- N-LITHIUM DERIVATIVES OF ALIPHATIC AMINES IN THE SYNTHESIS OF 1-ALKYL-2-PHENYLDIAZENE 2-OXIDES
-
Magnesium derivatives of aliphatic amines containing α-hydrogen atoms, in contrast to t-BuNHMgBr, do not form phenylaliphatic diazene oxides upon reaction with nitrobenzene, but rather reduce it to azobenzene and azoxybenzene.Asymmetric diazene oxides are formed when the magnesium derivatives are replaced by lithium derivatives.The reaction of t-BuNHLi with dimethylnitramine gives 1,3,5-trimethyl-1,3,5-triazacyclohexane.
- Shepelev, E. V.,Kostikova, N. N.,Dzhetigenov, B. A.,Kalinin, A. V.
-
-
Read Online
- ELECTRONIC STRUCTURES AND THERMOLYSES OF 2-TETRAZENES
-
The electronic structures and gas phase termolyses of the cyclic 2-tetrazenes 2 and 3 of open chain 1,1,4,4-tetramethyl-2-tetrazene (1) have been studied by photoelectron spectroscopy.While the six-membered ring compound 2 yields 1-methylmethylenamine (6) and nitrogen as fragments, the seven-membered ring compound 3 is contracted to 1,2-dimethylpyrazolidine (11).The acyclic 2-tetrazene 1 prefers disproportionation to 6 and dimethylamine (7).Based on MNDO calculations the ionization potentials of 1 - 3 were assigned to molecular orbitals.Several conformations of 2 and 3 were calculated.Compound 2 shows a rigid boat conformation with equatorial methyl groups, while 3 can occupy several conformations of similar energies.The different thermal decompositions of 1 - 3 are explained.
- Heymanns, Peter,Rademacher, Paul
-
-
Read Online
- Flash Vacuum Thermolysis of α-Aminonitriles and Subsequent HCN Removal on Solid Base, a 'One Line' Multistep Sequence to Reactive N-Methyleneamines
-
Reactive methyleneamines bearing alkyl or functional groups are isolated at low temperature in the condensate state by flash vacuum thermolysis of α-aminonitriles and subsequent vapour phase HCN removal on solid base.
- Guillemin, J. C.,Denis, J. M.
-
-
Read Online
- Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP
-
The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP weith N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and micranalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6,9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6-CARB-6-MP prodrugs reverted to 6-MP in water by an S(N)1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N-methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone.
- Siver,Sloan
-
-
Read Online
- One-step synthesis of substituted 3,5-dinitropiperidines and 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonanes from 1,3-dinitropropanes
-
1,5-Dinitro-3,7-diazabicyclo[3.3.1]nonane derivatives were synthesized in up to 83%yields by the Mannich reaction of 1,3-dinitropropanes with excess formaldehyde and primary amines. In some cases, for instance, when 2,2-dimethyl-1,3-dinitropropane and benzylamine or monoethanolamine are used, the reaction occurs with low yields or stops at the step of formation of 3,5-dinitropiperidines. The influence of the structure of the starting compounds and reaction conditions on the yields of 1,5-dinitro-3,7-diazabicyclo[3.3.1] nonanes and 3,5-dinitropiperidines was studied.
- Yarmukhamedov,Baibulatova,Dokichev,Khakimova,Spirikhin,Tomilov,Yunusov
-
-
Read Online
- Multiple N-H and C-H Hydrogen Atom Abstractions through Coordination-Induced Bond Weakening at Fe-Amine Complexes
-
We report the use of the reported Fe-phthalocyanine complex, PcFe (1; Pc = 1,4,8,11,15,18,22,25-octaethoxy-phthalocyanine), to generate PcFe-amine complexes 1-(NH3)2, 1-(MeNH2)2, and 1-(Me2NH)2. Treatment of 1 or 1-(NH3)2 to an excess of the stable aryloxide radical, 2,4,6-tritert-butylphenoxyl radical (tBuArO?), under NH3 resulted in catalytic H atom abstraction (HAA) and C-N coupling to generate the product 4-amino-2,4,6-tritert-butylcyclohexa-2,5-dien-1-one (2) and tBuArOH. Exposing 1-(NH3)2 to an excess of the trityl (CPh3) variant, 2,6-di-tert-butyl-4-tritylphenoxyl radical (TrArO?), under NH3 did not lead to catalytic ammonia oxidation as previously reported in a related Ru-porphyrin complex. However, pronounced coordination-induced bond weakening of both α N-H and β C-H in the alkylamine congeners, 1-(MeNH2)2 and 1-(Me2NH)2, led to multiple HAA events yielding the unsaturated cyanide complex, 1-(MeNH2)(CN), and imine complex, 1-(MeN═CH2)2, respectively. Subsequent C-N bond formation was also observed in the latter upon addition of a coordinating ligand. Detailed computational studies support an alternating mechanism involving sequential N-H and C-H HAA to generate these unsaturated products.
