Fluorinated phosphorus compounds: Part 10. Bis(fluoroalkyl) S-alkyl phosphorothiolates and tris(fluoroalkyl) phosphorothionates

Treatment of bis(fluoroalkyl) phosphites (R_FCH₂O)₂P(O)H, where R_F was CF₃ or C₂F₅ with sulfur in pyridine at 80 °C gave salts of structure [(R_FCH₂O)₂P(O)SH]NC₅H₅ in 90 and 88% yield, respectively. The salts reacted with alkyl iodides in acetonitrile at 50 °C to furnish bis(fluoroalkyl) S-alkyl phosphorothiolates (R_FCH₂O)₂P(O)SR, where R was Me, Et, n- and i-Pr (when R_F = CF₃) and Me (when R_F = C₂F₅). Yields ranged from 21 to 57%. Bis(trifluoroethyl) S-methyl phosphorothiolate (CF₃CH₂O)₂P(O)SMe underwent fluorination by silver(I) fluoride in acetonitrile at room temperature to yield the phosphorofluoridate (CF₃CH₂O)₂P(O)F in 75% yield. Tris(fluoroalkyl) phosphorothionates (R_FCH₂O)₃P = S, where R_F was CF₃, C₂F₅ and C₃F₇, were prepared in 30-34% yield by heating the tris(fluoroalkyl) phosphites (R_FCH₂O)₃P and sulfur to 200 °C in a sealed tube for 8 h.     

全氟或多氟烷基氯代烷在保险粉引发下与芳香烃 的反应

全氟或多氟烷基氯代烷在保险粉引发下在DMSO溶剂中可以与富电子芳香烃反应,方便地得到氟烷基化的产物。氟烷基化产物的结构和产率主要取决于取代基的供电子能力和位置。     

Fluorinated phosphorus compounds: Part 6. The synthesis of bis(fluoroalkyl) phosphites and bis(fluoroalkyl) phosphorohalidates

Reaction of phosphorus trichloride with tert-butanol and fluoroalcohols gave bis(fluoroalkyl) phosphites (R_FO)₂P(O)H in 42-89% yield, where R_F=HCF₂CH₂, H(CF₂)₂CH₂, H(CF₂)₄CH₂, CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂, (CF₃)₂CH, (FCH₂)₂CH, CF₃(CH₃)₂C, (CF₃)₂CH₃C, CF₃CH₂CH₂, C₄F₉CH₂CH₂ and C₆F₁₃CH₂CH₂. Treatment of these with chlorine in dichloromethane gave the bis(fluoroalkyl) phosphorochloridates (R_FO)₂P(O)Cl in 49-96% yield. The chloridate (CF₃CH₂O)₂P(O)Cl was isolated in much lower yield from the interaction of thionyl chloride with bis(trifluoroethyl) phosphite. Heating the latter in dichloromethane with potassium fluoride and a catalytic amount of trifluoroacetic acid gave the corresponding fluoridate (CF₃CH₂O)₂P(O)F in 84% yield. Treatment of bis(trifluoroethyl) phosphite with bromine or iodine gave the bromidate (CF₃CH₂O)₂P(O)Br and iodidate (CF₃CH₂O)₂P(O)I in 51 and 46% yield, respectively. The iodidate is the first dialkyl phosphoroiodidate to have been isolated and characterised properly—its discovery lags behind the first isolation of a dialkyl phosphorochloridate by over 130 years. The fluoroalkyl phosphoryl compounds are generally more stable than known unfluorinated counterparts.     

