Phthalocyanines Synthesis: A State-of-The-Art Review of Sustainable Approaches Through Green Chemistry Metrics
Abstract
Driven by escalating environmental concerns, synthetic chemistry faces an urgent need for a green revolution. Green chemistry, with its focus on low environmental impacting chemicals and minimized waste production, emerges as a powerful tool in addressing this challenge. Metrics such as the E-factor guide the design of environmentally friendly strategies for chemical processes by quantifying the waste generated in obtaining target products, thus enabling interventions to minimize it. Phthalocyanines (Pcs), versatile molecules with exceptional physical and chemical properties, hold immense potential for technological applications. This review aims to bridge the gap between green chemistry and phthalocyanine synthesis by collecting the main examples of environmentally sustainable syntheses documented in the literature. The calculation of the E-factor of a selection of them provides insights on how crucial it is to evaluate a synthetic process in its entirety. This approach allows for a better evaluation of the actual sustainability of the phthalocyanine synthetic process and indicates possible strategies to improve it.
1 Introduction
The complex and urgent issue of climate change demands action on multiple fronts.
气候变化这一复杂而紧迫的问题需要在多个方面采取行动。
Mitigating its effects in the coming years will require a fundamental reevaluation of how many technologies are developed and utilized.
在未来几年减轻其影响将需要对众多技术的开发和应用方式进行根本性的重新评估。
This encompasses the acquisition and preparation of materials necessary for their advancement, procedures which must prioritize environmental sustainability.
这包括获取和制备推进其发展所需的材料,这些程序必须优先考虑环境可持续性。
Over the past three decades, green chemistry1 has emerged as a powerful discipline in this regard.
过去三十年间,绿色化学 1 已发展成该领域的重要学科。
Its proposed paradigm shift embodies a holistic approach to environmental issues, focusing on the development of increasingly efficient methods to minimize waste throughout the production, processing, and utilization of materials and associated devices.
这一提出的范式转变体现了应对环境问题的整体性方法,其核心在于开发日益高效的技术,以最大限度减少材料及相关器件在生产、加工和使用全过程中的废弃物产生。
Multiple strategies can be employed to satisfy this premise, such as opting for safer and less polluting reagents, solvents and reaction conditions, as well as designing synthetic pathways that retain the majority of the atoms of the reactants in the products.
为满足这一前提,可采用多种策略,例如选择更安全、污染更小的试剂、溶剂和反应条件,以及设计能将反应物中大部分原子保留在产物中的合成路径。
Additionally, identifying low-impact techniques to process target materials in the technology for which it was designed is crucial.
此外,确定低影响技术以处理设计用途技术中的目标材料至关重要。
To assess the environmental impact of chemical processes, a set of metrics is utilized.
为评估化学过程对环境的影响,采用了一系列衡量指标。
Among these, the E-factor is widely recognized.
其中,E 因子被广泛认可。
It is defined as the ratio of the mass of waste generated per mass of product obtained and quantifies various components including byproducts, unreacted substrates, non-recyclable solvents, catalysts, and any irrecoverable chemicals, offering valuable insights into the overall environmental footprint of a process.
该指标定义为每获得单位质量产品所产生的废弃物质量之比,可量化包括副产物、未反应底物、不可回收溶剂、催化剂及任何不可再生化学品在内的多种组分,为评估工艺整体环境足迹提供重要依据。
Phthalocyanines (Pcs) are versatile planar, aromatic molecules that have been of great interest to the scientific community due to their outstanding chemical, electronic and optical properties.
酞菁(Pcs)是一类多功能的平面芳香分子,因其卓越的化学、电子和光学特性而备受科学界关注。
In fact, in the last decades the interest in phthalocyanines, in addition to fundamental research, has been extended to technology applications such as chemical sensing,2, 3 organic electronics (organic thin film transistors (OTFTs), Organic Field-Effect Transistors (OFETs))4-7 photodynamic therapy,8-10 CO2 conversion in valuable chemicals11-13 and hybrid photovoltaic technologies such as dye-sensitized solar cells (DSSCs),14-16 organic solar cells17-19 and perovskite solar cells (PSCs)20-24 Their structure consists in an isoindolic 18-π aromatic electron ring system having an oxidation state of −2.
事实上,近几十年来,酞菁类化合物的研究兴趣已从基础研究扩展到技术应用领域,如化学传感、 2, 3 有机电子学(有机薄膜晶体管(OTFTs)、有机场效应晶体管(OFETs)) 4-7 光动力疗法、 8-10 二氧化碳 2 转化为高附加值化学品 11-13 以及混合光伏技术,包括染料敏化太阳能电池(DSSCs)、 14-16 有机太阳能电池 17-19 和钙钛矿太阳能电池(PSCs)。 20-24 其结构由一个氧化态为-2 的异吲哚 18-π芳香电子环系构成。
Therefore, its central cavity is capable of hosting a variety of metal ions mostly in the +2 oxidation state.
因此,其中心空腔能够容纳多种主要以+2 氧化态存在的金属离子。
Derivatives bearing two monovalent cations, such as lithium, sodium, and potassium, can be synthesized and isolated; however, they are not very stable in acidic conditions and in the presence of humidity, which can lead to demetallation (Figure 1c).
带有单价阳离子(如锂、钠和钾)的衍生物能够被合成并分离;然而,它们在酸性条件和潮湿环境下不太稳定,可能导致脱金属化(图 1c)。
Ions in the +3 state, such as aluminum and indium, can be coordinated too, in the presence of an anionic ligand such as a halide (Figure 1d).
处于+3 价态的离子,如铝和铟,在卤化物等阴离子配体存在下也能形成配位(图 1d)。
Larger trivalent cations, such as those from lanthanides and actinides, cannot be fully accommodated within the phthalocyanine ring.
较大的三价阳离子,如镧系和锕系元素的阳离子,无法完全容纳在酞菁环内。
Instead, two phthalocyanine ligands may surround the same ion, forming a so-called “sandwich” type double-decker complex (Figure 1e).
相反,两个酞菁配体可以围绕同一个离子,形成所谓的"三明治"型双层复合物(图 1e)。

a) Structure of a metal phthalocyanine in which the α and β positions are marked. b) Typical phthalocyanine spectrum in tetrahydrofuran (THF). c) Phthlaocyanine complex with monovalent cations d) Phthalocyanine complex with trivalent cations. e) double-decker phthalocyanine. The torsion angle between neighboring Pc depends on the nature of the metal ion.
The carbon atoms in the α- and β- positions of the macrocycle (Figure 1) can be widely functionalized to finely tune the optoelectrochemical properties according to specific needs.
大环结构α位和β位的碳原子(图 1)可根据特定需求进行广泛功能化,从而精细调控其光电化学性质。
Given their wide aromatic delocalization, phthalocyanines in solution show typical absorption spectra composed by two main contributions: a Q band typically ranging in the 600–700 nm and a B (Soret) band between 300 and 400 nm.
由于具有广泛的芳香离域特性,酞菁在溶液中呈现出典型的吸收光谱,主要由两个特征峰组成:Q 带通常位于 600-700 纳米范围内,B 带(索雷特带)则介于 300-400 纳米之间。
The sharpness of the bands depends on the degree of aggregation of the macrocycles, frequently affected by the donating or non-donating nature of the chosen solvent.
谱带的锐度取决于大环化合物的聚集程度,这通常受所选溶剂的给电子或非给电子性质影响。
The phthalocyanine ring is typically synthesized via a cyclocondensation reaction involving several starting materials summarized in Scheme 1.
酞菁环通常通过环缩合反应合成,该反应涉及方案 1 中总结的几种起始原料。
Phthalimides, phthalic anhydrides, and phthalic acid can all serve as useful precursors for synthesizing both metal-free and metal-containing phthalocyanines, as summarized in Scheme 1.
邻苯二甲酰亚胺、邻苯二甲酸酐和邻苯二甲酸均可作为合成无金属及含金属酞菁化合物的有效前驱体,如方案 1 所示。
Most commercial processes utilize these compounds, particularly phthalic anhydride, due to its lower cost with respect to other precursors.
大多数商业工艺采用这些化合物,尤其是邻苯二甲酸酐,因其相较于其他前体具有更低的成本优势。
Along with the appropriate metal salt, if needed, urea is required as a nitrogen source, and ammonium molybdate ((NH4)2MoO4) as a catalyst.
在需要时,除适当的金属盐外,还需尿素作为氮源,钼酸铵((NH₄)₂MoO₄)作为催化剂。

General reaction conditions scheme for the synthesis of phthalocyanines starting from phthalic acid, phthalic anhydride, phthalimide, phthalimide, 1,3-diiminoisoindoline or phthalonitrile. No metal salt is required for the synthesis of metal-free derivatives (M=2H).
These reactions typically require heating and are conducted in the melt,25, 26 although solvents such as nitrobenzene have also been employed.27, 28 Even though the reaction mechanism is not fully understood, some key steps appear to be sufficiently clear: phthalic anhydride initially reacts with urea or its decomposition products, progressively replacing oxygen atoms with nitrogen to ultimately form the key intermediate 1,3-diiminoisoindoline.
这些反应通常需要加热并在熔融状态下进行,尽管也曾使用硝基苯等溶剂。虽然反应机理尚未完全阐明,但一些关键步骤似乎已足够明确:邻苯二甲酸酐最初与尿素或其分解产物反应,逐步用氮原子取代氧原子,最终形成关键中间体 1,3-二亚氨基异吲哚啉。
The presence of ammonium molybdate is essential to catalyze this part of the sequence.
钼酸铵的存在对于催化该反应序列至关重要。
Subsequently, this intermediate undergoes tetramerization with cyclization, possibly aided by the presence of a metal ion, to form the desired phthalocyanine.
随后,该中间体在金属离子可能的辅助作用下,通过环化反应发生四聚,形成目标酞菁化合物。
When employed as starting materials, 1,3-diiminoisoindolines undergo self-condensation at high temperatures.
当作为起始原料使用时,1,3-二亚氨基异吲哚啉在高温下会发生自缩合反应。
A typical procedure for obtaining the phthalocyanine macrocycle therefore consists of dissolving them in an appropriate solvent, for example N,N-dimethylaminoethanol (DMAE), N,N-dimethylformamide (DMF) or quinoline, and allowing them to react under reflux.29, 30 For syntheses conducted on a laboratory scale, however, phthalonitrile and its derivatives are by far the most versatile and used precursors.
