Dialkylaminomethyl Group Research Articles

Palladium-Catalyzed Synthesis of 1-Alkylidene-2-dialkylaminomethyl Cyclobutane Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions: Influence of Nucleophile and Water on the Reaction Mechanism.

The Pd-catalyzed coupling of 1,5-diene-2-yl triflates with amine nucleophiles affords exomethylenecyclobutanes bearing dialkylaminomethyl groups at C2. The strained carbocyclic products are obtained in moderate to excellent yields, with regioselectivities of up to >95:5 for four-membered ring formation. The mechanism of these reactions, which provides products resulting from anti-addition to alkenes, differs from related reactions involving malonate nucleophiles that provide syn-addition products.

Pd-Catalyzed Alkene Diamination Reactions with O-Benzoylhydroxylamine Electrophiles: Evidence Supporting a Pd(II/IV) Catalytic Cycle, the Role of 2,4-Pentanedione Derivatives as Ligands, and Expanded Substrate Scope.

This article describes continued studies on Pd-catalyzed alkene diamination reactions between N-allylguanidines or ureas and O-benzoylhydroxylamine derivatives, which serve as N-centered electrophiles. The transformations generate cyclic guanidines and ureas bearing dialkylaminomethyl groups in moderate to good yield. We describe new mechanistic experiments that have led to a revised mechanistic hypothesis that involves a key oxidative addition of the electrophile to a PdII complex, followed by reductive elimination from PdIV to form the alkyl carbon-nitrogen bond. In addition, we demonstrate that acac, not phosphine, serves as a key ligand for palladium. Moreover, simple acac derivatives bearing substituted aryl groups outperform acac in the catalytic reactions, and phosphines inhibit catalysis in many cases. These discoveries have led to a significant expansion in the scope of this chemistry, which now allows for the coupling of a variety of cyclic amines, acyclic secondary amines, and primary amines. In addition, we also demonstrate that these new conditions allow for the use of amide nucleophiles, in addition to guanidines and ureas.

One pot synthesis of aminohydroxylated triglycerides under aqueous biphasic conditions

Herein is reported the one pot cascade hydroaminomethylation (HAM)/hydrohydroxymethylation (HHM) of triolein (T) using hydroformylating and hydrogenating Rh-catalysts stabilized by both phosphanes and amines under aqueous biphasic conditions. While T are mainly functionalized by N,N′-dialkylaminomethyl groups in organic solvents, they are predominantly functionalized by hydroxymethyl groups under aqueous biphasic conditions. The change in chemoselectivity is a consequence of both the displacement of the enamine-aldehyde equilibrium upon addition of water, and the partition of Rh-catalysts between the organic and the aqueous phases.

Pd-Catalyzed Alkene Diamination Reactions of Nitrogen Electrophiles: Synthesis of Cyclic Guanidines and Ureas Bearing Dialkylaminomethyl Groups.

The Pd-catalyzed coupling of N-allylguanidines or N-allylureas with O-benzoylhydroxylamine derivatives affords cyclic guanidines or cyclic ureas bearing dialkylaminomethyl groups. The desired products are obtained in good yield, and substrates bearing substituents at the allylic position are transformed with moderate diastereoselectivity. The mechanism of these reactions appears to involve anti-aminopalladation of the alkene, followed by a rare sp3C-sp3N bond-forming reductive elimination from an alkylpalladium complex that contains β-hydrogen atoms.

Synthesis of 3,5-di-tert-butyl-4-hydroxyphenylsulfanylmethyl-substituted tetramethylcalix[4]resorcinarenes

Dialkylaminomethyl-substituted calix[4]resorcinarenes have been reported long ago [1], but further transformations of these compounds were reported in a few publications [2–4], and the described transformations did not involve the dialkylaminomethyl group therein. An exception was the formation of the corresponding ammonium salts [5, 6] and thioamides [7]. Products of nucleophilic replacement of dialkylamino group in the above calix[4]resorcinarenes were not reported. On the other hand, deamination of phenolic Mannich bases is their typical reaction [8].

