Reaction Of Secondary Amines Research Articles

Improved synthesis of 3-(dialkylaminomethyl)-indole in acetic acid aqueous solution under ultrasound irradiation

Synthesis of Mannich bases related to gramine via Mannich reaction of secondary amine, formaldehyde and indole or N-methylindole can be carried out in 69–98% yields in acetic acid aqueous solution at 35 °C under ultrasound irradiation. Compared with the method using stirring, the present procedure provided several advantages such as milder conditions, shorter reaction time and higher yield.

Efficient One-Pot Synthesis of 6-Arylpyrrolo[3,2-d]pyrimidines from 6-Arylethynyl-5-nitropyrimidines

A highly concise one-pot synthesis of 6-arylpyrrolo[3,2-d]pyrimidines via conjugative addition reaction of secondary amines to 6-arylethynyl-5-nitropyrimidines and subsequent reduction is described.

Nucleophilic Reactivities of Primary and Secondary Amines in Acetonitrile

AbstractThe kinetics of the reactions of primary and secondary amines with benzhydrylium ions and quinone methides in acetonitrile have been studied under pseudo‐first‐order conditions (high excess of amines) by UV/Vis spectrophotometry. Generally, the plots of kobs versus amine concentration were linear, in line with a second‐order rate law. However, for some reactions of secondary amines with quinone methides, the plots of kobs versus amine concentration showed an upward curvature, which indicates rate‐limiting deprotonation of the initially formed adduct by a second molecule of amine. From the second‐order rate constants k2 for the attack on the electrophiles by the amines, the nucleophilicity parameters N and s for the amines were determined from the linear free energy relationship log k2 (20 °C) = s(N + E). The rates of the reactions of the amines with benzhydrylium ions are strongly affected by solvent polarity, in sharp contrast to the analogous reactions of other neutral nucleophiles.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Oxidative N-nitration of secondary amines

Reaction of secondary amines with the nitrite anion assisted by diacetoxyiodobenzene results in respective N-nitroamines. It is the first example of oxidative nitration of the amino group. N-Nitrosoamines are by-products. The yields and the ratio of the nitration and nitrosation products depend on the nature of the starting amine, cation of the salt used, and the solvent.

Efficient Synthesis of 3,5,6,7-Tetrahydro-4H-cyclopenta [4,5] thieno [2,3-d] Pyrimidin-4-ones

Abstract The title compounds 3,5,6,7-tetrahydro-4 H -cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-ones(6) were synthesized by base catalytic reactions of secondary amines with carbodiimides 4, which were obtained from the aza-Wittig reaction of iminophosphoranes(3) with aromatic isocyanates.

Efficient synthesis of 4(3 H)-quinazolinones using a soluble polymeric support

4(3 H)-Quinazolinones have been synthesized from poly(ethylene glycol) (PEG) supported aza-Wittig reaction. 2-Dialkylamino-4(3 H)-quinazolinones 6 were synthesized efficiently by reaction of secondary amine with PEG-supported carbodiimides 4, which were obtained from aza-Wittig reaction of PEG-supported iminophosphoranes 3 with isocyanates.

Diarylborinic Acid Derivatives as a Catalytic Iminium Ion Generator in the Mannich-Type Reaction Using Secondary Amines, Aldehydes, and Ketene Silyl Acetals

Reactions of secondary amines, aldehydes, and ketene silyl acetals were efficiently promoted by catalytic amounts of diarylborinic acid esters, Ar2B(OR), affording β-amino esters selectively with no formation of the corresponding β-hydroxy esters.

