The mannich reaction-II : Derivatization of aldehydes and ketones using dimethyl(methylene)ammonium salts

Aldehydes and ketones have been converted efficiently to their corresponding Mannich products by various dimethyl(methylene)ammonium salts under a range of reaction conditions. The several methods used to form these derivatives are compared. Excellent approaches to aldehyde derivatives involve treating the enol silyl ether of the carbonyl compound with methyllithium and then an iminium salt, or directly adding the iminium salt to the enol silyl ether. Ketones may be derivatized effectively by treatment with potassium hydride, followed by an iminium salt, or from the enol silyl ether by addition of the iminium reagent. Use of iminium reagents in the Mannich reaction is recommended because the yields are often good and the site of attachment on an unsymmetrical ketone is both predictable and controllable.     

New antimetastatic preparations based on chlorodinitromethyl-1,3,5-triazines

An approach to the synthesis of water-soluble chlorodinitromethyl-1,3,5-triazines was developed. For this purpose, a diamine bound to the 1,3,5-triazine cycle and capable to form hydrochloride salts on chlorination is introduced in a molecule.     

Trinitromethylation reactions of chloro-1,3,5-triazines

Reactions of chloro-1,3,5-triazines with trinitromethane salts were studied. Depending on conditions, trinitromethane salts used and special additives, six types of 2,4,6-trichloro-1,3,5-triazine trinitromethylation reactions were revealed, namely, bis-trinitromethylation-nitro-nyloxylation, bis-trinitromethylation-amination, bis-trinitromethylation-hydroxylation, trinitromethylation-dialkoxylation, trinitromethylation-diaryloxylation, and trinitromethylation-alkoxylation-aryloxylation. The mechanisms of reactions are proposed.     

Preparation and reactions of isocyano-1,3,5-triazines

The title compounds 3 were prepared in low yields from the carbylamine reaction of amino-1,3,5-triazines 1 under phase-transfer conditions. Isocyanotriazine 3a readily reacted with amines in the presence of copper salts to afford triazinylformamidines 4 , and also with active methylene compounds in the presence of base to afford addition products 5 and 6 , indicating the high electrophilicity of 3. The reactions of isocyanotriazine with electrophiles such as carbonyl compounds and bromine are also described.     

Synthesis of 2,4-diaryloxy-6-trinitromethyl-1,3,5-triazines

Reactions of 2,4,6-trichloro-1,3,5-triazine with trinitromethane salts in the presence of phenol and substituted phenols gave previously unknown 2,4-diaryloxy-6-trinitromethyl-1,3,5-triazines. Their yields strongly depend on the nature and position of substituent in the benzene ring of phenol.     

The Synthesis and Reactions of 1-(2-Propynyl)pyidinium Salts

The synthesis of 1-(2-propynyl)pyridinium salts 3 described. Compounds 3 react with a second pyridine molecule, in the presence of the corresponding hydrochloride, to form products of type 4, Certain bases cause the 1-(2-propynyl)pyridinium salts 3 to rearrange into 1-propadienylpyridinium salts. 5 . Diethylamine converts compounds 3 into 1-acetonylpyridinium salts 8 . Moreover, treatment of 3 or 5 with sodium methoxide gives enol ether sof type 9, which can be hydrolyzed to teh ketones 8 . Addition of bromine to some of teh unsaturated compounds is also reported.     

Reaction of β-amino-α,β-unsaturated esters and amides with aryl diazonium salts : Synthesis of cinnoline derivatives

Conjugated esters and amides react with aryldiazonium salts at room temperature (MeCN) to form the corresponding iminium hydrazone derivatives, which can be thermally cyclized to cinnoline-3-esters and cinnoline-3-amides. In general the intermediate iminium salts derived from the enamine amides cyclize faster than those from the enamine esters. Furthermore, the ease of cyclization depends upon the structure of the base-component of the enamine ester or the amide and the substituent in the aryl moiety of the diazonium salt. The configurational structure of the iminium hydrazones, studied by NMR spectroscopy, has been shown to involve H-bonding of the hydrazonyl N-H with the ester or the amide CO group.     