Synthesis of new o-isobornylphenol derivatives

The hydroxymethyl, pyridinium methyl, or dialkylaminomethyl groups were introduced into the aromatic ring of the o-isobornylphenol molecule.

Modified Coumarins. 11. Synthesis and Biological Activity of Mannich Bases of Substituted 1,3-Dihydrocyclopenta[c]chromen-4-ones

Mannich bases containing the dialkylaminomethyl group in the 6- and 8-positions of 2,3-di-hydrocyclopenta[c]chromen-4-ones were prepared by condensation of 7- and 9-hydroxy-2,3-dihydrocyclopenta[c]chromen-4-ones with substituted 1,1-diaminomethanes. The effects of 8-chloro-7-hydroxy-6-(1-pyrrolidinylmethyl)-2,3-dihydrocyclopenta[c]chromen-4-one and 8-chloro-7-hydroxy-6-(morpholinomethyl)-2,3-dihydrocyclopenta[c]chromen-4-one on the central and peripheral nervous systemwere defined and enable the presence of tranquilizing and neuroleptic properties to be predicted.

Peri-Naphthylenediamines. 35. Unusual behavior of “proton sponge”-derived Mannich bases

Aminomethylation of 1,8-bis(dimethylamino)naphthalene (“proton sponge”) afforded a series of its 4-dialkylaminomethyl-substituted derivatives. An attempt to introduce the second peri-dialkylaminomethyl group unexpectedly led to the formation of salts with the 2,2-dialkyl-6,7-bis(dimethylamino)-2-azonia-2,3-dihydrophenalene cation. The structure of one of these salts was established by X-ray diffraction analysis. Treatment of 1,8-bis(dimethylamino)-4-piperidinomethylnaphthalene with iodomethane gave a spiro compound rather than the expected N-[4,5-bis(dimethylamino)-1-naphthylmethyl]-N-methylpiperidinium iodide. This spiro compound was generated through cyclodimerization of the 1-naphthylmethyl carbocations. These transformations provide evidence that “proton sponge”-derived Mannich bases quaternized at the dialkylaminomethyl group are unstable and undergo the spontaneous transformation into the resonance-stabilized 4,5-bis(dimethylamino)-1-naphthylmethyl carbocation. By contrast, 4-dialkylamino-1-dimethylaminomethylnaphthalenes gave methoiodides, which are stable under standard conditions. The latter compounds undergo the nucleophilic substitution of the NR3 group typical of such salts.

Modified Coumarins. 7. Synthesis and Biological Activity of Mannich Bases of Substituted 7,8,9,10-Tetrahydrobenzo[c]chromen-6-ones

Condensation of 1- and 3-hydroxy-7,8,9,10-tetrahydrobenzo[c]chromen-6-ones with substituted 1,1- diaminomethanes produced Mannich bases containing a dialkylaminomethyl group in the 2- and 4-positions of 7,8,9,10-tetrahydrobenzo[c]chromen-6-one. Pharmacological screening of 2-chloro-3-hydroxy-4-(1- pyrrolidinylmethyl)-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one in Wistar rats showed that it possesses low toxicity and acts as a stimulant of the central and peripheral nervous systems with indications of neuroleptic and tranquilizing activities.

Synthesis of unsymmetrical methylene derivatives of benzopyran‐4‐ones from mannich bases

AbstractThe formation of methylene‐bis derivatives of benzopyran‐4‐ones from their Mannich bases was studied. On these grounds, unsymmetrical methylene derivatives have been synthesized by reacting Mannich bases of benzopyran‐4‐ones with structurally related compounds lacking the dialkylaminomethyl group.

