Science of Synthesis Knowledge Updates 2017 Vol. 2 E-Book

• Herausgeber: Thieme
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1019

Veröffentlichungsjahr: 2017

Beschreibung

The Science of Synthesis Editorial Board, together with the volume editors and authors, is constantly reviewing the whole field of synthetic organic chemistry as presented in Science of Synthesis and evaluating significant developments in synthetic methodology. Several annual volumes updating content across all categories ensure that you always have access to state-of-the-art synthetic methodology.

Leseprobe

Science of Synthesis

Science of Synthesis is the authoritative and comprehensive reference work for the entire field of organic and organometallic synthesis.

Science of Synthesis presents the important synthetic methods for all classes of compounds and includes:

Methods critically evaluated by leading scientists

Background information and detailed experimental procedures

Schemes and tables which illustrate the reaction scope

Preface

As the pace and breadth of research intensifies, organic synthesis is playing an increasingly central role in the discovery process within all imaginable areas of science: from pharmaceuticals, agrochemicals, and materials science to areas of biology and physics, the most impactful investigations are becoming more and more molecular. As an enabling science, synthetic organic chemistry is uniquely poised to provide access to compounds with exciting and valuable new properties. Organic molecules of extreme complexity can, given expert knowledge, be prepared with exquisite efficiency and selectivity, allowing virtually any phenomenon to be probed at levels never before imagined. With ready access to materials of remarkable structural diversity, critical studies can be conducted that reveal the intimate workings of chemical, biological, or physical processes with stunning detail.

The sheer variety of chemical structural space required for these investigations and the design elements necessary to assemble molecular targets of increasing intricacy place extraordinary demands on the individual synthetic methods used. They must be robust and provide reliably high yields on both small and large scales, have broad applicability, and exhibit high selectivity. Increasingly, synthetic approaches to organic molecules must take into account environmental sustainability. Thus, atom economy and the overall environmental impact of the transformations are taking on increased importance.

The need to provide a dependable source of information on evaluated synthetic methods in organic chemistry embracing these characteristics was first acknowledged over 100 years ago, when the highly regarded reference source Houben–Weyl Methoden der Organischen Chemie was first introduced. Recognizing the necessity to provide a modernized, comprehensive, and critical assessment of synthetic organic chemistry, in 2000 Thieme launched Science of Synthesis, Houben–Weyl Methods of Molecular Transformations. This effort, assembled by almost 1000 leading experts from both industry and academia, provides a balanced and critical analysis of the entire literature from the early 1800s until the year of publication. The accompanying online version of Science of Synthesis provides text, structure, substructure, and reaction searching capabilities by a powerful, yet easy-to-use, intuitive interface.

From 2010 onward, Science of Synthesis is being updated quarterly with high-quality content via Science of Synthesis Knowledge Updates. The goal of the Science of Synthesis Knowledge Updates is to provide a continuous review of the field of synthetic organic chemistry, with an eye toward evaluating and analyzing significant new developments in synthetic methods. A list of stringent criteria for inclusion of each synthetic transformation ensures that only the best and most reliable synthetic methods are incorporated. These efforts guarantee that Science of Synthesis will continue to be the most up-to-date electronic database available for the documentation of validated synthetic methods.

Also from 2010, Science of Synthesis includes the Science of Synthesis Reference Library, comprising volumes covering special topics of organic chemistry in a modular fashion, with six main classifications: (1) Classical, (2) Advances, (3) Transformations, (4) Applications, (5) Structures, and (6) Techniques. Titles will include Stereoselective Synthesis, Water in Organic Synthesis, and Asymmetric Organocatalysis, among others. With expertevaluated content focusing on subjects of particular current interest, the Science of Synthesis Reference Library complements the Science of Synthesis Knowledge Updates, to make Science of Synthesis the complete information source for the modern synthetic chemist.

The overarching goal of the Science of Synthesis Editorial Board is to make the suite of Science of Synthesis resources the first and foremost focal point for critically evaluated information on chemical transformations for those individuals involved in the design and construction of organic molecules.

Throughout the years, the chemical community has benefited tremendously from the outstanding contribution of hundreds of highly dedicated expert authors who have devoted their energies and intellectual capital to these projects. We thank all of these individuals for the heroic efforts they have made throughout the entire publication process to make Science of Synthesis a reference work of the highest integrity and quality.

The Editorial Board

July 2010

E. M. Carreira (Zurich, Switzerland)

C. P. Decicco (Princeton, USA)

A. Fuerstner (Muelheim, Germany)

G. Koch (Basel, Switzerland)

G. A. Molander (Philadelphia, USA)

E. Schaumann (Clausthal-Zellerfeld, Germany)

M. Shibasaki (Tokyo, Japan)

E. J. Thomas (Manchester, UK)

B. M. Trost (Stanford, USA)

Abstracts

17.9.24 Phthalocyanines and Related Compounds

M. S. Rodríguez-Morgade and T. Torres

This review updates the original Science of Synthesis chapter (Section 17.9) on phthalocyanines and various ring-fused, ring-contracted, and ring-expanded analogues. It adds some recently published methods, examples, and variations on the synthesis of unsubstituted phthalocyanines and metal phthalocyanines, as well as identically and nonidentically substituted phthalocyanine derivatives. Besides peripheral substitution, axial functionalization is also discussed, but attention is focused only on those methods that represent appreciable progress for a particular type of metal coordination and axial functionalization, provide phthalocyanines with specific features such as chirality, or allow the functionalization of phthalocyanines with entities that are difficult to introduce at the peripheral sites. This account also includes sections on new types of phthalocyanine derivatives and analogues that were not covered in the original chapter, as well as the progress made in the synthesis of some of these families in the decade since 2003.

Keywords: phthalocyanines • phthalocyanine–metal complexes • porphyrazines • tetraazaporphyrins • naphthalocyanines • phenanthrenocyanines • triphenylenocyanines • anthracenocyanines • pyrenocyanines • benzoperylenocyanines • helicenocyanines • azulenocyanines • tetraazachlorins • tetraazabacteriochlorins • azaphthalocyanines • triazacorroles • subphthalocyanines • subporphyrazines • superazaporphyrins • pyrenocyanines • phthalonitriles • phthalic anhydrides • phthalic acids • phthalimides • isoindolinediimines • condensation reactions • substituent modification • ligand substitution

34.1.1.8 Synthesis of Fluoroalkanes by Substitution of Hydrogen

M. Rueda-Becerril and G. M. Sammis

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.1.1) describing methods for the synthesis of fluoroalkanes by substitution of hydrogen. The increasing importance of fluorine-containing molecules in the health, pharmaceutical, and agrochemical sectors has resulted in the rapid development of more-selective, morecontrolled, and safer methods for the insertion of a fluorine atom into structurally diverse molecules. Herein, the most synthetically useful methods reported from 2006 until mid-2016 to achieve such transformations are described.

Keywords: fluorination • hydrogen substitution • alkanes • cycloalkanes • fluorine compounds • fluorine transfer • Selectfluor • photocatalysis • organometallic reagents

34.1.4.1 Synthesis of Fluoroalkanes by Substitution of a Halogen

T. P. Lequeux

This chapter is a revision of the earlier Science of Synthesis contribution describing methods for the synthesis of fluoroalkanes by substitution of a halogen atom. It includes additional methods published up until 2016. Newer approaches involve the use of fluoride complex reagents and the use of solvent effects to avoid competitive elimination reactions.

Keywords: fluoroalkanes • nucleophilic substitution • fluorides • halides • alkanes • cycloalkanes • nucleosides • amines • steroids • ammonium compounds • copper complexes

34.1.4.3 Synthesis of Fluoroalkanes by Substitution of Oxygen and Sulfur Functionalities

T. P. Lequeux

This chapter is a revision of the earlier Science of Synthesis contribution describing methods for the synthesis of fluoroalkanes by substitution of oxygen and sulfur functionalities. It now includes the literature published up until 2016. The additional material focuses on new reagents and their applications. For example, the effect of an ionic liquid on the rate of the displacement of sulfonates by cesium fluoride, and expeditious synthesis of nucleoside derivatives are described.

Keywords: fluoroalkanes • nucleophilic substitution • fluorides • sulfonates • alkanes • cycloalkanes • pyrans • nucleosides • carbohydrates • steroids • sulfur compounds • copper complexes

34.1.6.4 Synthesis of Fluoroalkanes with Retention of the Functional Group

T. Yamazaki

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.1.6) describing methods for the synthesis of monofluorinated compounds with a C(sp3)─F bond by way of a wide variety of transformations of molecules already bearing the key C─F bond. The focus is on methods published in the period 2005–2015.

Keywords: alkylation • crossed aldol reactions • conjugate addition • SN2′ reactions • hydrogenation • reduction • cycloadditions • iodolactonization

34.2.2 Fluorocyclopropanes

P. Jubault, T. Poisson, and X. Pannecoucke

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.2) describing methods for the synthesis of fluorocyclopropanes. The most important breakthrough described in this update is the development of asymmetric syntheses of fluorocyclopropanes based on various approaches, such as the use of chiral fluorinated scaffolds or the development of catalytic enantioselective sequences. This review focuses on the contributions published between 2005 and 2016.

Keywords: fluorocyclopropanes • cyclopropanes • fluorine compounds • conjugate addition • carbenoids • diazo compounds • asymmetric catalysis • alkenes

34.3.2 (Fluoromethyl) cyclopropanes

P. Jubault, T. Poisson, and X. Pannecoucke

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.3) describing methods for the synthesis of (fluoromethyl) cyclopropanes. In this review, new methods, published since 2006, by means of direct or two-step fluorodehydroxylation and by rearrangement of fluoroepoxides are described.

Keywords: (fluoromethyl) cyclopropanes • cyclopropanes • fluorine compounds • nucleophilic fluorination • carbenoids • rearrangement

34.4.2 Fluorocyclobutanes

T. Poisson, P. Jubault, and X. Pannecoucke

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.4) describing methods for the synthesis of fluorocyclobutanes. In this review, progress made in the field since 2006 is reported. The use of cycloaddition reactions as well as rearrangement reactions to access the fluorocyclobutane motif are significant advances in this area.

Keywords: fluorocyclobutanes • cyclobutanes • fluorine compounds • nucleophilic fluorination • [2 + 2] cycloaddition • rearrangement

34.7.4 Allylic Fluorides

C. R. Pitts and T. Lectka

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.7) regarding the synthesis of allylic monofluorides. Herein, literature from 2005–2015 is discussed. Advancements during this time period include the employment of milder fluorinating reagents, methods that favor alkene migration or retention, tactics for catalytic and asymmetric reactions, and the introduction of a creative array of functional-group interconversions.

