Acyclic Tertiary Amines Research Articles

Cine-Silylative Ring-Opening of α-Methyl Azacycles Enabled by the Silylium-Induced C-N Bond Cleavage.

Described herein is the development of a borane-catalyzed cine-silylative ring-opening of α-methyl azacycles. This transformation involves four-step cascade processes: (i) exo-dehydrogenation of alicyclic amine, (ii) hydrosilylation of the resultant enamine, (iii) silylium-induced cis-β-amino elimination to open the ring skeleton, and (iv) hydrosilylation of the terminal olefin. The present borane catalysis also works efficiently for the C-N bond cleavage of acyclic tertiary amines. On the basis of experimental and computational studies, the silicon atom was elucidated to play a pivotal role in the β-amino elimination step.

B(C6F5)3-Catalyzed redox-neutral β-alkylation of tertiary amines using p-quinone methides via borrowing hydrogen.

Herein, we present the first example of catalytic redox-neutral β-functionalization of tertiary amines through a borrowing hydrogen process. This B(C6F5)3-catalyzed procedure utilizes commercially or readily available catalysts and substrates and promotes a direct functionalization of the C(sp3)-H bond at the β-position of acyclic tertiary amines through conjugate addition to para-quinone methides. Compared to previous work on direct β-functionalization of tertiary amines under oxidative conditions, besides being metal-free, the significant advantage of this method is that neither stoichiometric oxidants nor reductants are needed which may otherwise generate unnecessary waste.

Synthesis and Biological Evaluation of Stilbene Analogues as Hsp90 C-Terminal Inhibitors.

The design, synthesis, and biological evaluation of stilbene-based novobiocin analogues is reported. Replacement of the biaryl amide side chain with a triazole side chain produced compounds that exhibited good antiproliferative activities. Heat shock protein 90 (Hsp90) inhibition was observed when N-methylpiperidine was replaced with acyclic tertiary amines on the stilbene analogues that also contain a triazole-derived side chain. These studies revealed that ≈24 Å is the optimal length for compounds that exhibit good antiproliferative activity as a result of Hsp90 inhibition.

ChemInform Abstract: Aromatic Nucleophilic Substitution of Halobenzenes with Amines Under High Pressure.

The nucleophilic substitution reactions of aromatic halides having electron-attracting groups on ortho or para position with various primary and secondary amines were accelerated by high pressure to give the corresponding N-substituted anilines in high yields. The bulkiness of amines affects its reactivity to lower the yields of the products. Although the secondary amines are usually less reactive than primary amines, cyclic secondary amines such as morpholine, piperidine, and pyrrolidine were found very reactive. 1,4-Diazabicyclo[2.2.2]octane and quinuclidine gave N-quaternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines. Dichloro- and trichloro-nitrobenzenes also react with diethylamine, pyrrolidine, and morpholine to give mono-, di-, and trisubstitution products depending upon the amount of amine and the position of nitro group in these chlorides.

ChemInform Abstract: Acyclic Tertiary Amines as Nucleophiles in Substitution Reactions of Aromatic and Heteroaromatic Halides.

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ChemInform Abstract: Direct, One‐Pot Sequential Reductive Alkylation of Lactams/Amides with Grignard and Organolithium Reagents Through Lactam/Amide Activation.

AbstractThe title reaction provides a highly efficient and general method to prepare cyclic and acyclic tertiary amines.

Selective Reactivity of the Phosphorus-Chlorine and Carbon-Chlorine Bonds in Cyclic Chlorocarbaphosphazenes: An Unusual Activation of a Carbon-Nitrogen Bond in Trialkylamines.

