Free Secondary Amine Research Articles

Ring-Opening Polymerization of rac-Lactide Catalyzed by Octahedral Nickel Carboxylate Complexes

To date, nickel(II) complexes have not been practically investigated as catalysts in ring-opening polymerization (ROP) of lactide to produce biodegradable poly(lactic acid), which is in demand in biomedicine and industry. In this study, carboxylate complexes of nickel(II) containing various N-donor ligands with different nuclearity, metal core rigidity and nature of carboxylate ligands were synthesized and studied by infrared spectroscopy, X-ray diffraction, elemental and thermogravimetric analyses. The obtained complexes were examined in the ROP of the rac-lactide in bulk and in toluene solution with and without the addition of a benzyl alcohol initiator. In the series of complexes studied, the complex [Ni(DBED)2(O2CC(CH3)3)2]·(CH3)3CCO2H (DBED is N,N′-dibenzylethylenediamine) was a syndioselective catalyst and showed the highest catalytic ability in the polymerization without the addition of benzyl alcohol. For this complex, according to 1D DOSY 1H NMR spectroscopy and mass spectrometry with electrospray ionization, polymerization is initiated by a free secondary amine, DBED, leaving the metal’s inner coordination sphere. Based on the experimental data obtained, a comprehensive density functional theory (DFT) study of the ROP pathways including the initiation and first chain growth cycle steps with a detailed description of the intermediates and evaluation of the energy barriers of the steps was carried out. It was shown that one of the key roles in the reaction process is played by carboxylate ligands, which act as proton carriers from the initiator molecule and have a significant influence on the reactivity of the catalytic metal complexes.

Nickel-Catalyzed Annulations of ortho-Haloarylimines.

We report the discovery, development, and mechanism of a nickel-catalyzed annulation reaction between o-haloarylimines and electron-poor olefins. The reaction produces two adjacent anti stereocenters and a free secondary amine. Spirocycles are formed from cyclic imines. We characterized the key oxidative addition intermediate and identified a major path leading to competing homocoupling products. The activation energy of oxidative addition and the rate of oxidative addition complex isomerization were determined. The sensitivity of the reaction to reaction conditions was established in a quantitative manner and both the scope and limitations of the method are presented.

Doubly prenylated tryptamines: cytotoxicity, antimicrobial activity and cyclisation to the marine natural product flustramine A

The marine natural product flustramine A was synthesised via oxidative cyclisation of Nb-methylated 1-prenyl-2-tert-prenyl-6-bromotryptamine and subsequent reduction of the resulting amidinium salt. Only the tert-prenyl group migrated, whereas the 1-prenyl group remained in place. Interestingly, the 2-tert-prenylated precursor revealed to be the biologically most active of our entire series of 21 compounds. Required for cytotoxicity and antimicrobial activity was the presence of a non-cyclised tryptamine side chain carrying a free secondary amine, whereas the presence of a 6-bromo substituent did not enhance cytotoxicity. In a panel of 42 human tumor cell lines, most sensitive were the lung and mammary cancer cell lines LXFA629L (IC50 1.9 μM) and MAXF401NL (IC50 2.4 μM), respectively. In a serial dilution assay, satisfying IC50 values of 5.9 μM against Micrococcus luteus and 7.7 μM each against Mycobacterium phlei were determined for Nb-methyl-1-prenyl-2-tert-prenyl-6-bromotryptamine.

Development of New Visible Spectrophotometric Methods for Quantitative Determination of Almotriptan Malate Using Quinones as Chromogenic Reagents

Two simple, sensitive and cost effective visible spectrophotometric methods (M 1-M2) were developed for the estimation of almotriptan malate in bulk and dosage forms. The first method (M 1) is based on the formation of radical anion with the involvement of basic nitrogen in drug (free base form) (n-donor) and chloranilic acid (DHQ) ( �-acceptor). The purple colored product exhibits absorption maximum at 544 nm in methanol. The second method (M2) is based on the interaction of N-alkyl vinyl amine formed from the condensation of the free secondary amine group in the drug and acetaldehyde with p-chloranil (TQ) to give vinyl amino substituted quinone. The blue colored product exhibits an absorption maximum at 660 nm in dioxane. Beer's law obeyed in the concentration range of 25-125 µg/mL and 20 - 60 µg/mL for method M1 and M 2 respectively. Commercially available tablets were analyzed; the results obtained by the proposed methods were in good agreement with the labeled amounts. These methods offer the advantages of rapidity, simplicity, sensitivity and normal cost and can be easily applied to resource-poor settings without the need for expensive instrumentation and reagents.

