Structural analysis of unstable norbixin isomers guided by pure shift nuclear magnetic resonance

We report the analysis of complex samples obtained during the microwave irradiation/heating of norbixin, which has been identified as a potential therapeutic target for age-related macular degeneration (AMD). In this context, identifying the different isomers that are obtained during its degradation is of primary importance. However, this characterization is challenging because, on the one hand, some of these isomers are unstable, and on the other hand, the ¹H spectra of these isomeric mixtures are poorly resolved. We could successfully apply 1D pure shift experiments to obtain ultrahigh-resolution ¹H nuclear magnetic resonance (NMR) spectra of the norbixin isomer samples and exploit their information content to analyze complementary 2D NMR data and describe accurately their isomeric composition.     

Generalized and rapid supramolecular solvent-based sample treatment for the determination of annatto in food

A supramolecular solvent (SUPRA) made up of octanoic acid aggregates is proposed for the microextraction of bixin and norbixin, the two major components of the natural food colouring annatto, in food. The procedure involved the extraction of sub-gram quantities (200mg) of homogenized food with 0.8mL of the supramolecular solvent. The overall sample treatment took about 20 min, and several samples could be simultaneously treated using conventional lab equipment. No clean-up or solvent evaporation were required. Extraction efficiencies mainly depended on the major components making up the SUPRAS (i.e. octanoic acid and tetrahydrofuran) and were not affected by the pH or the temperature in the ranges studied (1-4 and 10-80°C, respectively). Bixin and norbixin in the extracts were quantified by liquid chromatography (LC) and diode array detection (DAD). They were separated in a Hypersil C18 column using a mobile phase consisting of 5% acetic acid and methanol (15:85, v/v). The retention times for norbixin and bixin standards were 5.1 and 8.6 min, respectively. Recoveries in samples ranged between about 78% and 113%. The precision of the method, expressed as relative standard deviation, was about 1.5% and the quantitation limits for bixin and norbixin were 0.19 and 0.23 mg kg(-1), respectively, which were far below the maximum limits permitted by the European Union for the level of addition to food. Concentration of norbixin in samples belonging to the five major groups of food commodities defined in the literature, ranged between 3.75 and 43.8 mg kg(-1) whereas bixin was only found in one snack sample (6.6 mg kg(-1)). The method is simple and rapid, while delivering accurate and precise results, and can be used for the routine determination of annatto in food for the control of the compliance of current legislation.     

A straight synthesis of 2–(α-substituted N-tosylaminomethyl)-2,5-dihydrofurans by the reaction of N-sulfonylimines with arsonium 4-hydroxyl- cis -2-butenylides

On treatment of N-tosylimines (1) and 4-hydeoxyl- cis-butenyl arsonium salt (5) with KOH in acetonitrile at room temperature, 2–(α-substituted N-tosylaminomethyl)-2, 5-dihydrofurans (4) were obtained in moderate yields. The arsonium salt (5) acts formally as an equivalent of 2,5-dihydrofuran synon. A plausible mechanism was proposed for this new 5-membered cyclization reaction.     

Synthesis of 2, 5-divinylpyridine by the mannich reaction

The Mannich reaction is used to obtain 2-(β-diethylaminoethyl)-5-vinylpyridine from 2-methyl-5-vinylpyridine. Decomposition of a quaternary salt of 2-(β-diethylaminoethyl)-5-vinylpyridine gives 2, 5-divinylpyridine.     

Reinvestigation of the Synthesis of Ketanserin (5) and its Hydrochloride Salt (5.HCl) via 3‐(2‐Chloroethyl)‐2,4‐(1H,3H)‐quinazolinedione (2) or Dihydro‐5H‐oxazole(2,3‐b)quinazolin‐5‐one (1)

The synthesis of ketanserin ( 5 ) and its hydrochloride salt ( 5.HCl ) using respectively equimolar amounts of 3‐(2‐chloroethyl)‐2,4‐(1H,3H)‐quinazolinedione ( 2 ) with 4‐(parafluorobenzoyl)piperidine ( 3 ) and dihydro‐5H‐oxazole(2,3‐b)quinazolin‐5‐one ( 1 ) with hydrochloride salt of 4‐(parafluorobenzoyl)piperidine ( 3.HCl ) is reinvestigated. The one‐pot reaction of ethyl‐2‐aminobenzoate with ethyl chloroformate and ethanol amine has afforded 3‐(2‐chloroethyl)‐2,4‐(1H,3H)‐quinazolinedione ( 2 ) (86%) that was then refluxed with 4‐(parafluorobenzoyl)piperidine ( 3 ) in ethyl methyl ketone in the presence of sodium carbonate to obtain free base of ketanserin (87%). In another attempt, a very pure hydrochloride salt of ketanserin ( 5.HCl ) was synthesized using equimolar amounts of dihydro‐5H‐oxazole(2,3‐b)quinazolin‐5‐one ( 1 ) and hydrochloride salt of 4‐(parafluorobenzoyl)piperidine ( 3.HCl ) by a solvent‐less fusion method. Thus, under optimized conditions, 180°C and a reaction time of 30 min, the powder mixture was transformed into glassy crystals that were initially readily soluble in chloroform but were transformed afterwards over time (2 h) to white precipitates ( 5.HCl ) suspended in chloroform with a yield of 72%.     