Azo-1,3,5-triazines

The synthesis of variously substituted bis-triazinylhydrazines and their subsequent oxidation preferably with chlorine in a two-phase system to azo-1,3,5-triazines starting from cyanuric chloride is reported. Reaction of ethoxycarbonylhydrazine with cyanuric chloride followed by oxidation gave access to mono- and bis-ethoxycarbonyl-1,3,5-triazines, respectively. Azo-1,3,5-triazines proved to be very reactive dienophiles.     

Indium-mediated beta-allylation,beta-propargylation,and beta-allenylation onto alpha,beta-unsaturated ketones: reactions of in-situ-generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts with in-situ-generated organoindium reagents

3-tert-Butyldimethylsilyloxyalk-2-enylsulfonium salts, generated in situ from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf, underwent a novel nucleophilic substitution with allylindiums to give silyl enol ethers of delta,epsilon-alkenyl ketones in good yields, which correspond to formal Michael addition products. In a similar manner, 1,4-propargylation of propargylindiums onto the sulfonium salts produced the corresponding silyl enol ethers of delta,epsilon-alkynyl ketones in good yields. Organoindium reagents derived from gamma-substituted propargyl bromide and indium afforded the corresponding silyl enol ethers of beta-allenyl ketones in good yields. The reaction proceeds via an addition-substitution mechanism involving the formation of allylic sulfonium salts. The presence of the intermediate sulfonium salt was confirmed by observation of the low-temperature (1)H NMR spectra.     

Spectroscopic and X-ray crystallographic evidence for electrostatic effects in 4-substituted cyclohexanone-derived hydrazones, imines, and corresponding salts

The axial conformer of several 4-substituted cyclohexanone hydrazone salts was found to predominate in solution. Changes in the charge of the molecule and the polarity of the solvent led to changes in the conformational preference of each molecule that were consistent with electrostatic stabilization of the axial conformer. (1)H NMR spectroscopic analysis was utilized to determine the structure of cyclohexanone-derived substrates by comparison to conformationally restricted trans-decalone derivatives and computational models. X-ray crystallography demonstrated that the axial configuration of a pendant benzyloxy group is the preferred conformation of an iminium ion in the solid state. The structure of a neutral hydrazone was also determined to favor the axial configuration for a pendant benzyloxy group in the solid state.     

Condensed tetrazolo-1,3,5-triazines. 4. Synthesis of salts of 5-aminotetrazolo[1,5-a]-1,3,5-triazin-7-one

2-Amino-4-azido-1,3,5-triazin-6(1H)-ones were synthesized by successive substitution of the trinitromethyl groups in 2-amino-4,6-bis(trinitromethyl)-1,3,5-triazines under the influence of azide and nitrite ions. Interaction of 2-amino-4-azido-1,3,5-triazin-6(1H)-ones with bases led to the azido-tetrazole tautomeric conversion give salts of 5-aminotetrazolo[1,5-a]-1,3,5-triazin-7-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1211–1219, August, 2006.     

Synthesis and molecular structure of 2-methoxy-4-amino-6-dinitromethyl-1,3,5-triazines zwitterionic salts

Zwitterionic salts of 2-methoxy-4-amino-6-dinitromethyl-1,3,5-triazines were synthesized. The structure of the compounds and the site of nitrogen protonation in the 1,3,5-triazine ring were established based on IR and ¹H NMR spectra and on the data of X-ray diffraction analysis.     

Synthesis of a stable iminium salt and propellane derivatives

The treatment of morphinan 1 with NaH and MsCl provided very stable iminium salt 7 possessing propellane skeleton. One of the synthesized iminium salts 7, isobutyl derivative 7b, was crystallized and its structure was determined by X-ray crystallography. The natural bond orbital analysis suggested that the stability of the iminium should result from the stereoelectronic effect (hyperconjugation) attributed to their own structures.     

