The use of 2,2′-thiodiethanol in the fluorimetric determination of secondary amines with o-phthalaldehyde and 2-mercaptoethanol

The fluorimetric determination of secondary amines based on conversion with sodium hypochlorite to primary amines and the o-phthalaldehydemercaptoethanol (OPA) reagent is discussed. Interference by excess hypochlorite (e.g., oxidation of OPA or conversion of primary amines to chloramines) were suppressed by 2,2′-thiodiethanol. Two spectrophotofluorimetric method are reported, one for aromatic and the other for aliphatic secondary amines. These methods permitted determinations at nanomolar levels; relative standard deviations were 4% for 5 nmol of N-methylaniline and 13% for 5 nmol of sarcosine.     

One-pot synthesis of sulfonamides from methyl sulfinates using ultrasound

Room temperature ultrasonic irradiation of neat mixtures of methyl sulfinates and primary or secondary amines (1.5 equiv) produced sulfinamides, which on m-CPBA oxidation (in dichloromethane) were converted into the corresponding sulfonamides. The two steps can be accomplished in one pot, in good overall yields, when using secondary amines, but primary amines give better sulfonamide yields when the peracid oxidation is effected on the purified sulfinamide. This constitutes a mild, efficient, and potentially scalable route to sulfonamides, which obviates the use of water sensitive, often lachrymatory sulfonyl chlorides and large reagent excesses.     

Determination of alkylamines by high-performance liquid chromatography with post-column fluorescence derivatization

A styrene/divinylbenzene polymer column and an amino column are compared for the non-aqueous separation of primary, secondary and tertiary alkylamines. Post-column derivatization with o-phthalaldehyde/2-mercaptoethanol is selective for primary amines and derivatization with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) is selective for secondary amines after on-line masking of primary amines. This procedure can tolerate 0.4 M butylamine. The limit of detection is 18.5 mM for dioctylamine (with NBD-Cl) and 0.18 mM for decylamine and tetraethylenepentamine (with o-phthalaldehyde/2-mercaptoethanol).     

Three-component one-pot process to propargylic amines and related amide and sulfonamide compounds: application to the construction of 2-(aminomethyl)benzofurans and indoles

An efficient palladium-copper-catalyzed three-component assembling of propargyl halides, aryl or heteroaryl halides, and secondary amines is described. A wide variety of tertiary propargylic amines were synthesized in good to excellent yields from easily accessible starting materials. This three-component assembling was also effective when using potassium phthalimide or di-tert-butyliminodicarbonate instead of secondary amines. Consequently, it provides a quick entry to N-protected propargylic amines suitable intermediates for the synthesis of primary and secondary propargylic amines. In a similar way, related compounds including propargylic amide, carbamate and sulfonamide derivatives were efficiently obtained. This catalytic domino three-component process has been applied successfully to the construction of functionalized 2-(aminomethyl)benzo[b]furan or indole derivatives of biological interest.     

Synthesis of chiral vicinal C2 symmetric and unsymmetric bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine by aminolysis of N-tosylaziridines

The ring opening of N-tosylaziridines with aliphatic amines can be efficiently catalyzed by lithium perchlorate to provide derivatives of the trans-1,2-diamine in high yields. The reaction was used in desymmetrization of several cyclic N-tosylaziridines using chiral amines. Using this strategy, an efficient synthesis of chiral vicinal C₂ symmetric bis(sulfonamide) and unsymmetrical bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine was developed.     

Fluorous scavenger for parallel preparation of tertiary sulfonamides leading to secondary amines

Alkylation of secondary sulfonamides by alkyl halides or alcohols (Mitsunobu reaction) is an efficient method for secondary amines preparation. However, its application to parallel chemistry is often difficult due to partial reaction. In this Letter, we propose a fluorous technique to bypass this problem. Thus, o-nitrobenzenesulfonamides were prepared and alkylated in parallel (Fukuyama method) with various alkyl halides or alcohols. Depending on the nature of the alkyl halide or alcohol, this step remained incomplete. A reactive fluorous alkyl iodide was then used to trap the unreacted sulfonamide allowing for a rapid and efficient fluorous solid-phase extraction (FSPE). Some examples of the isolated tertiary sulfonamides were converted in parallel to the corresponding secondary amines with good purity.     

Tandem addition–cyclization of o-ethynylphenyl isothiocyanates with N nucleophiles; difference of cyclization mode between primary and secondary amines

Silver triflate promotes the 6-exo-dig mode cyclization of the N-(2-ethynylphenyl)thioureas, which were easily obtained from the o-ethynylphenyl isothiocyanates and the primary amines, to provide the 2-imino-4-methylidene-1H-benzo[d][1,3]thiazines as the sole product in excellent yields. The secondary amines reacted with the o-ethynylphenyl isothiocyanates to give both the 6-exo and 5-endo-dig mode cyclization products under the same conditions.     