Electrophilic Reactions of Triadamantylated Calix[4]arenes at the Upper Rim

Chemical transformations of partially adamantylated calix(4)arenes at the upper rim are described. Starting from triada- mantylated calix(4)arene, it is possible to obtain adamantane-con- taining macrocycles with formyl, acyl, sulfo, azo, 3-substituted 1- adamantyl, and dialkylaminomethyl groups at the upper rim. Syn- thesis of a new type of double adamantane containing calix(4)- arenes is also reported.

Acid-base properties of phosphine oxides in nitromethane

1. The acid-base properties of the phosphine oxides were studied by the method of potentiometric titration in nitromethane. The titration curve has two potential jumps at the points of 50% and 100% neutralization, which is due to the formation of complexes of the BHB+ type at the first stages of protonation. 2. A linear correlation was obtained between the values of pK a (CH3NO2) and the σσϕ constants of the substituents at the phosphorus atom, which permitted a calculation of the σϕ constants of the -CH2OR and -CH2COOH groups. 3. Aminomethylphosphine oxides are titrated as nitrogen bases. Substantial differences in the values of pK a (CH3+NO2) of different degrees of protonation of the molecules of these compounds are probably due to the formation of intramolecular hydrogen bonds (of the type N+-H ... N) and the inductive effect of the protonated dialkylaminomethyl group.

The radiation stability and polymerization of vinylacetylene and its derivatives

A study was made of the radiation stability of vinylacetylene and its derivatives, namely, diethylaminomethylvinylacetylene, dipropargylaminomethylvinylacetylene, trimethylvinylethinylsilane and dimethylvinylethinylcarbinol. It was found that the main direction of radiation transformation of these compounds takes the form of polymerization reactions. The latter have two stages, the first featuring the formation of mainly soluble linear polymers, and the second resulting in the formation of insoluble space network polymers. On replacing the methine hydrogen in vinylacetylene by the relatively apolar trialkylsilyl and dialkylaminomethyl groups, a wider range of linear transformations is observed, while substitution of the hydrogen by the polar dimethylcarbonyl group extends the range of linear transformations, and leads to the formation of space network polymers.

Chemistry of 2-aryl-substituted 3-hydroxypyridines

1. A study was made of the aminomethylation of the 2-(4′-methoxyphenyl)- and 2-(4′-hydroxyphenyl)-3-hydroxypyridines. 2. Based on the data of the NMR and IR spectra the amino methylation of 2-(4′-methoxyphenyl)-3-hydroxypyridine is directed to theβ-pyridol ring with the initial formation of the 6-mono- and then the 4,6-bis-Mannich bases; attempts to introduce the dialkylaminomethyl group into the anisole ring proved unsuccessful. 3. The aminomethylation of 2-(4′-hydroxyphenyl)-3-hydroxypyridine is initially directed to the phenol ring with the formation of the ortho- and then the di-ortho- derivatives, and only after this to theβ-pyridol ring, with successive substitution in the 6 and then in the 4 position of the pyridine ring.

アルキル化剤としてのMannich塩基に就いて (第3報)

Various Mannich bases with dialkylaminomethyl group in the 5-position were prepared by reacting 2-acetamido-4-methyl- and 2-acetamidothiazoles with formaldehyde and various secondary amines. The Mannich reaction of 2-acetamido-4-methylthiazole is completed in a short time by mixing the reactants, without the use of a solvent, but that of 2-acetamidothiazole requires heating of 1-2 hours in a water bath. Alkylation of triethoxycarbonylmethane with 2-acetamido-4-methyl-5-morpholinomethylthiazole thereby obtained afforded 2-acetamido-4-methyl-5-(2-triethoxycarbonylethyl) thiazole of m.p. 107°, whose hydrolysis gave 2-amino-4-methyl-5-thiazolepropionic acid, m.p. 257°, in a good yield. The latter was identified by admixture with the substance of m.p. 257° obtained by the condensation of ethyl 4-acetylbutyrate and thiourea.