THE TELESCOPIC APPROACH AS A TOOL FOR GREEN CHEMISTRY. One-pot reactions have become a powerful tool for the development of sustainable protocols in organic synthesis. In particular, the telescoping of multi-step reactions, i.e., the execution of sequential reactions without isolating and purifying intermediates, reduces the number of steps while preventing waste generation. Additionally, the processes become more sustainable through time, reagents/solvents, energy and cost savings. Therefore, the aim of this work is to summarize and discuss representative one-pot telescoped strategies involving heterocyclic construction, cross-coupling and continuous-flow reactions.

A facile and efficient method for esterification and amidation of carboxylic acids under neutral conditions has been developed. Esters and amides can be prepared by reacting a carboxylic acid (1 mmol) with tribromoisocyanuric acid (0.37 mmol) and triphenylphosphine (1 mmol) in dichloromethane at room temperature, followed by addition of an alcohol or an amine, respectively.

Foi desenvolvido um método fácil e eficiente para a conversão de alcoóis em brometos de alquila em meio neutro, utilizando ácido tribromoisocianúrico e trifenilfosfina (razão molar 1,0:0,7:2,0, álcool/ácido tribromoisocianúrico/trifenilfosfina) em diclorometano à temperatura ambiente. Esse método pode ser aplicado para a conversão de alcoóis primários, secundários, benzílicos e alílicos, sendo os brometos correspondentes obtidos em 67-82% de rendimento. Alcoóis terciários não são reativos sob estas condições.

An efficient and facile method has been developed for the conversion of alcohols into alkyl bromides under neutral conditions using tribromoisocyanuric acid and triphenylphosphine (molar ratio 1.0:0.7:2.0, alcohol/tribromoisocyanuric acid/triphenylphosphine) in dichloromethane at room temperature. This method can be applied for the conversion of primary, secondary, benzylic and allylic alcohols, and their corresponding bromides are obtained in 67-82 % yield. Tertiary alcohols do not react under these conditions.

Os ácidos tribromo- e tricloro-isocianúricos reagem com ácidos cinâmicos na presença de NaOH/H2O/Et2O à temperatura ambiente para produzir regiosseletivamente (E)-2-halo-estirenos em 25-95% de rendimento. Estudo sobre o mecanismo da reação utilizando correlações Hammett e cálculos DFT (teoria do funcional da densidade) mostraram que esta reação tem como passo determinante a velocidade da adição eletrofílica de um átomo de cloro à ligação dupla.

Tribromo- and trichloroisocyanuric acids react with cinnamic acids in NaOH/H2O/Et2O at room temperature to produce (E)-2-halostyrenes regioselectively in 25-95% yield. Mechanism studies using Hammett correlations and DFT (density functional theory) calculations have shown that this reaction has as rate determining step the electrophilic addition of chlorine atom to the double bond.

Primary, secondary and tertiary alcohols can be easily distinguished due to their reactivity towards tribromoisocyanuric acid (TBCA). The test is performed by adding TBCA to the alcohol in a test tube heated in a boiling water bath. Orange color develops in the tube containing the primary alcohol, light yellow is observed in the tube containing the secondary alcohol while the tertiary alcohol results in a colorless mixture.

O ácido dicloro-iodo-isocianúrico foi preparado em 93% de rendimento através do aquecimento do ácido tricloro-isocianúrico com 1,05 equiv. mol de iodo. Esse novo reagente se mostrou bastante eficiente para a iodação regiosseletiva de arenos ativados. Os alquenos reagem com o ácido dicloro-iodo-isocianúrico na presença de solventes nucleofílicos oxigenados (água, álcoois, ácido acético) para gerar, respectivamente, iodoidrinas, β-iodoéters e β-iodoacetatos em menos de um minuto de reação e em alto grau de regiosseletividade. Enol-éteres levam à formação regiosseletiva dos iodo-dialquilacetais correspondentes. Os resultados experimentais juntamente com os cálculos por DFT mostraram que, para reações com sistemas insaturados, o ácido dicloro-iodo-isocianúrico é mais reativo do que o ácido triiodo-isocianúrico.

Dichloroiodoisocyanuric acid was prepared in 93% by heating trichloroisocyanuric acid with 1.05 mol equiv. of iodine. This new reagent is very efficient for regioselective electrophilic iodination of activated arenes. Alkenes react with dichloroiodoisocyanuric acid in the presence of oxygenated nucleophiles (water, alcohols, and acetic acid), leading to the corresponding iodohydrins, β-iodoethers and β-iodoacetates with reaction times of less than one minute and with a high degree of regioselectivity. Enol ethers resulted in the regioselective formation of the corresponding iodine-dialkylacetals. Experimental results and DFT calculations showed that dichoroiodoisocyanuric acid is more reactive with unsaturated systems than triiodoisocyanuric acid.

Use of clays as catalyzers in heterogeneous processes has increased significantly given their low cost, safety and commercial availability. However, interconnected political, economic, social, environmental, geological, and chemical aspects should be considered for chemical processes to satisfy sustainable development concepts. This concept requires complex thinking involving different areas of knowledge in dialogue, contrasting with classical thought, which is linear and Cartesian. Thus, this paper discusses the principles of complex thought in the concept of sustainable development exemplified by use of clay as a clean technology in organic synthesis.

