Dayse N. Moreira

Ionic Liquids in Heterocyclic Synthesis

2.5. Ionic Liquids Presented in This Review 2020 3. Cyclocondensation Reactions 2020 4. Synthesis of Three-Membered Heterocycles 2022 4.1. Aziridines 2022 5. Synthesis of Five-Membered Heterocycles 2022 5.1. Pyrroles 2022 5.2. Furans 2022 5.3. Thiophenes 2023 5.4. Pyrazoles 2024 5.5. Imidazoles 2025 5.6. Isoxazoles 2027 5.7. Oxazoles, Oxazolines, and Oxazolidinones 2027 5.8. Thiazoles and Thiazolidinones 2028 6. Synthesis of Six-Membered Heterocycles 2030 6.1. Pyridines 2030 6.2. Quinolines 2031 6.3. Acridines 2033 6.4. Pyrans 2033 6.5. Flavones 2035 6.6. Pyrimidines and Pyrimidinones 2035 6.7. Quinazolines 2037 6.8. -Carbolines 2038 6.9. Dioxanes 2039 6.10. Oxazines 2039 6.11. Benzothiazines 2040 6.12. Triazines 2040 7. Synthesis of Seven-Membered Heterocycles: Diazepines 2041

Solvent-Free Heterocyclic Synthesis

6.1. Oxadiazoles 4154 6.2. Diazaphospholes 4154 7. Six-Membered Heterocycles with One Heteroatom 4155 7.1. Pyridines 4155 7.2. Pyridinones 4155 7.3. Quinolines 4156 7.4. Quinolinones 4157 7.5. Isoquinolines 4157 7.6. Acridines 4158 7.7. Pyranones 4158 7.8. Flavones 4159 8. Six-Membered Heterocycles with Two Heteroatoms 4159 8.1. Pyridazinones 4159 8.2. Pyrimidines 4159 8.3. Pyrimidinones 4160 8.4. Quinazolines 4162 8.5. Quinazolinones 4162 8.6. Quinoxalines 4164 8.7. Quinoxalinediones 4165 8.8. Oxazines 4165 8.9. Oxazinones 4166 8.10. Thiazines 4166 9. Six-Membered Heterocycles with Three Heteroatoms 4166

Reaction of β-alkoxyvinyl halomethyl ketones with cyanoacetohydrazide

The synthesis of thirteen 1-cyanoacetyl-5-hydroxy-5-halomethyl-1H-4,5-dihydropyrazoles from the reaction of 4-alkoxy-3-alken-2-ones [R3C(O)C(R2)=C(R1)(OR), where R3 = CF3, CCl3, CHCl2, CO2Et; R2 = H, Me; R1 = H, Me, Et, Pr, Pentyl, c-Hexyl, Ph, and R = Me, Et] with cyanoacetohydrazide is reported. In order to show the versatility of using the 1-cyanoacetyl-substituted pyrazoles as important building blocks in organic synthesis, some attempts to obtain pyrazole derivatives also are described.

Pyrazole synthesis under microwave irradiation and solvent-free conditions

This paper presents a study of solvent-free reaction conditions using microwave irradiation (MW) to obtain 4,5-dihydro-1H-pyrazoles and dehydrated pyrazoles by the cyclocondensation reaction of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones [CF3C(O)CH=C(R1)OR, where R/R1 = Et/H, Me/Me and Me/Ph] with hydrazines [NH2NH-R2, where R2 = CO2Me, Ph, CH2CH2OH]. Some reactions were performed under the same reaction conditions using methanol as solvent. The results obtained using MW equipment for synthesis under solvent-free conditions were also compared with those described in literature for conventional thermal heating and heating with a domestic MW oven. In general, the products furnished by reaction in MW equipment for synthesis presented better yields and shorter reaction times. In addition, it was demonstrated that the reaction temperature altered the formation of products for each hydrazine showing that MW equipment for synthesis is efficient for reacting hydrazines and 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones to procedure the products 4,5-dihydro-1H-pyrazoles and dehydrated pyrazoles.

Ultrasound promoted the synthesis of N-propargylic β-enaminones.

The synthesis of 14 novel N-propargylic β-enaminones from the reaction of β-alkoxy vinyltrihalomethyl[carboxyethyl] ketones [R(3)C(O)CHC(R(1))OMe, where R(3)=CF(3), CCl(3), CO(2)Et and R(1)=Me, Et, Pr, Bu, i-Pent, CH(2)CH(2)CO(2)Me] with propargyl amines [R(2)NHCH(2)CCH, where R(2)=Pr, PhCH(2)] is reported. Yields, solvents and reaction times needed for reaction completion, by microwave irradiation (MW), conventional thermal heating (TH) and under ultrasound irradiation (US) are compared. The best results were obtained under US irradiation in good to excellent yields (70-93%).

Synthesis of novel quinolines using TsOH/ionic liquid under microwave

2 = Me, Et, Pr, Bu, i-Bu and i-Pe) and 2-aminoacetophenone. The reaction was performed in ionic liquid and 4-toluene sulfonic acid under microwave irradiation. Results showed that the catalytic method was effective. Products were formed in a short time (10-20 min) and presented good yields (70-91%).

