Study on 1,3,5‐Triazine Chemistry in Dehydrocondensation: Gauche Effect on the Generation of Active Triazinylammonium Species

The reaction of 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine (CDMT) with various nitrogen‐containing compounds, particularly tertiary amines (tert‐amines), has been studied for the preparation of 2‐(4,6‐dimethoxy‐1,3,5‐triazinyl)trialkylammonium salts [DMT‐Am(s)]. DMT‐Ams derived from aliphatic tert‐amines exhibited activity for the dehydrocondensation between a carboxylic acid and an amine to form an amide in a model reaction. Based on a conformational analysis of DMT‐Ams and tert‐amines by NMR and X‐ray diffraction methods, we concluded that a β‐alkyl group maintained in a gauche relationship with the nitrogen lone pair of tert‐amines significantly hinders the approach of CDMT to the nitrogen. Thus, trimethylamine and quinuclidine without such alkyl groups readily react with CDMT whereas triethylamine, possessing two or three such gauche β‐alkyl groups in the stable conformations, does not react at all. The theory of “gauche β‐alkyl group effect” proposed here provides useful guidelines for the preparation of DMT‐Ams possessing various tertiary amine moieties. An investigation of the dehydrocondensation activity of tert‐amines in a CDMT/tert‐amine system that involves in situ generation of DMT‐Am, showed that the gauche effect of the β‐alkyl group becomes quite pronounced; the yield of the amide decreases significantly with tert‐amines possessing an unavoidable gauche β‐alkyl group. Thus, the tert‐amine/CDMT systems are useful for judging whether tert‐amines can readily react with CDMT without isolation of DMT‐Ams.     

Efficient indoles and anilines syntheses employing tert-butyl sulfinamide as ammonia surrogate

tert-Butyl sulfinamide is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that indoles and anilines with sensitive functional groups can be readily prepared. This surrogate has also been used for the synthesis of indoles from 2-halophenols using palladium catalyzed cross coupling reaction as the key step.     

Effects of solvent and base on the palladium-catalyzed amination: PdCl2(Ph3P)2/Ph3P-catalyzed selective arylation of primary anilines with aryl bromides

A readily accessible catalytic system, PdCl₂(Ph₃P)₂/Ph₃P, was developed for the selective arylation of primary anilines with aryl bromides. The strong influence of solvents and bases on the catalytic activity was observed. In refluxing o-xylene, triphenylphosphine shows high efficiency for Pd-catalyzed intermolecular amination reactions. By changing the bases, mono- and diarylation of primary amines could be selectively achieved in high yields. Moreover, the catalytic system showed good toleration for the steric hindrance of anilines. A series of N,N,N′,N′-tetraaryl-1,1′-biphenyl-4,4′-diamines, important intermediates of OLED hole transport materials, were synthesized facilely via coupling reactions between 4,4′-diaminobiphenyls and aryl bromides.     

Excited-state palladium-catalysed reductive alkylation of imines: scope and mechanism

Palladium catalysis induced by visible-light irradiation is a promising tool for promoting unusual chemical transformations. We describe the development of excited-state palladium-catalyzed reductive alkylation of imines with alkyl bromides. The new methodology shows broad functional group tolerance and can additionally be applied in the direct three-component reaction of aldehydes, anilines, and alkyl bromides to give the alkyl amines under mild reaction conditions. Time-resolved photoluminescence experiments allowed the determination of the excited-state reaction kinetics and indicate that the reaction is proceeding via the inner-sphere electron transfer mechanism.

Palladium catalysis induced by visible-light irradiation is a promising tool for promoting unusual chemical reactivity. Here, the hybrid alkyl radical/Pd(i) species generated is used to promote the reductive alkylation of imines.     

N-triflyl-propiolamides: Preparation and transamidation reactions

N-Trifluoromethylsulfonyl-propiolamides have been prepared by two methods: a) N-triflation of secondary acetylenic carboxanilides, prepared in two steps from terminal alkynes, with triflic anhydride (Tf₂O) and b) from terminal alkynes and an aryl or alkyl isocyanate followed by Tf₂O in a consecutive one-pot reaction. The title compounds are bench-stable and insensitive to water and alcohols but amenable to transamidation reactions with a wide range of amine nucleophiles. Conversely, they are excellent reagents for the propynoylation of ammonia, primary and secondary amines, anilines, and hydrazines.     