Synthesis and Liquid Crystal Properties of Aryl Esters of Laterally Substituted 5-Pyrimidinecarboxylic Acids

(p-R-phenyl)-4-methyl-, 4-methoxy-, and 4-hydroxy-5-pyrimidinecarboxylates have been synthesized and their liquid crystal properties examined. Compounds containing methyl and methoxy groups in the lateral position of the molecule are nematic liquid crystals with a mesophase range of 30-50°C, but the 4-hydroxy derivatives are smectic liquid crystals. With variants of the substituents in a series of (p-R-phenyl)-4-substituted 5-pyrimidinecarboxylates the mp of individual representatives were successfully reduced by 50°C in comparison with the 4-unsubstituted analogs and the range of the mesomorphic state was extended to 190°C.     

Synthesis of Substituted Pyridyl‐Pyrimidines as Potential Protein–Protein Interaction Inhibitors

An efficient synthetic method for the preparation of pyridyl‐pyrimidines as potential inhibitors of protein–protein interactions is described. The key transformation is the reaction of a pyrimidine enaminone with phenyl ethyl acetate and NH⁴OAc to yield the desired pyridyl‐pyrimidine.     

Synthesis of 2-Arylthiopyrano[2, 3-d]Pyrimidines and Thieno[2, 3-D]Pyrimidines

Diethyl thiopyrano[2,3-d]pyrimidine-6,7-dicarboxylates 2a, b ; thiopyrano[23-d]pyrimidines 3a-c and 4a-c thieno[2,3-d]pyrimidine-6-carbonitriles 5a-c and thieno[2, 3-d]pyrimidine-6-carboxamides 5d-f have been prepared.     

Design,Synthesis, Pharmacodynamic and In Silico Pharmacokinetic Evaluation of Some Novel Biginelli-Derived Pyrimidines and Fused Pyrimidines as Calcium Channel Blockers

Some new pyrimidine derivatives comprising arylsulfonylhydrazino, ethoxycarbonylhydrazino, thiocarbamoylhydrazino and substituted hydrazone and thiosemicarbazide functionalities were prepared from Biginelli-derived pyrimidine precursors. Heterocyclic ring systems such as pyrazole, pyrazolidinedione, thiazoline and thiazolidinone ring systems were also incorporated into the designed pyrimidine core. Furthermore, fused triazolopyrimidine and pyrimidotriazine ring systems were prepared. The synthesized compounds were evaluated for their calcium channel blocking activity as potential hypotensive agents. Compounds 2, 3a, 3b, 4, 11 and 13 showed the highest ex vivo calcium channel blocking activities compared with the reference drug nifedipine. Compounds 2 and 11 were selected for further biological evaluation. They revealed good hypotensive activities following intravenous administration in dogs. Furthermore, 2 and 11 displayed drug-like in silico ADME parameters. A ligand-based pharmacophore model was developed to provide adequate information about the binding mode of the newly synthesized active compounds 2, 3a, 3b, 4, 11 and 13. This may also serve as a reliable basis for designing new active pyrimidine-based calcium channel blockers.     

Convenient and Efficient Synthesis of Some Novel Fused Thieno Pyrimidines Using Gewald's Reaction

Abstract

Several functionalized thienopyrimidines were synthesized by a facile synthetic method, which includes Gewald's reaction, and were characterized by spectral and analytical data. These functionalized thienopyrimidines were converted to various new chemical entities of biological importance, such as 2-piperazinymethyl thienopyrimidines (6, 8), 4-dimethylaminoethoxy thienopyrimidines (11), and 3-dimethylaminoethyl thienopyrimidines (12). All the compounds thus synthesized were screened for their invitro biological activities. Some of the compounds displayed promising serotonin 5-HT₆ receptor antagonist activities.

Manganese‐Catalyzed Multicomponent Synthesis of Pyrimidines from Alcohols and Amidines

The development of catalytic reactions for synthesizing different compounds from alcohols to save fossil carbon feedstock and reduce CO₂ emissions is of high importance. Replacing rare noble metals with abundantly available 3d metals is equally important. We report a manganese‐complex‐catalyzed multicomponent synthesis of pyrimidines from amidines and up to three alcohols. Our reaction proceeds through condensation and dehydrogenation steps, permitting selective C−C and C−N bond formations. β‐Alkylation reactions are used to multiply alkylate secondary alcohols with two different primary alcohols to synthesize fully substituted pyrimidines in a one‐pot process. Our PN₅P‐Mn‐pincer complexes efficiently catalyze this multicomponent process. A comparison of our manganese catalysts with related cobalt catalysts indicates that manganese shows a reactivity similar to that of iridium but not cobalt. This analogy could be used to develop further (de)hydrogenation reactions with manganese complexes.     