因此,获得酞菁大环化合物的典型步骤包括将其溶解在适当的溶剂中,例如 N,N-二甲基氨基乙醇(DMAE)、N,N-二甲基甲酰胺(DMF)或喹啉,并在回流条件下使其反应。 29, 30 然而,对于实验室规模的合成而言,邻苯二甲腈及其衍生物是目前用途最广泛且最常用的前体。
The reaction is conducted at temperatures ranging from 130 to 250 °C in solvents such as alkyl alcohols, DMF, DMAE, quinoline, or α-chloronaphthalene, in an alkaline environment.
该反应在 130 至 250°C 温度范围内进行,溶剂选用烷基醇类、DMF、DMAE、喹啉或α-氯萘,并在碱性环境中完成。
An organic non nucleophilic base such as 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) or an in-situ generated lithium alcolate are frequently used to assist the formation of the macrocycle.
一种有机非亲核碱,如 1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)或原位生成的醇锂盐,常被用于辅助大环结构的形成。
The most plausible mechanism for the formation of the phthalocyanine ring starting from phthalonitrile is shown in Scheme 2 and involves the interaction between a CN and a nucleophile, followed by intramolecular nucleophilic attack on the carbon of the ortho cyano group and further cascade steps that ultimately lead to the formation of the final product.
由邻苯二甲腈形成酞菁环最可能的机理如方案 2 所示,涉及氰基与亲核试剂的相互作用,随后发生对邻位氰基碳的分子内亲核进攻,以及最终导致产物形成的后续级联步骤。
The presence of a templating metal significantly aids the tetramerization, instead of promoting side oligomerizations or polymerizations.
模板金属的存在显著促进了四聚反应,而非引发副反应如低聚或聚合。
Typically, the nucleophilic function is carried out by the deprotonated form of a protic polar solvent or by the counterion of the selected salt.
通常,亲核功能由质子极性溶剂的去质子化形式或所选盐的反离子实现。
In recent years, alongside conventional procedures, alternative methodologies have emerged with the goal of conducting reactions under milder and less environmentally impactful conditions.
近年来,除传统方法外,还涌现出一些替代性方法,旨在实现反应条件更温和、对环境更友好的目标。
These approaches often involve the utilization of alternative energy sources or innovative reaction protocols and reactants.
这些方法通常涉及利用替代能源或创新的反应方案和反应物。
Despite the attention given to this issue by many research groups, as evidenced by the specific literature on the topic, there are relatively few and outdated reviews on synthetic methodologies with low environmental impact published thus far.31, 32 Furthermore, to the best of our knowledge the discussion about the environmental impact itself is limited to the proposed synthetic approaches without discussing their environmental footprint more in detail.
尽管许多研究团队已关注这一问题(该主题的专门文献可资证明),但迄今为止发表的关于低环境影响合成方法的综述相对较少且内容陈旧。此外,据我们所知,关于环境影响本身的讨论仅限于所提出的合成方法,而未更详细地探讨其环境足迹。
Evidence of this can be seen in the limited inclusion of green metrics in these discussions.
这一点可以从这些讨论中绿色指标的有限纳入得到印证。
Only very recently, some evaluations on the Environmental Factor (E-factor) related to the synthesis of unsubstituted and tetra-tert-butyl substituted phthalocyanines have been made.33, 34 In contrast, examples of E-factor calculations in porphyrin synthesis have been available for some time.35-38 This important metric is defined as the ratio between the mass of waste generated and the mass of product obtained.
直到最近,才有学者对未取代和四叔丁基取代酞菁合成相关的环境因子(E 因子)进行了一些评估。 33, 34 相比之下,卟啉合成中的 E 因子计算实例早已有之。 35-38 这一重要指标被定义为废弃物生成质量与产物获得质量之比。
It does not differentiate between various types of waste, thus it should be complemented with other metrics to assess toxicity.
它不区分各类废弃物,因此需要结合其他指标来评估毒性。
However, even when used alone, it can offer valuable insights into the studied synthetic process.
然而,即使单独使用,它也能为所研究的合成过程提供有价值的见解。
Its simple calculation procedure, based on objective data, makes it a useful tool for a quick evaluation of the environmental impact of a synthetic process.
其基于客观数据的简单计算程序,使其成为快速评估合成工艺环境影响的实用工具。
This review describes the main advances in the field of research into synthetic protocols with reduced environmental impact to produce phthalocyanines over the last 25 year.
本综述阐述了近 25 年来在降低环境影响条件下合成酞菁类化合物的研究领域取得的主要进展。
Our goal is to provide an updated state-of-the-art understanding of the topic and offer an exhaustive overview of the progress made in this field.
我们的目标是提供对该主题最新前沿的理解,并全面概述该领域取得的进展。
Furthermore, as a first step towards the evaluation of synthetic processes for obtaining phthalocyanines through ex post evaluations, we will present the calculation of the E-factor of a selection of procedures taken from the articles under examination.
此外,作为通过事后评估来评价酞菁合成工艺的第一步,我们将从所审查的论文中选取部分流程,展示其 E 因子的计算过程。
These reference values will serve as useful benchmarks for an initial assessment of the “greenness” of a synthesis based on the generated waste materials.
这些参考值将作为初步评估合成过程"绿色程度"的有用基准,该评估基于所产生的废弃物。
Far from being exhaustive, this approach can indeed facilitate the development of more sustainable synthetic methodologies for phthalocyanine ring synthesis.
这种方法虽非详尽无遗,但确实有助于开发更可持续的酞菁环合成方法。

Proposed mechanism for the synthesis of phthalocyanines starting from phthalonitriles.
2 Discussion
We have categorized the various synthetic methodologies into three primary groups: the utilization of alternative energy sources for heating, the selection of reaction environments with a low environmental footprint, and synthetic strategies aimed at reducing reaction temperatures using specific reagents.
我们将各种合成方法归纳为三大类:利用替代能源进行加热、选择环境足迹较低的反应环境,以及通过特定试剂降低反应温度的合成策略。
In cases where an article encompasses more than one of these types–for instance, microwave reactions conducted in an environmentally compatible solvent–it will be categorized under the most relevant classification for discussion.
若一篇文章涉及多种类型(例如在环境友好型溶剂中进行的微波反应),则将其归入最适合讨论的相关分类中。
2.1 Alternative Energy Inputs
In this section, we will discuss examples of phthalocyanine synthesis conducted with alternative energy inputs such as microwave (MW) radiation, ultraviolet (UV) radiation, and ultrasound.
本节将探讨采用替代能源输入(如微波辐射、紫外辐射和超声波)进行酞菁合成的实例。
One advantage of these approaches is the localized generation of hot spots within the reaction environment, where very high temperatures are rapidly attained and dissipated.
这些方法的一个优势在于反应环境中能局部产生热点区域,可迅速达到并消散极高温度。
This enables a significant amount of energy to be delivered to the system while minimizing the risk of thermal degradation of reactants or products.
这能够在向系统输送大量能量的同时,最大限度降低反应物或产物发生热降解的风险。
However, it is crucial to ensure that the energy is uniformly distributed throughout the system, particularly when considering process scaling-up.
然而,确保能量在整个系统中均匀分布至关重要,尤其是在考虑工艺放大时。
In the case of UV irradiation, it is especially important to carefully design the synthesis process, as the interaction between photons and matter often results in the formation of highly reactive radical species that may induce unwanted side reactions.
在紫外线照射的情况下,特别需要精心设计合成工艺,因为光子与物质的相互作用常会形成高活性自由基物种,可能引发不必要的副反应。
2.1.1 Microwave Irradiation
Microwave irradiation has emerged as a powerful technique for promoting chemical reactions.
微波辐射已成为促进化学反应的一种强效技术。
Microwaves are electromagnetic radiation ranging from 0.3 to 300 GHz, absorbed by materials that exhibit dipolar polarization or ionic conduction.
微波是一种频率范围在 0.3 至 300 GHz 的电磁辐射,可被具有偶极极化或离子传导特性的材料吸收。
The impact of microwave irradiation on chemical reactions arises from a combination of thermal and non-thermal effects.
微波辐射对化学反应的影响源于热效应与非热效应的共同作用。
The former effects primarily stem from dipolar and interfacial polarization, although conduction losses can also become significant at elevated temperatures.
前者的影响主要源于偶极极化和界面极化,尽管在高温下传导损耗也可能变得显著。
When a molecule is exposed to microwaves, it rotates to align with the applied field, resulting in continuous attempts to realign with changing fields, leading to energy absorption.
当分子暴露在微波中时,它会旋转以与施加的电场对齐,从而不断尝试与变化的电场重新对齐,导致能量吸收。
The latter effects may primarily arise from an increased probability of molecular collisions, a reduction in activation energy, and the occurrence of localized hot spots.
后者的效应可能主要源于分子碰撞概率的增加、活化能的降低以及局部热点现象的出现。
Microwaves improve synthetic processes by accelerating reaction rates, thereby reducing reaction times.
微波通过加速反应速率改善合成过程,从而缩短反应时间。
Additionally, they enable working with reduced quantities of solvent or even in solvent-free conditions.
此外,它们还能在减少溶剂用量甚至无溶剂条件下进行反应。
Furthermore, microwaves can enhance the selectivity of a synthetic process by favoring desired reactions over potential collateral processes.39, 40 This approach is by far the most represented green synthetic method in literature for the synthesis of phthalocyanines.
此外,微波能通过促进目标反应而非潜在的副反应,从而提高合成过程的选择性。 39, 40 迄今为止,这种方法在文献中报道的酞菁合成绿色方法中占据主导地位。
Microwave-assisted synthesis has successfully provided macrocycles functionalized with halides,41-44 terminal alkynes,45 crown ethers,46 substituted phenoxy47-49 and 1-naphthyloxy50 groups, tetraaza,51 tetraoxamonoaza,52 tetrathiacyclohexadecane,53 dithiadiazadioxa,54 diazadithio55 and tetrathiadiaza rings,56, 57 thiazoles,58 functionalized triazoles,59-62 phenylthioethanol,63 monoterpenes like (1R)-(−) myrtenol and (1R,2S,5R)-(−)-menthol,64 benzenesulfonamide,65 pyridine66 and azo compounds.67 Microwaves have been also employed to synthesize silicon68 lanthanide(III),69 lead,49, 70 and platinum71 derivatives, and phthalocyanine-based polymers.72-74 Kantar et al.