Indium-mediated cleavage of diphenyl diselenide and diphenyl disulfide: efficient one-pot synthesis of unsymmetrical diorganyl selenides, sulfides, and selenoesters

A convenient and efficient method was developed for the synthesis of alkyl phenyl selenides, sulfides, and selenoesters in one-pot reaction by using indium metal. The reaction showed the selectivity for tert-alkyl, benzylic, and allylic halides over primary and secondary alkyl halides. For the reaction of primary and secondary alkyl iodides and bromides, the yields of selenides were improved by the addition of a catalytic amount of iodine.     

PS-SNAP, a practical polymer-supported nitrosation reagent in organic synthesis

PS-SNAP was designed and evaluated as a practical nitrosating polymer-supported reagent for the nitrosation of sec-amines. Nitrosated dialkyl amines, alkyl anilines, and bis-anilines were obtained in good yields and high purities after shaking the corresponding amines in the presence of an excess of the newly described reagent followed by simple filtration and removal of solvents.     

A convenient method for the preparation of primary amines using tritylamine

A simple method for the preparation of primary amines by treating N-tritylamines with trifluoroacetic acid has been established. The N-tritylamines were prepared by the reaction of alkyl halides or alkyl p-toluenesulfonates with tritylamine, or by the reaction of alkyl bromides with lithium tritylamide.     

Conversion of tertiary alcohols to tert-alkyl azides by way of quinone-mediated oxidation-reduction condensation using alkyl diphenylphosphinites

A novel method for the preparation of alkyl azides from alcohols by way of oxidation-reduction condensation is described. In this reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted into tert-alkyl azides with almost complete inversion of their stereochemistry: the obtained alkyl azides are then successfully reduced to afford the corresponding amines on treatment with LiAlH₄, thus, a versatile method for the preparation of chiral amines from the corresponding chiral alcohols is established.     

An inexpensive cyclodiphosphazane as an efficient ligand for the palladium-catalyzed amination of aryl bromides and chlorides

An economic and novel ligand, cyclodiphosphazane [ClPN(t-Bu)]₂ (1), was introduced in the palladium-catalyzed amination of unactivated aryl halides. The catalyst allows for the amination of aryl chlorides and bromides with secondary cyclic amines and anilines in good yields.     

Approaches to primary tert-alkyl amines as building blocks

Primary tert-alkyl amines include analogues of amantadine, a fragment commonly linked to pharmacophoric groups to enhance biological activity. The preparation of primary tert-alkyl amines is considered to be a difficult problem. Four synthetic procedures, some of which have been previously reported for the synthesis of amines with primary (RCH₂NH₂) or secondary (RR'CHNH₂) alkyl and/or aryl groups, were tested for the synthesis of primary tert-alkyl amines (RR′R″CNH₂) in aliphatic series including adamantane adducts. These procedures included the formation and reduction of tert-alkyl azides, the Ritter reaction in standard and modified conditions, the addition of organometallic reagents to N-tert-butyl sulfinyl ketimines and one-pot reactions between nitriles and organometallic reagents in the presence of a Lewis acid, Τi(iPrO)₄ or CeCl_3. These synthetic routes are unexplored for primary tert-alkyl amines. Studies on the synthetic routes for primary tert-alkyl amines are currently lacking. The reaction conditions and substrate limitations were studied for each procedure, with the first procedure being the most general and applicable also for compounds bearing bulky adducts.     

Unexpected conversion of alkyl azides to alkyl iodides and of aryl azides to N-tert-butyl anilines

In the presence of tert-butyl iodide, alkyl azides are converted into the corresponding iodides at room temperature, whereas, N-t-Bu anilines are obtained from aryl azides under the same experimental conditions. A mechanism is proposed to explain this unusual reactivity.     