Synthesis and Antiinflammatoryand Anticancer Activity Evaluation of Some Condensed Pyrimidines

Summary.  Upon condensation with 4-isothiocyanato-4-methyl-2-pentanone, 2,3-diaminonaphthalene and N-aminoethyladenosine gave in good yields substituted pyrimidonaphthoimidazole and imidazopyrimidine thione. Refluxing pyrimidobenzthiazole with methanol H₂SO₄ at pH∼1 resulted in S-methyl pyrimidobenzthiazole in moderate yield. Pyrimidobenzimidazole derivatives could be reacted to S-alkylated and N-acylated derivatives by refluxing with ethyl bromoacetate in the presence of anhydrous potassium carbonate in THF and by heating in an acetic acid/acetic anhydride mixture. Heating of pyrimidobenzimidazole with 75% aqueous H₂SO₄ on a water bath ended up in a rearranged product. All compounds gave correct ¹H NMR, IR, and HR mass spectra. Results of antiinflammatory, analgesic, and anticancer activity screening of the new compounds are described. Received October 29, 1999. Accepted (revised) January 13, 2000     

A facile synthesis of per (poly )fluoroalkyl substituted α-amino acid derivatives

Initiated by CrCl3/Fe redox couple, per(poly)fluoroalkyl iodides added to methyl a-acetylamino acrylate, giving B-per(poly)fluoroalkyl a-amino acid derivatives in good yields.     

Synthesis of per(poly)fluoroalkyl substituted alkenes and alkynes—Utilizing potassium fluoride supported on alumina as a dehydrohalogenating agent

Potassium fluoride on alumina was proved to be an efficient dehydrohalogenating agent for the synthesis of per(poly)fluoroalkyl substituted alkenes and alkynes. The reaction was simple, mild and the yields ranged from good to excellent.     

Fluorinated phosphorus compounds: Part 9. The reactions of bis(fluoroalkyl) phosphorochloridates with oxygen nucleophiles

Twenty nine bis(fluoroalkyl) phosphates (R_FO)₂P(O)OR were prepared in 18-75% yield by treating phosphorochloridates (R_FO)₂P(O)Cl, where R_F was HCF₂CH₂, HCF₂CF₂CH₂, H(CF₂)₄CH₂, C₂F₅CH₂, C₃F₇CH₂, (CF₃)₂CH, (FCH₂)₂CH and (CH₃)₂CF₃C with methanol, ethanol, propanol and isopropanol in diethyl ether in the presence of triethylamine. The bulky chloridate [(CH₃)₂CF₃CO]₂P(O)Cl reacted with methanol, ethanol and propanol, but not with isopropanol - even on heating in the presence of the catalyst 4-dimethylaminopyridine - due to steric hindrance at phosphorus. The relative reactivities of three of the chloridates decreased in the order [(CF₃)₂CHO]₂P(O)Cl > [(FCH₂)₂CHO]₂P(O)Cl > [(CH₃)₂CF₃CO]₂P(O)Cl. Also described is the synthesis of phosphates (CF₃CH₂O)₂P(O)OCH₂R, where R = CH₂Br, CH₂Cl, CH₂F and CHF₂, and diphosphates [H(CF₂)_nCH₂O]₂P(O)OCH₂(CF₂)₂CH₂OP(O)[OCH₂(CF₂)_nH]₂, where n = 1, 2 and 4.     

