Chromatography of xanthines on ion-exchange resins.

Short columns of a 4% crosslinked cation-exchange resin gave good chromatography of xanthines, including caffeine, theophylline and hypoxanthine, and related polar aromatic compounds. Elution volumes and sequences can be modified by changing pH, solvent composition and resin counter-ion. A macroporous cation-exchange resin showed exaggerated counter-ion effects. A method is described for determining caffeine and theophylline in blood serum, using the 4% crosslinked resin with aqueous sodium phosphate eluent of pH 7.5; the temperature was 65 degrees. Detection limits are 10 ng and less.     

Cation-exchange resin as an efficient hetero-geneous catalyst for one-pot three-component synthesis of 2,3-dihydro-4(1H)-quinazolinones

Various mono- and disubstituted 2,3-dihydro-4(1H)-quinazolinones were synthesized efficiently by a one-pot three-component condensation of isatoic anhydride, aromatic aldehydes, and ammonium salts or primary amines using a strong acidic cation-exchange resin as the catalyst in EtOH–H₂O solution. The catalyst is cheap, efficient, stable, and reusable under the reaction conditions. The novel method offers several advantages, such as excellent yields, environmentally friendly reaction media, and simple procedure.     

聚苯乙烯基N,O-二酰基磺酰羟胺树脂: 一种双酰基转移试剂在合成酰胺库中的应用

用聚苯乙烯基磺酰羟胺树脂1与酰氯2反应合成了聚苯乙烯基N,O-二酰基磺酰羟胺树脂3. 树脂3作为一种新的双酰基转移试剂可与胺4发生酰基转移反应, 合成了含有24个结构类似的酰胺化合物库. 改变酰氯的种类, 结果发现双对硝基苯甲酰树脂3a的活性较高. 双酰基树脂3胺解结果表明, 由脂肪族胺得到的酰胺收率较芳香族胺高. 当解脱试剂同时含有羟基和氨基时, 双酰基树脂3能选择性地在氨基端发生酰基转移, 而羟基端不受影响.     

Solid-phase synthesis of urea and amide libraries using the T2 triazene linker

Starting from Merrifield resin, primary amines were immobilized in two steps by triazene linkage (T2-linker). While reaction with isocyanates gave rise to resin-bound urea derivatives, acylation by acid chlorides or anhydrides furnished amides bound to solid support via the nitrogen atom, therefore representing a novel backbone amide linker. Cleavage from the resin was conducted using dilute trimethylsilyl chloride or trifluoroacetic acid, respectively, to yield ureas and amines/amides in a library format (altogether 60 examples; manual synthesis: 17 ureas, 6 mono-alkylated ureas [including dihydroxylation and ozonolysis/Wittig reaction]; automated synthesis: 15 ureas, 15 amides) in high purities and good overall yields. The synthesis of a small library (4 x 4 member) was successfully conducted on a Bohdan Neptune synthesizer.     

Development of a new linker for the solid-phase synthesis of N-hydroxylated and N-methylated secondary amines

Merrifield resin was modified by the introduction of an ortho-nitrophenylethanal group that served as a linker moiety to attach amines to the resin by reductive amination. Resin-bound tertiary amines were shown to be readily transferred into the respective liberated N-hydroxylated or N-methylated derivatives by either an oxidation/Cope elimination or a permethylation/Hofmann elimination protocol. With these two divergent liberation/derivatization options, the new resin offers new flexibility in the solid phase synthesis of N-modified secondary amines, for instance in spider toxin synthesis.     

Grafting of Polymers onto a Crosslinked Polymer Carrying Carboxyl Groups as a Model Compound for Carbon Black

Abstract

A cation-exchange resin (a crosslinked polymer carrying carboxyl groups) was used as a model compound for carbon black, and the grafting of several polymers to the resin was investigated. Reaction of acyl chloride groups that had been placed on the ion-exchange resin with polymers having hydroxyl or amino groups, such as polypropylene glycol, polyethylene glycol, polybutadiene glycol, polyvinyl alcohol, silicone diol, silicone diamine, and polyethyleneimine, resulted in grafting to the ion-exchange resin. In further experiments, primary amino groups were placed on the cation-exchange resin by reaction of acyl chloride groups with ethylenediamine. It was found that ring-opening polymerization of γmethyl L-glutamate N-carboxyanhydride is initiated by the amino groups on the resin, and polypeptide was grafted from the cation-exchange resin. Therefore, the reactivity of carboxyl groups on the resin was found to be similar to that on carbon black. However, carboxyl groups on the resin failed to initiate the cationic polymerization of vinyl monomers, in contrast to those on carbon black. This suggested that the acidity of carboxyl groups on carbon black is greater than on the cation-exchange resin.     