Keywords: fluorination • halogenation • allylic fluorides • carbon─halogen bonds • allylic substitution • electrophilic fluorination • nucleophilic fluorination • asymmetric fluorination • regioselectivity

34.9.3 β-Fluoro Alcohols

K. Shibatomi

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.9) describing methods for the synthesis of β-fluoro alcohols. It focuses on enantioselective synthetic approaches, and includes methods based on the α-fluorination of carbonyl compounds and subsequent reduction.

Keywords: β-fluoro alcohols • fluorine compounds • asymmetric fluorination • decarboxylation • decarbonylation • aldol reaction • reduction • enantioselectivity • Lewis acid catalysts • chiral amine catalysts

34.10.5 β-Fluoroamines

L. Hunter

This chapter is an update to the earlier Science of Synthesis contribution (Section 34.10) describing methods for the synthesis of β-fluoroamines. This topic has continued to attract signficant attention from the synthetic community, largely due to the medicinal importance of this class of compounds. A wide variety of new methods have been developed, and this review focuses on examples that were published between 2005 and 2015.

Keywords: aminofluorination • carbon─fluorine bonds • electrophilic fluorination • nucleophilic fluorination • radical fluorination • stereoselective reactions

40.1.6.2 Azetidines

F. Couty

This chapter is an update to the earlier Science of Synthesis contribution (Section 40.1.6) describing methods for the synthesis of azetidines. This review focuses on contributions in this field published between 2008 and 2015 (with some exceptions of papers published as early as 2006, which were not covered in the earlier review). This period has witnessed an impressive breakthrough of pharmaceutical agents bearing an azetidine ring in medicinal chemistry and the first examples of organocatalyzed enantioselective syntheses of nonracemic azetidines.

Keywords: azetidines • small rings • ring strain • nitrogen heterocycles • ring closure • ring contraction • β-lactams

Science of Synthesis Knowledge Updates 2017/2

Preface

Abstracts

Table of Contents

17.9.24 Phthalocyanines and Related Compounds (Update 2017)

M. S. Rodríguez-Morgade and T. Torres

34.1.1.8 Synthesis of Fluoroalkanes by Substitution of Hydrogen (Update 2017)

M. Rueda-Becerril and G. M. Sammis

34.1.4.1 Synthesis of Fluoroalkanes by Substitution of a Halogen

T. P. Lequeux

34.1.4.3 Synthesis of Fluoroalkanes by Substitution of Oxygen and Sulfur Functionalities

T. P. Lequeux

34.1.6.4 Synthesis of Fluoroalkanes with Retention of the Functional Group (Update 2017)

T. Yamazaki

34.2.2 Fluorocyclopropanes (Update 2017)

P. Jubault, T. Poisson, and X. Pannecoucke

34.3.2 (Fluoromethyl) cyclopropanes (Update 2017)

P. Jubault, T. Poisson, and X. Pannecoucke

34.4.2 Fluorocyclobutanes (Update 2017)

T. Poisson, P. Jubault, and X. Pannecoucke

34.7.4 Allylic Fluorides (Update 2017)

C. R. Pitts and T. Lectka

34.9.3 β-Fluoro Alcohols (Update 2017)

K. Shibatomi

34.10.5 β-Fluoroamines (Update 2017)

L. Hunter

40.1.6.2 Azetidines (Update 2017)

F. Couty

Author Index

Abbreviations

Table of Contents

Volume 17: Six-Membered Hetarenes with Two Unlike or More Than Two Heteroatoms and Larger Hetero-Rings

17.9 Product Class 9: Phthalocyanines and Related Compounds

17.9.24 Phthalocyanines and Related Compounds

M. S. Rodríguez-Morgade and T. Torres

17.9.24 Phthalocyanines and Related Compounds

17.9.24.1 Metal-Free Phthalocyanines

17.9.24.1.1 Method 1: Synthesis from Phthalonitrile

17.9.24.1.2 Method 2: Synthesis from Bicyclo[2.2.2]octadiene-Fused Tetraazaporphyrins (Porphyrazines)

17.9.24.1.3 Method 3: Synthesis from Phthalimide, Phthalic Anhydride, or Phthalic Acid

17.9.24.1.4 Method 4: Demetalation of a Zinc Complex

17.9.24.2 Metal–Phthalocyanine Complexes

17.9.24.2.1 Method 1: Synthesis from Phthalonitrile

17.9.24.2.2 Method 2: Synthesis from Phthalic Anhydride

17.9.24.2.3 Method 3: Synthesis from Phthalic Acid

17.9.24.2.4 Method 4: Synthesis from Phthalimide

17.9.24.3 1,8(11),15(18),22(25)-Tetrasubstituted Phthalocyanines and 1:25,11:15-Bridged Phthalocyanines

17.9.24.3.1 Method 1: Synthesis from 3-Substituted Phthalonitriles

17.9.24.3.1.1 Variation 1: Regioselective Preparation of 1,8,15,22-Tetrasubstituted Phthalocyanines from 3-Substituted Phthalonitriles

17.9.24.3.2 Method 2: Side-Strapped 1:25,11:15-Tetrasubstituted Phthalocyanines from Bis (isoindolinediimines)

17.9.24.3.3 Method 3: Postfunctionalization of Phthalocyanines

17.9.24.3.3.1 Variation 1: Derivatization of Peripheral Substituents

17.9.24.3.3.2 Variation 2: Chiral 1,8,15,22-Tetrasubstituted Phthalocyanines

17.9.24.4 2,9(10),16(17),23(24)-Tetrasubstituted Phthalocyanines and 2:24,10:16-Bridged Phthalocyanines

17.9.24.4.1 Method 1: Synthesis from 4-Substituted Phthalonitriles

17.9.24.4.1.1 Variation 1: Side-Strapped 2:24,10:16-Bridged Phthalocyanines from 4,4′-Substituted Bis (phthalonitriles)

17.9.24.4.2 Method 2: Synthesis from 4-Substituted Phthalic Anhydrides

17.9.24.4.3 Method 3: Synthesis from 4-Substituted Phthalimides

17.9.24.4.4 Method 4: Derivatization of Peripheral Substituents

17.9.24.4.5 Method 5: Postfunctionalization of Axial Substituents

17.9.24.5 1,3,8,10(9,11),15,17(16,18),22,24(23,25)-Octasubstituted Phthalocyanines

17.9.24.5.1 Method 1: Synthesis from 3,5-Disubstituted Phthalic Acids

17.9.24.5.2 Method 2: Postfunctionalization of Phthalocyanines

17.9.24.6 1,4,8,11,15,18,22,25-Octasubstituted Phthalocyanines

17.9.24.6.1 Method 1: Synthesis from 3,6-Disubstituted Phthalonitriles

17.9.24.6.2 Method 2: Derivatization of Peripheral Substituents

17.9.24.6.3 Method 3: Postfunctionalization of Axial Substituents

17.9.24.7 2,3,9,10,16,17,23,24-Octasubstituted Phthalocyanines

17.9.24.7.1 Method 1: Synthesis from 4,5-Disubstituted Phthalonitriles

17.9.24.7.1.1 Variation 1: Octasubstituted Phthalocyanines Possessing Two Types of Substituents

17.9.24.7.2 Method 2: Synthesis from 4,5-Disubstituted Phthalic Anhydrides

17.9.24.7.3 Method 3: Synthesis from 5,6-Disubstituted Isoindoline-1,3-diimines

17.9.24.7.4 Method 4: Derivatization of Peripheral Substituents

17.9.24.7.5 Method 5: Postfunctionalization of Axial Substituents

17.9.24.8 2:3,9:10,16:17,23:24-Bridged Phthalocyanines

17.9.24.8.1 Method 1: Synthesis from 4:5-Bridged Phthalonitriles

17.9.24.8.2 Method 2: Synthesis from 5:6-Bridged Isoindoline-1,3-diimines

17.9.24.8.3 Method 3: Synthesis from 5:6-Bridged Phthalic Anhydrides

17.9.24.8.4 Method 4: Derivatization of Peripheral Substituents

17.9.24.9 Dodecasubstituted Phthalocyanines

17.9.24.9.1 Method 1: Synthesis from 3,4,5-Trisubstituted Phthalonitriles

17.9.24.9.2 Method 2: Synthesis from 3,4,5-Trisubstituted Phthalic Acids

17.9.24.9.3 Method 3: Synthesis from 3,4,6-Trisubstituted Phthalonitriles

17.9.24.10 1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-Hexadecasubstituted Phthalocyanines, 1:2,3:4,8:9,10:11,15:16,17:18,22:23,24:25-Bridged Phthalocyanines, and 1,2:3,4,8,9:10,11,15,16:17,18,22,23:24,25-Bridged Phthalocyanines

17.9.24.10.1 Method 1: Synthesis from 3,4,5,6-Tetrasubstituted Phthalonitriles

17.9.24.10.1.1 Variation 1: Hexadecasubstituted Phthalocyanines Possessing Two Types of Substituents from Symmetrical 3,4,5,6-Tetrasubstituted Phthalonitriles

17.9.24.10.1.2 Variation 2: Hexadecasubstituted Phthalocyanines Possessing Two Types of Substituents from Unsymmetrical 3,4,5,6-Tetrasubstituted Phthalonitriles

17.9.24.10.1.3 Variation 3: Hexadecasubstituted Phthalocyanines Possessing Three Types of Substituents

17.9.24.10.1.4 Variation 4: 1,4,8,11,15,18,22,25-Octasubstituted 2:3,9:10,16:17,23:24-Bridged Phthalocyanines from Phthalonitriles

17.9.24.10.1.5 Variation 5: 2,3,4,8,9,10,16,17,18,22,23,24-Dodecasubstituted 1:25,11:15-Bridged Phthalocyanines from Bis (phthalonitriles)

17.9.24.10.2 Method 2: Synthesis from 3,4,5,6-Tetrasubstituted Phthalic Anhydrides

17.9.24.10.3 Method 3: Synthesis from 3,4,5,6-Tetrasubstituted Phthalimides

17.9.24.10.4 Method 4: Synthesis from 3,4,5,6-Tetrasubstituted Isoindoline-1,3-diimines

17.9.24.10.5 Method 5: Derivatization of Peripheral Substituents

17.9.24.10.6 Method 6: Postfunctionalization of Axial Substituents

17.9.24.11 5,10,15,20-Tetraazaporphyrins (Porphyrazines)