Bis(fluoroalkyl)acrylic and methacrylic phosphate monomers, their polymers and some of their properties

Ten fluoromonomers of structure (R_FO)₂P(O)OCH₂CH₂OC(O)CRCH₂ were made in 30-64% yield by treating the chloridates (R_FO)₂P(O)Cl with HOCH₂CH₂OC(O)CRCH₂ in chloroform in the presence of triethylamine [R_F=CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂, C₄F₉CH₂, C₄F₉CH₂CH₂ or C₆F₁₃CH₂CH₂; R  H or Me]. The chloromonomer (CCl₃CH₂O)₂P(O)OCH₂CH₂OC(O)CHCH₂ was obtained analogously in 29% yield. Polymerisation of the acrylate monomers, but not the methacrylate monomers, could be effected using α-azoisobutyronitrile as a radical initiator. Acrylic polymers having CF₃CH₂O, CCl₃CH₂O and C₆F₁₃CH₂CH₂O side-chains were obtained as translucent rubbers. Specimens of cotton fabric were treated with solutions of the polymers, and average water and oil repellency ratings measured. Fabric coated with the polymer with the C₆F₁₃CH₂CH₂O side-chain afforded protection from penetration of the test liquids. Treated fabrics were subjected to the limiting oxygen index (LOI) test according to BS EN ISO 4589-2 (1999): this test determines the point at which a material just burns in a volumetric flow of oxygen and nitrogen. The treated fabrics were more fire-resistant (LOI 22-29%) than the untreated fabric (LOI 18%). Fabric coated with the CCl₃CH₂O-based polymer can be considered fire-retardant (LOI 29%). The fluoromonomers were tested for anti-acetylcholinesterase activity and were found to be poor enzyme inhibitors; they are predicted to possess low acute toxicity.     

Synthesis and Biological Activity of a Series of New Thieno[2,3-d]Pyrimidines

Ethyl 2-amino-5-ethylthiophene-3- carboxylate 1, obtained from the reaction of butyraldehyde, ethyl cyanoacetate, sulfur, and triethylamine, reacted with benzoylisothiocyanate to give the corresponding ureido derivatives 2 in a high yield. Further reactions of the compound 2 with an aqueous-alcohol solution of potassium hydroxide and then with hydrochloric acid gave the 2-thio-thieno[2,3-d]pyrimidine-4-ones 3, which were reacted with RX to give novel compounds 4a–4i. Treating the compound 3 with dibromoalkane led to the formation of triacylic compounds 5j–5m. Their structures were clearly verified by IR, ¹H NMR, EI-MS spectroscopy, and elemental analysis. The results of a preliminary bioassay indicated that some compounds possess excellent inhibitory activities against the root and the stalk of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Copolymers of methyl methacrylate and fluoroalkyl methacrylates: Effects of fluoroalkyl groups on the thermal and optical properties of the copolymers

Fluoroalkyl methacrylates, 2,2,2‐trifluoroethyl methacrylate ( 1 ), hexafluoroisopropyl methacrylate ( 2 ), 1,1,1,3,3,3‐hexafluoro‐2‐methyl‐2‐propyl methacrylate ( 3 ), and perfluoro t‐butyl methacrylate ( 4 ) were synthesized. Homopolymers and copolymers of these fluoroalkyl methacrylates with methyl methacrylate (MMA) were prepared and characterized. With the exception of the copolymers of MMA and 2,2,2‐trifluoroethyl methacrylate ( 1 ), the glass transition temperatures (T_gs) of the copolymers were found to deviate positively from the Gordon‐Taylor equation. The positive deviation from the Gordon‐Taylor equation could be accounted for by the dipole–dipole intrachain interaction between the methyl ester group and the fluoroalkyl ester group of the monomer units. These T_g values of the copolymers were found to fit with the Schneider equation. The fitting parameters in the Schneider equation were calculated, and R² values, the coefficients of determination, were almost 1.0. The refractive indices of the copolymers, measured at 532, 633, and 839 nm wavelengths, were lower than that of PMMA and showed a linear relationship with monomer composition in the copolymers. 2 and MMA have a tendency to polymerize in an alternating uniform monomer composition, resulting in less light scattering. This result suggests that the copolymer prepared with an equal molar ratio of 2 and MMA may have useful properties with applications in optical devices. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4748–4755, 2008     