Acyclic tertiary amines such as triethylamine and tri-n-propylamine used as HCl scavengers in nucleophilic substitution reactions of cyclic chlorocarbaphosphazenes [N(3)PC(2)Cl(4) (I) and N(3)P(2)CCl(5) (II)] with (CF(2))(n)()(CF(2)CH(2)OH)(2) [n = 0 (III) or 1 (IV)] are found to undergo a facile C-N bond cleavage with the regiospecific substitution of the dialkylamino groups on the ring carbon atoms of the carbaphosphazene. In the case of cyclic amines such as 1-methylpiperidine and 4-methylmorpholine, the cleavage was found to occur regiospecifically at the N-CH(3) bond, resulting in the ring substitution of the cyclic secondary amino group on the dicarbaphosphazene ring carbon atoms. The polyfluoro diol III forms a spirocyclic ring exclusively at the phosphorus site in compounds [CF(2)CH(2)O](2)PN(3)C(2)[N(C(2)H(5))(2)](2) (1), [CF(2)CH(2)O](2)PN(3)C(2)[N(C(3)H(7))(2)](2) (2), [CF(2)CH(2)O](2)PN(3)C(2)[NCH(2)(CH(2))(3)CH(2)](2) (3), and [CF(2)CH(2)O](2)PN(3)C(2)[N(CH(2))(2)O(CH(2))(2)](2) (5) along with the formation of carbon-substituted carbaphosphazenes, Cl(2)PN(3)C(2)[NCH(2)(CH(2))(3)CH(2)](2) (4) and Cl(2)PN(3)C(2)[N(CH(2))(2)O(CH(2))(2)](2) (6). Reaction of II with III in the presence of triethylamine affords the dispiro product [CF(2)CH(2)O)(2)](2)P(2)N(3)C[N(C(2)H(5))(2)] (7), which crystallizes in a polar orthorhombic space group, Cmc2(1). Upon refluxing of I or II with R(3)N (R = C(2)H(5), n-C(3)H(7)) in toluene, the amino-substituted carbaphosphazenes, Cl(2)PN(3)C(2)[N(C(2)H(5))(2)](2) (8), Cl(4)P(2)N(3)C[N(C(2)H(5))(2)] (9), and Cl(4)P(2)N(3)C[N(n-C(3)H(7))(2)] (10) are obtained in good yields. Hydrolysis of 8 leads to the formation of Cl(O)PN(H)N(2)C(2)[N(C(2)H(5))(2)](2) (11). When lithium salts of the fluoro diols III and IV are reacted with I or II in diethyl ether, the P-Cl bond is selectively substituted, yielding the spirocyclic [CF(2)CH(2)O](2)PN(3)C(2)Cl(2) (12), [CF(2)(CF(2)CH(2)O)(2)]PN(3)C(2)Cl(2) (13), [CF(2)CH(2)O](2)P(2)N(3)CCl(3) (14), and [(CF(2)CH(2)O)(2)](2)P(2)N(3)CCl (15). The C-Cl bonds in 12 and 14 were easily substituted by their reaction with 4-FC(6)H(4)XNa (X = O or S) to form [CF(2)CH(2)O](2)PN(3)C(2)[4-FC(6)H(4)O](2) (16) and [CF(2)CH(2)O](2)PN(3)C(2)[4-FC(6)H(4)S](2) (17). Reactions of 12 and 13 with (CH(3))(3)SiN(CH(3))(2) under mild conditions result in the elimination of (CH(3))(3)SiCl along with the formation of [CF(2)CH(2)O](2)PN(3)C(2)[N(CH(3))(2)](2) (18). The X-ray analyses of 13 and 18 represent the first examples of eight-membered spirocyclic phosphazenes. The thermal behavior of II, 9, 10, 14, and15 has also been investigated at 120 degrees C. Single-crystal X-ray diffraction studies were carried out for 1, 2, 7, 9-14, and 16-19, and these compounds are also characterized using IR, (1)H, (13)C, (19)F and (31)P NMR spectroscopy, MS, and elemental analysis.

Effect of branching in alkylgroups of tertiary amines on their performance as catalysts in the high pressure promoted Baylis-Hillman reaction

Receptors 1 were tested as catalysts for the high pressure promoted Baylis-Hillman reaction. Surprisingly most of the compounds were found to be catalytically inactive. With model compounds (simple acyclic tertiary amines) it could be shown that tertiary amines with branches at their α-carbon atoms show a remarkable decreased activity. It is proposed that the branches prevent attack of the lone pair of the amine on the double bond of the alkene. This explains why only receptors without this feature are catalytically active.