On the reaction of 5-aminopyrimidine with diazonium salts

The reaction of 5-aminopyrimidine with benzenediazonium chloride, p-methylbenzenediazonium chloride and p-bromobenzenediazonium chloride is described. The reaction leads to a mixture of compounds, i.e. 1-aryl-3-(pyrimidin-5-yl)triazene ( 6 ), 5-amino-4-aryl-6-arylazopyrimidine ( 7 ) and 4-aryl-6-arylazo-5-hydroxypyrimidine ( 8 ). The yields are found to be strongly dependent on the substituent present in the diazonium salt. Attempts to rearrange 1-(p-bromophenyl)-3-(pyrimidin-5-yl)triazene ( 6c ) under basic and acidic conditions into a 1,2,3-triazole derivative failed.     

Reactions of 3-cyclopropyl-3-oxopropionitrile anion generated by electroreduction of 5-cyclopropylisoxazole

3-Cyclopropyl-3-oxopropionitrile anion obtained by cathodic reduction of 5-cyclopropylisoxazole in an aprotic medium was used as an example to demonstrate that cyano ketone anions show a dual reactivity. The reaction of acetyl chloride with the electrogenerated tetrabutylammonium salt of 3-cyclopropyl-3-oxopropionitrile gave O-acylation products, whereas the reaction with its sodium salt gives C-acylation products. The reactions of these salts with hydroxylamine hydrochloride follow a different route: in the case of the tetrabutylammonium salt, resinification takes place, while in the case of the sodium salt, 5-amino-3-cyclopropylisoxazole is formed. The condensation of this product with 4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dione in glacial AcOH affords 3-cyclopropyl-6-(2-thienyl)-4-(trifluoromethyl)isoxazolo[5,4-b]pyridine in 85% yield. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2110–2114, November, 2007.     

Nucleophilic Functionalization of 2-Alkylidene-4-Oxothiazolidines at C(5)-Position Induced by Formation of Novel Pyridinium Salt

Abstract

The synthesis of unsubstituted pyridinium salt containing the 4-oxothiazolidine moiety bondedviaC(5) to the N position of the pyridine nucleus is reported. The nucleophilic displacement of pyridine from pyridinium salt by the selected nucleophiles leads to the formation of new 5-substituted 4-oxothiazolidines in good yields.     

The parent of 2-(4,5-dihydro-1H-tetrazol-5-ylidene)-2-cyanoacetate: Synthesis and reactivity X-ray structure of (E)2-[1-(2,2-dimethylpropyl)-4,5-dihydro-1H-tetrazol-5-ylidene]-2-cyanoacetate

Reaction of 3,3-diazido-2-cyanoacrylate 5 with four moles of ammonia gives tetrazolyl-bisammonium salt 7 . The key-intermediate is the amino-vinyl azide 6 which spontaneously undergoes a 1,5′ ring-closure reaction followed by double deprotonation. Treatment of 7 with hydrochloric acid yields the parent of 2-(4,5-dihydro-1H-tetrazol-5-ylidene)-2-cyanoacetate 9 (R = Me, Et) as the only tautomer. Regiospecific monoalkylation of bisammonium salt 7a with dimethyl sulfate and reaction of ammonium salt 12 with hydrochloric acid gives (E)2-(1-methyl-4,5-dihydro-1H-tetrazol-5-ylidene)-2-cyanoacetate ( 13 ) (X-ray structure of derivative 14 ). Compound 13 can also be obtained from vinyl azide 10 and methylamine. This experiment as well as AM1 calculations of 9a, 23 and 24 strongly favour tautomer 9a .     

2-Phosphorylation of D-Erythorbic Acid

Abstract

D-Erythorbate 2-phosphate (3) was prepared by phos phorylation of 5, 6-0-isopropylidene-D-erythorbate (5) with phosphoryl chloride at high pH in the presence of pyridine. Following removal of the 5, 6-acetal, a crude magnesium salt of 3 was isolated in 67–71% yield. The salt contained 74% of 3, 9% of D-erythorbate 2-diphosphate (7), and 5% of bis-(D-erythorbyl) 2, 2′-phosphate (6). Analytically pure 3 was obtained as its crystalline magnesium and tricyclohexyl-ammonium salts in 26 and 47% yields, respectively, from 5.     

