whereas in the second case, the P-reactant is probable Cl2P-O-S(O)2Me. It can be said that the mechanism proposed for the formation of pamidronic acid is highly influenced by the solvent used, as it determines the necessary P-reagent(s). Our results promote the 'on purpose' planning of the synthesis of dronates. [ABSTRACT FROM AUTHOR]

ABSTRACT To further broaden the methods for the heterogeneous phase alkylation of CH acidic compounds, the dialkylation of diethyl ethoxycarbonylmethylphosphonate was studied in the presence of Cs2CO3 under microwave and solvent-free conditions. It was found that after repeating the alkylations by the addition of newer portions of the alkylating agent and the base on a few occasions, the dialkylation was quite efficient. Even dialkyl derivatives with different alkyl groups could be synthesized. The presence of a phase-transfer catalyst was harmful, as prevented the formation of the dialkyl products. [ABSTRACT FROM AUTHOR]

Twenty-five amides were synthesized in almost quantitative yields by microwave-assisted condensation of arylacetic acids and 2-aryl-ethylamines under solventless conditions. The N-arylethyl-arylacetylamides are intermediates of the corresponding isoquinoline derivates. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® to view the free supplemental file. [ABSTRACT FROM PUBLISHER]

ABSTRACT A series of substituted diethyl arylphosphonates was synthesized by the microwave-assisted Arbuzov reaction of triethyl phosphite and aryl bromides in the presence of NiCl2 as the catalyst under solvent-free conditions in good yields. The resulting phosphonates were hydrolyzed to the corresponding arylphosphonic acids whose acidity was evaluated by physicochemical methods. [ABSTRACT FROM AUTHOR]

The reaction of 4-chlorophenol and 4-nitrophenol with diethyl chlorophosphate carried out in a liquid-liquid and solid-liquid two phase system, respectively, was monitored by in situ Fourier transform IR spectroscopy. [ABSTRACT FROM AUTHOR]

The solid-liquid phase alkylation of a variety of five-membered N-heterocycles (carbazole, imidazole, benzimidazole, and indole-3-carbaldehyde) was carried out under different conditions. The use of alkali carbonate in dimethylformamide or in MeCN (in the latter case, in the presence of a phase-transfer catalyst) is a suitable method to prepare the corresponding N-alkylated products in an efficient way. In most cases, the solventless, microwave-assisted reaction is an environmentally friendly alternative to traditional methods. [ABSTRACT FROM AUTHOR]