Synthesis of new 3-pyridinecarboxylates of potential vasodilation properties

2-(Alicyclic-amino)-4,6-diaryl-3-pyridinecarboxylates 5a– d were prepared via aromatic nucleophilic substitution reaction of secondary amines (piperidine or morpholine) with 2-bromo-3-pyridinecarboxylate derivatives 3a, b. The latters were obtained through bromination of 3-aryl-4-benzoyl-2-cyanobutyrates 2a and 2b, which were obtained from the base promoted addition of ethyl cyanoacetate to 2-propen-1-ones 1a and 1b, with bromine in glacial acetic acid. Reaction of 3 with piperazine hexahydrate in 2:1 molar ratio afforded 1,4-bis[(ethyl 4,6-diaryl-3-pyridinecarboxylate)-2-yl]piperazines 6a, b. Reaction of 3 with anilines in refluxing pyridine unexpectedly gave 2-(aryl-amino)-3-pyridinecarboxylates 8a– g and 2-amino-3-pyridinecarboxylates 9a and 9b. Vasodilation activity screening for the synthesized pyridinecarboxylates using isolated thoracic aortic rings' standard method of rats shows considerable properties. Compounds 5b, 5c, 6b and 8g reveal remarkable vasodilation potency (IC 50, concentrations necessary for 50% reduction of maximal norepinephrine hydrochloride induced contracture) 0.175, 0.146, 0.229 and 0.233 mM, respectively.

Palladium(0)-Catalyzed Allylic Aminations: Kinetics and Mechanism of the Reaction of Secondary Amines with Cationic [(η3-allyl)PdL2]+ Complexes

The mechanism of the reaction of secondary amines (piperidine, morpholine) with the cationic complexes [(η3-PhCHCHCHR)PdL2]+BF4- (R = Ph, L = PPh3 or L2 = dppb; R = H, L2 = dppb) has been investigated in DMF. The reaction, which affords the tertiary allylic amine, is irreversible when L is a monodentate ligand such as PPh3, whereas the reaction is reversible when L2 is a bidentate ligand such as dppb. In all cases, piperidine is more reactive than morpholine. The rate and equilibrium constants have been determined in DMF. These results can be combined with our previous results on the mechanism of the reversible formation of cationic [(η3-PhCHCHCHPh)PdL2]+AcO- by reacting Pd0L2 complexes with (E)-PhCHCHCH(Ph)OAc. Fully established catalytic cycles are now proposed for the Pd-catalyzed allylic amination of (E)-PhCHCHCH(Ph)OAc by piperidine and morpholine. The amine and AcO- are in competition in their reaction with the cationic complexes [(η3-PhCHCHCHPh)PdL2]+. The nucleophilic attack of the amine may be fa...

Efficient and Practical Synthesis of Mannich Bases Related to Gramine Mediated by Zinc Chloride.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Kinetics and mechanism of reactions of substituted (methylthio)benzylidene Meldrum's acids with primary amines in aqueous DMSO

AbstractA kinetic study of the aminolysis of substituted (methylthio)benzylidene Meldrum's acids, 2‐SMe‐Z with the aliphatic primary amines, n‐butylamine, glycinamide, methoxyethylamine, and aminoacetonitrile, in aqueous DMSO at 20 °C is reported. With all amines the reaction is strictly second‐order, that is, first‐order in 2‐SMe‐Z and first‐order in the amine. A three steps mechanism has been proposed. The first step is a rate‐limiting attachment of the amine to form the tetrahedral intermediate (T), and the subsequent steps are a fast acid–base equilibrium followed by a fast R‴CH2NH or H2O catalyzed expulsion of the leaving group. The Brönsted plot for k1 for the reaction of 2‐SMe‐H with four primary amines showed a good correlation between log k1 and pK with βnuc = 0.32 ± 0.02, a slightly lower value than that for the reactions of secondary amines (βnuc = 0.41 ± 0.01). The Hammett plot for n‐butylamine yields ρ(k1) = 0.40 ± 0.05 which is smaller than that for the reaction of piperidine with the same substrates (ρ(k1) = 0.72 ± 0.07) and also for the reactions of HOCH2CH2S− (ρ(k1) = 1.18), CF3CH2O− (ρ(k1) = 1.14) and OH− (ρ(k1) = 1.11) addition to 2‐H‐H (ρ(k1) = 1.11). All these observations are consistent with the suggested mechanism. Copyright © 2006 John Wiley & Sons, Ltd.