Fluorescence self-quenching in saturated tertiary amines: the role of a “non-emissive” excimer

The temperature dependence of the fluorescence self-quenching of two acyclic tertiary amines ( N,N-dimethylbutylamine (DM4) and N,N-dimethyloctylamine (DM8) in hydrocarbon solvents was investigated by transient decay measurements. These amines exhibit moderately efficient self-quenching (with rate constants k sq equal to about 10%–50% of diffusion-controlled values) in the temperature range of our investigation. The k sq values of the amines do not show normal (linear) Arrhenius plots; the plots are curved and exhibit maxima. The results are rationalized by means of a kinetic scheme which invokes the intermediacy of an excited dimer (excimer) of the amines. The Arrhenius parameters of the photophysical rate constants and the excimer binding energies of the amines are estimated. The low binding energies of the amines (approximately 5 kJ mol −1), in comparison with those of rigid cage amines (approximately 22–51 kJ mol −1), are explained in terms of the larger steric hindrance in the excimers of the acyclic amines.

Acyclic tertiary amines as nucleophiles in substitution reactions of aromatic and heteroaromatic halides

Even acyclic tertiary amines such as triethylamine, tri-n-propylamine and tri-n-butylamine, which have been believed to be inert to aromatic and heteroaromatic halides, underwent SNAr reactions with aromatic and heteroaromatic halides to give the dialkylamino derivatives; in the case of monocyclic amines like N-methylpyrrolidine and N-methylpiperidine, the dealkylation being regioselective.

Aromatic Nucleophilic Substitution of Halobenzenes with Amines under High Pressure

Abstract The nucleophilic substitution reactions of aromatic halides having electron-attracting groups on ortho or para position with various primary and secondary amines were accelerated by high pressure to give the corresponding N-substituted anilines in high yields. The bulkiness of amines affects its reactivity to lower the yields of the products. Although the secondary amines are usually less reactive than primary amines, cyclic secondary amines such as morpholine, piperidine, and pyrrolidine were found very reactive. 1,4-Diazabicyclo[2.2.2]octane and quinuclidine gave N-quaternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines. Dichloro- and trichloro-nitrobenzenes also react with diethylamine, pyrrolidine, and morpholine to give mono-, di-, and trisubstitution products depending upon the amount of amine and the position of nitro group in these chlorides.

Nucleophilic Substitution of Aromatic Halides with Amines under High Pressure

Abstract The reaction of aromatic chlorides, bromides and iodides with various primary or secondary amines in a tetrahydrofuran solution under high pressure of 6–12 kbar gave the corresponding secondary and tertiary aromatic amines. The yields of the products depend on the bulkiness of amines used. 1,4-Diazabicyclo[2.2.2]octane and quinuclidine gave N-aryl quarternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines.

Inversion at trivalent nitrogen: application of the MNDO and MINDO/3 semiempirical molecular orbital methods

The recently developed MNDO SCF method with full geometry optimization and standard parameterization gives nitrogen inversional barriers in aziridine derivatives which are in close agreement with experimental data (mean deviation 1.7 kcal mol–1). Results for acyclic amino compounds are less accurate (mean deviation 3.5 kcal mol–1). The calculated barriers in some primary NH2X compounds are too high whereas those in acyclic tertiary amines tend to be too low. The older MINDO/3 method gives better results for ammonia and some primary NH2X molecules, but seriously underestimates inversional potentials in amines and aziridines. Both rotational and nitrogen inversional potential co-ordinates are calculated for hydroxylamines and methyleneamine.

Fragmentation reactions promoted by cyanogen bromide

The fragmentation of α-4-dimethylamino-3-methyl-1,2-diphenylbutan-2-ol to cis H/Ph 3-methyl-1,2-diphenylprop-2-ene, normally induced by treating the corresponding 2-chloro derivative with a base, also results when the alcohol itself is treated with cyanogen bromide; related γ-hydroxy acyclic tertiary amines similarly undergo fragmentation in this reaction. In contrast, cyclic analogues such as β-1,3-dimethyl-4-phenyl-4-piperidinol are not cleaved by cyanogen bromide (corresponding N-cyano derivatives are formed in low yield) even though β-4-chloro-1,3-dimethyl-4-phenylpiperidine is fragmented by potassium cyanide to trans H/Ph 5(N-cyanomethyl-N-methylamino)-3-phenylpent-2-ene.