微波辅助合成已成功制备出多种功能化大环化合物,包括卤化物 41-44 、末端炔烃 45 、冠醚 46 、取代苯氧基 47-49 与 1-萘氧基 50 基团、四氮杂 51 、四氧单氮杂 52 、四硫杂环十六烷 53 、二硫二氮二氧杂 54 、二氮二硫 55 及四硫二氮杂环 56, 57 、噻唑 58 、功能化三唑 59-62 、苯硫基乙醇 63 、单萜类如(1R)-(−)桃金娘烯醇与(1R,2S,5R)-(−)-薄荷醇 64 、苯磺酰胺 65 、吡啶 66 以及偶氮化合物 67 。该技术还应用于合成硅 68 、镧系(III) 69 、铅 49, 70 、铂 71 等金属衍生物及酞菁基聚合物 72-74 。Kantar 等研究者
used the microwave-assisted approach for the tetramerization of phthalonitriles bearing different substituents at positions 4- and 5-.
采用微波辅助法对 4 位和 5 位带有不同取代基的邻苯二甲腈进行四聚反应。
They successfully synthesized tetra- and octa-substituted metal-free, zinc, and copper phthalocyanines and compared the alternative procedure with the standard solution-based method.75 By exploiting the different reactivity of the two chlorine atoms of 4,5 dichlorophthalonitrile when one of them is subjected to nucleophilic aromatic substitution (SNAr), they synthesized two asymmetric precursors: 4-chloro-5-(3,5-dimethoxyphenoxy)phthalonitrile and 4-octanethio-5-(3,5-dimethoxyphenoxy)phthalonitrile.
他们成功合成了四取代和八取代的无金属酞菁、锌酞菁及铜酞菁,并将该替代方案与标准溶液法进行了对比。通过利用 4,5-二氯邻苯二甲腈中两个氯原子在亲核芳香取代反应(SNAr)中的差异性反应活性,研究者制备出两种不对称前驱体:4-氯-5-(3,5-二甲氧基苯氧基)邻苯二甲腈和 4-辛硫基-5-(3,5-二甲氧基苯氧基)邻苯二甲腈。
Subsequently, these precursors reacted in DBU or DMAE for 8 minutes at a power of 350 W using microwave irradiation to provide MW1 and MW2 derivatives.
随后,这些前体在 DBU 或 DMAE 中通过 350 瓦功率的微波辐射反应 8 分钟,得到 MW1 和 MW2 衍生物。
In all cases investigated, the yields were at least 75 %, surpassing those of the corresponding standard procedures conducted for comparison.
在所有研究案例中,产率均不低于 75%,优于用于对比的相应标准流程所得结果。
DMAE was chosen as the reaction solvent for the synthesis of the polyfluorinated zinc phthalocyanine MW3,44 which was subsequently grafted onto a suitably functionalized silica.
选择 DMAE 作为反应溶剂用于合成多氟化锌酞菁 MW3,随后将其接枝到适当功能化的二氧化硅上。
The resulting inorganic–organic hybrid material was used as a catalyst for the solvent-free synthesis of biologically important 1,5-benzodiazepines, and proved to be recoverable and reutilized.
所得无机-有机杂化材料被用作无溶剂合成具有重要生物活性的 1,5-苯并二氮杂䓬类化合物的催化剂,并证实其具备可回收再利用特性。
The use of the MW3-based catalyst in solvent-free reaction conditions at room temperature, led to an improvement in conversions with respect to control experiments.
在室温无溶剂反应条件下使用 MW3 基催化剂,相较于对照实验提高了转化率。
The environmentally friendly synthesis of its precursor adds significant value, further advancing the target application towards greater sustainability.
其前体的环保合成工艺显著提升了价值,进一步推动目标应用向更高可持续性发展。
Acetynyl-substituted zinc phthalocyanines have been synthesized by Koyun et al.
Koyun 等人成功合成了乙炔基取代的锌酞菁化合物。
in a similar way.45 By irradiating the precursors in n-pentanol at 360 W, yields up to 86 % for MW4 and 81 % for MW5 were obtained.
以类似方式。 45 通过在正戊醇中以 360 瓦功率辐照前驱体,MW4 的产率可达 86%,MW5 的产率达 81%。
The MW-based approach outperformed the conventional one (79 % and 74 % yields for MW4 and MW5 respectively) and reduced the reaction time from 6 hours to 15 minutes.
微波法优于传统方法(MW4 和 MW5 的产率分别为 79%和 74%),并将反应时间从 6 小时缩短至 15 分钟。
Remarkably, the synthetic approach was efficient in providing the target products without needing to protect the terminal acetynyl functional group.
值得注意的是,该合成方法无需保护末端乙炔基官能团即可高效获得目标产物。
Chiral monoterpene derivatives (MW6 and MW7) have been recently synthesized by Gonzalez et al.64 yielded the desired phthalocyanines with comparable yields to the conventional procedure.
手性单萜衍生物(MW6 和 MW7)最近由 Gonzalez 等人合成, 64 以与传统方法相当的产率获得了目标酞菁化合物。
The copper derivatives exhibited slightly higher yields than the zinc derivatives.
铜衍生物的产率略高于锌衍生物。
Notably, a significant reduction in reaction time from seven hours to one hour was observed.
值得注意的是,反应时间从七小时显著缩短至一小时。
Taking advantage of the local generation of large amounts of energy, microwaves can be exploited to obtain products that would not be synthesized using conventional methods.
利用局部产生的大量能量,微波可被用于获取那些通过传统方法无法合成的产物。
Makhseed et al.
succeeded in obtaining hexadeca(2,6-dimethylphenoxy)phthalocyanines76 (MW8) in a 9 % yield by reacting 3,4,5,6-tetrakis(2,6-dimethylphenoxy)phthalonitrile in the presence of hydroquinone in hexanol at 350 W for 10 minutes.
通过将 3,4,5,6-四(2,6-二甲基苯氧基)邻苯二甲腈与氢醌在己醇中于 350 瓦功率下反应 10 分钟,成功以 9%的收率制得十六(2,6-二甲基苯氧基)酞菁 76 (MW8)。
Microwaves irradiation mitigated the decrease in reactivity of the cyano groups due to the steric hinderance and electron-donating nature of the bulky 2,6-dimethylphenoxy substituents.
微波辐射减轻了氰基反应活性的下降,这是由于体积庞大的 2,6-二甲基苯氧基取代基的空间位阻和给电子性质所致。
The related metallated derivatives were obtained in 18 %–24 % yields by adding the desired salt to the mixture.
通过向混合物中添加所需盐类,相关金属化衍生物的产率为 18%至 24%。
On the contrary, attempts using the lithium pentoxide/pentanol system to obtain the free-base or metal ion-template reactions in hexanol led to inseparable mixtures of byproducts with an overall very low yield.
相反,尝试使用五氧化二锂/戊醇体系在己醇中进行游离碱或金属离子模板反应时,生成了难以分离的副产物混合物,且总产率极低。
Several solvent-free procedures have also been reported.
此外,也有报道称存在若干无溶剂合成方法。
Sharma et al. Sharma 等人
straightforwardly synthesized 2,9,16,23-tetrachlorophthalocyanines MW9 starting from the cheap sodium 2-carboxy-4-chlorobenzoate and a suitable anhydrous metal salt (CoCl2, CuCl2, NiCl2, ZnCl2) in presence of urea as the source of nitrogen.42 The reported yields are generally high (75–92 %).
以廉价的 2-羧基-4-氯苯甲酸钠和适宜的无水金属盐(CoCl 2 、CuCl 2 、NiCl 2 、ZnCl 2 )为原料,在尿素作为氮源的条件下,直接合成了 2,9,16,23-四氯酞菁 MW9。 42 文献报道的产率普遍较高(75-92%)。
The absence of a proper solvent enhanced the interaction between microwaves and reactants and drove the chemical reaction toward completion.
缺乏适当溶剂增强了微波与反应物之间的相互作用,促使化学反应趋于完全。
Moiseeva et al.
succeeded in synthesizing 1.9 grams of 2(3),9(10),16(17),23(24)-tetraiodophthalocyanine MW10 in a single batch by irradiating a mixture of 4-iodophthalonitrile and Zn(quinoline)2Cl2 salt in a microwave reactor at 150 W for 7 minutes.43 The authors achieved a high 83 % yield at analytical grade (≥98 %) purity.
通过微波反应器在 150 瓦功率下辐照 4-碘代邻苯二甲腈与 Zn(喹啉) 2 Cl 2 盐混合物 7 分钟,成功单批次合成了 1.9 克 2(3),9(10),16(17),23(24)-四碘代酞菁 MW10。作者实现了分析纯级(≥98%)纯度下 83%的高产率。
This result is promising as this molecule is a versatile intermediate, whose iodide atoms can be widely substituted by exploiting the rich palladium-catalyzed chemistry to provide functionalized derivatives with high complexity.
这一结果颇具前景,因为该分子是一种多功能中间体,其碘原子可通过丰富的钯催化化学反应被广泛取代,从而制备出具有高度复杂性的功能化衍生物。
Furthermore, it is interesting to report here the synthesis of the MW11 cobalt derivative starting from 1,2,4-benzene tricarboxylic anhydride, urea, cobalt chloride and (NH4)2MoO4, carried out on a total of approximately 100 grams of reagents.
此外,值得在此报告的是以 1,2,4-苯三甲酸酐、尿素、氯化钴和钼酸铵为原料,通过总计约 100 克反应物合成 MW11 钴衍生物的实验过程。
The authors report a very high yield, equal to 90 %, validating the use of microwaves even on large quantities, although still on a laboratory scale.77 Solventless microwave-assisted syntheses have been reported also for unsubstituted Cu(II), Mn(II), Al(III), Co(II) and Zn(II) Pcs,78 and for nitro- and poli chlorinated-derivatives.79, 80 Lead phthalocyanine and lead 2(3),9(10),16(17),23(24)tetra-nitrophthalocyanine were obtained in 90–92 % yields by reacting phthalonitriles and lead oxide in a domestic microwave oven for 13–15 minutes with a range of power irradiation.70 The method was applied to batches of reagents up to approximately six grams. Comparison reactions carried out in molten phthalonitrile at 140–180 °C for 1–4 hours consistently resulted in lower overall yields.