Polymerization of free secondary amine bearing monomers by RAFT polymerization and other controlled radical techniques

AbstractThis work describes the polymerization of the free secondary amine bearing monomer 2,2,6,6‐tetramethylpiperidin‐4‐yl methacrylate (TMPMA) by means of different controlled radical polymerization techniques (ATRP, RAFT, NMP). In particular, reversible addition‐fragmentation chain transfer (RAFT) polymerization enabled a good control at high conversions and a polydispersity index below 1.3, thereby enabling the preparation of well‐defined polymers. Remarkably, the polymerization of the secondary amine bearing methacrylate monomer was not hindered by the presence of the free amine that commonly induces degradation of the RAFT reagent. Subsequent oxidation of the polymer yielded the polyradical poly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl methacrylate), which represents a valuable material used in catalysis as well as for modern batteries. The obtained polymers having a molar mass (Mn) of 10,000–20,000 g/mol were used to fabricate well‐defined, radical‐bearing polymer films by inkjet‐ printing. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Substantive intumescence from phosphorylated 1,3‐propanediol derivatives substituted on to cellulose

AbstractCellulose flame retarded with an ammonia‐cured, polycondensed tetrakis(hydroxymethyl)phosphonium–urea derivative (as Proban CC®, Rhodia) phosphorylated by cyclic 1,3‐propanediol phosphoryl chloride and cyclic 2,2‐diethyl‐1,3‐propanediol phosphoryl chloride can give phosphorus levels up to 6.9% (w/w). Such high levels suggest up to 35.5% yields of reaction if the free secondary amine groups present in the crosslinked flame retardant and the C(6) primary hydroxyl groups are the assumed phosphorylation sites. The presence of substituted propanediol phosphonate moieties in the fibers significantly increases char formation above 400©C and scanning electron microscopy indicates that the char has an intumescent structure. The influence of the chemical structure of the propanyl moeity to the reaction extent of the possible phosphorylation sites and the char formation mechanism during thermal pyrolysis of the modified samples are discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3165–3172, 2003

Enhancing polymer flame retardancy by reaction with phosphorylated polyols. Part 2. Cellulose treated with a phosphonium salt urea condensate (proban CC®) flame retardant

AbstractPhosphorylation of cellulose flame retarded with an ammonia‐cured, polycondensed tetrakis(hydroxymethyl) phosphonium‐urea derivative (as Proban CC, Rhodia) with a polyol diphosphoryl chloride or phosphorochloridate like spirocyclic pentaerythritol di(phosphoryl chloride) or diphosphorochloridate, SPDPC can yield phosphorus levels in excess of 10% (w/w). Such high levels suggest up to 82% yields of reaction if phosphorylation of the free secondary amine groups present in the cross‐linked flame retardant is the assumed site.The presence of substituted pentaerythritol phosphate moieties significantly increases char formation above 400°C and scanning electron microscopy indicates that the char has an intumescent structure. The char‐forming characteristic is not influenced by subjecting the phosphorylated flame retardant cellulose to boiling in a 1% detergent solution in water thereby suggesting that the product is durable. The potential of this reaction to create a durable, intumescent flame retardant for cellulose is discussed. Copyright © 2002 John Wiley & Sons, Ltd.

Use of charge-transfer complex formation for the spectrophotometric determination of nortriptyline

Three simple and selective methods are proposed for the determination of nortriptyline hydrochloride in bulk form and in tablets. The first two methods are based on the formation of charge-transfer complexes between the drug base as a n-donor and quinhydrone or p-chloranil as π-acceptor. The products exhibit absorption maxima at 497 and 560 nm in acetonitrile for quinhydrone and p-chloranil, respectively. The third method is based on the interaction of N-alkylvinylamine formed from the condensation of the free secondary amine group and acetaldehyde with p-chloranil to give a vinylamino substituted quinone. The coloured product exhibits an absorption maximum at 650 nm in dioxane. All variables were studied to optimize reaction conditions. Beer's law was obeyed and the relative standard deviations were found to be less than 1.5%. The methods have been applied to the analysis of nortriptyline hydrochloride in the bulk drug and in tablets.

Glycosylation of fluoroquinolones through direct and oxygenated polymethylene linkages as a sugar-mediated active transport system for antimicrobials.