The chlorination of activated aromatic rings is efficiently achieved under mild conditions by reaction of aromatic compounds with trichloroisocyanuric acid in acetonitrile, at room temperature, leading to products in 60-95% isolated yields and good regioselectivity.

O ácido triiodo-isocianúrico (TICA) foi preparado em 90% de rendimento a partir do aquecimento do ácido tricloro-isocianúrico com iodo em um tubo selado. A reação do TICA com arenos ativados em acetonitrila gera regiosseletivamente os respectivos iodo-arenos em 73-93% de rendimento isolado. Anilina e fenol também são monoiodados seletivamente usando MeOH (53%) e CH2Cl2 (88%) como solventes, respectivamente.

Triiodoisocyanuric acid (TICA) was prepared in 90% yield by heating trichloroisocyanuric acid with iodine in a sealed tube. The reaction of TICA with activated arenes in acetonitrile led to an efficient and highly regioselective formation of the corresponding iodoarenes, in 73-93% isolated yield. Aniline and phenol are monoiodinated regioselectively using MeOH (53%) and CH2Cl2 (88%) as solvents, respectively.

A reação de alquenos com ácidos trialo-isocianúricos / NaX em acetona aquosa produz os dialo-alcanos vicinais em rendimentos de moderados a excelentes

The reaction of alkenes with easily handled trihaloisocyanuric acids / NaX in aqueous acetone produces the corresponding vicinal dihaloalkanes in moderate to excellent yields.

A reação do (R)-limoneno com uma quantidade equimolar de ácidos S-tioacético ou S-tiobenzóico em tolueno sob refluxo ocorre com regiosseletividade anti-Markovnikoff produzindo os 9-[(4R, 8RS)-p-mentenil] S-tiocarboxilatos em 71 e 61% de rendimento, respectivamente. A mesma reação do ácido S-tioacético catalisada pela argila montmorilonita K-10 levou ao S-tioéster em 65% de rendimento, além de p-mentadienos e p-cimeno. Foi observado que a argila K-10 promove a isomerização do limoneno aos mentadienos, e sua disproporcionação para o p-cimeno.

The reaction of (R)-limonene with equimolar amount of S-thioacetic or S-thiobenzoic acids in refluxing toluene proceeded regioselectively in anti-Markovnikoff fashion forming 9-[(4R, 8RS)-p-menthenyl] S-thiocarboxylates (71 and 61% yield, respectively). The montmorillonite K-10 clay-catalyzed reaction of (R)-limonene with S-thioacetic acid led to the S-thioester (65%) along with p-menthadienes and p-cymene. It was observed that K-10 clay promoted the isomerization of limonene to p-menthadienes and further disproportionation to p-cymene.

A reação de alquenos com o ácido tricloro-isocianúrico ou N-bromo-sacarina ou I2 / Fe2(SO4)3 na presença de DMF, seguida de tratamento em meio aquoso, leva à formação dos respectivos beta-halo-formatos com alta regio- e estereosseletividade.

The reaction of alkenes with trichloroisocyanuric acid or N-bromosaccharin or I2 / Fe2(SO4)3 in the presence of DMF followed by aqueous work-up led to the corresponding beta-haloformate in high regio- and stereoselectivity.

N-halosaccharins proved to be useful and alternative reagents for diverse organic transformations, such as halogenation of aromatic compounds, benzylic and alpha-carbonylic positions, cohalogenation of alkenes, oxidation of secondary alcohols, etc. Their preparation from saccharin, a cheap and readly available starting material, is simple.

O ácido tricloro-isocianúrico (TICA) em H2SO4 é um reagente eficiente para a cloração regioseletiva da isatina na posição 5 e compostos aromáticos desativados, como o nitro-benzeno. Cálculos de DFT sugerem a formação de uma espécie supereletrofílica poliprotonada que pode transferir Cl+ ao anel aromático mais eficientemente do que o TICA devido ao alívio da repulsão carga-carga.

Trichloroisocyanuric acid (TICA) in H2SO4 is an efficient reagent for regioselective chlorination of isatin at the 5-position and deactivated aromatic compounds, such as nitrobenzene. DFT calculations suggest formation of a superelectrophilic polyprotonated species that can transfer Cl+ to the aromatic ring more efficiently than TICA due to charge-charge repulsion relief.

As argilas naturais brasileiras F-101, F-117 e caulim foram caracterizadas através de análises química e textural, difração de raios X e RMN no estado sólido de 27Al e 29Si. A argila F-101 é uma esmectita, a F-117 é uma estrutura interestratificada contendo esmectita, caulinita e mica como argilominerais. O caulim é essencialmente uma caulinita. As argilas F-101 e F-117 são catalisadores mais eficientes para a coiodação de estireno e ciclo-hexeno com água e álcoois para produzir iodoidrinas e beta-iodo-éteres, respectivamente, comparadas ao caulim e a argila montmorilonita K-10.

The natural Brazilian clays F-101, F-117 and kaolin were characterized by chemical and textural analysis, XRD, and 27Al and 29Si MAS-NMR. The F-101 clay is a smectite, while F-117 is an interstratified structure with smectite, kaolinite and mica as clay-minerals. Kaolin is mainly kaolinite. F-101 and F-117 clays were more efficient catalysts for the coiodination of styrene and cyclohexene with water and alcohols to produce iodohydrins and beta-iodoethers, respectively, than the kaolin and montmorillonite K-10 clay.