17.9.24.11.1 Method 1: Synthesis from 2,3-Disubstituted Maleonitriles

17.9.24.11.1.1 Variation 1: 2:3,7:8,12:13,17:18-Bridged Tetraazaporphyrins from Cyclic Maleonitriles

17.9.24.11.2 Method 2: Synthesis from 3,4-Disubstituted Pyrrole-2,5-diimines

17.9.24.11.3 Method 3: Nonuniformly Substituted Tetraazaporphyrins

17.9.24.11.3.1 Variation 1: A2B2-Type Tetraazaporphyrins from Crossover Macrocyclization Reactions

17.9.24.11.4 Method 4: Post-Functionalization of Porphyrazines

17.9.24.12 1,2-Naphthalocyanines

17.9.24.12.1 Method 1: Synthesis from Naphthalene-1,2-dicarbonitriles

17.9.24.13 2,3-Naphthalocyanines

17.9.24.13.1 Method 1: Synthesis from Naphthalene-2,3-dicarbonitriles

17.9.24.13.2 Method 2: Synthesis from Benzoisoindolinediimines

17.9.24.13.3 Method 3: Synthesis from Naphthalene Anhydrides

17.9.24.13.4 Method 4: Synthesis from Naphthalimides

17.9.24.13.5 Method 5: Synthesis from Bicyclo[2.2.2]octene-fused Phthalocyanines

17.9.24.13.6 Method 6: Postfunctionalization of Axial Substituents

17.9.24.14 9,10-Phenanthrenocyanines and 2,3-Phenanthrenocyanines

17.9.24.14.1 Method 1: 9,10-Phenanthrenocyanines from Phenanthrene-9,10-dicarbonitriles

17.9.24.14.2 Method 2: 2,3-Phenanthrenocyanines from Phenanthrene-2,3-dicarboxylic Acid Imides

17.9.24.15 2,3-Triphenylenocyanines

17.9.24.15.1 Method 1: Synthesis from Triphenylene-2,3-dicarbonitriles

17.9.24.16 2,3-Anthracenocyanines

17.9.24.16.1 Method 1: Synthesis from Anthracene-2,3-dicarbonitriles

17.9.24.17 4,5-Pyrenocyanines

17.9.24.17.1 Method 1: Synthesis from Pyrene-4,5-dicarbonitriles

17.9.24.18 4,5-Benzoperylenocyanines

17.9.24.18.1 Method 1: Synthesis from Benzo[ghi]perylene-1,2-dicarbonitriles

17.9.24.19 Helicenocyanines and Benzohelicenocyanines

17.9.24.19.1 Method 1: Synthesis from [5]Helicene-7,8-dicarbonitriles

17.9.24.19.2 Method 2: Synthesis from Benzo[5]helicene-8,9-dicarbonitriles

17.9.24.20 Azulenocyanines

17.9.24.20.1 Method 1: Synthesis from Azulene-5,6-dicarbonitriles

17.9.24.21 Tetraazachlorins and Tetraazabacteriochlorins

17.9.24.21.1 Method 1: Mixed Condensation of Succinonitrile Derivatives and Another Dinitrile

17.9.24.21.2 Method 2: Mixed Condensation of Succinonitrile Derivatives with Phthalic Anhydrides or Phthalimides

17.9.24.21.3 Method 3: Cycloaddition Reactions of Tetraazaporphyrins

17.9.24.22 Tetra- and Octaazaphthalocyanines

17.9.24.22.1 Method 1: Synthesis from Pyridine-3,4-dicarbonitrile

17.9.24.22.2 Method 2: Synthesis from Pyridine-3,4-dicarboxylic Acid

17.9.24.22.3 Method 3: Synthesis from 1H-Pyrrolo[3,4-c]pyridine-1,3(2H)-diimine

17.9.24.22.4 Method 4: Synthesis from Diazaisoindoline-1,3-diimines

17.9.24.22.5 Method 5: Synthesis from Pyrazine-2,3-dicarboxylic Acid

17.9.24.22.6 Method 6: Modification of Preformed Azaphthalocyanines

17.9.24.23 Triazacorroles

17.9.24.23.1 Method 1: Synthesis from Isoindoline-1,3-diimines

17.9.24.23.2 Method 2: Synthesis from Phthalocyanines

17.9.24.23.3 Method 3: Synthesis from Tetraazaporphyrins

17.9.24.23.4 Method 4: Modification of Preformed Triazacorroles

17.9.24.23.4.1 Variation 1: Demetalation of Phosphorus(V) Triazacorroles

17.9.24.23.4.2 Variation 2: Metalation of Free-Base Triazacorroles

17.9.24.23.4.3 Variation 3: Modification of the Central Metal

17.9.24.24 Subphthalocyanines

17.9.24.24.1 Method 1: Synthesis from Phthalonitriles

17.9.24.24.1.1 Variation 1: 1,8,15(18)-Trisubstituted Subphthalocyanines from 3-Substituted Phthalonitriles

17.9.24.24.1.2 Variation 2: 2,9,16(17)-Trisubstituted Subphthalocyanines from 4-Substituted Phthalonitriles

17.9.24.24.1.3 Variation 3: 2,3,9,10,16,17-Hexasubstituted Subphthalocyanines and 2,3-Subnaphthalocyanines from 4,5-Disubstituted Phthalonitriles

17.9.24.24.1.4 Variation 4: Hexasubstituted Subphthalocyanines and 1,2-Subnaphthalocyanines from 3,4- and 3,5-Disubstituted Phthalonitriles