Separation of selenite,sulkate and iron by cation-exchange resin

Selenite, sulfate and iron(III) are separated by cation-exchange resin. Microgram amounts of selenite in iron(III) sulfate solution at pH 2 are completely adsorbed on the resin together with the large excess of iron(III). while sulfate passes through. Selenite is eluted with 0.5 N hydrochloric acid, leaving iron(III) in the resin. The procedure is applied to the determination of these elements in natural iron sulfides.     

CAN-promoted, diastereoselective synthesis of fused 2,3-dihydrofurans and their transformation into tetrahydroindoles

The reaction between 1,3-cyclohexanediones and chalcones (or their vinilogs) in the presence of 2.5 equiv of cerium(IV) ammonium nitrate afforded trans-2-arylcarbonyl-3-aryl (or styryl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-ones in good to excellent yields and in high diastereoselectivities. The method was also extended to the preparation of derivatives of the 5,6-dihydro-2H-cyclopenta[b]furan-4(3H)-one system. The fused 2,3-dihydrofuran derivatives were transformed into 1-alkyl-2-acyl-3-aryl-6,7-dihydroindole-4(5H)-ones by 2,3-dehydrogenation followed by reaction with primary amines. The direct reaction of the tetrahydrobenzofuran-4(5H)-one compounds derived from dimedone with amines gave 1-alkyl-2-alkylimino-3-aryl-6,7-dihydroindole-4(5H)-ones, while starting materials derived from 1,3-cyclohexanedione underwent an unprecedented 2-deacylation reaction and gave 1-alkyl-3-aryl-6,7-dihydroindole-4(5H)-ones.     

Amberlite IRA-400 Cl resin catalyzed synthesis of secondary amines and transformation into N-((1H-indol-3-yl) (heteroaryl) methyl)-N-heteroaryl benzenamines and bis-indoles via multicomponent reaction

A one-pot Amberlite IRA-400 Cl resin catalyzed the in-situ generation of imines from various aldehydes and primary amines followed by reduction with sodium borohydride affording corresponding secondary amines. The secondary amines thus obtained were utilized for the IRA-400 Cl resin catalyzed multicomponent synthesis of 3-aminoalkylated indoles using a number of aldehydes and indole. Mild condition, easy work-up, and environmentally benign nature of the synthetic strategy make it both practical and attractive.     

New approaches to pyrimido[4,3-b][1,3,5]selenadiazines

The Mannich reactions of (arylmethylidene)(cyano)selenoacetamides with primary amines and formaldehyde gave 3,7-disubstituted 8-R-3,4,7,8-tetrahydro-2H,6H-pyrimido[4,3-b]-[1,3,5]selenadiazine-9-carbonitriles. Alternatively, these compounds can be obtained by reactions of 4-R-2,6-diamino-4H-selenopyran-3,5-dicarbonitriles with primary amines and form-aldehyde or by multicomponent condensation of an appropriate aldehyde, cyanoselenoacet-amide, a primary amine, and formaldehyde.     

A novel solid-phase synthesis of di- and trisubstituted N-acyl ureas

A novel, mild method for the synthesis of di- and trisubstituted N-acyl ureas on solid support is described. Addition of carboxylic acids to a resin-bound carbimidoyl chloride gave, initially, an O-acyl isourea which subsequently rearranged to the corresponding N-acyl urea. Trisubstituted N-acyl ureas were assembled on a Wang resin from a wide range of Fmoc amino acids, secondary amines and carboxylic acids. Acid mediated cleavage yielded the products in good yields and excellent purities. In addition, the regioselective synthesis of disubstituted N-acyl ureas is demonstrated with four examples.     

PS-IIDQ: a supported coupling reagent for efficient and general amide bond formation

Polystyrene-IIDQ, a polymer-supported coupling reagent, was synthesized in three steps from Merrifield resin in 86% overall conversion. This reagent efficiently coupled carboxylic acids to amines in good yields and high purities, required no pre-activation step, and was tolerant of the order of reagent addition. PS-IIDQ was observed to be more efficient than polymer-supported carbodiimides (PS-EDC and PS-DCC) and gave higher yields than HATU for general amide bond formation, including the coupling of anilines and hindered substrates. When evaluated with five carboxylic acids and nine amines (including anilines and secondary amines) PS-IIDQ gave an average isolated yield of 73%.     

Solid-phase synthesis of trisubsituted guanidines

The solid-phase library synthesis of trisubstituted guanidines was accomplished. Amines were loaded onto the 4-formyl-3,5-dimethoxyphenoxymethyl linker via reductive amination. Subsequent acylation with Fmoc-4-aminomethylbenzoic acid followed by Fmoc deprotection gave solid-supported primary amines. Alternatively, sulfonylation of resin-bound secondary amines with 4-cyanobenzenesulfonyl chloride followed by borane reduction also gave solid-supported primary amines. Both resins were acylated with isocyanates to furnish solid-supported ureas. Dehydration of ureas with p-toluenesulfonyl chloride in pyridine gave solid-supported carbodiimides. Nucleophilic addition of amines to the carbodiimide bond followed by cleavage off the solid support gave trisubstituted guanidines.     