We report herein the synthesis and biological testing of several glycosylated derivatives of some fluoroquinolone antibiotics. In particular, we have prepared several glycosylated derivatives of ciprofloxacin (2) in which the carbohydrate units are linked to the free secondary amine of the piperazine unit by: (a) no linker (e.g., a glycosylamine), (b) a beta-oxyethyl linker, and (c) a gamma-oxypropyl linker. Both glucose and galactose were used as carbohydrates so that six compounds of this type were prepared, e.g., no linker 4a,b, oxyethyl linker 5a,b, and oxypropyl linker 6a,b. In addition the aryl glycosides of glucose and galactose (7a,b) were prepared from the active 1-(4-hydroxyphenyl)fluoroquinolone (3.) The syntheses of the glycosylamines 4a,b involved the direct condensation of glucose and galactose with the hydrochloride salt of ciprofloxacin (2). For the oxyalkyl-linked compounds, we first prepared the peracetylated omega-bromoalkyl glycopyranosides 14a,b and 15a,b and then coupled them to the allyl ester of ciprofloxacin (11) to give, after saponification to remove all of the esters, the desired fluoroquinolone carbohydrates 5a,b and 6a,b. The final series was prepared from 2,4,5-trifluorobenzoyl chloride (22) which gave 3 in four precedented steps. Coupling of 3 with the peracetylated glucosyl and galactosyl halides 12a,b and 26 afforded, after saponification, the desired aryl glycosides 7a,b. Six of these derivatives of ciprofloxacin-4a,b, 5a,b, and 6a,b-were subjected to microbiological screening. Of the six, compound 6a showed the highest activity. Since 6a would give the hydroxypropyl-substituted ciprofloxacin on hydrolysis and its activity is approximately 4-8 times less than that of ciprofloxacin (2), this implies that compound 6a is probably being actively transported. Thus preliminary results suggest that some of the compounds are stable in culture conditions and may be differentially transported by multiple resistant organisms. In some cases, the addition of a linker and a carbohydrate to ciprofloxacin lessens, but does not eliminate, antimicrobial activity.

Syntheses of Tertiary Tetraamines and Quaternary Pentaamines with Three and Four Methylene Chain Units.

Tertiary tetraamines and quaternary pentaamines composed of aminopropyl and/or aminobutyl groups were synthesized as authentic samples for the identification of naturally occurring branched polyamines. Four tertiary tetraamines were obtained by alkylating the free secondary amine group of diphthaloyl derivatives of sym-norspermidine or sym-homospermidine with N-(3-bromopropyl)phthalimide or N-(4-bromobutyl)phthalimide in the presence of KF-Celite. Five quaternary pentaamines were obtained by fusing triphthaloyl derivatives of the tertiary tetraamines with an excess amount of N-(3-iodopropyl)phthalimide or N-(4-iodobutyl)phthalimide. The present methods are simple and achieved high yields. The 13C-NMR spectra of these branched polyamines were recorded in D2O as fully protonated forms, and all 13C chemical shifts were assigned consistently.

Reaction of living polyTHF with amines: 4. Primary amines

Cationic living polyTHF reacts with primary amine rapidly under ambient conditions. When the amine is in excess the main product is a polymer possessing a terminal secondary amine ligand, and near quantitative conversion is achieved at ten fold excess. The proportion of mono- and disubstituted polymer formed at a given reagent ratio is insensitive to the nature of the amine. Surprisingly, therefore, it is found that the form of the un-neutralized amine product is dependent on the primary amine used, that from aniline exists as the free secondary amine whilst those from cyclohexylamine and n-butylamine exist as the acid salt. A hypothesis is put forward to explain these observations.

Spectrophotometric Determination of Ephedrine Hydrochloride and Phenylephrine Hydrochloride

A method is described for quantitative determination of the sympathomimetic amines ephedrine HCl and phenylephrine HCl. The method is based on the interaction of N-alkylvinylamine formed from the condensation of the free secondary amine group and acetaldehyde with chloranil to give a vinylamino-substituted quinone. The colored product for ephedrine HCl and phenylephrine HCl exhibits 2 maxima at about 320 and 680 nm. All variables were studied to optimize reaction conditions. The relationship between absorbance and concentration was linear within 1-25 micrograms/mL under the conditions studied for both drugs at both wavelengths. The method has been applied to the analysis of some pharmaceutical formulations including tablets and eye drops with good recoveries (98.75-100.4%).

Chemistry of bleomycin. XXV. Reductive methylation of bleomycin, a chemical proof for the presence of the free secondary amine in bleomycin.

Chemistry of bleomycin. XXV. Reductive methylation of bleomycin, a chemical proof for the presence of the free secondary amine in bleomycin.