17.9.24.24.1.5 Variation 5: 1,4,8,11,15,18-Hexasubstituted Subphthalocyanines from 3,6-Disubstituted Phthalonitriles

17.9.24.24.1.6 Variation 6: Dodecasubstituted Subphthalocyanines from 3,4,5,6-Tetrasubstituted Phthalonitriles

17.9.24.24.2 Method 2: Nonuniformly Substituted Subphthalocyanines by Crossover Cyclotrimerization

17.9.24.24.3 Method 3: Postfunctionalization of Subphthalocyanines

17.9.24.24.3.1 Variation 1: Derivatization of Peripheral Substituents

17.9.24.24.3.2 Variation 2: Reactions at the B─X Bond

17.9.24.25 Subporphyrazines

17.9.24.25.1 Method 1: Synthesis from Maleonitriles

17.9.24.25.2 Method 2: Postfunctionalization of Subporphyrazines

17.9.24.25.2.1 Variation 1: Derivatization of Peripheral Substituents

17.9.24.25.2.2 Variation 2: Reactions at the B─X Bond

17.9.24.26 Superazaporphyrins

17.9.24.26.1 Method 1: Synthesis from Pyrrole-2,5-diimines

17.9.24.27 Nonuniformly Substituted Phthalocyanines

17.9.24.27.1 Method 1: Crossover Cyclotetramerizations

17.9.24.27.1.1 Variation 1: Synthesis of A3B Nonuniformly Substituted Phthalocyanines

17.9.24.27.1.2 Variation 2: Side-Strapped AABB-Type Phthalocyanines

17.9.24.27.1.3 Variation 3: Synthesis of ABAB-Type Nonuniformly Substituted Phthalocyanines

17.9.24.27.2 Method 2: A3B-Type Phthalocyanines by Ring Expansion of Subphthalocyanines

17.9.24.27.3 Method 3: Synthesis of A3B-Type Phthalocyanines Using a Polymer Support

17.9.24.27.3.1 Variation 1: Synthesis of A3B-Type Phthalocyanines via ROMP–Capture–Release

17.9.24.27.4 Method 4: ABAB-Type Phthalocyanines from 1,1,3-Trichloroisoindole Derivatives

17.9.24.27.5 Method 5: Synthesis of ABAC-Type Phthalocyanines from Crossover Cyclotetramerization Reactions

17.9.24.27.6 Method 6: Postfunctionalization of Phthalocyanines

17.9.24.28 Multinuclear Phthalocyanines

17.9.24.28.1 Method 1: Cyclotetramerization Reactions Using Phthalonitriles, Oligo (phthalonitriles), or Derivatives

17.9.24.28.1.1 Variation 1: Dimeric Phthalocyanines from Bisphthalonitriles

17.9.24.28.1.2 Variation 2: Trimeric Phthalocyanines from Phthalonitriles

17.9.24.28.1.3 Variation 3: Dimeric Phthalocyanines from Fused Bis (pyrrolidinediimines)

17.9.24.28.1.4 Variation 4: Oligomeric Phthalocyanines from Phthalonitriles

17.9.24.28.2 Method 2: Synthesis by Connecting Preformed Phthalocyanines

17.9.24.28.2.1 Variation 1: Reaction of Peripheral Substituents

17.9.24.28.2.2 Variation 2: Axial Coordination

Volume 34: Fluorine

34.1 Product Class 1: Fluoroalkanes

34.1.1.8 Synthesis of Fluoroalkanes by Substitution of Hydrogen

M. Rueda-Becerril and G. M. Sammis

34.1.1.8 Synthesis of Fluoroalkanes by Substitution of Hydrogen

34.1.1.8.1 Method 1: Reaction with Fluoride Ion Sources

34.1.1.8.1.1 Variation 1: Using Metal Fluoride Reagents

34.1.1.8.1.2 Variation 2: Using Ammonium Fluoride Salts

34.1.1.8.2 Method 2: Reaction with Selectfluor

34.1.1.8.2.1 Variation 1: Using Metal Catalysts

34.1.1.8.2.2 Variation 2: Using Organocatalysts

34.1.1.8.2.3 Variation 3: Using Light-Mediated Processes

34.1.1.8.3 Method 3: Reaction with Selectfluor II

34.1.1.8.4 Method 4: Reaction with N-Fluorobenzenesulfonimide

34.1.4.1 Synthesis of Fluoroalkanes by Substitution of a Halogen

T. P. Lequeux

34.1.4.1 Synthesis of Fluoroalkanes by Substitution of a Halogen

34.1.4.1.1 Method 1: Substitution of Primary Halides

34.1.4.1.1.1 Variation 1: Using Metal Fluorides

34.1.4.1.1.2 Variation 2: Using Hydrogen Fluoride Complexes

34.1.4.1.1.3 Variation 3: Using Tetraalkylammonium Fluorides

34.1.4.1.1.4 Variation 4: Using Fluorosilicate Derivatives

34.1.4.1.2 Method 2: Substitution of Secondary Halides

34.1.4.1.2.1 Variation 1: Using Metal Fluorides

34.1.4.1.2.2 Variation 2: Using Hydrogen Fluoride Complexes

34.1.4.1.3 Method 3: Substitution of Tertiary Halides

34.1.4.1.3.1 Variation 1: Using Metal Fluorides

34.1.4.1.3.2 Variation 2: Using Base–Hydrogen Fluoride Complexes

34.1.4.1.3.3 Variation 3: Using Silver(I) Tetrafluoroborate

34.1.4.1.3.4 Variation 4: Using Ruthenium Complexes

34.1.4.3 Synthesis of Fluoroalkanes by Substitution of Oxygen and Sulfur Functionalities

T. P. Lequeux

34.1.4.3 Synthesis of Fluoroalkanes by Substitution of Oxygen and Sulfur Functionalities

34.1.4.3.1 Method 1: Substitution of Trifluoromethanesulfonates and Imidazolesulfonates

34.1.4.3.1.1 Variation 1: Using Difluorosilicate Derivatives

34.1.4.3.1.2 Variation 2: Using Tetrabutylammonium Fluoride

34.1.4.3.1.3 Variation 3: Using Base–Hydrogen Fluoride Complexes

34.1.4.3.1.4 Variation 4: Using Metal Fluoride

34.1.4.3.2 Method 2: Substitution of Cyclic Sulfates

34.1.4.3.2.1 Variation 1: Using Ammonium Fluorides

34.1.4.3.2.2 Variation 2: Using Tetrabutylammonium Fluoride for the Substitution of Cyclic Sulfamates

34.1.4.3.3 Method 3: Substitution of Carboxylic Esters and Cyclic Carbonates

34.1.4.3.4 Method 4: Substitution of O, S-Dialkyl Dithiocarbonates

34.1.4.3.5 Method 5: Substitution of Primary Sulfonates

34.1.4.3.5.1 Variation 1: Using Potassium Fluoride

34.1.4.3.5.2 Variation 2: Using an Ionic Liquid and Cesium Fluoride

34.1.4.3.5.3 Variation 3: Using Ammonium Fluorides under High Pressure

34.1.4.3.5.4 Variation 4: Using Ammonium Fluorides or Hydrogen Difluorides

34.1.4.3.5.5 Variation 5: Using Difluorosilicate Derivatives

34.1.4.3.6 Method 6: Substitution of Secondary Sulfonates

34.1.4.3.6.1 Variation 1: Using Potassium Fluoride

34.1.4.3.6.2 Variation 2: Using Ammonium Fluorides

34.1.4.3.6.3 Variation 3: Using Reagents Containing Hydrogen Fluoride

34.1.4.3.6.4 Variation 4: Using Difluorosilicate

34.1.4.3.6.5 Variation 5: Using Cesium Fluoride and Polymer-Supported Pentaethylene Glycol

34.1.4.3.7 Method 7: Substitution of Sulfides

34.1.4.3.7.1 Variation 1: Substitution of Alkyl Sulfides

34.1.4.3.7.2 Variation 2: Substitution of Thioglycosides

34.1.4.3.8 Method 8: Substitution of Ethers Using a Hydrofluoric Acid Complex

34.1.4.3.9 Method 9: Substitution of a Carbamimidate Using Hydrofluoric Acid Complex

34.1.6.4 Synthesis of Fluoroalkanes with Retention of the Functional Group

T. Yamazaki

34.1.6.4 Synthesis of Fluoroalkanes with Retention of the Functional Group

34.1.6.4.1 Method 1: Substitution of α-Halogen Atoms

34.1.6.4.1.1 Variation 1: Dechlorinative Carbon–Carbon Bond Formation at an α-sp3 Carbon Center

34.1.6.4.1.2 Variation 2: Debrominative Carbon–Carbon Bond Formation at an α-sp3 Carbon Center

34.1.6.4.1.3 Variation 3: Deiodinative Carbon–Carbon Bond Formation at an α-sp3 Carbon Center

34.1.6.4.1.4 Variation 4: Debrominative Carbon–Carbon Bond Formation at a γ-sp3 Carbon Center

34.1.6.4.2 Method 2: Substitution of Carboxy or Alkoxycarbonyl Groups

34.1.6.4.3 Method 3: Substitution of Other Groups

34.1.6.4.4 Method 4: Deprotonation

34.1.6.4.4.1 Variation 1: Deprotonative Construction of a Carbon–Carbon Single Bond

34.1.6.4.4.2 Variation 2: Deprotonative Construction of a Carbon-Carbon Single Bond under an SN2 or SN2′ Mechanism

34.1.6.4.4.3 Variation 3: Deprotonative Construction of a Carbon–Carbon Single Bond by Conjugate Addition

34.1.6.4.4.4 Variation 4: Deprotonative Construction of a Carbon–Carbon Single Bond by Addition to a C═X Bond

34.1.6.4.5 Method 5: Hydrogenation (Reduction)

34.1.6.4.5.1 Variation 1: Hydrogenation of a Carbon–Carbon Double Bond

34.1.6.4.5.2 Variation 2: Reduction of a Carbon–Nitrogen Double Bond

34.1.6.4.6 Method 6: Ring Formation

34.1.6.4.6.1 Variation 1: By Cycloaddition

34.1.6.4.6.2 Variation 2: By Iodolactonization

34.2 Product Class 2: Fluorocyclopropanes

34.2.2 Fluorocyclopropanes

P. Jubault, T. Poisson, and X. Pannecoucke

34.2.2 Fluorocyclopropanes

34.2.2.1 Method 1: Carbene and Carbenoid Addition to Fluoroalkenes

34.2.2.1.1 Variation 1: Simmons–Smith Reaction of Fluorinated Allylic Alcohols Using Diethylzinc/Diiodomethane

34.2.2.1.2 Variation 2: Simmons–Smith Reaction of Fluorinated Silyl Enol Ethers Using Diethylzinc/Diiodomethane

34.2.2.1.3 Variation 3: Addition of Diazoacetic Esters to Fluoroalkenes

34.2.2.1.4 Variation 4: Enantioselective Addition of Methyl 2-Diazo-2-phenylacetate to Fluoroalkenes

34.2.2.1.5 Variation 5: Racemic and Catalytic Enantioselective Addition of Diacceptor Diazo Derivatives to Fluoroalkenes

34.2.2.1.6 Variation 6: Intramolecular Cyclopropanation of (Z)-3-Bromo-3-fluoroallyl 2-Cyano-2-diazoacetate

34.2.2.2 Method 2: 1-Fluoro-1-halocyclopropanes via Addition of Fluorohalocarbenes to Alkenes

34.2.2.2.1 Variation 1: Phase-Transfer-Catalyzed Formation of Chlorofluorocyclopropanes

34.2.2.2.2 Variation 2: Bromofluorocarbene Addition to Alkenes Using Phase-Transfer Catalysis

34.2.2.3 Method 3: Direct Fluorocarbene Addition to Alkenes

34.2.2.3.1 Variation 1: Fluorocyclopropanes from Chlorofluoromethyl Phenyl Sulfide and Alkenes

34.2.2.3.2 Variation 2: Fluorocyclopropanes from Difluoroiodomethane and Alkenes

34.2.2.4 Method 4: Fluorocyclopropanes via Michael-Initiated Ring-Closure Reaction

34.2.2.4.1 Variation 1: Fluorocyclopropanes from α-Fluorinated Sulfoximides and α,β-Unsaturated Weinreb Amides

34.2.2.4.2 Variation 2: Fluorocyclopropanes from a (1-Fluorovinyl) diphenylsulfonium Salt and Active Methylene Compounds

34.2.2.4.3 Variation 3: Fluorocyclopropanes from Michael Acceptors and Ethyl 2,2-Dibromo-2-fluoroacetate

34.2.2.4.4 Variation 4: Fluorocyclopropanes from Michael Acceptors and Quaternary Ammonium Salts of Bromo Fluoro Amide Derivatives

34.2.2.5 Method 5: Fluorohydroxylation of Alkylidenecyclopropanes

34.2.2.6 Method 6: Reaction of Chlorocyclopropanes with Fluoride Anion

34.3 Product Class 3: (Fluoromethyl) cyclopropanes

34.3.2 (Fluoromethyl) cyclopropanes

P. Jubault, T. Poisson, and X. Pannecoucke

34.3.2 (Fluoromethyl) cyclopropanes

34.3.2.1 Method 1: Fluorodehydroxylation of Cyclopropylmethanols with N, N-Diethylaminosulfur Trifluoride or Bis (2-methoxyethyl) aminosulfur Trifluoride (Deoxo-Fluor)

34.3.2.2 Method 2: Formation of Cyclopropylmethyl Sulfonates and Displacement by Fluoride

34.3.2.3 Method 3: Rearrangement of Fluoro Epoxides

34.4 Product Class 4: Fluorocyclobutanes

34.4.2 Fluorocyclobutanes

T. Poisson, P. Jubault, and X. Pannecoucke

34.4.2 Fluorocyclobutanes

34.4.2.1 Method 1: Fluorodehydroxylation of Cyclobutanols

34.4.2.1.1 Variation 1: Fluorodehydroxylation Using Bis (2-methoxyethyl) aminosulfur Trifluoride (Deoxo-Fluor)

34.4.2.1.2 Variation 2: Fluorodehydroxylation Using Tetramethylfluoroformamidinium Hexafluorophosphate (TFFH)

34.4.2.2 Method 2: Reactions of Cyclobutanes Bearing a Leaving Group with Fluorinating Agents

34.4.2.2.1 Variation 1: Reaction of a Bridged Halocyclobutane with Silver(I) Fluoride

34.4.2.2.2 Variation 2: Reactions of Cyclobutane Trifluoromethanesulfonates with Tetrabutylammonium Fluoride

34.4.2.3 Method 3: Ring-Expansion Reactions of Cyclopropyl Carbinols with Nucleophilic Fluoride

34.4.2.3.1 Variation 1: N, N-Diethylaminosulfur Trifluoride Promoted Ring Expansion of a Methylenecyclopropyl Carbinol

34.4.2.3.2 Variation 2: Nonafluorobutanesulfonyl Fluoride Promoted Ring Expansion of Methylenecyclopropyl Carbinols

34.4.2.4 Method 4: Addition of Halogen Fluorides to Methylenecyclobutane and Cyclobutenes

34.4.2.4.1 Variation 1: Addition of Bromine Monofluoride to Methylenecyclobutane

34.4.2.4.2 Variation 2: Rearrangement of 2-(Benzyloxycarbonyl)-2-azabicyclo[2.2.0]hex-5-ene in the Presence of Bromine Monofluoride

