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

Ionic liquids in 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

Solvent-free heterocyclic synthesis.

Direct and rapid heating by microwave irradiation in combination with sealed vessel processing in many cases enables reactions to be carried out in a fraction of the time generally required using conventional conditions. This makes microwave chemistry an ideal tool for rapid reaction scouting and optimization of conditions, allowing very rapid progress through hypotheses–experiment–results iterations. The speed at which multiple variations of reaction conditions can be performed allows a morning discussion of “What should we try?” to become an after-lunch discussion of “What were the results” Not surprisingly, therefore, many scientists both in academia and industry have turned to microwave synthesis as a front-line methodology for their projects. In this review, more than 220 published examples of microwave-assisted synthetic organic transformations from the 2004 to 2008 literature are discussed. An additional ca. 500 reaction schemes are presented in the Electronic Supplementary Material, providing the reader with an overall number of ca. 930 references in this fast-moving and exciting field.

Controlled microwave heating in modern organic synthesis: highlights from the 2004–2008 literature

http://aether.cmi.ua.ac.be/artikels/Artikels%20Gitte/Artikels/Reviews/microwave%20enhanced%20synthesis%20Caddick%202009.pdf

Microwave enhanced synthesis

Coumarin heterocyclic derivatives: chemical synthesis and biological activity

Microwave reactions of primary and secondary amines with imidoylbenzotriazoles 6a−w gave diversely substituted amidines 7a−Aa in 76−94% yields. Convenient preparations of a variety of amides 5a−Ab (87−96%) and imidoylbenzotriazoles 6a−w (56−95%) have also been developed using microwave irradiation under mild conditions and short reaction times. These results demonstrate further the advantages of microwave synthesis and introduce a new application of imidoylbenzotriazoles in the preparation of polysubstituted amidines.

Efficient microwave access to polysubstituted amidines from imidoylbenzotriazoles.

Microwave reactions of 2-amino-2-methyl-1-propanol (2) or 2-aminoethanethiol hydrochloride (4) with readily available N-acylbenzotriazoles 1a−j in the presence of SOCl2 produced 2-substituted 2-oxazolines 3a−j in 84−98% yields and 2-substituted thiazolines 5a−i in 85−97% yields, respectively. With use of this method chiral oxazoline 6, bisoxazoline 7, bisthiazoline 8, and 5,6-dihydro-4H-1,3-oxazines 9 or 10 have also been prepared in 82−96% yields. These results demonstrate a new application of N-acylbenzotriazoles in the preparation of oxazolines and thiazolines under mild conditions and short reaction times with microwave irradiation.

Facile syntheses of oxazolines and thiazolines with N-acylbenzotriazoles under microwave irradiation.

A general method for the synthesis of 1,5-disubstituted tetrazoles from imidoylbenzotriazoles that involves mild reaction conditions and short reaction times.

Efficient Synthesis of 1,5-Disubstituted Tetrazoles

A facile method for the activation of hydroxy-substituted carboxylic acids using benzotriazole chemistry without prior protection of the hydroxy substituents is presented. The N-acylbenzotriazole intermediates 2a−g, 6a−d, and 9a−c have been used for high-yielding synthesis of both aliphatic (3a−l) and aromatic (7a−h, 10a−f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a−h and 13a−i were obtained using either neat alcohols in neutral microwave conditions or nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate yields were obtained in the case of aliphatic hydroxy esters 11a,b and thiolesters 11e−g from the intermediates 2a−c.

Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxylic acids.

As the acceptance of microwave synthesis grows, it becomes increasingly important for undergraduate chemists to fully learn about this emerging technology. Advances have made microwave use in the undergraduate laboratory safe, easy, and affordable. Herein we describe a simple way to effectively implement microwave synthesis into the undergraduate organic laboratory curriculum.

Chunming Cai

Papers

Efficient microwave access to polysubstituted amidines from imidoylbenzotriazoles.

Facile syntheses of oxazolines and thiazolines with N-acylbenzotriazoles under microwave irradiation.

Efficient Synthesis of 1,5-Disubstituted Tetrazoles

Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxylic acids.

Incorporation of Microwave Synthesis into the Undergraduate Organic Laboratory