作者报道了高达 90%的产率,验证了微波技术即使在大规模(尽管仍属实验室规模)应用中的有效性。 77 无溶剂微波辅助合成法同样适用于未取代的铜(II)、锰(II)、铝(III)、钴(II)和锌(II)酞菁化合物 78 ,以及硝基与多氯代衍生物。 79, 80 通过在家用微波炉中以不同功率辐照 13-15 分钟,使邻苯二甲腈与氧化铅反应,可获得酞菁铅和 2(3),9(10),16(17),23(24)-四硝基酞菁铅,产率达 90-92%。 70 该方法适用于单批约六克试剂的反应。对比实验显示,在 140-180°C 熔融邻苯二甲腈中反应 1-4 小时,总体产率始终较低。
On the contrary, more complex lead derivatives (MW12, MW13) synthesized in pentanol using DBU as base provided lower yields, ranging between 19 and 46 %.49 Although a direct comparison of such different synthetic procedures is inappropriate, it is possible that the absence of solvent may be particularly advantageous for the synthesis of this family of metallophthalocyanines.
相反,在戊醇中使用 DBU 作为碱合成的更复杂铅衍生物(MW12、MW13)产率较低,介于 19%至 46%之间。虽然直接比较这些不同的合成方法并不合适,但无溶剂条件可能特别有利于这类金属酞菁化合物的合成。
Alternatively, pentanol may not be the most suitable choice as a reaction medium in this particular case.
或者,戊醇可能并非此特定情况下最适宜的反应介质选择。
The chemical structures of the phthalocyanines discussed in this paragraph are gathered in Figure 2.
本段讨论的酞菁类化合物的化学结构汇总于图 2 中。

Phthalocyanines synthesized using MW-assisted methods.
2.1.2 UV Irradiation
Photochemical substrate activation with UV irradiation frequently occurs without the need for additional reagents, leading to reduced formation of byproducts.
紫外光照射下的光化学底物活化通常无需额外试剂即可发生,从而减少副产物的生成。
This feature makes photochemical reactions particularly attracting within the framework of green chemistry.
这一特性使得光化学反应在绿色化学框架下显得尤为引人注目。
Moreover, certain reactions can be carried out using visible light or sunlight as a renewable energy source, further enhancing their environmental appeal.
此外,某些反应可以利用可见光或阳光作为可再生能源进行,从而进一步提升其环保吸引力。
The study of UV light to assist the synthesis of phthalocyanines dates to 1976, when Tomoda et al.
利用紫外光辅助合成酞菁的研究可追溯至 1976 年,当时 Tomoda 等人。
observed that room light could positively affect the formation of phthalocyanines, and that UV irradiation could promote it even at room temperature.81 Kharisov et al.31, 82 then studied the effect of solvent on the synthesis of metal-free phthalocyanine (PcH2) in the temperature range 0–60 °C choosing different linear, branched, and cyclic alcohols, as well as in ethylene glycol and dimethylaminoethanol (DMAE) as reaction media.
研究发现,室内光线能促进酞菁化合物的形成,而紫外线照射甚至在室温条件下也能加速这一过程。 81 随后 Kharisov 等人 31, 82 以不同直链、支链和环状醇类,以及乙二醇和二甲基氨基乙醇(DMAE)作为反应介质,在 0-60℃温度范围内研究了溶剂对无金属酞菁(PcH 2 )合成的影响。
Under the best experimental conditions, using the Ethanol/CH3ONa and Methanol/CH3ONa systems could produce quantitative yields in the 30–60 °C temperature range.
在最佳实验条件下,使用乙醇/CH 3 ONa 和甲醇/CH 3 ONa 体系可在 30-60℃温度范围内实现定量产率。
The rationalization of this evidence involves the formation of free RO⋅ radicals upon irradiation with UV light, which increases the effectiveness of nucleophilic attacks on the cyano group of phthalonitrile.
这一现象的解释涉及紫外线照射下形成游离 RO 自由基的过程,该过程增强了亲核试剂对邻苯二甲腈氰基的攻击效率。
Experimental evidence suggests that the presence of more than one hydroxy group in solvents, such as in ethylene glycol and glycerol, can enhance yields and enable reaction temperatures to be lowered, even to near-zero degrees.
实验证据表明,在溶剂中存在多个羟基(如乙二醇和甘油中)可提高产率,并能使反应温度降低,甚至接近零度。
However, it is important to note that the authors report difficulties in precisely calculating these effects due to the high viscosity of these solvents, that made the isolation of the product from the reaction mixture challenging.
然而,需要指出的是,作者报告称由于这些溶剂的高粘度,精确计算这些效应存在困难,这使得从反应混合物中分离产物具有挑战性。
Therefore, while this evidence is promising, it should be considered probable rather than fully verified.
因此,尽管这一证据前景看好,但仍应视为可能而非完全确证。
In 2010, Youssef reported the UV-assisted synthesis of metal-free 2,3,9,10,16,17,23,24-octamethoxyphthalocyanine (UV1, Figure 3) in DMAE, as a precursor for more complex alkynyl substituted derivatives.60 The yield obtained was 60 % starting from 3.5 g of phthalonitrile, a quantity still on a lab-scale, but significant in phthalocyanine synthesis, often carried out in quantities much lower than one gram.
2010 年,Youssef 报道了在 DMAE 溶剂中通过紫外辅助合成无金属 2,3,9,10,16,17,23,24-八甲氧基酞菁(UV1,图 3)的方法,该产物可作为合成更复杂炔基取代衍生物的前驱体。 60 实验以 3.5 克邻苯二甲腈为起始原料,获得了 60%的收率——虽然仍属实验室规模,但在通常以低于 1 克量级进行的酞菁合成中,这一产量已颇具意义。
Instead, any attempt to synthesize the corresponding metallophthalocyanines in the same reaction conditions failed.
然而,在相同反应条件下尝试合成相应金属酞菁的所有努力均告失败。
Saito et al.
reported the first direct synthesis of Cu and Zn phthalocyanines in nanosized micelles irradiated with UV light.83 The size of the micelles, that was found to be averagely 24.7 nm, allowed to control the morphology of target products, obtaining CuPc in α-form.
报道了首例在紫外光照射下纳米胶束中直接合成铜和锌酞菁的方法。研究发现平均尺寸为 24.7 纳米的胶束可调控目标产物的形貌,最终获得α晶型的铜酞菁。
The order in which the reagents are added was found to be crucial for the success of the reaction: adding CuCl2 before the surfactants resulted in large aggregates caused by the formation of complexes between Cu2+ and isoindoline intermediates outside the micelles.
研究发现,试剂的添加顺序对反应成功至关重要:若在表面活性剂之前加入 CuCl 2 ,会因 Cu 2+ 与胶束外异吲哚啉中间体形成复合物而导致大量聚集体的产生。
This approach was subsequently applied to the synthesis of unsubstituted crystalline naphthalocyanines and tetrapyridoporphyradine, thus demonstrating its potential versatility.84
该方法随后被应用于未取代结晶萘酞菁和四吡啶并卟啉的合成,从而展示了其潜在的多功能性。 84

Chemical structure of 2,3,9,10,16,17,23,24-octamethoxyphthalocyanine.
2.1.3 Ultrasounds
For over 80 years, sonochemistry, or ultrasound-driven chemical reactions, has captivated researchers as a powerful tool.
八十余年来,声化学(即超声波驱动的化学反应)作为一种强大工具始终令研究者着迷。
The effectiveness of ultrasound stems from cavitation, where bubbles form, expand, and violently collapse within a liquid.
超声波的有效性源于空化作用,即液体中气泡形成、膨胀并剧烈破裂的过程。
These collapsing bubbles generate intense, localized bursts of high pressure (up to 1,000 bar) and temperatures up to 5,000 K, initiating high-energy radical reactions.
这些坍塌的气泡会产生强烈的局部高压(高达 1000 巴)和高温(高达 5000K),从而引发高能自由基反应。
However, sonochemistry is more than just brute force; it also facilitates micro-mixing, ensuring thorough interaction between reaction components, and enhances mass transport, allowing materials to move more freely within the system.
然而,声化学不仅仅是蛮力作用;它还能促进微观混合,确保反应组分间的充分接触,并增强传质效率,使物质在体系中更自由地移动。
Additionally, it can reduce particle size, resulting in a larger surface area and faster reaction rates.
此外,它还能减小颗粒尺寸,从而增大表面积并加快反应速率。
Studies have shown that sonochemistry can significantly enhance reaction efficiency by accelerating rates, increasing yields, and influencing product selectivity in specific cases.
研究表明,声化学能通过加速反应速率、提高产率并在特定情况下影响产物选择性,从而显著提升反应效率。
This influence may even lead to the discovery of entirely new reaction pathways.
这种影响甚至可能促成全新反应路径的发现。
Several ultrasounds-assisted organic reactions have been reported, such as the synthesis of esters,85 hydrolysis of nitriles,86 nucleophilic aromatic substitutions64 and preparation of metal-organic frameworks (MOFs).87, 88 The literature concerning this approach for the synthesis of phthalocyanines is scarce and notably dated.
已有数例超声辅助有机反应的报道,例如酯类合成、腈类水解、亲核芳香取代反应以及金属-有机框架材料(MOFs)的制备。而关于该方法应用于酞菁类化合物合成的文献则十分稀少,且明显陈旧。
There is evidence of ultrasound-assisted synthesis of PcH2 at low temperature (0–40 °C) using zeolites of the clinoptilolite type as solid support.89, 90 Ultrasound accelerates the reaction by 2–3 times compared to control experiments conducted without it.
有证据表明,在低温(0-40°C)条件下,以斜发沸石型分子筛作为固体载体,通过超声辅助可合成 PcH 2 。 89, 90 与未使用超声的对照实验相比,超声使反应速度加快 2-3 倍。
The authors hypothesize that this acceleration is attributable to the improved generation of radical species and the continuous exposure of new active catalytic surfaces of the zeolites themselves.
作者推测这种加速效应源于自由基物种生成效率的提高以及沸石自身新活性催化表面的持续暴露。
Differences in reaction yields observed depending on the zeolite used were attributed to calcite impurities present in the composition of one of them, which are inert with respect to the phthalonitrile cyclization reaction.
观察到的反应产率差异归因于其中一种沸石成分中存在的方解石杂质,这些杂质对邻苯二甲腈环化反应呈惰性。
As a side note, ultrasonic treatments were reported to obtain lithium phthalocyanine nanotubes from micrometer-sized particles in water.91 Combinations of high frequency ultrasound and a surfactant like sodium dodecyl sulfate (SDS) reduced their size to diameters of tens of nanometers.