34.4.2.4.3 Variation 3: Addition of Iodine Monofluoride to N-Protected 2-Azabicyclo[2.2.0]hexenes

34.4.2.5 Method 5: Synthesis of Fluorocyclobutanes by [2 + 2] Photocycloaddition Reactions

34.4.2.5.1 Variation 1: Intramolecular [2 + 2] Photocycloaddition Reactions

34.7 Product Class 7: Allylic Fluorides

34.7.4 Allylic Fluorides

C. R. Pitts and T. Lectka

34.7.4 Allylic Fluorides

34.7.4.1 Method 1: Allylic Substitution of Oxygen-Based Leaving Groups

34.7.4.1.1 Variation 1: From Allylic Alcohols

34.7.4.1.2 Variation 2: From Allylic Carbonates

34.7.4.1.3 Variation 3: From Allylic Esters

34.7.4.1.4 Variation 4: From Allylic Imidates

34.7.4.2 Method 2: Allylic Substitution of Sulfur-Based Leaving Groups

34.7.4.3 Method 3: Allylic Substitution of Silicon-Based Leaving Groups

34.7.4.4 Method 4: Allylic Substitution of Halogen Leaving Groups

34.7.4.5 Method 5: Ring Opening/Fluorination

34.7.4.5.1 Variation 1: From Vinyl Epoxides

34.7.4.5.2 Variation 2: From Oxabicyclic Alkenes

34.7.4.6 Method 6: Fluorination of Allenes

34.7.4.6.1 Variation 1: Carbofluorination

34.7.4.6.2 Variation 2: Iodofluorination

34.7.4.7 Method 7: Fluorination of Alkenes

34.7.4.7.1 Variation 1: Electrophilic Fluorination with Directing Groups

34.7.4.7.2 Variation 2: One-Pot Fluoroselenation/Elimination

34.7.4.8 Method 8: Fluorination of Vinylic Diazoacetates

34.7.4.9 Method 9: One-Pot α-Fluorination/Wittig-Type Reaction

34.7.4.10 Method 10: Fluorination of Allylic C─H Bonds

34.9 Product Class 9: β-Fluoro Alcohols

34.9.3 β-Fluoro Alcohols

K. Shibatomi

34.9.3 β-Fluoro Alcohols

34.9.3.1 Method 1: Fluorination of Allylic Alcohols

34.9.3.2 Method 2: Aldol Reaction of α-Fluoro Carbonyl Compounds

34.9.3.2.1 Variation 1: Enzyme-Catalyzed Aldol Reaction

34.9.3.2.2 Variation 2: Decarboxylative Aldol Reaction

34.9.3.2.3 Variation 3: Detrifluoroacetylative Aldol Reaction

34.9.3.3 Method 3: Synthesis via α-Fluorination of Carbonyl Compounds

34.9.3.1.1 Variation 1: Via Fluorination Using Enamine Catalysis

34.9.3.1.2 Variation 2: Via Fluorination of Active Methine Compounds

34.10 Product Class 10: β-Fluoroamines

34.10.5 β-Fluoroamines

L. Hunter

34.10.5 β-Fluoroamines

34.10.5.1 Method 1: Reduction of β-Fluoro Azides

34.10.5.2 Method 2: N-Substitution of a Leaving Group β to Fluorine

34.10.5.3 Method 3: Ring Opening of Aziridines with Hydrogen Fluoride Equivalents

34.10.5.3.1 Variation 1: Ring Opening of Aziridines with the Fluoride Ion

34.10.5.4 Method 4: Ring Opening of Cyclic Sulfamates with the Fluoride Ion

34.10.5.5 Method 5: C─H Activation and Fluorination of Alkylamines

34.10.5.5.1 Variation 1: Photocatalytic C─H Activation and Fluorination

34.10.5.6 Method 6: Electrophilic Fluorination of Enamines and Related Substrates

34.10.5.7 Method 7: Fluoroalkylation of Imines

34.10.5.8 Method 8: Electrophilic Fluorination of β-Amino Carbonyl Compounds

34.10.5.9 Method 9: Reductive Amination of α-Fluoro Carbonyl Compounds

34.10.5.9.1 Variation 1: Nucleophilic Addition to α-Fluorinated Imine Derivatives

34.10.5.10 Method 10: Fluorination of Allylic Amines

34.10.5.10.1 Variation 1: Electrophilic Fluorination of Allylic Amines

34.10.5.11 Method 11: Addition of an N-Nucleophile to a Fluoroalkene

34.10.5.12 Method 12: Aminofluorination of Alkenes

34.10.5.12.1 Variation 1: Aminofluorination of Unactivated Alkenes

34.10.5.13 Method 13: Decarboxylative Fluorination

34.10.5.14 Method 14: Reduction of an Unsaturated β-Fluoroamine Precursor

34.10.5.15 Method 15: 1,3-Dipolar Cycloadditions

34.10.5.16 Method 16: Fluorocyclopropanation of an Unsaturated Amine

Volume 40: Amines, Ammonium Salts, Amine N-Oxides, Haloamines, Hydroxylamines and Sulfur Analogues, and Hydrazines

40.1 Product Class 1: Amino Compounds

40.1.6.2 Azetidines

F. Couty

40.1.6.2 Azetidines

40.1.6.2.1 Ring-Closure Reactions

40.1.6.2.1.1 Method 1: Ring Closure of Amines and 1,3-Functionalized Hydrocarbons

40.1.6.2.1.1.1 Variation 1: From Amines and 1,3-Dihalo Compounds

40.1.6.2.1.1.2 Variation 2: From Amines and 1,3-Diol Derivatives

40.1.6.2.1.2 Method 2: Organocatalyzed [2 + 2] Cycloaddition of Imines and Alkenes

40.1.6.2.1.3 Method 3: Ring Closure of Acyclic Amines

40.1.6.2.1.3.1 Variation 1: Ring Closure of γ-Haloamines

40.1.6.2.1.3.2 Variation 2: Ring Closure of γ-Hydroxy Amines and Derivatives

40.1.6.2.1.3.3 Variation 3: Ring Closure of γ-Alkenylamines

40.1.6.2.1.3.4 Variation 4: Ring Closure of γ,δ-Epoxyamines

40.1.6.2.1.3.5 Variation 5: Ring Closure of β,γ-Epoxyamines

40.1.6.2.1.3.6 Variation 6: Ring Closure of N-(Aziridin-2-ylmethyl) amines

40.1.6.2.1.3.7 Variation 7: Ring Closure of γ-Amino Sulfonium Ions

40.1.6.2.1.3.8 Variation 8: Ring Closure of γ-Amino Selenones

40.1.6.2.1.3.9 Variation 9: Ring Closure of β-Alkenylamines

40.1.6.2.1.4 Method 4: Ring Closure of Acyclic Imines

40.1.6.2.1.5 Method 5: Ring Closure of Stabilized Carbanions (C─C Bond Formation)

40.1.6.2.1.5.1 Variation 1: Intramolecular Alkylation of β-Amino Halides

40.1.6.2.1.5.2 Variation 2: Intramolecular Alkylation of 2-(Aminomethyl) oxiranes

40.1.6.2.2 Reduction of Four-Membered Ring Compounds

40.1.6.2.2.1 Method 1: Reduction of Azetidin-2-ones (β-Lactams)

40.1.6.2.2.2 Method 2: Reduction of Azetes

40.1.6.2.3 Ring Transformation Reactions

40.1.6.2.3.1 Method 1: Ring Expansion of Three-Membered Rings

40.1.6.2.3.2 Method 2: Ring Contraction of Five-Membered Rings

40.1.6.2.3.3 Method 3: Substitution at Ring Carbons

40.1.6.2.3.4 Method 4: Substitution at the Ring Nitrogen

40.1.6.2.3.5 Method 5: Resolution of Racemic Azetidines

40.1.6.2.4 Miscellaneous Reactions

Author Index

Abbreviations

17.9.24 Phthalocyanines and Related Compounds (Update 2017)

M. S. Rodríguez-Morgade and T. Torres

General Introduction

Phthalocyanines,[1,2] represented in ▶ Scheme 1 by the metal complex 1, are one of the bestknown synthetic porphyrin analogues, consisting of four isoindole units linked together through four nitrogen atoms. Phthalocyanines can therefore also be referred to as tetrabenzotetraazaporphyrins or tetrabenzoporphyrazines. These macrocycles possess an 18-π-electron aromatic cloud delocalized over an arrangement of alternated carbon and nitrogen atoms. A great number of properties arise from this electronic delocalization, which makes phthalocyanines valuable in various fields of science and technology.

Scheme 1 Structure of a Phthalocyanine–Metal Complex

The replacement of the meso-carbons in porphyrin molecules by aza linkages in phthalocyanines is reflected in the absorption properties of these macrocycles by a blue shift of the B-band and a red shift of the Q-band, with concomitant decrease and increase, respectively, of the apparent absorption coefficients with respect to the corresponding absorptions in porphyrins. Moreover, the four benzo groups of phthalocyanines also produce a red-shifted Q-band in the 670 nm region, in addition to a hypsochromically shifted B-band, appearing at around 300 nm for phthalocyanine metal complexes with D4h symmetry. Here, the forbidden and very weak Q-band of the porphyrins is transformed in an intense absorption in the case of phthalocyanine–metal complexes.[3]

Phthalocyanines have been reported hosting a variety of central metals (more than 70) in their central cavity, and bearing different types of peripheral and axial substituents. All these changes allow the modulation of their electrophysical parameters over a broad range, giving rise to compounds with tailor-made electronic properties and optical features.

Apart from their traditional use as colorants and pigments, the optical properties of phthalocyanines and their analogues have found application in new areas of technological interest such as organic solar cells,[4] organic light-emitting diodes (LEDs),[5,6] optical recording media,[7] nonlinear optics,[8] optical limiting,[8] two-photon absorption,[9,10] and photodynamic therapy,[11,12] among others.

Since the 1990s, the search for new phthalocyanines for applications in the above technological areas has been stimulating the chemistry of these compounds. However, the demand for the preparation of new samples of these materials for testing in a short period of time is not always associated with great development of new and efficient synthetic methods. In fact, the rapid synthesis of some milligrams of a new phthalocyanine is often prioritized over developing a more convenient synthetic protocol for a given compound.