Multicomponent Synthesis of Purines and Pyrimidines: From the Origin of Life to New Sustainable Approaches for Drug-Discovery Applications

It is widely accepted that purines and pyrimidines, the building blocks that gave origin to life on our planet, were created through multicomponent reactions (MCRs) on early abiotic Earth. These heterocyclic scaffolds gradually evolved into a wide range of biologically relevant molecules regulating many different physiological processes and thus becoming widely exploited as templates for the development of new drugs. Accordingly, over the years, the synthetic community has dedicated many efforts in the attempt to hypothesize and replicate the original abiotic synthesis of purines and pyrimidines, thus developing a number of multicomponent synthesis to access these scaffolds. The following evolution of synthetic chemistry towards green approaches for the production of new molecules and the recent interest in pharmaceutical sustainability underlines the importance of multicomponent synthesis of new heterocycles. This review article provides an overview of the most important multicomponent approaches for the synthesis of purine and pyrimidine derivatives for potential pharmacological applications.     

Rhodium(II)-catalyzed addition of 2-diazo(fluoroalkyl)acetoacetates to sulfides: a simple synthesis of stable sulfonium ylides

2-Diazo(fluoroalkyl)acetoacetates 1 reacted readily with many sulfides under mild reaction conditions in the presence of catalytic Rh₂(OAc)₄ affording to the corresponding sulfonium ylides. While thianthrene gave trans-thianthrenium 5,10-di(fluoroalkylacetoethoxycarbonyl)methylides (7a and 7b) under the same reaction condition, the structure of 7btrans-thianthrenium 5,10-di(bromodifluoroacetoethoxy-carbonyl)methylides was fully confirmed by spectral methods and X-ray single crystal diffraction analysis. All the ylide products obtained are fairly stable due to the strong electron-withdrawing properties of the fluorine atom.     

Well‐defined poly[(dimethylamimo)ethyl methacrylate]‐b‐poly(fluoroalkyl methacrylate) diblock copolymers: Effects of different fluoroalkyl groups on the solution properties

A series of well‐defined, fluorinated diblock copolymers, poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,2‐trifluoroethyl methacrylate) (PDMA‐b‐PTFMA), poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate) (PDMA‐b‐PHFMA), and poly[2‐(dimethylamino)ethyl methacrylate]‐b‐poly(2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate) (PDMA‐b‐POFMA), have been synthesized successfully via oxyanion‐initiated polymerization. Potassium benzyl alcoholate (BzO^?K⁺) was used to initiate DMA monomer to yield the first block PDMA. If not quenched, the first living chain could be subsequently used to initiate a feed F‐monomer (such as TFMA, HFMA, or OFMA) to produce diblock copolymers containing different poly(fluoroalkyl methacrylate) moieties. The composition and chemical structure of these fluorinated copolymers were confirmed by ¹H NMR, ¹⁹F NMR spectroscopy, and gel permeation chromatography (GPC) techniques. The solution behaviors of these copolymers containing (tri‐, hexa‐, or octa‐ F‐atom)FMA were investigated by the measurements of surface tension, dynamic light scattering (DLS), and UV spectrophotometer. The results indicate that these fluorinated copolymers possess relatively high surface activity, especially at neutral media. Moreover, the DLS and UV measurements showed that these fluorinated diblock copolymers possess distinct pH/temperature‐responsive properties, depending not only on the PDMA segment but also on the fluoroalkyl structure of the FMA units. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2702–2712, 2009