Reactions of some 4-methylene-4H-pyran derivatives with primary and secondary amines

4-Dicyanomethylene-4H-pyrans react with secondary amines to give 2-aminopyridine and 2-pyridone derivatives which, in turn, have been used to prepare copyrine derivatives. These pyrans and primary amines gave copyrine and iminopyridone derivatives in addition to the dicyanomethylene-1,4-dihydropyridines, which had been reported previously. Reaction of cyanocarbamoylmethylene-4H-pyrans with secondary amines gave 2-pyrones, and with primary amines, gave copyrines and 1,4-dihydropyridine derivatives.     

Synthesis of new acetal aza-cage compounds via ozonolysis of bis-endo-diol- and diacylnorbornene derivatives

We synthesized acetal aza-cage compounds directly via ozonolysis of 2,3-bis-endo-diol- and diacylnorbornenes in dichloromethane at ?78 °C. Ozonolysis of the diols followed by addition of amines gave the aza-cage compounds in high yields. The reaction mechanism for the formation of this type of aza-cage compounds is proposed to proceed via the hydroperoxide intermediate. Ozonolysis of the diacetyl norbornene followed by addition of (1) primary amines gave monoaza-cages and diaza-cage, (2) tert-butylamine gave hydroxyl lactone and diaza-cages, and (3) amino acid ester gave optically active aza-cages, in which one compound was converted into chiral aminoalcohol and structure of another was proven by X-ray analysis. A mechanism via the final ozonide and the imine intermediates is proposed for the formation of this type of aza-cages.     

Versatile solid-phase synthesis of secondary amines from alcohols. Development of an N-Boc-(o-nitrobenzene)sulfonamide linker

The development of a versatile amine releasing linker based on the modified o-nitrobenzene sulfonamide protective group is described. This new N-Boc-o-nitrobenzenesulfonamide (Boc-ONBS) linker enables the elaboration on resin of primary and secondary amines by sequential substitution of the sulfonamide moiety using the Mitsunobu reaction. A 16-member array of secondary and Boc protected primary amines was then prepared using this linker.     

Access to chiral tertiary amines via the iridium-catalyzed asymmetric hydrogenation of enamines

The asymmetric hydrogenation of N,N-dialkyl and N-alkyl-N-aryl enamines to chiral tertiary amines was studied. All the N,P-ligated iridium complexes investigated were active catalysts for the reaction, but only those with bicycle-supported oxazoline-phosphine ligands gave reasonable stereoinduction. The best catalyst produced a range of chiral tertiary amines in up to 87% ee.     

Flame retardant epoxy polymers based on all phosphorus-containing components

A phosphorus-containing epoxy resin, bis(3-t-butyl-4-glycidyloxyphenyl-2,4-di-t-butylphenyl)resorcinol diphosphate, was synthesized and subsequently cured with non-phosphorus containing amines, and/or novel phosphorus-containing aromatic or polyoxyalkylene amines. Chemical structures of these materials were characterized with FTIR, NMR, elemental analysis, and amine titration. The introduction of soft -P-O- linkage, polyoxyalkyene, or hard aromatic group into the backbones of the synthesized phosphorus-containing amines provides epoxy polymers with high phosphorus contents and tailored flexibility. Thermal analysis of differential scanning calorimeter and thermal gravimetric analysis (TGA) reveals that these resulted epoxy polymers possess moderate T_gs and thermal stability. Furthermore, high char yields in TGA analysis and high limited oxygen index values indicate that these phosphorus-containing epoxy polymers possess excellent flame retardant properties.     

Synthesis of 1-ethylpyrazole-4-carbaldehydes, 1,1’-methylenebis(3,5-dimethylpyrazole-4-carbaldehyde), and Schiff bases derived therefrom

New pyrazole-containing aldehydes, 1-ethylpyrazole-4-carbaldehyde, 1-ethyl-3,5-dimethylpyrazole-4-carbaldehyde, and 1,1’-methylenebis(3,5-dimethylpyrazole-4-carbaldehyde), were synthesized by the Vilsmeier reaction. Their reactions with primary amines (aniline, hydrazine, ethylenediamine, p-phenylenediamine, benzidine) gave the corresponding Schiff bases.     

Polyfunctional imidazoles: VII. 1-aryl-4-chloro-5-[hydroxy(halo)methyl]-1H-imidazoles and their derivatives

The reduction of 1-aryl-4-chloro-1H-imidazole-5-carbaldehydes with sodium tetrahydridoborate gave 1-aryl-4-chloro-1H-imidazol-5-ylmethanols which were converted into 5-chloromethyl and 5-fluoromethyl derivatives. 1-Aryl-4-chloro-5-chloromethyl-1H-imidazoles reacted with sodium azide, secondary amines, thiols, and triphenylphosphine to produce the corresponding products of chlorine replacement in the 5-chloromethyl group.