Acid-promoted reaction of trimethylsilylketene bis(ethylthio)acetal with imines. Synthesis of gamma,gamma-bis(ethylthio)allylamines

Acid-catalyzed reaction of silylketene dithioacetal 1 with iminium salts or imines 3b,d-h gave the corresponding gamma,gamma-bis(ethylthio)allylamines 2a-h or 5b,d-h in generally high yields. Similar reactions of 1 with (salicylidene)amines 6a-e afforded 4-amino-2,2-bis(ethylthio)chromans 8a-e in good to moderate yields.     

Magnesium ion mediated protonation of imines in acetonitrile

Addition of magnesium perchlorate to a solution of imine PhCHN-C₄H₉ ($\text{1}$) and diimine PhCHN(CH₂)₃NCHPh ($\text{4}$), in acetonitrile, results in the formation of the corresponding iminium salts due to traces of water present in the solvent. This conclusion is based upon infrared spectra of solutions of imines, iminium salts, deuterated iminium salts and mixtures of imines and magnesium perchlorate in acetonitrile, containing varying amounts of water. The results suggest that magnesium ion catalyzed reactions of imines in CH₃CN involve iminium intermediates.     

NMR spectra of 1,3,5-triazines with fluorinated substituents

The NMR spectra of a series of 1,3,5-triazines (1) in which one or more of the substituent groups are fluorinated are described, and the results are discussed in terms of bonding and geometry of the molecules. Remote effects of unsymmetrical substitution are observed in the fluorine-19 and carbon-13 spectra, in some molecules indicating restricted rotation about the bond joining an amino group to a ring carbon.     

Trisubstituted 1,3,5-triazines 3. Synthesis of substituted 2,4,6-tris(hydroxyiminomethyl)-1,3,5-triazines

Previously undescribed substituted 2,4,6-tris(hydroxyiminomethyl)-1,3,5-triazines, including 2,4,6-(1,3,5-triazinetriyl)trinitrolic acid, have been synthesized.For Communication 2, see [1].N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 117913. Institute of Chemical Physics in Chernoglovka, Chernoglovka, Moscow Oblast, 142432, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 76–78, January, 1999.     

Preparation and Structures of 2‐Substituted 5‐Benzyl‐3‐methylimidazolidin‐4‐one‐Derived Iminium Salts,Reactive Intermediates in Organocatalytic Transformations Involving α,β‐Unsaturated Aldehydes

Preparations of the title compounds, 5 – 7 (Scheme 1 and Table 1), of their ammonium salts, 9 – 11 (Scheme 2 and Table 2), and of the corresponding cinnamaldehyde‐derived iminium salts 12 – 14 (Scheme 3 and Table 3) are reported. The X‐ray crystal structures of 15 cinnamyliminium PF₆ salts have been determined (Table 4). Selected ¹H‐NMR data (Table 5) of the ammonium and iminium salts are discussed, and structures in solution are compared with those in the solid state.     

One-pot synthesis of tropinone by tandem (domino) ene-type reactions of acetone silyl enol ethers

A synthetic approach for tropane alkaloids on the basis of tandem (domino) ene-type reactions of acetone silyl enol ethers with iminium ions is shown to be triggered by intermolecular ene-type reactions followed by 6-(2,5) silatropic ene-type cyclizations.     

Reactions of diphenyldithiophosphinic acid with <Emphasis Type="Italic">N</Emphasis>-alkyl-2-chloro-2-methylpropanimines

In contrast to O,O-dialkyldithiophosphoric acids, the reactions of more weak diphenyldithiophosphinic acid with N-alkyl-2-chloro-2-methylpropanimines at a 1 : 1 reagent ratio follow two pathways. The first route is nucleophilic substitution of the chlorine atom of the initially formed iminium salt with the diphenylthiophosphinylthio moiety and the second route is the reduction of the C–Cl bond of this iminium salt cation. The main reaction direction is nucleophilic substitution producing new iminium salts, namely, N-alkyl-2-(di phenyl thiophosphinylthio)-2-methylpropaniminium chlorides. These salts were used as the starting material to synthesize new organophosphorus compounds bearing aldehyde, imine, and acetal groups and 1,3-diazolidine cycle.