64469-32-5Relevant academic research and scientific papers
Selective Monomethylation of Amines with Methanol as the C1 Source
Choi, Geunho,Hong, Soon Hyeok
supporting information, p. 6166 - 6170 (2018/04/30)
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
Synthesis and study of 1-aryl-1H-4,5-dihydroimidazoles
Perillo, Isabel,Caterina, M. Cristina,Lopez, Julieta,Salerno, Alejandra
, p. 851 - 856 (2007/10/03)
An easy synthesis of 1-aryl-1H-4,5-dihydroimidazoles 1 by cyclocondensation of N-aryl-N′-formylethylenediamines 2 is described. Such precursors were synthesized by selective formylation of N-arylethylenediamines 3 with p-nitrophenyl formate. Cyclizations were performed using trimethylsilyl polyphosphate. Chemical properties of compounds 1, typical of amidine system, were studied. Reaction of 1 with methyl iodide leads to the corresponding 1-aryl-3-methyl-1H-4,5-dihydroimidazolium salts 5. Reduction of dihydroimidazoles 1 with sodium cyanoborohydride provides a convenient access to N-aryl-N′-methylethylenediamines 4.
Synthesis of substituted 1H-4,5-dihydroimidazolium salts by dehydrogenation of imidazolidines
Salerno, Alejandra,Caterina, Cristina,Perillo, Isabel A.
, p. 3369 - 3382 (2007/10/03)
A study is presented on the scope of the method to obtain 1H-4,5-dihydroimidazolium salts 3 by dehydrogenation of 1,3-di and 1,2,3-trisubstituted imidazolidines 2. Of the dehydrogenating agents used, N-bromoacetamide leads to the best results, providing a
Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type ii diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'- dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline
Le Bihan, Ga?lle,Rondu, Frédéric,Pelé-Tounian, Agnès,Wang, Xuan,Lidy, Sandrine,Touboul, Estéra,Lamouri, Aazdine,Dive, Georges,Huet, Jack,Pfeiffer, Bruno,Renard, Pierre,Guardiola-Lema?tre, Béatrice,Manéchez, Dominique,Pénicaud, Luc,Ktorza, Alain,Godfroid, Jean-Jacques
, p. 1587 - 1603 (2007/10/03)
Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl- 4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2',4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H- imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of α2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4',5'-dihydro-1'H-imidazol-2'- yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro- 1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 μmol/kg) as after ip administration and appears as a good candidate for clinical investigations.
Nucleophilic Addition to Substituted 1H-4,5-Dihydroimidazolium Salts
Salerno, Alejandra,Ceriani, Vanina,Perillo, Isabel A.
, p. 709 - 716 (2007/10/03)
1H-4,5-Dihydroimidazolium salts 1 react readily with nucleophilic reagents originating cyclic products which may be stable or become transformed into acyclic compounds maintaining the structural ethylenediamine unit. With methylmagnesium iodide compound le affords the expected imidazolidine, but in the case of substituted 1-aryl-3-methyl-2-phenyl salts 1b-d the N-aryl-N'-methylethylenediamines 3b-d and acetophenone (4) were isolated, the process representing the transfer of the C-2 unit to a nucleophilic carbon. With alkaline cyanides salts 1 react efficiently affording α,α-diaminonitriles 5. In these compounds the cyano group may be readily substituted by nucleophiles (hydroxyl anion, species with nucleophilic carbon and reagents that act by hydride ion transfer), in a way similar to the salts but with better yields.
5-Lipoxygenase inhibitors: Synthesis and structure-activity relationships of a series of 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones
Bhatia, Pramila A.,Brooks, Clint D. W.,Basha, Anwer,Ratajczyk, James D.,Gunn, Bruce P.,Bouska, Jennifer B.,Lanni, Carmine,Young, Patrick R.,Bell, Randy L.,Carter, George W.