New Coupling Reaction of Secondary Amines, Aldehydes, and Alkynes Catalyzed by an Iridium Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Polyvinyl Pyridine as a Novel Solid Heterogeneous, Recyclable Catalyst for aza-Michael Reaction

Polyvinyl pyridine (PVP) is prepared by radical polymerization of 4-vinyl pyridine. PVP was used as a heterogeneous basic catalyst for the aza-Michael reaction of secondary amines and carbamates with α,β-unsaturated esters, cyanides and ketones to obtain the corresponding adducts in excellent yields (70-90%).

Efficient and Practical Synthesis of Mannich Bases Related to Gramine Mediated by Zinc Chloride

An efficient and practical procedure for the Mannich reaction of secondary amine, formaldehyde, and indole or N‐methylindole employing zinc chloride is presented. A series of gramine derivatives were obtained in 58–98% yields at room temperature in EtOH by using this method.

New Coupling Reaction of Secondary Amines, Aldehydes, and Alkynes Catalyzed by an Iridium Complex

A new reductive coupling reaction of secondary amines, aldehydes, and alkynes using an iridium complex as catalyst has been developed. For example, dibutylamine was allowed to react with butyraldehyde and 1-octyne in 1,4-dioxane at 50 degrees C under the influence of a catalytic amount of [IrCl(cod)](2) to give the corresponding allylamines such as N,N-dibutyl-2-butylideneoctylamine and N,N-2-tributyl-2-octenylamine in excellent yields. [reaction: see text]

Novel synthesis of nicotinamide derivatives of cytotoxic properties

A variety of 2-substituted-4,6-diaryl-3-pyridinecarboxamides 5 were synthesized through aromatic nucleophilic substitution reaction of secondary amines with 2-bromo analogues 4. The latter were obtained via bromination of 2-cyano-3,5-diaryl-5-oxo-N-substituted pentamides 3 in glacial acetic acid. Moreover, pentamide derivatives 3 were prepared through base-catalyzed Michael addition of cyanacetanilides 2 with 1,3-diaryl-2-propen-1-ones 1. Otherwise, reaction of 2-bromo-3-pyridinecarboxamides 4 with primary aromatic amines in refluxing pyridine afforded the corresponding 2-(arylamino)-3-pyridinecarboxamides 6 besides the unexpected 2-unsubstituted amino analogues 7. Antitumor properties of the synthesized pyridinecarboxamides utilizing 59 different human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate as well as kidney, were screened. Many of the tested compounds show considerable in vitro antitumor properties especially 5c and 7a, which reveal moderate activities against most of the used human tumor cell lines. It has also been achieved that, all the tested nicotinamide derivatives reveal promising antitumor properties against MDA-MB-231/ATCC (breast cancer).

Reevaluation of the Mechanism of the Amination of Aryl Halides Catalyzed by BINAP-Ligated Palladium Complexes