值得一提的是,有研究报道通过超声波处理可在水中将微米级颗粒转化为锂酞菁纳米管。 91 高频超声波与十二烷基硫酸钠(SDS)等表面活性剂的联合使用,可将其直径缩小至数十纳米。
Lastly, ultrasounds have found application in processes aimed at destroying the phthalocyanine aromatic ring in decolorization processes of industrial waste.92, 93
最后,超声波技术已应用于工业废水脱色过程中破坏酞菁芳香环的工艺。
2.2 Alternative Reaction Media
Solvents represent a significant fraction of the whole material involved in a chemical process and play many roles in the success of a synthesis.
溶剂在化学过程中占据整个物料的重要部分,对合成反应的成功起着多重关键作用。
They can homogenize the concentration of reactants in the reaction medium and its temperature, improve its efficiency through favorable interactions with the reagents, induce the activation of specific molecular positions among others, suppress the formation of byproducts, and promote a straightforward purification of the resulting crude mixture.
它们能够均匀反应介质中反应物的浓度和温度,通过与试剂间的有利相互作用提高反应效率,诱导特定分子位点的活化,抑制副产物的形成,并促进粗产物混合物的简易纯化。
All this leads to an increase in the reaction yields and indirectly contributes to reducing the production of waste, as well as the economic cost, of a synthetic process.
这一切都提高了反应产率,并间接有助于减少合成过程中废物的产生以及经济成本。
The investigation of low-impact reaction media alternative to those conventionally used can therefore translate in many advantages in addition to the reduction of environmental criticalities of a synthesis.94-96 Water is the solvent of choice for green chemistry given its abundance and lack of toxicity.
因此,研究传统反应介质的低影响替代品不仅能减少合成过程对环境的影响,还能带来诸多优势。 94-96 水因其储量丰富且无毒,成为绿色化学的首选溶剂。
However, the alkaline environment required for generating nucleophilic species that promote ring cyclization leads to the production of OH− ions, which undergo unwanted reactions with the precursors, particularly phthalonitriles.97, 98 Consequently, water not only becomes unsuitable as a solvent but also an unwanted impurity, even in small quantities, in the reaction environment.
然而,生成促进环化反应的亲核物种所需的碱性环境会导致 OH − 离子的产生,这些离子会与前驱体(尤其是邻苯二甲腈)发生副反应。 97, 98 因此,水不仅不适合作为溶剂,即使微量存在于反应环境中也会成为有害杂质。
The development of micellar approaches, building on the extensive research already conducted for numerous organic synthesis reactions,99 could overcome the issue.
基于已对众多有机合成反应开展的广泛研究,胶束方法的发展 99 或许能解决这一问题。
However, to date, the synthesis of phthalocyanines in micelles is limited to a few examples in polar organic solvents,83 rendering it a relatively underexplored area with significant potential.
然而迄今为止,酞菁在胶束中的合成仅限于极性有机溶剂中的少数案例,这使得该领域仍存在巨大潜力却研究不足。
2.2.1 Benign Solvents
Zanotti et al.100 tested anisole, glycerol, and their mixtures as solvents for the ring formation of unsubstituted and tetra-tert-butyl substituted cobalt, copper, and zinc phthalocyanines.
Zanotti 等人测试了苯甲醚、甘油及其混合物作为溶剂,用于未取代和四叔丁基取代的钴、铜、锌酞菁的环形成反应。
Anisole was chosen because of its low toxicity and biodegradability,96, 101 and because it can be obtained by renewable feedstocks like lignin and guaiacol.102-104 Glycerol is a low-impact solvent that is already utilized in organic synthesis,105 is available on a large scale from the vegetable oil industry and can solubilize both inorganic salts and a large variety of organic species.106, 107 (Figure 4).
选择苯甲醚是因为其低毒性和可生物降解性, 96, 101 并且它可以从木质素和愈创木酚等可再生原料中获得。 102-104 甘油是一种低影响溶剂,已用于有机合成, 105 可从植物油工业大规模获取,并能溶解无机盐和多种有机物质。 106, 107 (图 4)。
The formation of phthalocyanines in the various solvents and mixtures was found to be dependent on the nature of the templating metal.
研究发现,酞菁在不同溶剂及其混合物中的形成取决于模板金属的性质。

A selection of benign solvents explored as reaction media for the synthesis of metallophthalocyanines in solution, along with renewable feedstocks from which they can currently be obtained.
The trend Cu(II)>Co(II)>Zn(II) is in agreement with the greater templating power of copper compared to the other two ions Conversely, zinc was found to be the least reactive metal, due to its 3d10 shell.
铜(II)的活性趋势高于钴(II)和锌(II),这与铜离子比其他两种离子具有更强的模板效应相符。相反,由于锌的 3d 10 电子层结构,其反应活性最低。
Some exceptions were rationalized by analyzing the reaction environment and the interactions of the solvent with the reacting species.
通过分析反应环境及溶剂与反应物间的相互作用,这些例外情况得到了合理解释。
For example, the synthesis of CuPc in anisole using DMAE as the base had the lowest yield among all, probably because of the polar aprotic nature of the solvent that may have favored competitive copper-catalyzed reactions rather than templating the tetramerization of phthalonitrile.
例如,在苯甲醚中使用 DMAE 作为碱基合成 CuPc 的产率最低,这可能是由于溶剂的极性非质子特性更有利于铜催化竞争反应,而非促进邻苯二甲腈的四聚化模板效应。
Instead, the formation of CuPc in the same solvent when using potassium hydroxide as the base provided a yield as high as 76 %.
然而,当使用氢氧化钾作为碱基时,在相同溶剂中形成的铜酞菁产率高达 76%。
It is possible that the greater nucleophilicity of KOH compared to DBU in a relatively non-polar environment allowed an effective attack on the cyano groups of phthalonitrile, aided by the extreme coordinating capacity of copper, promoting the Pc ring formation among other processes.
在相对非极性的环境中,KOH 相比 DBU 具有更强的亲核性,加之铜极强的配位能力,可能使其能有效进攻邻苯二甲腈的氰基,从而促进酞菁环的形成及其他反应过程。
KOH has generally provided much lower yields for the other metal ions because of a side-reaction involving the hydration of nitrile groups in polar environments and subsequent formation of phthalimides.
对于其他金属离子,KOH 通常产率较低,这是由于在极性环境中发生了腈基水合的副反应,并随后生成了邻苯二甲酰亚胺。
Copper has been the best performing ion also in the synthesis of tetra-tert-butylphthalocyanines, yielding the desired product in all the screened conditions although in smaller amounts than the standard protocols.
在四叔丁基酞菁的合成中,铜离子同样表现出最佳性能,在所有筛选条件下都能获得目标产物,尽管产量低于标准方案。
This evidence highlights how the choice of an alternative reaction environment can depend on parameters such as the nature of one or more reagents, in a manner that is not always easily predictable.
这一证据凸显出替代反应环境的选择可能取决于一种或多种试剂的性质等参数,而这种关联性往往难以轻易预测。
Consequently, it can be challenging to develop a general procedure with a broad spectrum of applicability.
因此,要开发出一种具有广泛适用性的通用方法可能颇具挑战性。
As a follow up of this work, Podapangi, Mancini et al.34 investigated a propane-1,2-diol/anisole mixture with DBU as the base for the synthesis of the same derivatives, obtaining yields close to those of standard conditions at least for the copper and zinc tetra-tert-butylphthalocyanines.
作为这项工作的后续研究,Podapangi、Mancini 等人 34 采用丙烷-1,2-二醇/苯甲醚混合溶剂体系,以 DBU 作为碱基合成了相同衍生物,至少对于四叔丁基铜酞菁和四叔丁基锌酞菁而言,其产率接近标准条件下的水平。
In the literature, propane-1,2-diol has been utilized as a solvent or co-solvent in reactions involving ionic liquids.108 An intriguing extension of this study, aimed at broadening the range of alternative reaction media, could involve solvents like polyethylene glycols (PEGs), which have already demonstrated success in the synthesis of organic materials with high added value.109, 110
文献中,1,2-丙二醇已被用作离子液体反应中的溶剂或共溶剂。 108 本研究的一个有趣延伸方向是探索聚乙二醇(PEGs)等替代反应介质,这类溶剂在高附加值有机材料合成中已展现出显著成效,这将有助于拓宽绿色反应介质的选择范围。 109, 110
2.2.2 Solvothermal Synthesis
Solvothermal synthesis is a method used to produce chemical compounds that involves placing a solvent containing reagents into an autoclave and subjecting it to high pressure and temperature.
溶剂热合成法是一种用于制备化合物的方法,其过程是将含有反应试剂的溶剂置于高压釜中,并施以高温高压条件。
Under these conditions, many substances dissolve more readily in the solvent compared to standard conditions.
在此条件下,相较于标准条件,许多物质更容易溶解于溶剂中。
This increased solubility enables reactions that might not occur under normal circumstances otherwise.
这种增加的溶解度使得在通常情况下可能不会发生的反应得以进行。
This approach is mostly applied to synthesize inorganic materials, while for the synthesis of phthalocyanines there have been limited successful attempts starting from several organic precursors, the first of which dates to 2008 and involves the use of harmful solvents like quinoline at temperatures >200 °C.111 Over the past fifteen years, research efforts in solvothermal synthesis have mainly focused on identifying solvents with fewer environmental concerns.
该方法主要应用于无机材料的合成,而在酞菁类化合物的合成中,从多种有机前驱体出发的成功尝试较为有限,其中最早可追溯至 2008 年——该方案需在 200℃以上高温环境中使用喹啉等有害溶剂。 111 过去十五年间,溶剂热合成领域的研究重点主要集中在寻找环境友好型溶剂。
This focus has resulted in the synthesis of phthalocyanines with diverse central metals and a restricted range of ring substituents.
这种关注导致了酞菁化合物的合成具有多样化的中心金属和有限的环取代基范围。
Notably, the products are often obtained as single crystals, rendering the solvothermal approach a valuable strategy for synthesizing highly organized materials.
值得注意的是,产物通常以单晶形式获得,这使得溶剂热法成为合成高度有序材料的一种重要策略。
These materials offer a platform for investigating fundamental and structural properties that would otherwise be inaccessible.
这些材料为研究原本无法触及的基础和结构特性提供了平台。
In 2015, Li et al.
2015 年,Li et al.
reported the synthesis of manganese phthalocyanine in ethanol at 190 °C for 3 hours.112 Interestingly, both the synthesis and the purification steps do not require obnoxious solvents, since water is the only other chemical required to accomplish the task.
报道了在 190℃乙醇中反应 3 小时合成锰酞菁的方法。值得注意的是,该合成与纯化步骤均无需使用有害溶剂,仅需水作为辅助化学试剂即可完成。
The size of the crystals obtained is considerable, and in some cases exceeds 10 mm.