Photostabilizing activity of tertiary hindered amines

The influence of the N-alkyl group of tertiary hindered amines on the photostabilization of polymers was studied. The photostabilizing effects of the tertiary amine derivatives of 4-benzoyloxy-2,2,6,6-tetramethylpiperidine ( 1a ) in polypropylene were compared. All tertiary amine derivatives having α-H to hindered N showed higher effectiveness than 1a . Model liquid phase photoxidations were carried out by irradiating (UV-lamp) the solutions of tertiary hindered amines containing tert-butyl hydroperoxide as a photoinitiator. The tertiary hindered amines were oxidized more easily than corresponding parent hindered amine and converted to the parent amine, which was identified as its salt, resulting from the carboxylic acid produced from the N-alkyl group by oxidation. The thermal reaction of the tertiary hindered amines with tert-butyl hydroperoxide was also studied in the liquid phase. The tertiary hindered amines decomposed tert-butyl hydroperoxide more rapidly than the parent secondary hindered amine, and generated the parent amine. It was also found that the photostabilizing effects of tertiary hindered amines for polyolefins were higher than that of the parent secondary hindered amine.     

2-(Trimethylsilyl)ethanesulfonyl amide as a new ammonia equivalent for palladium-catalyzed amination of aryl halides

2-(Trimethylsilyl)ethanesulfonyl amide (SES-NH₂) is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that anilines and anilines with sensitive functional groups can be readily prepared.     

A convenient synthesis of some α-oxoketene-N,S- and N,N-acetals

Some α-oxoketene-N,S- and N,N-acetals were selectively synthesized in good to excellent yields by the reaction of 1,1-dimethoxy-4,4-di(methylthio)-3-buten-2-one with primary and secondary amines under moderate conditions. Secondary amines in reaction with α-oxoketene dithioacetal yielded double-substitution products exclusively, whereas primary amines under the same conditions yielded the mono-substituted products as exclusive or main products.     

Cu2O/1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide catalyzed C-N cross-coupling reaction in aqueous media

An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of imidazole, indole, pyrrole, alkyl alcohol amines, and alkyl amines with aryl iodides and bromides. The reaction proceeds in water-ethanol media at 120 °C for 12 h with Cu₂O as the catalyst, 1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide (L2) as the ligand, NaOH as the base to generate a wide range of N-arylated products in moderate to excellent yields. Aqueous medium, ease of operation, and broad substrate scope give the process a benign environmental profile.     

Ligand-free CuCl-catalyzed C-N bond formation in aqueous media

CuCl-catalyzed N-arylation of alkyl amines and N-heterocycles with substituted aryl iodides and bromides can be carried out in 40% ⁿBu₄N⁺OH⁻ aqueous solution without any ligands.     

Synthesis of substituted N-hydroxyureas via the in situ generation of t-butoxy isocyanate

Treatment of primary and secondary amines with tert-butylmesitylenesulfonoxycarbamate and a base afforded tert-butoxyurea, which when treated with an acid ultimately yielded substituted N-hydroxyureas. It is proposed that this proceeded via the generation of t-butoxy isocyanate in situ. This method allows for the synthesis of both mono and disubstituted N-hydroxyureas.     

A new synthesis of 1,3-aminols from direct double reduction of β-enamino ketones formed in situ by reaction of β-dicarbonyl compounds with anilines

A new one-pot synthesis of 1,3-aminols by direct reduction of β-enamino ketones, formed in situ by reaction of easily available β-dicarbonyl compounds, with anilines were described. In the case of aliphatic amines such as benzyl amine, n-butyl amine and β-hydroxy ethyl amine, the corresponding 1,3-minols were not obtained. In fact, the β-enamino ketone formed was failed to accomplish further reduction to 1,3-aminol. This approach is the most direct available method for the synthesis of 1,3-aminols.     

(NH 4 )Zn 2 (PO 4 )(HPO 4 ): Hydrothermal Synthesis and Reaction with n-Alkylamine Vapours

(NH₄)Zn₂(PO₄)(HPO₄) was synthesized under mild hydrothermal conditions in the presence of urea. The reaction with n-alkylamines has been investigated by exposing the solid to amines vapor. The new materials were characterized by chemical and thermal analysis, powder X-ray diffraction, and IR spectroscopy. In addition, the simultaneous reaction of this compound with two or more n-alkylamine different molecules was investigated. The reaction of large n-alkylamine molecules was observed to be faster if there is a shorter alkyl chain amine acting as a catalyst, yielding on completion single amine materials. In the case of a vapor mixture of several amines, the compound obtained depends on the reaction time.