, p. 3938 - 3950 (2007/10/03)
Synthetic routes were developed to access a variety of novel 1-aryl- 2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5- lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro- 1,2,4-triazin-3-one (4), was found to be a
Disproportionation reactions from glyoxal and difunctional basic molecules
Chassonnery, Dominique,Chastrette, Francine,Chastrette, Maurice,Blanc, Alain,Mattioda, Georges
, p. 188 - 199 (2007/10/02)
Glyoxal was reacted with basic difunctional molecules in order to study the disproportionation reaction.Symmetrical and unsymmetrical 1,2-diamines gave rise to piperazinones; their 1,3-diamine analogues yielded hexahydrodiazepinones; and β-aminoalcohols yielded morpholinones and hydroxyamino acids.Aminoamides gave the expected piperazinediones in low yields and no reaction was observed with diamides.The first step of the reaction consists of the formation of dihydroxy compounds, from which the more basic function assists the departure of OH, providing the expected more stable iminium ion.The observed regioselectivity is consistent with the relative basicities of the two functions; a 100percent regioselectivity is observed with aminoalcohols (giving way to morpholinones and not to amides), a good regiposelectivity with most of N-alkyl-N'-aryl-diamines and a rather low one with N-methyl-N'-ethyl- or N-methyl-N'-p-methoxyphenyl-diamines.Geometry factors were related to the better yield obtained with 1,2-diamines compared with 1,3-diamines.The mechanism was investigated.When deutared glyoxal and diamines were reacted in D2O, incorporation of deuterium was observed, in accordance with the formation of an enolate in the course of the oxidoreduction.The low reactivity of aminoamides and the observed regioselectivities could be related to both the weak basicity of the function that is supposed to allow the formation of the iminium ion and the basicity of the other function that accepts a positive charge and which, if too weak, impedes the reaction because of the instability of the intermediate iminium ion. glyoxal / disproportionation rules / basic difunctional molecules
The Use of 2-Oxazolidinones as Latent Aziridine Equivalents. 2. Aminoethylation of Aromatic Amines, Phenols, and Thiophenols
Poindexter, Graham S.,Owens, Donald A.,Dolan, Peter L.,Woo, Edmund
, p. 6257 - 6265 (2007/10/02)
The utility of 2-oxazolidinones 1 as latent, carboxylated aziridine functionalities was examined.Reaction of 2-oxazolidinone (1a), 3-methyl2-oxazolidinone (1b), 3-(phenylmethyl)-2-oxazolidinone (1c), 3-phenyl-2-oxazolidinone (1d) 4,4-dimethyl-2-oxazolidinone (1e), and 5-ethyl-2-oxazolidinone (1f) with aromatic amine salts, phenol, or thiophenols at elevated temperatures (> 130 deg C) afforded aminoethylated adducts.The aminoethylation occurred with concomitant loss of carbon dioxide to furnish variously substituted N-aryl-1,2-ethanediamines 4, 1-(2-phenoxyethyl)-2-imidazolidinone (8), or 2-(arylthio)ethanamines 9 on reactions of 1 with aromatic amine salts, phenol, and thiophenols, respectively.Imidazolidinone 8 is believed to be a secondary reaction product resulting from the condensation of the initially formed 2-phenoxyethanamine with starting oxazolidinone 1a.The aminoethylation reaction did not proceed with aliphatic amine hydrochlorides or alkyl mercaptans.Preliminary mechanistic pathways for these ring openings were also investigated employing a specific, C-5 deuterium-labeled oxazolidinone 1b-d2.Ring-opening experiments of 1b-d2 with N-methylaniline hydrochloride suggest reaction can occur through either a dioxazolinium 5 and/or 5 intermediate.In contrast, reaction of 1b-d2 with thiophenol suggests ring-opening to proceed only via the dioxazolinium pathway.
Selective Reductions of 3-Substituted Hydantoins to 4-Hydroxy-2-imidazolidinones and Vicinal Diamines
Cortes, Sergio,Kohn, Harold
, p. 2246 - 2254 (2007/10/02)
N3-Substituted hydantoins (1) have been shown to undergo LiAlH4 reduction (THF, room temperature, 2 days) to give 4-hydroxy-2-imidazolidinones (3) in good yields.Reduction of 3,5-disubstituted hydantoins in which an aliphatic substituent was present at nitrogen 3 led to the preferential formation of the cis adduct 3.Conversely, disubstituted hydantoins possessing an aryl moiety at nitrogen 3 gave the trans derivative 3 as the major product.Treatment of the N3-substituted hydantoins (1) under more vigorous conditions (THF, reflux, 3 days) led to selective ring opening of 1 to yield N-methylethylenediamines (7).The scope of both of these reductive processes has been explored, and explanations are offered to account for the observed results.Full spectral (infrared, 1H and 13C NMR, and mass spectra) data on all three classes of compounds (1, 3, and 7) have been collected.Together this information provides a consistent data set which is useful in structure elucidation.Moreover, various NMR aids have been discerned for the isomeric cis- and trans-4-hydroxy-2-imidazolidinones (3) which permitted stereochemical assignments for these compounds.
Aminoethylation process
-
, (2008/06/13)
2-Oxazolidinone or N-substituted derivatives thereof are reacted with aromatic amine hydrochlorides at elevated temperatures to produce 1,2-ethanediamines.