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.     

Novel one-step synthesis of 2-carbonyl/thiocarbonyl isoindolinones and mechanistic disclosure on the rearrangement reaction of o-phthalaldehyde with amide/thioamide analogs

A rearrangement reaction of o-phthalaldehyde with urea/thiourea analogs or amides/thioamides under the catalysis of TMSCl (trimethylchlorosilane) is described, whereby a series of 2-carbonyl isoindolinones and 2-thiocarbonyl isoindolinones are afforded. This is the first time that the N-carbonyl/thiocarbonyl isoindolinones are synthesized in a single step from o-phthalaldehyde. Similar reactions using primary amines also proceed smoothly to give corresponding N-alkyl or N-aryl isoindolinones in this mild catalytic system. The mechanism of this kind of rearrangement is discussed based on new evidences observed from the ESI-MS time-interval monitoring of the full reaction course and deuterium exchange experiments.     

A novel ruthenium-catalyzed amination of primary and secondary alcohols

An improved method for the N-alkylation of primary amines with primary and secondary alcohols has been developed. Novel, effective catalyst systems, for example, Ru₃(CO)₁₂ combined with tri-o-tolylphosphine or n-butyl-di-1-adamantylphosphine, allow for aminations in a good yield under comparatively mild conditions.     

Retro-Mannich reactions of 3-alkyl-3,4-dihydro-2H-1,3-benz[e]oxazines and the synthesis of axially chiral resorcinarenes

Intermediates involved in the conversion of 3-alkyl-3,4-dihydro-2H-1,3-benz[e]oxazines into 2-N,N-dialkylaminomethylphenol derivatives, using morpholine and other high boiling secondary amines, have been identified and characterised. Additional experiments have established the involvement of o-quinone methide intermediates in the retro-Mannich reactions. Axially chiral resorcinarenes have been prepared by utilising the exchange reactions.     

Base and catalyst-free synthesis of nitrobenzodiazepines via a cascade N-nitroallylation-intramolecular aza-Michael addition involving o-phenylenediamines and nitroallylic acetates

A [4+3] annulation of o-phenylenediamines with primary nitroallylic acetates affords nitrobenzodiazepines (NBDZs) in good to excellent yield. The reaction which proceeds in MeOH at room temperature in the absence of any base or catalyst involves a cascade S_N2 N-nitroallylation-intramolecular aza-Michael addition sequence. In the case of mono-N-arylated o-phenylenediamines and o-aminobenzamides, the reaction stops at the S_N2 stage affording nitroallylic amines. On the other hand, reaction of o-aminobenzamides with secondary nitroallylic acetates delivers S_N2′ products. Formation of stable S_N2 and S_N2′ products provides insights into the reactivity of primary and secondary nitroallylic acetates and also the mechanism of formation of nitrobenzodiazepines.     

N-烷基-N-酰基磺酰胺聚苯乙烯基微球作为固相酰化剂的研究

一种可循环使用的固相试剂：N-烷基-N-酰基磺酰胺聚苯乙烯基微球(5), 通过对聚苯乙烯磺酰氯微球树脂进行两步功能基化的修饰反应来制备. 制备过程如下：聚苯磺酰氯树脂(1)与伯胺(2)反应得到聚苯乙烯基N-烷基磺酰胺树脂(3), 树脂3用酰氯(4)或酸酐酰化得到N-烷基-N-酰基磺酰胺聚苯乙烯基树脂(5). 酰化的树脂5作为酰基转移试剂与亲核试剂胺反应得到二级酰胺. 根据5上取代基对酰胺生成的程度的影响结果表明, 烷基R¹和酰基(R²CO)对酰基转移反应活性的大小依次分别为：苯基＞苄基＞甲基＞正丁基＞＞H和对硝基苯甲酰基(苯甲酰基＞乙酰基. 胺的亲核能力对酰胺的收率也有一定的影响. N-苯基-N-苯甲酰基磺酰胺树脂重复使用3次没有发现活性降低.     

Selective Analysis of Secondary Amines Using Liquid Chromatography with Electrochemical Detection (LC‐EC)

In a mixture of primary and secondary aliphatic amines, the primary amines were derivatized (masked) with o‐phthalaldehyde (OPA) followed by derivatization of the remaining secondary amines with ferrocenecarboxylic acid chloride (FAC). The “tagged” amines were analyzed by LC‐EC (liquid chromatography with electrochemical detection) using in‐series dual electrode detection. Chemically‐reversible oxidation of the FAC tagged secondary amines and their subsequent complementary oxidation and reduction signals coupled with chemically‐irreversible oxidation of OPA tagged primary amines provided the selectivity for quantitative secondary amine analysis. The procedure was also applied for the selective identification of fragment 4–11 (N‐terminus‐proline) of Substance P in the presence of other Substance P fragments with primary amino acids as their N‐termini.     

Interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines—a pathway to new sterically hindered N,N-disubstituted o-aminophenols

The interaction of 3,5-di-tert-butyl-o-benzoquinone with secondary amines has been studied. The synthetic procedure was developed in order to synthesize a series of new N,N-disubstituted o-aminophenols. The interaction of 3,5-di-tert-butyl-o-benzoquinone with dimethylamine leads to 2-(N,N-dimethylamino)-4,6-di-tert-butyl-phenol, which is oxidized in the reaction medium by the parent 3,5-di-tert-butyl-o-benzoquinone forming spirocompound 4,5′,6,7′-tetra-tert-butyl-3′-methyl-3′H-spiro[1,3-benzodioxol-2,2′-[1,3]benzoxazole].     

Reactivity of 3-formyl- and 3-cyanothiochromones toward some N- and C-nucleophiles. Novel synthesis of 3-substituted 2-aminothiochromones

The reactions of 3-formylthiochromone with o-phenylenediamines, o-aminobenzenethiol, and indoles proceeded at the aldehyde group to give 3-(benzimidazol-2-yl)thiochromone, 3-(benzothiazol-2-yl)thiochromone, and 3-di(indol-3-yl)methylthiochromones, respectively. 3-Formyl- and 3-cyanothiochromones react with primary aromatic amines and phenylhydrazine to give the corresponding anils and phenylhydrazones of 3-formyl- and 2-amino-3-formylthiochromones. The reaction of 3-cyanochromones with o-phenylenediamines gave 2-amino-3-[(2-aminophenyl)iminomethyl]-4H-chromen-4-ones.     

Protonation constants and thermodynamic properties of amines for post combustion capture of CO2

The leading process for the post combustion capture (PCC) of CO₂ from coal-fired power stations and hence reduction in greenhouse gases involves capture by aqueous amine solutions. Of the reactions that occur in solution, which include CO₂ hydration, de-protonation of carbonic acid, amine protonation and carbamate formation, the protonation of the amine in the absorber and its subsequent de-protonation in the stripper involve the greatest enthalpy changes. In this study, protonation constants (reported as log₁₀ K_prot) of selected series of primary, secondary and tertiary alkanolamines/amines over the temperature range 288–318 K are reported. Selected series studied involve primary, secondary and tertiary mono-, di- and tri-alkanolamines, secondary amines including heterocyclic species, and both –CH₂OH and –CH₂CH₂OH substituted piperidines. van’t Hoff analyses have resulted in the standard molar enthalpies, ΔH_m^o, and molar entropies, ΔS_m^o, of protonation. Trends in ΔH_m^o are correlated with systematic changes in composition and structure of the selected series of amines/alkanolamines, while ΔH_m^o–ΔS_m^o plots generated linear correlations for the mono-, di-, and tri-alkanolamines, the –CH₂OH and –CH₂CH₂OH substituted piperidines, and the alkylamines. These relationships provide a guide to the selection of an amine(s) solvent for CO₂ capture, based on a greater difference in log₁₀ K_prot between the absorber and stripper temperatures.     

CN bond formation and cyclization: A straightforward and metal-free synthesis of N-1-alkyl-2-unsubstituted benzimidazoles

A straightforward and metal-free synthesis of N-1-alkyl-2-unsubstituted benzimidazoles from the corresponding o-fluoro aryl formamidines and primary amines using microwave irradiation is described. The displacement of -F by the primary amine and cyclization to form the corresponding benzimidazoles took place in one pot.     

A mild method for cleavage of N-Tos protected amines using mischmetal and TiCl4

The para-toluenesulfonyl (Tos) protecting group is removed efficiently and quickly under neutral conditions from the corresponding protected primary and secondary amines using mischmetal in moderate to excellent yields.     

Expedient synthesis of secondary amines bound to indole resin and cleavage of resin-bound urea, amide and sulfonamide under mild conditions

Highly efficient, new protocols for the attachment of primary amines to indole aldehyde resin using Ti(OⁱPr)₄-NaBH₄ and CH(OMe)₃-NaBH₃CN-HOAc are reported. Mild cleavage conditions for the release of urea, amide and sulfonamide products from the solid support using 1% trifluoroacetic acid (TFA) are developed.