The synthesis and chemistry of phthalocyanines have been reviewed as a specific topic in a chapter of the four-volume series Phthalocyanines: Properties and Applications.[1] In addition, volume 15 of the series The Porphyrin Handbook also covered the synthesis of these macrocycles up to 2003. In addition, there is an earlier specific entry in the Houben–Weyl series, namely Vol. E 9d, pp 717–842, and the previous, exhaustive Science of Synthesis chapter on the synthesis of phthalocyanines, Section 17.9, which covers progress up to 2003.

The current chapter represents a supplementary update of the previous Science of Synthesis review by N. B. McKeown in 2003 (Section 17.9). The account adds some recently published methods, examples, and variations on the synthesis of unsubstituted phthalocyanines and metal phthalocyanines, as well as identically and nonidentically substituted phthalocyanine derivatives. Besides peripheral substitution, axial functionalization is also discussed; however, due to the vast amount of work carried out on axial ligand insertion and exchange reactions, attention is focused only on several methods that represent appreciable progress for a particular type of metal coordination and axial functionalization, provide phthalocyanines with specific features such as chirality, or allow the functionalization of phthalocyanines with entities that are difficult to introduce at the peripheral sites. A comprehensive review on the coordination chemistry of phthalocyanines is beyond the scope of this chapter. This account also includes sections on new types of phthalocyanine derivatives and analogues that were not covered in the original chapter, as well as the progress made in the synthesis of some of these families in the decade since 2003.

17.9.24.1 Metal-Free Phthalocyanines

The preparation of metal-free phthalocyanine was reviewed in Section 17.9.1. Phthalonitrile or isoindoline-1,3-diimine have traditionally been the typical precursors for this compound. Since 2003, efforts have been devoted to the investigation of mild conditions, such as lower temperatures and neutral media, by employing special additives, nucleophiles, and catalysts or by using microwave irradiation. Perhaps the main advance in the synthesis of metal-free phthalocyanines has been the incorporation of less-elaborated, readily available phthalic derivatives such as phthalic acid, phthalic anhydride, or phthalimide in the list of possible precursors of free-base phthalocyanines. Although anhydride and imide derivatives were already of general use in the synthesis of metal phthalocyanines, a substitute of the metal template salt is necessary in order to perform cyclotetramerization reactions that can afford the free-base derivatives in reasonable yields. In this case, additional nitrogenated reagents, which are able to “replace” the nitrogen atoms provided by nitriles and their derivatives, as well as hydrogen donors, are necessary.

17.9.24.1.1 Method 1: Synthesis from Phthalonitrile

The synthesis of phthalocyanine (2) from phthalonitrile (▶ Scheme 2) was reviewed in Section 17.9.1.1. Typically, the reaction is performed at high temperatures for prolonged periods of time and often requires the presence of a nucleophile, such as an alkoxide. There are very few reports on the synthesis of metal-free phthalocyanine under mild conditions. The cyclotetramerization of phthalonitrile to afford phthalocyanine involves the donation of two protons and a two-electron reduction. Therefore, efficient promoters should include H+ donors that exhibit high nucleophilic/reducing properties.

Scheme 2 Synthesis of Phthalocyanine from Phthalonitrile[13–20]

Oximes such as acetone oxime or butan-2-one oxime can be used as the nucleophiles to prepare phthalocyanine from phthalonitrile. The reaction has been suggested to occur by the addition of two oxime molecules to one nitrile group.[13] The high reducing ability of N, N-dialkylhydroxylamines has also been used to promote this type of cyclotetramerization reaction. In particular, the use of N, N-diethylhydroxylamine provides a mild protocol for the preparation of phthalocyanine.[14]

In 2004, the use of bis (trimethylsilyl) amine (hexamethyldisilazane) as a reagent for the preparation of different types of phthalocyanine derivatives was reported. For the preparation of metal-free phthalocyanine, the reaction is performed by heating phthalonitrile with bis (trimethylsilyl) amine and dimethylformamide in a sealed tube for 10–24 hours.[15] Since a template effect is not present under these conditions, an additive such as ammonium sulfate is necessary for acceleration of the cyclization. As depicted in ▶ Scheme 3, bis (trimethylsilyl) amine is postulated to activate the nitrile group of phthalonitrile for intramolecular cyclization affording an isoindoline-1,3-diimine derivative, which in turn undergoes intermolecular condensation. Other additives that can be used in place of ammonium sulfate are 4-toluenesulfonic acid, trifluoromethanesulfonic acid, hydroquinone, chlorotrimethylsilane, imidazole, pyridine, and tributyltin hydride.[15]

Scheme 3 Proposed Role of Bis (trimethylsilyl) amine in the Cyclotetramerization Reaction[15]

Additional activation by microwaves has been investigated. Thus, the reaction time using bis (trimethylsilyl) amine is drastically reduced from 24 hours to 6 minutes when microwave irradiation is used.[16] The use of sodium sulfide hydrate (Na2S•xH2O) and propane-1,2-diol under microwave irradiation affords similar yields of phthalocyanine free base.[16] In the latter case, classical conditions (heating at 160–170 °C) does not afford any phthalocyanine after 7 hours. Other conditions using microwaves include the use of urea and basic alumina with and without ammonium molybdate as a catalyst.[17]

Ionic liquids such as 1,1,3,3-tetramethylguanidinium trifluoroacetate (TMGT) or butyl (2-hydroxyethyl) dimethylammonium bromide can be used as the reaction solvents, both under classical and microwave macrocyclization conditions.[18,19] In addition, phthalocyanine free base has been obtained as a pure monoclinic β-phase by reaction between molten ferrocene and phthalonitrile at 210 °C.[20] In this reaction, ferrocene plays the role of both a template agent and a hydrogen donor, forming a polyferrocenylene film on the walls of the reactor; needle-shaped crystals of phthalocyanine grow on this very film.

Phthalocyanine (2); Typical Procedure:[15]

A glass tube was charged with phthalonitrile (300 mg, 2.34 mmol), (NH4)2SO4, (31 mg, 0.234 mmol), (TMS)2NH (0.99 mL, 4.69 mmol), and DMF (0.18 mL, 2.33 mmol) under argon. The tube was sealed and heated at 150 °C for 24 h. The mixture was cooled and filtered. The solid was washed with MeOH and then dissolved in concd H2SO4 (10 mL). The resulting soln was poured into H2O (200 mL) to give a blue precipitate, which was collected by filtration and washed with H2O. The solid was further purified in a Soxhlet extractor with MeOH; yield: 217 mg (72%).

17.9.24.1.2 Method 2: Synthesis from Bicyclo[2.2.2]octadiene-Fused Tetraazaporphyrins (Porphyrazines)

Phthalocyanines fused with bicyclo[2.2.2]octadienes have been used as precursors for preparation of free-base, unsubstituted phthalocyanine (2). The method provides an obvious advantage in terms of allowing the preparation of free-base phthalocyanine with a high degree of purity: the tetrameric intermediates of this process, i.e. the compounds obtained after the cyclotetramerization reaction, are soluble in organic solvents and so are easily purified by standard chromatographic techniques. The Diels–Alder reaction of cyclohexa-1,3-diene 3 with but-2-ynedinitrile gives a mixture of the syn-and anti-bicyclic dinitriles 4 (▶ Scheme 4). Cyclotetramerization of the dinitriles 4 affords the corresponding tetraazaporphyrin 5 as a mixture of diastereomers, which, after purification, can be subjected to retro-Diels–Alder reaction at 250 °C, resulting in formation of pure free-base phthalocyanine (2). The tricky step of this procedure is the generation of pure 5, because during the macrocyclization reaction under heating, some of the bicyclic subunits can undergo retro-Diels–Alder processes giving rise to a difficult-to-purify mixture of tetraazaporphyrins. In order to obtain pure tetraazaporphyrin 5 for a clean reaction, the more stable (up to 190 °C) syn-4 isomer is separated from the anti-isomer and treated with lithium butoxide to give 5, free of any retro-Diels–Alder macrocycles; intermediate 5 is then further purified by column chromatography.[21]

Scheme 4 Synthesis of Phthalocyanine by Retro-Diels–Alder Reaction of a Bicyclo[2.2.2]octadiene-Fused Tetraazaporphyrin[21]

5,10,15,20-Tetraazaporphyrin 5; Typical Procedure:[21]

To a degassed soln of but-2-ynedinitrile (1.1 g, 14 mmol) in CHCl3 (3 mL) was added a soln of cyclohexa-1,3-diene 3 (2.1 g, 14 mmol) in CHCl3 (15 mL) at 0 °C. The resulting mixture was stirred at rt overnight. The mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (alumina, CHCl3) to give a mixture of syn- and anti-4 [yield: 1.8 g (57%)], which were separated by column chromatography (silica gel, hexane/EtOAc 1:3). To a mixture of Li wire (26 mg, 3.8 mmol) and a small amount of I2 in a 5-mL reaction vessel, dry BuOH (3.8 mL) was added at rt under argon and the mixture was heated at reflux. Then, dinitrile syn-4 (0.19 g, 0.82 mmol) was added at rt and the resulting mixture was heated at 110 °C for 24 h. After addition of MeOH/H2O (1:1; 20 mL), the mixture was extracted with CHCl3. The organic layer was washed with H2O and brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography (alumina, CHCl3). Subsequent column chromatography (silica gel, CHCl3) and gel permeation chromatography gave tetraazaporphyrin 5; yield: 4 mg (2%).

17.9.24.1.3 Method 3: Synthesis from Phthalimide, Phthalic Anhydride, or Phthalic Acid

The preparation of phthalocyanines from phthalimides, phthalic anhydrides, or phthalic acids is very convenient, in particular, for the synthesis of peripherally functionalized phthalocyanines, owing to the availability of these types of precursors; however, the use of these precursors is usually limited to the synthesis of metallophthalocyanines. Bis(trimethylsilyl)amine is a known dehydrating agent and source of nitrogen, and these features enable the use of this reagent in the direct formation of metal-free phthalocyanines under neutral and mild conditions. Free-base phthalocyanine (2) is prepared in 58% yield from unsubstituted phthalimide by heating in dimethylformamide in the presence of bis (trimethylsilyl) amine (4 equiv) and 4-toluenesulfonic acid (▶ Scheme 5).[22] The reaction from phthalic anhydride also gives phthalocyanine (2), although the best result is obtained by using 5 equivalents of bis (trimethylsilyl) amine, apparently because in this case one more nitrogen is required to form the phthalocyanine skeleton. Other disilazanes have been tested in the cyclotetramerization reaction of phthalimide;[23] bis[dimethyl (phenyl) silyl]amine (1,1,3,3-tetramethyl-1,3-diphenyldisilazane) affords the best yields and thus has been used in the preparation of phthalocyanine (2) in the presence of ammonium sulfate as the disilazane activator.