所得晶体尺寸相当可观,部分情况下甚至超过 10 毫米。
The resulting crystals were characterized by SEM measurements, which showed a well-defined quadrangular shape and different morphologies on the top/bottom planes.
通过扫描电子显微镜(SEM)表征显示,所得晶体呈现明确的四边形结构,且上下晶面具有不同形貌特征。
X-ray diffraction disclosed a monoclinic phase.
X 射线衍射显示为单斜晶相。
The same author successfully synthesized ZnPc and CoPc with a similar procedure, screening three different alcohols to individuate the best experimental conditions to maximize the length of the resulting crystals.113 Benzyl alcohol gave the best performances among the choices, providing ZnPc crystals up to 8 mm and CoPc up to 1 mm.
同一作者采用类似流程成功合成了锌酞菁(ZnPc)和钴酞菁(CoPc),通过筛选三种不同醇类确定了最佳实验条件以最大化晶体生长尺寸。 113 在候选溶剂中,苯甲醇表现最优异,最终获得长达 8 毫米的 ZnPc 晶体和 1 毫米的 CoPc 晶体。
TEM images of ZnPc crystals obtained in different solvents provide interesting information, as their morphology significantly changes with the reaction media: benzyl alcohol gave quadrangular prisms with smooth surfaces along with some multilayer plates.
在不同溶剂中获得的酞菁锌晶体 TEM 图像提供了有趣的信息,其形貌随反应介质发生显著变化:苯甲醇溶剂中形成了表面光滑的四方棱柱体,同时伴随有多层板状结构生成。
1-pentanol provided rougher surfaces with nanosheet arrays intersecting on the exterior surface.
1-戊醇产生了更粗糙的表面,其外表面交错排列着纳米片阵列。
Ethanol-derived crystals displayed a quadrangular contour with additional secondary structures observed on their surface.
乙醇衍生的晶体呈现出四边形轮廓,其表面还观察到次级结构。
Conversely, the smoothest surface for CoPc was obtained with ethanol.
相反,使用乙醇可获得最光滑的 CoPc 表面。
This evidence suggests that the reaction media interactions with the reactants and the induced reactivity on the OH and cyano group, perhaps as well as the reaction temperature, play a crucial role in defining the morphology of the resulting products.
这一证据表明,反应介质与反应物的相互作用以及对羟基和氰基基团诱导的反应活性(可能还包括反应温度)在决定产物形貌方面起着关键作用。
The synthesis of a ZnPc hierarchical nanostructure with hollow interior space using ethylene glycol as a solvent has also been reported.114 More recently, the solvothermal synthesis of a metal-free Pc in non-harmful solvents was achieved.115 Since the reaction cannot take advantage of the templating effect of metal ions, DBU or 1,5-diazabicyclo-[4.3.0]-non-5-ene (DBN) were necessary to obtain the final product.
以乙二醇为溶剂合成具有中空内部结构的酞菁锌分级纳米结构已有报道。 114 最近,研究人员在无害溶剂中实现了无金属酞菁的溶剂热合成。 115 由于该反应无法利用金属离子的模板效应,必须使用 DBU 或 1,5-二氮杂双环[4.3.0]壬-5-烯(DBN)才能获得最终产物。
Additionally, ethanol emerged as the better solvent option.
此外,乙醇被证明是更优的溶剂选择。
The presence of a protic functional group on the solvent was found to be fundamental for the reaction to happen, attempts in pyridine, tetrahydrofuran, and acetonitrile failed in giving the phthalocyanine.
研究发现,溶剂中质子性官能团的存在是该反应发生的关键因素,在吡啶、四氢呋喃和乙腈中尝试合成酞菁均未成功。
Solvothermal synthesis has also been exploited to obtain rod-like iron phthalocyanine116, 117 and hierarchical tetranitrophthalocyanines with potential application in photocatalysis and for capacitive energy storage118, 119 The solvothermal synthesis of copper phthalocyanine nanotubes and nanostructures in ethylene glycol has been recently reported for the electrosynthesis of urea120 and ammonia121 respectively.
溶剂热合成法也被用于制备棒状铁酞菁 116, 117 和具有光催化及电容储能应用潜力的多级结构四硝基酞菁 118, 119 。近期研究报道了在乙二醇中溶剂热合成铜酞菁纳米管及纳米结构,分别用于电合成尿素 120 和氨 121 。
2.2.3 Ionic Liquids
Ionic liquids have gained momentum as appealing reaction media for organic synthesis because of their low vapor pressure, high thermal stability, high ionic conductivity, and ease of recovery.
离子液体因其低蒸气压、高热稳定性、高离子导电性和易于回收等特点,已成为有机合成中极具吸引力的反应介质。
Due to their ionic nature, ionic liquids are particularly advantageous for reactions involving charged reactive species.
由于其离子特性,离子液体特别适用于涉及带电活性物种的反应。
Their high chemical stability and low volatility guarantee that emissions from ionic liquids pose minimal environmental concerns.
它们的高化学稳定性和低挥发性确保了离子液体的排放对环境的影响微乎其微。
However, this same characteristic renders them persistent substances in natural environments, thus potentially leading to pollution.
然而,这一特性也使得它们在自然环境中成为持久性物质,从而可能造成污染。
The debate regarding the classification of ionic liquids as sustainable reaction media persists in the literature.
关于离子液体是否应归类为可持续反应介质的争论在文献中持续存在。
We include them in this review because, based on our analysis of the articles, they have demonstrated recyclability for a certain number of cycles under the specified conditions and are typically used in modest quantities on a lab-scale.
我们将这些方法纳入本综述,因为根据对文献的分析,它们已在特定条件下展现出一定次数的可循环使用性,且通常在实验室规模中以适量使用。
Their use in the formation of the phthalocyanine ring can be advantageous, as ionic liquids can generally enhance the reactivity of nucleophiles, thereby reducing the yield of side products formed.122, 123 In addition to their use as reaction media, ionic liquids have been employed in the removal of the central metal of the macrocycle.124 Some ionic liquids successfully used in the synthesis of phthalocyanines are shown in Figure 5. In 2005, Lo et al.
它们在酞菁环形成过程中的应用具有优势,因为离子液体通常能增强亲核试剂的反应活性,从而减少副产物的生成。 122, 123 除了作为反应介质外,离子液体还被用于脱除大环化合物的中心金属。 124 图 5 展示了部分成功应用于酞菁合成的离子液体。2005 年,Lo 等人
explored the potential of tetrabutylammonium bromide (TBAB) as a solvent for obtaining alkylthio, alkoxy, and phenoxy-substituted phthalonitriles by SNAr and for subsequent cyclization to obtain the corresponding phthalocyanines (IL1-IL6).125 It is interesting to note that the SNAr step did not require the presence of a base, as is normally necessary in this type of reaction, probably because the ionic nature of the solvent increases the nucleophilicity of the thiol and alcohol groups.
探讨了四丁基溴化铵(TBAB)作为溶剂在通过 S N Ar 反应获取烷硫基、烷氧基和苯氧基取代邻苯二甲腈,以及后续环化反应合成相应酞菁(IL1-IL6)中的应用潜力。 125 值得注意的是,该 S N Ar 反应步骤无需像此类反应通常所需的那样添加碱,这可能是由于溶剂的离子特性增强了硫醇和醇基团的亲核性。
The phthalocyanines were then synthesized in the same ionic liquid using varying amounts of DBU, in yields comparable to reactions carried out with conventional procedures.
随后在相同离子液体中,使用不同量的 DBU 合成了酞菁化合物,其产率与传统合成方法相当。
As a collateral reaction, the authors report the formation of significant amounts of metal-free tetrakis(alkylthio) phthalocyanines when four equivalents of thiols were used in the nucleophilic aromatic substitution of 4-nitrophthalonitrile.
作为副反应,作者报告称,在 4-硝基邻苯二甲腈的亲核芳香取代反应中使用四当量硫醇时,会生成大量无金属四(烷硫基)酞菁化合物。

Structure of ionic liquids mentioned in this review. From left to right, Tetrabutylammonium bromide (TBAB), 1,1,3,3-Tetramethylguanidinium trifluoroacetate (TMGT), 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) and butyl(2-hydroxyethyl)-dimethylammonium bromide ([bhyeda][Br]).
It would have been interesting to investigate this occurrence further, as the possibility of pushing this side reaction would have led to the final product reducing both reaction time and required chemicals.
若能进一步探究这一现象将颇具意义,因为推动该副反应的可能性有望缩短反应时间并减少所需化学品,从而获得最终产物。
TBAB has been employed also in the synthesis of unsubstituted, chlorinated and nitro phthalocyanines bearing several metal ions.126 Phthalonitriles, phthalimides and phthalic anhydrides have been used as reactants, in the classic reaction system involving urea and ammonium heptamolybdate.
TBAB 还被用于合成带有多种金属离子的未取代、氯化和硝基酞菁化合物。在包含尿素和七钼酸铵的传统反应体系中,邻苯二甲腈、邻苯二甲酰亚胺和邻苯二甲酸酐被用作反应物。
Overall, the reactions were found to proceed at least an order of magnitude faster than their standard counterparts.
总体而言,这些反应的进行速度至少比标准反应快一个数量级。
Tests have indicated a general tendency for phthalonitriles to necessitate shorter reaction times and achieve higher yields than other precursors.
测试表明,与其他前体相比,邻苯二甲腈通常需要更短的反应时间并能获得更高的产率。
Furthermore, phthalonitriles required lower amounts of urea, aligning with the reduced need for a nitrogen source compared to phthalimides and phthalic anhydrides.
此外,与邻苯二甲酰亚胺和邻苯二甲酸酐相比,邻苯二甲腈所需的尿素量更少,这符合对氮源需求的降低。
The ionic liquid was found to be recyclable up to 4 times, although with a progressive decrease in yield from 95 % to 70 %.
研究发现该离子液体可循环使用多达 4 次,但产率会从 95%逐步下降至 70%。
Nickel phthalocyanine has been synthesized in 1-butyl-3-methylimidazolium tetrafluoroborate giving a high yield of one-dimensional structures without using a template or stabilizing agent.127 This occurrence was rationalized with the unique π-π stacking of the imidazole ring that induces a specific directed growth of the phthalocyanine product.