Direct synthesis of pyrrole nucleosides by the stereospecific sodium salt glycosylation procedure

A stereospecific high-yield glycosylation of preformed fully aromatic pyrroles has been accomplished for the first time. Reaction of the sodium salt of pyrrole-2-carbonitrile ( 1a ) and pyrrole-2,4-dicarbonitrile ( 1b ) with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 2 ) gave exclusively the corresponding blocked nucleosides with β-anomeric configuration 3a and 3b , which on deprotection gave 1-(2-deoxy-β-D-erythro-pentofuranosyl) derivatives of 1a ( 3c ) and 1b ( 3d ). Functional group transformation of 3c and 3d provided a number of 2-monosubstituted 4a-c and 2,4-disubstituted 4d-f derivatives of 1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrrole. Similar glycosylation of the sodium salt of 1a and 1b with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 5 ) and further functional group transformation of the intermediate blocked nucleosides 6a and 6b provided 1-β-D-arabinofuranosyl derivatives of pyrrole-2-carboxamide ( 7b ) and pyrrole-2,4-dicarboxamide ( 7d ). The synthetic utility of this glycosylation procedure for the preparation of 1-β-D-ribofuranosylpyrrole-2-carbonitrile ( 12 ) has also been demonstrated by reacting the sodium salt of 1a with 1-chloro-2,3-O-isopropylidene-5-O-(t-butyl)dimethylsilyl-α-D-ribofuranose ( 10 ) and subsequent deprotection of the blocked intermediate 11 . This study provided a convenient route to the preparation of aromatic pyrrole nucleosides.     

7-Trifluoromethyl-5-phenyl-2-oxo-(1H)-oxazolo[5,4-b]pyridine and some of its properties

The potassium salt of 7-trifluoromethyl-5-phenyl-2-oxooxazolo[5, 4-bjpyridine (IV) was prepared from 3-aminocarbonyl-4-trifluoromethyl-6 phenyl-2(1H)-pyridone by the Hofmann reaction and was converted into 3-anuno-4-trifluoromethyl-6-phenyl-2(1H)-pyridone without isolation. 1-Substituted 7-trifluoromethyl-5phenyl-2-oxooxazolo[5, 4-b]pyridines were formed by alkylation of salt IV. 6-Halogeno-7-trifluoromethyl-S phenyl-2-oxo(1H)-oxazolo[5,4-b]pyridines have been prepared.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–545, April. 1996.     

Reaction of Allyl Phenylcarbamate with Benzaldehyde Oximes in the Presence of N-Chlorobenzenesulfonamide Sodium Salt

Allyl phenylcarbamate reacts with benzaldehyde oxime and ring-substituted benzaldehyde oximes in ethanol in the presence of N-chlorobenzenesulfonamide sodium salt to give the corresponding 3-aryl-5-(phenylcarbamoyloxymethyl)-4,5-dihydroisoxazoles.     

In-situ synthesis of nanoparticles via supersolubilizing micelle self-assembly

In-situ synthesis of nano-particles using the self-assembly of molten salt and super soluble micellae was proposed based on a phenomenon of super solubilization of molten salt in reverse micellae and its self-assembly when the concentration reached up to 95% (w/w). The mechanism of the self-assembly indicates that the self-assembly of molten salt occurs in a reverse micelle where a homogenous phase is established between 5% (w/w) of a surfactant with a VB value of less than 1 and a hydrocarbon species. This synthesis has some unique features, such as being free of water, highly effective deposition and narrow distribution of particle size.     

A convenient synthesis of 2′-deoxy-6-thioguanosine,ara-guanine,ara-6-thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure

A simple and high-yield synthesis of biologically significant 2′-deoxy-6-thioguanosine ( 11 ), ara-6-thioguanine ( 16 ) and araG ( 17 ) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6-chloro- and 2-amino-6-chloropurine ( 1 and 2 , respectively) with 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranose ( 3 ) gave the corresponding N-9 substituted nucleosides as major products with the β-anomeric configuration ( 4 and 5 , respectively) along with a minor amount of the N-7 positional isomers ( 6 and 7 ). Treatment of 4 with hydrogen sulfide in methanol containing sodium methoxide gave 2′-deoxy-6-thioinosine ( 10 ) in 93% yield. Similarly, 5 was transformed into 2′-deoxy-6-thioguanosine (β-TGdR, 11 ) in 71 % yield. Reaction of the sodium salt of 2 with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 8 ) gave N-7 and N-9 glycosylated products 13 and 9 , respectively. Debenzylation of 9 with boron trichloride at ?78° gave the versatile intermediate 2-amino-6-chloro-9-β-D-arabinofuranosyl-purine ( 14 ) in 62% yield. Direct treatment of 14 with sodium hydrosulfide furnished ara-6-thioguanine ( 16 ). Alkaline hydrolysis of 14 readily gave 9-β-D-arabinofuranosylguanine (araG, 17 ), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate afforded araG 5′-monophosphate ( 18 ).     