Microwave-assisted cyclotetramerization of phthalimide, phthalic anhydride, and even phthalic acid to afford free-base phthalocyanine (2) in 48–55% yield has been reported.[17] The reactions are performed in the presence of ammonium molybdate and urea. Under conventional heating conditions, these reactions are low yielding or do not take place at all.

Scheme 5 Synthesis of Phthalocyanine from Phthalimide, Phthalic Acid, or Phthalic Anhydride[17,22,23]

Substrate

Conditions

Yield(%)

Ref

phthalimide

(TMS)

2

NH (4 equiv), TsOH•H

2

O (0.1 equiv), DMF (1 equiv), 150 °C, 10 h

58

[

22

]

phthalic anhydride

(TMS)

2

NH (5 equiv), TsOH•H

2

O (0.1 equiv), DMF (1 equiv), 150 °C, 10 h

42

[

22

]

phthalimide

(PhMe

2

Si)

2

NH (4 equiv), (NH

4

)

2

SO

4

(0.1 equiv), DMF (1 equiv), 150 °C, 10 h

67

[

23

]

phthalic acid, phthalimide, or phthalic anhydride

urea (4.2 equiv), (NH

4

)

2

MoO

4

, basic alumina, microwave

48–55

[

17

]

Phthalocyanine (2); Typical Procedure:[23]

A mixture of phthalimide (100 mg, 0.68 mmol), bis[dimethyl (phenyl) silyl]amine (790 μL, 777 mg, 2.7 mmol), DMF (50 μL, 0.68 mmol), and (NH4)2SO4 (9 mg, 0.07 mmol) was heated at 150 °C for 10 h. The mixture was cooled and filtered. The collected solid was washed with MeOH and then dissolved in concd H2SO4 (5 mL). The soln was poured into H2O (100 mL). The resulting blue solid was collected by filtration and washed successively with dil H2SO4, H2O, and MeOH. The solid was further purified by washing with MeOH using a Soxhlet extractor; yield: 59 mg (67%).

17.9.24.1.4 Method 4: Demetalation of a Zinc Complex

Zinc(II) phthalocyanine undergoes demetalation by heating in pyridine hydrochloride at 120 °C (▶ Scheme 6). This method provides a high-yielding route to metal-free phthalocyanines. Other strongly coordinated metal ions such as copper(II), cobalt(II), nickel(II), and palladium(II) are not removed under these conditions.[24] The selectivity for zinc(II) in this reaction might be explained by the formation of a ternary pyridine–phthalocyanine–zinc complex with square pyramidal zinc coordination and a nonplanar, domeshaped macrocycle prior to demetalation.

Scheme 6 Synthesis of Phthalocyanine by Demetalation of the Zinc Complex[24]

Phthalocyanine (2); Typical Procedure:[24]

Zinc(II) phthalocyanine (190 mg, 0.329 mmol), pyridine (10 mL), and pyridine hydrochloride (5 g, 43 mmol) were stirred under N2 at 120 °C for 17 h. H2O (10 mL) was added while the mixture was still hot and the resulting precipitate was collected by centrifugation at 6500 rpm. The dark green-blue precipitate was washed with H2O (20 mL), EtOH (20 mL), and acetone (20 mL), and dried; yield: 155 mg (91%).

17.9.24.2 Metal–Phthalocyanine Complexes

Phthalocyanines can coordinate almost all the metal and metalloid elements within their central cavity by adapting their shape through ruffled and saddled conformations. Usually, the phthalocyanine oxidation state in phthalocyanine–metal complexes is –2. The tetradentate phthalocyanine ligand is able to bind the metal ion via two charged (pyrrolic) and two neutral (pyridinic) nitrogens. Sometimes the metal acquires its neutrality just by coordinating to the four available phthalocyanine sites, although very often additional charged or neutral ligands, sometimes including another phthalocyanine macrocycle, are necessary for the metal to complete its coordination sphere. Examples of different structures of phthalocyanine–metal complexes are provided in Section 17.9.2.

Phthalonitrile is the most common starting material for the small-scale synthesis of phthalocyanine–metal complexes, owing to the mild reaction conditions necessary for its cyclotetramerization; however, this precursor is relatively expensive for use in industrial production. Consequently, other less-expensive and less-nitrogenated derivatives such as phthalic anhydride and phthalimide were introduced very early for large-scale synthesis. The cyclotetramerization reaction of phthalic derivatives in the presence of a metal or a metal salt affords a metallophthalocyanine in a single pot. The use of this strategy is very convenient as the metal ion acts as a template and facilitates the macrocyclization reaction. As with free-base phthalocyanines, recent investigations into the synthesis of metallophthalocyanines has been focused essentially on the search for milder conditions for the macrocyclization reaction, particularly for cases in which these conditions were especially harsh or tedious.

17.9.24.2.1 Method 1: Synthesis from Phthalonitrile

Syntheses of phthalocyanines from phthalonitriles often involve treatment with strong bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, or lithium and sodium alkoxides, or heating at high temperature with ammonia or urea (see Section 17.9.2.1). The reactions in the presence of a strong base and in alcoholic solvents have provided mechanistic information through the isolation of some intermediates. In particular, dialkoxy-substituted species such as 6 have been obtained at low temperatures from phthalonitrile and lithium alkoxides in the presence of nickel(II) and copper(II) metal salts (▶ Scheme 7). These macrocycles are converted into phthalocyanines by simple heating at 250 °C, thus providing evidence for the intermediacy of these species in template cyclotetramerization reactions from phthalonitriles.[25,26]

Scheme 7 Species Involved in the Cyclotetramerization of Phthalonitrile To Afford a Metallophthalocyanine[25,26]

A mild procedure to obtain metallophthalocyanines 7 consists of the treatment of phthalonitriles with metal salts and bis (trimethylsilyl) amine in dimethylformamide.[27] The reaction can also be performed under microwave irradiation with consequent reduction of reaction times (▶ Scheme 8).[16]

Scheme 8 Synthesis of Metallophthalocyanines from Phthalonitrile Using Metal Salts and Bis (trimethylsilyl) amine[16,27]

Metal Salt

M

(TMS)

2

NH (Equiv)

Temp (°C)

Time (min)

Yield (%)

Ref

ZnBr

2

Zn

2.0

100

600

78

[

27

]

ZnCl

2

Zn

2.0

100

600

73

[

27

]

Zn(OTf)

2

Zn

2.0

100

600

73

[

27

]

Zn(OAc)

2

Zn

2.0

100

600

73

[

27

]

Zn(acac)

2

Zn

2.0

100

600

55

[

27

]

MgBr

2

Mg

2.0

100

600

75

[

27

]

InCl

3

InCl

2.0

100

600

59

[

27

]

FeBr

2

Fe

2.0

125

1560

43

[

27

]

CoBr

2

Co

2.0

100

600

37

[

27

]

CuCl

Cu

1.0

a

microwave

7

78

[

16

]

CuCl

2

•

2H

2

O

Cu

1.0

a

microwave

7

88

[

16

]

CoCl

2

Co

1.0

a

microwave

7

86

[

16

]

NiCl

2

Ni

1.0

a

microwave

7

50

[

16

]

FeCl

2

•

4H

2

O

Fe

1.0

a

microwave

7

78

[

16

]

ZnCl

2

Zn

1.0

a

microwave

7

69

[

16

]

PdCl

2

Pd

1.0

a

microwave

7

87

[

16

]

PtCl

4

PtCl

2

1.0

a

microwave

15

76

[

16

]

RuCl

3

RuCl

1.0

a

microwave

15

65

[

16

]

a

TsOH•H

2

O (0.41 equiv) was added.

Scheme 9 Synthesis of Metallophthalocyanines Using Oximes or N, N-Diethylhydroxylamine[13,14]

M

Solvent

Temp (°C)

Yield (%)

Ref

Zn

–

80

45

[

14

]

Cd

BuOH

reflux

50

[

14

]

Co

BuOH

reflux

55

[

14

]

Ni

BuOH

reflux

40

[

14

]

Other syntheses of phthalocyanines under mild conditions involve microwave irradiation,[28] the use of ionic liquids as solvents and activating agents,[29] or activated metals such as pyrophoric nickel, Rieke copper and nickel,[30,31] or supported copper and nickel on an alumina matrix.[32] By using these metal forms, metallophthalocyanines are obtained at low temperatures (0–50 °C) in nonaqueous solvents. The high-yielding synthesis of a large number of metal complexes has been reported using a modified microwave oven for dry reactions.[33]

A mixture of phthalonitrile (107 mg, 0.84 mmol), (TMS)2NH (0.35 mL, 1.66 mmol), ZnBr2 (50 mg, 0.22 mmol), and DMF (0.21 mL) was heated at 100 °C under argon for 10 h. The mixture was concentrated under reduced pressure. The residue was washed successively with MeOH (50 mL) and H2O (50 mL). The obtained crude product was extracted with CHCl3 (50 mL) using a Soxhlet, and dried; yield: 91 mg (78%).

A glass tube was charged with phthalonitrile (0.512 g, 4 mmol), CuCl (0.1 g, 1 mmol), (TMS)2NH (0.828 mL, 4 mmol), TsOH•H2O (0.078 g, 0.41 mmol), and DMF (0.077 mL, 1 mmol) and the mixture was stirred at rt under N2 for 20 min. The tube was sealed and irradiated in a domestic microwave oven for 7 min. The crude product was washed successively with H2O and acetone and then dried. Afterwards, the solid was dissolved in concd H2SO4. Addition of H2O afforded a precipitate, which was collected by filtration, washed with H2O, and dried; yield: 0.449 g (78%).

Phthalocyaninatonickel(II) (10); General Procedure:[13]

17.9.24.2.2 Method 2: Synthesis from Phthalic Anhydride

Although phthalic anhydride was the first precursor of phthalocyanine, which was discovered in a batch of phthalimide prepared from phthalic anhydride and urea at high temperature (see Section 17.9.2.2),[34] other, milder preparative methods for phthalocyanines with high purity starting from this inexpensive and accessible starting material have long been desired.