- Wang, Zongheng,Johnson, Samantha I.,Wu, Guang,Ménard, Gabriel
-
p. 8242 - 8251
(2021/06/25)
-
- Synthesis of N-substituted 1,3,5-triazacyclohexanes catalyzed by starch sulfuric acid
-
N-substituted 1,3,5-triazacyclohexanes were simply synthesized from the reaction of aromatic or fatty amines and formaldehyde catalyzed by recyclable starch sulfuric acid with good yields at room temperature.
- Wu, Hui,Yuan, Rui,Wan, Yu,Yin, Wei,Pang, Li-Ling
-
experimental part
p. 1097 - 1102
(2012/03/11)
-
- Method of preparing electron deficient olefins
-
This invention relates to a process for producing electron deficient olefins, such as 2-cyanoacrylates, using an iminium salt.
- -
-
Page/Page column 6
(2010/06/11)
-
- Ammonia-dimethylchloramine system: Kinetic approach in an aqueous medium and comparison with the mechanism involving liquid ammonia
-
After an exhaustive study of the system ammonia-dimethylchloramine in liquid ammonia, it was interesting to compare the reactivity of this system in liquid ammonia with the same system in an aqueous medium. Dimethylchloramine prepared in a pure state undergoes dehydrohalogenation in an alkaline medium: the principal products formed are N-methylmethanimine, 1,3,5- trimethylhexahydrotriazine, formaldehyde, and methylamine. The kinetics of this reaction was studied by UV, GC, and HPLC as a function of temperature, initial concentrations of sodium hydroxide, and chlorinated derivative. The reaction is of the second order and obeys an E2 mechanism (k1 =4.2 × 10-5 M-1 s-1, ΔH# = 82 kJ mol-1, ΔS# = -59 J mol-1 K-1) The oxidation of unsymmetrical dimethylhydrazine by dimethylchloramine involves two consecutive processes. The first step follows a first-order law with respect to haloamine and hydrazine, leading to the formation of an aminonitrene intermediate (k2 = 150 × 10-5 M-1 s -1). The second step corresponds to the conversion of aminonitrene into formaldehyde dimethylhydrazone at pH 13). This reaction follows a first-order law (k3 = 23.5 × 10-5 s-1) The dimethylchloramine-ammonia interaction corresponds to a SN2 bimoiecular mechanism (k4 = 0.9 × 10-5 M-1 s -1, pH 13, and T =25°C). The kinetic model formulated on the basis of the above reactions shows that the formation of the hydrazine in an aqueous medium comes under strong competition from the dehydrohalogenation of dimethylchloramine and the oxidation of the hydrazine formed by the original chlorinated derivative. A global model that explains the mechanisms both in an anhydrous and in an aqueous medium was elaborated.
- Stephan,Pasquet,Elkhatib,Goutelle,Delalu
-
p. 340 - 351
(2008/09/21)
-
- Benzo[b]thiophen-3(2H)-one 1,1-dioxide-a versatile reagent in the synthesis of spiroheterocycles
-
New applications of benzo[b]thiophen-3(2H)-one 1,1-dioxide have been investigated. The synthesis of a new heterocyclic system 3H,2′H-spiro[benzo[b]thieno[3,2-b]pyridine-3,2′-benzo[b]thiophene] is described and a mechanism for the cyclisation is proposed.
- Cekavicus, Brigita,Vigante, Brigita,Liepinsh, Edvards,Vilskersts, Reinis,Sobolev, Arkadij,Belyakov, Sergey,Plotniece, Aiva,Mekss, Kristaps,Duburs, Gunars
-
experimental part
p. 9947 - 9952
(2009/04/03)
-
- N-Alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of carboxylic acid containing drugs
-
Synthesis and hydrolysis in aqueous buffers of novel N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) and N-aryl-N-alkyloxycarbonylaminomethyl (NArNAOCAM) derivatives of carboxylic acid containing drugs were carried out. The hydrolysis follows a SN1 type mechanism and is dependent on the nucleofugacity of the leaving group. Topical delivery of the NANAOCAM derivative of naproxen from IPM across hairless mice skin was examined in in vitro diffusion cell experiments. The prodrug was 4.5-fold less lipid soluble, 2.4-fold less water soluble and 3.6-fold less permeable than the parent drug.