Two previous mechanistic studies of the amination of aryl halides catalyzed by palladium complexes of 1,1'-binaphthalene-2,2'-diylbis(diphenylphosphine) (BINAP) are reexamined by the authors of both studies. This current work includes a detailed study of the identity of the BINAP-ligated palladium complexes present in reactions of amines with aryl halides and rate measurements of these catalytic reactions initiated with pure precatalysts and precatalysts generated in situ from [Pd2(dba)3] and BINAP. This work reveals errors in both previous studies, and we describe our current state of understanding of the mechanism of this synthetically important transformation. 31P NMR spectroscopy shows that several palladium(0) species are present in the catalytic system when the catalyst is generated in situ from [Pd2(dba)3] and BINAP, and that at least two of these complexes generate catalytic intermediates. Further, these spectroscopic studies and accompanying kinetic data demonstrate that an apparent positive order in the concentration of amine during reactions of secondary amines is best attributed to catalyst decomposition. Kinetic studies with isolated precatalysts show that the rates of the catalytic reactions are independent of the identity and the concentration of amine, and studies with catalysts generated in situ show that the rates of these reactions are independent of the concentration of amine. Further, reactions catalyzed by [Pd(BINAP)2] with added BINAP are found to be first-order in bromoarene and inverse first-order in ligand, in contrast to previous work indicating zero-order kinetics in both. These data, as well as a correlation between the decay of bromobenzene in the catalytic reaction and the predicted decay of bromobenzene from rate constants of studies on stoichiometric oxidative addition, are consistent with a catalytic process in which oxidative addition of the bromoarene occurs to [Pd(BINAP)] prior to coordination of amine and in which [Pd(BINAP)2], which generates [Pd(BINAP)] by dissociation of BINAP, lies off the cycle. By this mechanism, the amine and base react with [Pd(BINAP)(Ar)(Br)] to form an arylpalladium amido complex, and reductive elimination from this amido complex forms the arylamine.

Synthesis, cytotoxicity, and DNA-topoisomerase inhibitory activity of new asymmetric ureas and thioureas

A new series of N-3,3-diphenylpropyl- N-( p-X-benzyl)- N′-phenylureas ( 5a– g) and thioureas ( 6a– g) were synthesized by the reaction of secondary amines and phenyl isocyanate or isothiocyanate. The cytotoxic effects of the urea and thiourea derivatives were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. Moreover, the activity of compounds in the inhibition of DNA topoisomerases I and II-α was tested. The results indicated that the compounds presented important and promising antiproliferative action.

The synthesis and properties of unsymmetrical 3,7-diaminophenothiazin-5-ium iodide salts: Potential photosensitisers for photodynamic therapy

A series of unsymmetrical 3,7-( N, N-disubstituted-amino)-phenothiazin-5-ium iodides have been prepared by stepwise reaction of secondary amines with phenothiazin-5-ium tetraiodide hydrate. The singlet oxygen generating efficiencies and polarity characteristics of the dyes are compared with those of Methylene Blue, and the factors influencing the potential value of these compounds as photosensitisers for photodynamic therapy are discussed. Preliminary data for the in vivo anti-tumour efficacy of the compounds suggest that high lipophilicity is an important requirement for high activity.

食品中の変異・発がん物質の生成とＤＮＡ損傷性，およびその低減に関する有機化学的研究

Organochemical studies on food-derived mutagenic/carcinogenic components were described. Regulation of formation of carcinogenic nitrosamines in the reaction of secondary amines with nitrite under acidic conditions by food factors was described: stimulation by ethanol and suppression by unsaturated fatty acids and protein digests. Unique mutagenic diazo compounds produced in the reaction of monophenolics with nitrite generated carbon-centered radicals that bound to the base moieties of DNA molecules and caused DNA single strand breaks. The nitrate content in Japanese vegetables was high enough to produce nitrosamines in stomach. Nitric oxide generated in the body may produce nitrosamines and reactive oxygen species under neutral conditions. Mutagenic/carcinogenic heterocyclic amines were found in processed foods, smoked-dried bonito meat, roasted coffee beans and charred egg. Loss of water increased the mutagenicity of heated meats. Reduction of heterocyclic amines in cooked hamburger was successful by suppressing intermediary pyrazine cation radical in two ways: addition of an appropriate amount of sugar or onion, and addition of ascorbate or erythorbate. Food reductones, hydroxyfuranones in soy sauce and Maillard reaction mixtures and hydroxyhydroquinone in coffee, generated reactive oxygen species in vitro to cause DNA single strand breaks. The reductones induced minor DNA damage in vivo, but caused increased type I and IV allergy responses.