The traditional method has been carried out for the synthesis of metallophthalocyanines (Cu, Fe, Co, Ni, Mn, RhCl, Ru, and Pd complexes) with moderate to very good yields using a mixture of water and tetrabutylammonium bromide as the ionic solvent, at 185 °C.[35] Moreover, yields of 80 and 52% have been obtained for copper(II) phthalocyanine (12) and cobalt(II) phthalocyanine, respectively, by performing the reaction of phthalic anhydride with urea under microwave irradiation (▶ Scheme 10).[28,36] The microwave synthesis of metallophthalocyanines (containing Cu, Mn, Al, Co, or Zn) can also be performed under solvent-free conditions affording yields ranging from 73 to 82%.[37] The use of bis (trimethylsilyl) amine as the nitrogen source and nucleophilic reagent has also been extended to the template synthesis of metallophthalocyanines 13 from phthalic anhydride (▶ Scheme 10).[38] The reaction has been suggested to proceed through the formation of a phthalimide (see ▶ Section 17.9.24.2.4). The addition of 1 equivalent of dimethylformamide and 5–6 equivalents of bis (trimethylsilyl) amine seems to be crucial in order to obtain the phthalocyanine in good yield. In addition, the inclusion of 4-toluenesulfonic acid monohydrate (0.1 equiv) or concentrated sulfuric acid is necessary when halogenated metal salts are used. The same reaction can also be performed under 10–15 minutes of microwave irradiation.[16]

Scheme 10 Synthesis of Metallophthalocyanines from Phthalic Anhydride[16,28,38]

Metal Salt

M

(TMS)

2

NH (Equiv)

Temp (°C)

Time (min)

Yield (%)

Ref

CuCl

2

Cu

5

150

600

61

[

38

]

CuCl

2

•

2H

2

O

Cu

1

microwave

8

62

[

16

]

ZnCl

2

Zn

1

microwave

8

33

[

16

]

PtCl

4

PtCl

2

1

microwave

12

17

[

16

]

CoCl

2

Co

1

microwave

8

48

[

16

]

NiCl

2

Ni

1

microwave

8

30

[

16

]

FeCl

2

•

4H

2

O

Fe

1

microwave

8

40

[

16

]

PdCl

2

Pd

1

microwave

8

72

[

16

]

Phthalocyaninatocopper(II) (12); Typical Procedure:[28]

Phthalic anhydride (1.49 g, 10 mmol), urea (1.2 g, 20 mmol), CuCl2•2H2O (0.425 g, 2.5 mmol), and (NH4)2MoO4 (0.47 g, 2.0 mmol, as reported) were ground together, placed in a tube, and irradiated in a microwave reactor at high power for 10 min. After completion of the reaction, the product was washed with hot H2O, acetone, and CH2Cl2. The product was dissolved in concd H2SO4, precipitated by adding distilled H2O, collected by filtration, washed with H2O to neutral pH, and dried; yield: 80%.

A glass tube was charged with phthalic anhydride (100 mg, 0.68 mmol), CuCl2 (23 mg, 0.17 mmol), TsOH•H2O (13 mg, 0.07 mmol), and (TMS)2NH (700 μL, 548 mg, 3.4 mmol), and the mixture was stirred at 100 °C for 1 h under an argon atmosphere. The mixture was cooled, and DMF (50 μL, 0.68 mmol) was added. Then, the tube was sealed and the mixture was heated at 150 °C. After being heated for 10 h, the mixture was cooled and filtered. The solid was washed with MeOH and then dissolved in concd H2SO4 (5 mL). The soln was poured into H2O (100 mL). The resulting blue precipitate was collected by filtration and washed successively with dil H2SO4, H2O, and MeOH. The solid was further purified by extraction with MeOH using a Soxhlet extractor to give a blue solid; yield: 60 mg (61%).

17.9.24.2.3 Method 3: Synthesis from Phthalic Acid

The preparation of nickel(II) phthalocyanine from phthalic acid has been reported in an ionic liquid, i.e. 1-butyl-3-methylimidazolium tetrafluoroborate, in the presence of urea and ammonium chloride (▶ Scheme 11).[39]

Scheme 11 Synthesis of Nickel(II) Phthalocyanine from Phthalic Acid[39]

Phthalocyaninatonickel(II) (14); Typical Procedure:[39]

1-Butyl-3-methylimidazolium tetrafluoroborate (20 mL, 0.1 mol), NiSO4•6H2O (1.31 g, 5.7 mmol, as reported), urea (9 g, 0.14 mol), phthalic acid (3.32 g, 0.019 mol), NH4Cl (2.13 g, 0.03 mol, as reported), and a trace amount of (NH4)2MoO4 catalyst (10 mg, 0.05 mmol) were added to a 100-mL, round-bottomed flask and the mixture was heated at 175 °C under vigorous stirring. After 5 h, the phthalic acid was totally consumed. The product was washed several times with MeCN, alcohol, and H2O to remove impurities, and subsequently dried under vacuum; yield: 0.98 g (36%).

17.9.24.2.4 Method 4: Synthesis from Phthalimide

Phthalimides already contain a nitrogen atom in their structure, so in principle their use as phthalocyanine precursors requires a lower amount of another nitrogen source. Moreover, phthalimides have been proposed as intermediates in the cyclotetramerization of phthalic anhydride to afford metallophthalocyanines in the presence of bis (trimethylsilyl) amine. Thus, it is not surprising that metallophthalocyanines 15 can be obtained directly from phthalimide (▶ Scheme 12). Use of 1 equivalent of dimethylformamide with respect to phthalimide is required for the high-yielding formation of the phthalocyanine framework. Besides this, addition of 4-toluenesulfonic acid monohydrate or concentrated sulfuric acid is necessary when halogenated metal salts are used. Notably, copper(II) and zinc(II) trifluoromethanesulfonates afford the corresponding metallophthalocyanines in high yield without 4-toluenesulfonic acid.[38] Other disilazanes, such as bis[dimethyl (phenyl) silyl]amine and bis (methyldiphenylsilyl) amine, afford copper(II) and zinc(II) phthalocyanine complexes in comparable yields.[23] The procedure has also been adapted to involve the use of microwaves.[16] In general, the yields are higher using phthalimide compared to phthalic anhydride.

Scheme 12 Synthesis of Metallophthalocyanines from Phthalimide Using Bis (trimethylsilyl) amine[16,38]

Metal Salt

M

(TMS)

2

NH (Equiv)

Additive (Equiv)

Temp (°C)

Time (min)

Yield (%)

Ref

CuBr

2

Cu

4

TsOH•H

2

O (0.1)

150

600

72

[

38

]

Cu(OTf)

2

Cu

4

–

150

600

71

[

38

]

ZnCl

2

Zn

4

TsOH•H

2

O (0.1)

150

600

47

[

38

]

Zn(OTf)

2

Zn

4

–

150

600

61

[

38

]

CoCl

2

Co

4

TsOH•H

2

O (0.1)

150

600

51

[

38

]

NiCl

2

Ni

4

TsOH•H

2

O (0.1)

150

240

53

[

38

]

MgBr

2

H

2

4

TsOH•H

2

O (0.1)

150

240

34

[

38

]

CuCl

2

Cu

4

TsOH•H

2

O (0.1)

150

600

63

[

38

]

CuCl

Cu

1

TsOH•H

2

O (0.1)

microwave

7

75

[

16

]

ZnCl

2

Zn

1

TsOH•H

2

O (0.1)

microwave

10

40

[

16

]

RuCl

3

RuCl

1

TsOH•H

2

O (0.1)

microwave

12

18

[

16

]

CoCl

2

Co

1

TsOH•H

2

O (0.1)

microwave

9

48

[

16

]

NiCl

2

Ni

1

TsOH•H

2

O (0.1)

microwave

9

45

[

16

]

FeCl

2

•

4H

2

O

Fe

1

TsOH•H

2

O (0.1)

microwave

9

44

[

16

]

PdCl

2

Pd

1

TsOH•H

2

O (0.1)

microwave

9

68

[

16

]

A glass tube was charged with phthalimide (100 mg, 0.68 mmol), CuCl2 (23 mg, 0.17 mmol), TsOH•H2O (13 mg, 0.07 mmol), and (TMS)2NH (560 μL, 438 mg, 2.7 mmol), and the mixture was stirred at 100 °C for 1 h under an argon atmosphere. The mixture was cooled, and DMF (50 μL, 0.68 mmol) was added. Then, the tube was sealed and the mixture was heated at 150 °C. A dark purple solid immediately appeared. After being heated for 10 h, the mixture was cooled and filtered. The solid was washed with MeOH and then dissolved in concd H2SO4 (5 mL). The soln was poured into H2O (100 mL). The resulting blue precipitates were collected by filtration and washed successively with dil H2SO4, H2O, and MeOH. The solid was further purified by extraction with MeOH using a Soxhlet extractor to give a blue solid; yield: 62 mg (63%). A reaction starting with 5.0 g of phthalimide was performed in a 100-mL SUS 316 pressure bottle (Taiatsu Techno Corp.) under identical conditions. Separation and purification afforded the product; yield: 2.7 g (56%).

17.9.24.3 1,8(11),15(18),22(25)-Tetrasubstituted Phthalocyanines and 1:25,11:15-Bridged Phthalocyanines

17.9.24.3.1 Method 1: Synthesis from 3-Substituted Phthalonitriles

The typical procedure to obtain this type of tetrasubstituted phthalocyanine is the cyclotetramerization of a 3-substituted phthalonitrile. In most cases this provides a mixture of four regioisomers, i.e. C4h, C2v, D2h, and Cs, which can sometimes be separated using chromatographic techniques (see Section 17.9.3.1).

17.9.24.3.1.1 Variation 1: Regioselective Preparation of 1,8,15,22-Tetrasubstituted Phthalocyanines from 3-Substituted Phthalonitriles

The regioselective preparation of the C4h phthalocyanine isomer from 3-substituted phthalonitriles using lithium octanolate at low and high temperatures was discussed in Section 17.9.3.1.1. Phthalonitriles bearing an aryl substituent at the 3-position afford the C4h isomer 16 exclusively and as the major product using lithium pentanolate/pentanol at reflux and lithium octanolate/octanol at 60 °C, respectively.[40] The C4h isomer of the bulky tetrakis[4-(1,1,3,3-tetramethylbutyl) phenoxy]-substituted phthalocyanine is isolated by standard flash chromatography.[41]