- Majumdar, Susruta,Sloan, Kenneth B.
-
p. 1447 - 1450
(2008/09/21)
-
- Synthesis, hydrolyses and dermal delivery of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of phenol, imide and thiol containing drugs
-
Synthesis, characterization and hydrolysis in aqueous buffers of novel N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of substituted phenols, theophylline (Th) and 6-mercaptopurine (6MP) were carried out. The mechanism of hydrolysis was further investigated by synthesis, characterization and hydrolysis of N-aryl-N-alkyloxycarbonylaminomethyl (NArNAOCAM) derivatives of phenols. The hydrolysis follows pseudounimolecular first order kinetics and operates by way of an SN1-type mechanism. Topical delivery of selected derivatives of acetaminophen (APAP), Th and 6MP was examined in in vitro diffusion cell experiments from IPM across hairless mice skins. The prodrug of APAP and 6MP increased permeation across the skin by about 2- and 4-fold, respectively, compared to the parent drug. NANAOCAM promoieties can act as novel prodrug derivatives of phenol, imide and thiol containing drugs for enhancing topical absorption.
- Majumdar, Susruta,Sloan, Kenneth B.
-
p. 3590 - 3594
(2007/10/03)
-
- Practical synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl prodrug derivatives of acetaminophen, theophylline, and 6-mercaptopurine
-
We report a novel synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6-mercaptopurine by alkylation of the corresponding drug molecule with N-alkyl-N- alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N-alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N-alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p-nitrophenylcarbonate esters, followed by their reaction with alkyl amines. Copyright Taylor & Francis Group, LLC.
- Majumdar, Susruta,Sloan, Kenneth B.
-
p. 3537 - 3548
(2007/10/03)
-
- Identification of regioisomers in a series of N-substituted pyridin-4-yl imidazole derivatives by regiospecific synthesis, GC/MS, and 1H NMR
-
The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.
- Wagner, Gerd K.,Kotschenreuther, Dunja,Zimmermann, Werner,Laufer, Stefan A.
-
p. 4527 - 4530
(2007/10/03)
-
- Titanium imido complexes containing 1,3,5-triazacyclohexane ligands
-
The syntheses of the 1,3,5-trimethyl- and tri-tert-butyl-1,3,5-triazacyclohexane-supported imido complexes [M(NR)(R′3tach)Cl2] (M = Ti or Zr (NMR only); R = But or 2,6-C6H3Pri2;
- Wilson, Paul J.,Blake, Alexander J.,Mountford, Philip,Schr?der, Martin
-
-
- Hexaazapolycycles by selective multimethylenations with dichloromethane and base or with hexamethylenetetramine
-
Multiple methylenations of 2-aminomethylbenzimidazole with dichloromethane and methylamine or ammonia or with hexamethylenetetramine lead to highly selective formations of 6 new single bonds to give only a polycyclic bis-spiro-1,5-diazocine 2 or only a polycyclic spiro-1,3,6-triazonine 4 or only a polycyclic 1,3,6,8-tetrazecine derivative 6. 4 and 6 may be equally well obtained starting with 2-chloromethyl-benzimidazole. All of these selectively formed products are concave cryptands with 6 amino nitrogen atoms. No template metals are used in their syntheses. The reasons for the unusual changes in selectivity are investigated using semi-empirical PM3 calculations and mechanistic considerations. Experimental and spectroscopic details are given. Johann Ambrosius Barth 1996.
- Kaupp, Gerd,Sailer, Klaus
-
-
- N-BH3 ADDUCTS OF TRIALKYL-1,3,5-TRIAZACYCLOHEXANES WITH STABLE STEREOGENIC NITROGEN ATOMS, STEREOCHEMICAL STUDY
-
The syntheses and stereochemical studies of N-BH3 adducts of trialkyl-1,3,5-triazacyclohexanes are reported.Different reagent ratios were used in order to obtain mono- and di-N-borane adducts.Tri-N-borane adducts were never observed; di-N-borane adducts were formed with triazine 1 and 2 whereas 3 and 4 afforded only the mono-boranes.It appears that low steric strain is an important factor in the syntesis of these compounds.Borane addition produced in all cases ring and nitrogen conformationally stable compounds which were studied by NMR All the reactions were 100percent stereoselective affording one isomer in each reaction.