Pharmaceutical Salts: Solids to Liquids by Using Ionic Liquid Design

Ionic liquids (ILs) have attracted increasing interest lately in several areas such as chemistry, physics, engineering, material science, molecular biochemistry, energy and fuels, among others. Scientific literature has been daily invaded by papers that show a variety of new ionic liquids and new applications. Furthermore, the range of ILs used has been broadened, and there has been a significant increase in the scope of both physical and chemical IL properties [1, 2]. ILs are defined as liquid organic salts composed entirely of ions, and a melting point criterion has been proposed to distinguish between molten salts and ionic liquids (mp< 100 °C) [3].

Regiospecific synthesis of new fatty N-acyl trihalomethylated pyrazoline derivatives from fatty acid methyl esters (FAMEs)

Uma serie de novas pirazolinas N-acil trialometiladas derivadas de esteres metilicos de acidos graxos foi sintetizada por reacao de ciclocondensacao entre hidrazidas graxas e 4-alcoxi-1,1,1-trialometil-3-alquen-2-onas. Ciclizacoes eficientes e regioespecificas catalisadas por BF3·MeOH levaram aos produtos desejados em rendimentos de bons a excelentes e alto grau de pureza.

Ionic Liquids: Applications in Heterocyclic Synthesis

Ionic liquids (ILs) have become omnipresent in the recent chemical literature; for they can be used as highly customizable solvents for almost any synthetic purpose [Wasserscheid & Welton, 2008]. Especially in the industry, their application goes beyond their use as solvents. The highly diverse properties of these materials make possible a surprising number of applications. In organic reactions, although ionic liquids were initially introduced as alternative green reaction media because of their unique chemical and physical properties of nonvolatility, nonflammability, thermal stability, and controlled miscibility, today they have marched far beyond this boundary, showing their significant role in controlling reactions as solvent or catalysts [Wasserscheid & Welton, 2008]. It is well-known that the microenvironment generated by a solvent can change the outcome of a reaction, in terms of both equilibria and rates [Pârvulescu & Hardacre, 2007]. Since ionic liquids have the potential to provide reaction media that are quite unlike any other available at room temperature, it is possible that they will dramatically affect reactions carried out in them. Undeniably, there have been many claims of great improvements in reaction yields and rates when using ionic liquids [Chiappe & Pieraccini, 2005]. Over the past decade, some authors have manifested interest in providing facts to clarify the question: “how do ionic liquids act in organic reactions?” They have found answers for particular reactions, in that ionic liquids play specific roles depending on the reaction [Martins et al., 2008]. This chapter presents some questions and the best results to afford answers about the role of ILs in the most important reactions involved in heterocyclic synthesis: cyclocondensation and 1,3dipolar cycloaddition reactions. Heterocycles form by far the largest of the classical divisions of organic chemistry. Moreover, they are of immense importance not only both biologically and industrially but to the functioning of any developed human society as well. Their participation in a wide range of areas cannot be underestimated. The majority of pharmaceutical products that mimic natural products with biological activity are heterocycles. Most of the significant advances against disease have been made by designing and testing new structures, which are often heteroaromatic derivatives. In fact, in the Comprehensive Medicinal Chemistry (CMC) database, more than 67% of the compounds listed contain heterocyclic rings [Xu & Stevenson, 2000]. Other important practical applications of heterocycles can also be cited, for instance, additives and modifiers in a wide variety of industries including cosmetics,

Sonochemical heating profile for solvents and ionic liquid doped solvents, and their application in the N-alkylation of pyrazoles.

The heating profile for 25 solvents was determined in ultrasonic probe equipment at amplitudes of 20%, 25%, and 30%. Each solvent was heated in accordance with its boiling point. The effect of vapor pressure, surface tension, and viscosity of the solvents in dissipated ultrasonic power (Up) was evaluated. Multiple regression analysis of these solvent properties and dissipated Up reveals that solvent viscosity is the property that most strongly affected dissipated Up. Experimentation involving acetonitrile doped with [BMIM][BF4] indicated faster heating than MeCN. Aprotic polar solvents such as DMSO, DMF, and MeCN were tested in the N-alkylation of pyrazoles under ultrasonic conditions. After 5min at 90°C, the reactants had been totally converted into product in these solvents. Solvents, with low dissipated Up (e.g., toluene) were tested. Conversions were lower compared to those of aprotic polar solvents. When the reactions were done in hexane, no conversion to product was observed. To check the effect of doping in solvents with low Up, [BMIM][BF4], DMSO, and DMF were selected. The conversions for toluene doped with [BMIM][BF4], DMSO, and DMF were 100%, 59%, and 25%, respectively. These conversions were greater than when done in just toluene (46%). Thus, [BMIM][BF4] was the best polar doping solvent, followed by DMSO. DMF was not considered to be a satisfactory doping solvent. No conversion was observed for reactions in the absence of base performed in DMSO, DMF, and MeCN doped with [BMIM][BF4].