Reaction of 2-Propynyl Phenylcarbamate with Benzaldehyde Oximes in the Presence of N-Chlorobenzenesulfonamide Sodium Salt

2-Propynyl phenylcarbamate reacts with substituted benzaldehyde oximes on heating in ethanol in the presence of N-chlorobenzenesulfonamide sodium salt, yielding the corresponding 3-aryl-5-(phenylcarbamoyloxymethyl)isoxazoles.     

Study of the carotenoid pigments of Bixa orellana L. Seeds by thin layer chromatography

Summary Two dimensional thin layer Chromatographic techniques have been used in the study of the carotenoid pigments in the seeds of Bixa orellana L. In addition to the two major carotenoids bixin and norbixin,-carotene, cryptoxanthin, lutein, zeaxanthin and methyl bixin have been tentatively identified by co-chromatography. There were other unidentified carotenoids in trace amounts. The probable biosynthetic significance of these carotenoids in relation to bixin is discussed.

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Untersuchung der Carotinoid-Farbstoffe in den Samen von Bixa orellana L. durch Dünnschicht-Chromatographie

Zusammenfassung Zweidimensionale Dünnschichtchromatographie wurde zur Untersuchung der Karotinoid-Farbstoffe in den Samen von Bixa orellana L. verwendet. Außer den beiden Hauptbestandteilen Bixin und Norbixin wurden-Karotin, Kryptoxanthin, Lutein, Zeaxanthin und Methylbixin chromatographisch festgestellt. Außerdem fanden sich andere nicht identifizierte Karotinoide in Spuren. Die wahrscheinliche biosynthetische Bedeutung dieser Karotinoide im Hinblick auf Bixin wurde diskutiert.

     

Epimerization of Lupinine to Epilupinine and vice versa. Reexamination of the Structures of Lupinal and Epilupinal

Although the epimerization of lupinine ( 1 ) has been largely investigated, a previously not observed compound of formula C₁₀H₁₇NO was now isolated from the mixture of alkaloids that remains after the separation of epilupinine ( 2 ). It is insoluble in dry Et₂O but soluble in EtOH, from which it is recovered as an Et₂O‐soluble oil that slowly returns to the Et₂O‐insoluble solid form. For these characteristics and based on GC/MS, ¹H‐NMR, and IR data, it is considered as the inner salt 6 of the common enolic form 5 of lupinal ( 3 ) and epilupinal ( 4 ), with which it is in equilibrium when standing in solution (see Scheme 1). The oily form, but not the solid one, is able to improve the conversion of 1 to 2 , establishing the role of the aldehydes in the epimerization process. It was observed that also 2 can be converted to 1 . Finally, the solid lupinal described by Zaboev should be considered as being identical to the now isolated inner salt 6 , while the oily epilupinal of Wicky and Schumann is, indeed, a mixture of epilupinal ( 4 ) with a minor amount of lupinal ( 3 ), which, on standing, is converted to the inner salt 6 of the common enolic form 5 .     

The rhodium-catalysed methanolysis of aryl acetates and of the hexafluorophosphate anion

Summary In nitromethane, the methanolysis of aryl acetates is catalysed by the tetrafluoroborate and hexafluorophosphate salts of the ( ⁵-ethyltetramethylcyclopentadienyl) ( ⁶-benzen)rhodium(III) cation. Under the conditions of the methanolysis, the anion of the latter salt reacts with methanol to give dimethyl phosphorofluoridate. The hydrogen fluoride formed also in this reaction is thought to be responsible for the greater efficiency of the hexafluorophosphate salt as a catalyst for the methanolysis.     

Imidazole‐coordinated monodentate NHC–Pd(II) complex derived from proline and its application to the coupling reaction of arylboronic acids with carboxylic acid anhydrides in water at room temperature

Cleavage of a C N bond of imidazolium salt derived from N‐phenyl‐substituted proline was observed in this laboratory. A novel imidazole‐coordinated monodentate NHC–Pd(II) complex 5 was obtained as the sole product in good yield in the reaction of imidazolium salt 4 with Pd(OAc)₂ in refluxing THF. The structure of complex 5 was determined unambiguously by an X‐ray diffraction. The complex was found to be a good catalyst in the cross‐coupling reaction of arylboronic acids with carboxylic acid anhydrides in water at room temperature. Copyright © 2011 John Wiley & Sons, Ltd.