- Martinez-Aguilera, Luz M. Ruth,Cadenas-Pliego, Gregorio,Contreras, Rosalinda,Flores-Parra, Angelina
-
p. 1585 - 1592
(2007/10/02)
-
- Acetylenes as Potential Antarafacial Components in Concerted Reactions. Formation of Pyrroles from Thermolyses of Propargylamines, of a Dihydrofuran from a Propargylic Ether, and of an Ethylidenepyrrolidine from a β-Amino Acetylene
-
A thermal cyclization of acetylenic compounds provides evidence for the ability of acetylenic links to act as antarafacial components in processes.The cyclization competes with the normally favored acetylenic retro-ene reaction.Propargylic amines, without substituents whose presence would hinder a tight cyclic transition state, yield intermediate pyrrolines whose subsequent hydrogen elimination affords pyrroles in small amounts.The same process in 2-ethynyltetrahydropyran affords 8-oxabicyclooctane in 35percent yield.A related thermal reaction of N-methyl-3-hexyn-1-amine provides a quantitative transformation to N-methyl-2-ethylidenepyrrolidine in a nominal s + 2a + 2s + 2s> Moebius process, wherein the acetylenic unit is the antarafacial component.Evidence for concertedness in these reactions is discussed.
- Viola, Alfred,Collins, John J.,Filipp, Nicholas,Locke, John S.
-
p. 5067 - 5075
(2007/10/02)
-
- Reaction of Rifamycins with Hexahydro-1,3,5-triazines Prepared from Formaldehyde and Primary Aliphatic Amines
-
Rifamicin S (1) and 25-O-deacetylrifamycin S reacted with 1,3,5-tributylhexahydro-1,3,5-triazine to give deep-blue compounds.The structures of the deep-blue compounds are discussed based on 13C NMR data, and it is concluded that the earlier structures should be partly re-revised.The mechanism of formation of the deep-blue compounds and the reaction of 1 with several hexahydro-1,3,5-triazines, which were prepared from formaldehyde and primary aliphatic amines, are also described.
- Taguchi, Masahiro,Aikawa, Norio,Tsukamoto, Goro
-
p. 2431 - 2436
(2007/10/02)
-
- OPEN-CHAIN NITROGEN COMPOUNDS. PART VI. THE FORMATION OF BIS(1-ARYL-3-METHYLTRIAZEN-3-YLMETHYL) METHYLAMINES IN THE REACTION OF DIAZONIUM IONS WITH MIXTURES OF FORMALDEHYDE AND METHYLAMINE
-
The synthesis of a series of N,N-bis(1-aryl-3-methyltriazen-3-ylmethyl) methylamines from coupling diazonium salts with mixtures of methylamine and formaldehyde is described.These novel bis-triazenes, or heptazanonadienes, have significant anti-tumour activity against the TLX5 lymphoma in mouse.The mechanism of formation of these triazenes is discussed with reference to the implication to the presumed equilibria taking place in the methylamine/formaldehyde solution.The formation of the bis-triazene is usually accompanied by the formation of a 3-hydroxymethyltriazene, and it has been shown that the hydroxymethyltriazene can be transformed into the bis-triazene.The proportions of the two products are strongly influenced by the relative amounts of methylamine and formaldehyde.Coupling the p-bromobenzenediazonium salt to a 1:1 methylamine/formaldehyde mixture affords mainly the bis-triazene, whereas a 1:50 mixture gives almost totally the hydroxymethyl triazene.These results suggest that the two triazenes arise from diazonium coupling to different species in the amine/formaldehyde mixture; this hypothesis is supported by the formation of identical product mixtures from coupling the diazonium ion with (a) a 1:1 MeNH2/CH2O mixture, and (b) the cyclic trimer of the carbinolamine MeNHCH2OH, and by the identification of a minor product from the reaction of p-chlorobenzenediazonium fluoroborate with MeNH2/CH2O as bis(1-p-chlorophenyl-3-methyltriazen-3-yl) methane.
- Manning, Hartford W.,Hemens, Chantal M.,LaFrance, Ronald J.,Tang, York,Vaughan, Keith
-
p. 749 - 754
(2007/10/02)
-