在 1-丁基-3-甲基咪唑四氟硼酸盐中成功合成了镍酞菁,无需使用模板或稳定剂即可获得高产率的一维结构。这一现象可归因于咪唑环独特的π-π堆积作用,它能诱导酞菁产物发生特定的定向生长。
1,1,3,3-Tetramethylguanidinium trifluoroacetate (TMGT) and TBAB have been investigated as ionic liquid and as phase transfer reagent, respectively, for the synthesis of PcH2.108 These studies were conducted under both conventional heating conditions or microwave irradiation using hexamethyldisylylazane, sodium sulfide or urea as co-reactants.
1,1,3,3-四甲基胍三氟乙酸盐(TMGT)和四丁基溴化铵(TBAB)分别作为离子液体和相转移试剂被研究用于酞菁(PcH)的合成。这些研究在常规加热条件或微波辐射下进行,使用六甲基二硅氮烷、硫化钠或尿素作为共反应物。
In all the examined cases, microwaves promoted the efficient formation of target product in 3–5 minutes depending on the reaction system, with high yields (up to 80 %) comparable to those of conventional heating.
在所有研究案例中,微波均能在 3-5 分钟内高效促成目标产物的形成(具体时长取决于反应体系),且产率高达 80%,与传统加热方式相当。
All in all, the best performances were obtained with TMGT regardless of the experimental procedure.
总体而言,无论采用何种实验方案,TMGT 均展现出最佳性能。
The authors rationalize this evidence with the formation of 1,1,3,3-tetramethylguanidine (TMG) and trifluoroacetic acid (TFA) due to thermal dissociation of TMGT.
作者们通过 1,1,3,3-四甲基胍(TMG)和三氟乙酸(TFA)的形成解释了这一现象,认为这是 TMGT 热解离的结果。
The nucleophilicity of the nitrogen atom of TMG is strong enough to react with one cyano group, assisted by its activation with a strong protic acid such as TFA or the conjugated acid of TMG itself, and initiate the tetramerization of phthalonitrile.
TMG 中氮原子的亲核性足够强,在强质子酸(如 TFA 或 TMG 自身共轭酸)的活化辅助下,可与一个氰基发生反应,从而引发邻苯二甲腈的四聚反应。
Chauchan et al. Chauchan 等
investigated the effect of ionic liquid composition on the synthesis of phthalocyanines IL1, IL7, IL8, and IL9.128 A selection of functional ammonium-, pyridinium- and imidazolium ILs in the presence of DBU were examined, resulting in a pyridinium>imidazolium>ammonium general reactivity scale.
研究了离子液体组成对酞菁 IL1、IL7、IL8 和 IL9 合成的影响。 128 在 DBU 存在下考察了一系列功能性铵盐、吡啶鎓盐和咪唑鎓盐离子液体,得出反应活性总体规律为:吡啶鎓盐>咪唑鎓盐>铵盐。
Pyridinium-based materials degraded quickly due to the presence of the organic base.
由于有机碱的存在,吡啶鎓基材料会快速降解。
The imidazolium-IL effectiveness was explained with the deprotonation of the ring with generation of a negatively charged nucleophilic ion reacting with CN groups of phthalonitrile.
咪唑鎓离子液体的有效性可通过环状结构的去质子化作用来解释,该过程会生成带负电的亲核离子,进而与邻苯二甲腈的氰基发生反应。
All in all, hydroxylated ionic liquids gave the best result due to the formation of alkoxy anions, that similarly attack cyano groups.
总体而言,羟基化离子液体因能形成同样可攻击氰基的烷氧基阴离子而展现出最佳反应效果。
A dependance on the nature of the ionic liquid anion was also reported.
研究还指出,这种依赖性受离子液体阴离子性质的影响。
Once that N-(2-hydroxyethyl)-N,N-dimethylbutan-1-aminium bromide ([bhyeda][Br]) was identified as the best-performing reaction medium, it was used to synthesize methyl-, methoxy-, alkoxy- and nitro-substituted phthalocyanines with several metal ions.
在确定 N-(2-羟乙基)-N,N-二甲基丁-1-溴化铵([bhyeda][Br])为最佳反应介质后,研究人员利用该介质合成了带有甲基、甲氧基、烷氧基和硝基取代基的多种金属酞菁化合物。
Target products were synthesized in generally high yields, up to 74 %.
目标产物的合成收率普遍较高,最高可达 74%。
The structures of the phthalocyanines discussed in this paragraph are illustrated in Figure 6.
本段讨论的酞菁结构如图 6 所示。

Phthalocyanines synthesized in ionic liquids.
2.2.4 Deep Eutectic Solvents
Deep eutectic solvents (DESs) have garnered widespread attention as efficient and innovative media in the past decade.
过去十年间,低共熔溶剂(DESs)作为一种高效创新的介质获得了广泛关注。
The environmentally friendly nature of deep eutectic solvents (DESs) stems from several key properties, including low vapor pressure, non-flammability, recyclability, biodegradability, and non-toxicity.
低共熔溶剂(DESs)的环保特性源于其多项关键性质,包括低蒸气压、不易燃性、可回收性、可生物降解性以及无毒特性。
DESs typically consist of two components: a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) the nature of which influences their physical properties.
DESs 通常由两种组分组成:氢键供体(HBD)和氢键受体(HBA),其性质会影响它们的物理特性。
By mixing the HBA and HBD components (quaternary ammonium salt or metal salt and species like alcohols, amides, amines, acids, urea, sugars, carboxylic acids, and glycerol, among others, respectively) in a specific molar ratio, a homogeneous solvent is commonly formed with a melting point lower than that of its pure constituents.129 DESs share similar features with ionic liquids but offer considerable advantages, including being derived from biodegradable and non-toxic starting materials, having a cheaper production process, lower cost of raw materials, and importantly, being obtainable from renewable feedstocks and rapidly degradable in the environment.130 Nowadays, DESs have been applied in fields such as inorganic131 and organic synthesis131-133 and biocatalysis.134 To the best of our knowledge, only a few papers discuss the synthesis of phthalocyanines in DESs.
将氢键受体(HBA)与氢键供体(HBD)组分(分别为季铵盐/金属盐和醇类、酰胺类、胺类、酸类、尿素、糖类、羧酸及甘油等物质)按特定摩尔比混合时,通常会形成熔点低于纯组分的均相溶剂。 129 低共熔溶剂(DESs)与离子液体特性相似,但具有显著优势:其原料可生物降解且无毒、生产工艺更经济、原料成本更低,更重要的是可从可再生原料获取并在环境中快速降解。 130 目前 DESs 已应用于无机 131 与有机合成 131-133 及生物催化 134 等领域。据我们所知,仅有少数文献探讨了酞菁类化合物在 DESs 中的合成。
Shaabani et al.135 report the use of several deep eutectic systems based on choline chloride (ChCl) and several hydrogen donors.
Shaabani 等人 135 报道了基于氯化胆碱(ChCl)与多种氢供体的几种低共熔体系的应用。
After optimizing the system and identifying urea as the best choice, ChCl-urea mixtures in a 2 : 1 molar ratio were used for the synthesis of a wide range of unsubstituted and tetra-nitro-substituted metallophthalocyanines with variable yields in times between 10 and 60 minutes.
在优化系统并确定尿素为最佳选择后,采用摩尔比为 2:1 的氯化胆碱-尿素混合物合成了多种未取代及四硝基取代的金属酞菁化合物,反应时间介于 10 至 60 分钟之间,产率各异。
In particular, the synthesis of copper phthalocyanine at 120 °C with a yield of 83 % in just 15 minutes deserves attention, as the result obtained is comparable to those deriving for example from microwave syntheses.
特别是铜酞菁在 120°C 下仅需 15 分钟即可获得 83%收率的合成方法值得关注,其效果可与微波合成等工艺相媲美。
The shorter reaction times, if compared with other procedures in solvents, makes this approach quite interesting and deserving more investigations, especially to evaluate the tolerance of the solvent system to the functional groups possibly present on the starting phthalonitrile and the possibility of recycling it to reuse it several times.
与其他溶剂工艺相比,更短的反应时间使该方法颇具研究价值,值得进一步探索,特别是评估该溶剂体系对起始邻苯二甲腈中可能存在的官能团的耐受性,以及回收溶剂实现多次循环利用的可能性。
In 2020 CuPc was synthesized using the same DES.136 The highest yield was 90 % and was obtained with 1 : 3–1 : 4 mixtures of choline chloride and urea.
2020 年,研究人员采用相同的低共熔溶剂(DES)合成了铜酞菁(CuPc)。当氯化胆碱与尿素以 1:3 至 1:4 的比例混合时,可获得最高 90%的产率。
The authors prove recyclability of the reaction medium up to five times before observing degradation of the components.
作者证实该反应介质可循环使用五次后才会出现组分降解。
2.2.5 Solid-State Synthesis
Solid state syntheses take the minimization of the quantities of solvent used to extreme consequences, avoiding its use altogether or reducing it by orders of magnitude compared to conventional procedures.
固态合成法将溶剂用量的最小化推向极致,与传统工艺相比完全避免使用溶剂或将其用量减少数个数量级。
Energy input can be provided by heating or mechanochemistry, thus employing mechanical forces to enable chemical reactivity.
能量输入可通过加热或机械化学方式提供,即利用机械力实现化学反应活性。
When heating, reaction temperatures equal to or higher than the melting temperature of one or more reagents are frequently chosen, to increase contact between them and improve yields.
加热时,常选择等于或高于一种或多种试剂熔点的反应温度,以增加它们之间的接触并提高产率。
We point out that, for simplicity, we will refer to this specific type of procedure as “solid state” even though it technically occurs in a liquid phase due to the reaction conditions.
需要说明的是,为简化表述,我们将这类特定操作流程统称为"固态"反应,尽管在反应条件下该过程实际发生于液相中。
The main drawback of syntheses in molten mixtures is the high temperatures required, often equal to or higher than those of corresponding solution-based methods.
熔融混合物合成的主要缺点在于所需温度较高,通常等于或高于相应溶液法的反应温度。
Additionally, the thermal energy involved, combined with the high concentration of reagents and reaction intermediates, can promote degradation processes or the formation of by-products, potentially catalyzed or influenced by impurities such as oxygen or humidity if the reaction setup is not meticulously controlled.
此外,所涉及的热能,加上高浓度的试剂和反应中间体,可能促进降解过程或副产物的形成,如果反应装置未得到精细控制,这些过程还可能受到氧气或湿度等杂质的催化或影响。
Nonetheless, we believe it is worthwhile to describe some methodologies where temperatures are kept within 150–170 °C, such as those reported for solvents like glycerol and anisole in this review.
尽管如此,我们认为仍有必要介绍一些将温度控制在 150-170°C 范围内的合成方法,例如本综述中提及的以甘油和苯甲醚为溶剂的案例。
Molten urea is typically employed both as a solvent and a source of nitrogen when phthalic precursors are used,137 though there are also reports of its use with phthalonitriles.138 In 2013, Lokesh et al.
当使用邻苯二甲酸前体时,熔融尿素通常既作为溶剂又作为氮源, 137 不过也有报道称其可与邻苯二甲腈配合使用。 138 2013 年,Lokesh 等人
reported on the synthesis of functionalized palladium phthalocyanines, achieving some derivatives by simply mixing phthalonitriles with a desired salt and heating to 140–160 °C.139 While the yields are promising, the authors suggest possible contaminations by impurities, likely due to the formation of phthalocyanine oligomers as suggested by evidence in the Q-band absorption region of the UV-Vis spectra and small discrepancies between theoretical and experimental elemental analysis values.
报道了功能化钯酞菁的合成方法,通过简单混合邻苯二甲腈与目标盐并在 140–160°C 加热即可获得部分衍生物。尽管产率表现良好,但作者指出可能存在杂质污染,这可能是由于酞菁低聚物的形成所致——紫外-可见光谱 Q 吸收带的证据及元素分析理论值与实验值的微小差异均支持这一推断。
Reducing the environmental impact of synthesizing palladium derivatives is a pertinent topic, given their potential catalytic activity in palladium-mediated C−C couplings.
鉴于钯衍生物在钯介导的碳-碳偶联反应中潜在的催化活性,降低其合成过程对环境的影响已成为一个重要议题。
This has recently been demonstrated to be feasible for Sonogashira coupling of triple bonds with aryl halides at room temperature without the need for phosphine ligands.140 Remaining within the topic of catalysis and transitioning to the equally broad and relevant subject of producing biofuels and carbon-based chemicals through CO2 reduction, we highlight the solventless synthesis of tetra-nitro cobalt phthalocyanine in molten urea starting from 4-nitrophthalonitrile, cobalt chloride hexahydrate, and a catalytic amount of ammonium heptamolybdate tetrahydrate ((NH4)6Mo7O24 ⋅ 4H2O), reported in 2019 by Wu et al.11 This compound, obtained in a 44 % yield, serves as a direct precursor to tetra-amino cobalt phthalocyanine, which is among the first transition-metal-based molecular electrocatalysts capable of performing the six-electron reduction of CO2 to methanol with an appreciable activity and selectivity when immobilized on carbon nanotubes.
最近研究表明,在室温下无需膦配体即可实现三键与芳基卤化物的 Sonogashira 偶联反应。 140 围绕催化主题,我们转向同样广泛且相关的领域——通过 CO 2 还原制备生物燃料及碳基化学品。值得关注的是 Wu 等人于 2019 年报道的无溶剂合成法:以 4-硝基邻苯二甲腈、六水合氯化钴及催化量四水合七钼酸铵((NH 4 ) 6 Mo 7 O 24 ·4H 2 O)为原料,在熔融尿素中合成四硝基钴酞菁。 11 该化合物以 44%收率获得,可作为四氨基钴酞菁的直接前体。后者作为首批过渡金属分子电催化剂,当固定在碳纳米管上时,能以显著活性和选择性实现 CO 2 六电子还原制甲醇。
In 2022, Langterreiter et al.
2022 年,Langterreiter 等人
investigated the solid-state synthesis of tetra-tert-butylphthalocyanines.141 They developed a synthetic procedure based on a combination of mechanochemical liquid-assisted grinding and aging at a certain temperature, optimizing it by systematically varying a series of variables.
研究了四叔丁基酞菁的固态合成方法。他们开发了一种基于机械化学液体辅助研磨与特定温度下老化相结合的合成工艺,并通过系统改变一系列变量对其进行了优化。
In particular, the use or not of the ball mill as the initial step, the quantity of DMAE and DBU and the temperature and aging time were systematically varied obtaining conversions of up to 99 %.
特别是通过系统调整是否使用球磨作为初始步骤、DMAE 和 DBU 的用量以及温度和老化时间,转化率最高可达 99%。
The procedure was then successfully applied to a series of metal ions to verify their tolerability.
随后,该方法被成功应用于一系列金属离子以验证其耐受性。
Regarding scalability, the reaction was tested up to 2 grams of reagent without substantial changes in conversion, a remarkable result in the context of the synthesis of phthalocyanines on a laboratory scale.
关于可放大性,该反应在试剂用量高达 2 克时仍能保持转化率基本不变,这一结果在实验室规模酞菁合成领域堪称卓越。
Mechanochemical synthesis is so far generally underexplored in the literature regarding phthalocyanines.
目前关于酞菁类化合物的机械化学合成在文献中研究相对不足。
Recently, Fan et al.
最近,Fan 等
reported the synthesis of a series of phthalocyanine polymeric materials with hierarchical porosity by exploiting a mechanochemical approach (Figure 7).142 The possibility of working with reagents that are poorly soluble and have a high melting temperature by exploiting the mechanical energy of the ball mill allows for easy access to classes of materials that would otherwise be difficult to obtain.
报道了通过机械化学方法合成一系列具有分级孔隙结构的酞菁聚合物材料(图 7)。 142 利用球磨机的机械能处理难溶且高熔点的试剂,使得这类通常难以获得的材料能够被轻松制备。

Two examples of polymeric phthalocyanines synthesized with ball-milling methods.
2.3 Alternative Experimental Conditions Aimed at Lowering the Reaction Temperature
Since the 1990s, literature has featured articles discussing the synthesis of phthalocyanines at low temperatures. The advantage of reducing the temperature for phthalocyanine ring formation lies in its capacity to minimize both the energy input required for the process and the formation of undesirable byproducts during synthesis. Achieving lower temperatures comes at the price of significantly longer reaction times, with the increase theoretically scaling proportionally with the desired temperature decrease. In 1996, Leznoff et al. reported the synthesis of several tetra- substituted zinc derivatives using lithium octan-1-olate in octan-1-ol at 20 °C or lithium-dimethylaminoethanolate in DMAE at 3, 20 and 50 °C.143.
Specifically, they tested their experimental procedures on phthalonitrile and several of its 3- and 4- derivatives like 4-neopentoxyphthalonitrile, 4-nitrophthalonitrile, 3-neopentoxyphthalonitrile, 3-p-butylbenzyloxyphthalonitrile and 3-methoxyphthalonitrile to obtain the derivatives RT1, 2, 3 and 4 respectively. As expected, the reaction time was inversely proportional to the temperature. The highest yield achieved was 56 % for PcH2 synthesized at 50 °C for 24 hours. In contrast, condensation of 4-nitrophthalonitrile in Li-DMAE at a temperature as low as 3–5 °C resulted in obtaining 2(3),9(10),16(17),23(24)-tetranitrophthalocyanine with a 45 % yield over a period of 3–5 weeks. This remarkable result is likely due to the activation of the CN group by the strongly electron accepting nitro group, along with the presence of THF in solution. Notably, the yields of other derivatives at that temperature did not exceed 10 %. While 2(3)9(10),16(17),23(24)-tetrasubstitited phthalocyanines were synthesized as mixtures of regioisomers, only one isomer was obtained for the 1,8,15,22-tetra-substituted phthalocyanines. The authors suggest that the observed phenomenon may be attributed to a combination of steric and electronic effects. This is evidenced by the fact that the formation of a single isomer occurs even for phthalonitriles with less bulky functional groups, such as methoxy groups. Various metals in their elemental state have been investigated in different alcohols to determine the most effective combination for achieving room-temperature access to tetra-substituted phthalocyanines.144 Metal-free and metal 2(3),9(10),16(17),23(24)-tetrasubstituted phthalocyanines were prepared at room temperature from phthalonitrile, 4-neopentoxyphthalonitrile (RT1), 4-bis(4-methoxyphenyl)methoxyphthalonitrile (RT5), and 4-[1-(4-ethoxy-3-methoxyphenyl)-1-phenyl]-methoxyphthalonitrile (RT6). The authors reported higher yields and quicker rates of Pc formation at room temperature when lithium metal and long-chain alcohols were used. They rationalize these results by postulating the formation of inverse micelles in which phthalonitriles may intercalate singularly, enhancing the formation of monomeric alkoxyisoindole intermediates,145 or in groups of four or more, favoring a template effect that would be responsible for higher reaction rates and yields. Interestingly, the resulting tetrasubstituted Pcs showed a non-statistical distribution of regioisomers, suggesting that electronic effects could play a crucial role in room-temperature phthalonitriles cyclotetramerization to form phthalocyanines. Uchida et al. investigated the metal-templated synthesis of unsubstituted phthalocyanines in DMF, employing hexamethyldisilazane (HMDS) as the base. They explored reaction temperatures ranging from 80 to 125 °C and tested various molar equivalents of HMDS.146 The procedure proved to be compatible with a variety of metal salts. Once the optimal reaction conditions were identified, they were applied to several 4-substituted phthalonitriles and to naphthalonitrile, yielding the related phthalocyanines and naphthalocyanine between 46 and 68 %. Although the temperature is higher than what would be expected for a synthesis process defined as “low temperature”, the experimental conditions are milder than several others published in the literature. Yields in the range 20–58 % were obtained for the synthesis of metal-free derivatives and 10–72 % for metalated phthalocyanines when using phthalimides and phthalic anhydrides in similar reaction conditions.147, 148 In the literature there are also examples of synthesis of phthalocyanine rings with Rieke metals, highly reactive metal powders generated by reduction of a metal salt with an alkali metal, in short alkyl chain alcohols at temperatures between 20 and 50 °C.82, 149 In 2015, Zheng et al. published a paper in which the tetramerization of unsubstituted and 4-alkyl (RT7) and thioalkyl (RT8, RT9) substituted phthalonitriles was performed at room temperature by using lithium diisopropylamide (LDA) as nucleophile in THF solution.150 By carefully studying the relationships between yields to reactant molar ratio, reaction temperature, and time, several interesting observations have been made. The ideal molar ratio between phthalonitrile and LDA is 1 : 1, since increasing the quantity of the base does not provide significant improvements in the yield of the reaction. The best results have been obtained at 25 °C, with some phthalocyanine formation even at temperatures as low as −20 °C. Also, after 10 minutes the reaction at 25 °C in the optimized experimental conditions afforded the phthalocyanine with a yield of 37.1 %, with no significant improvements if prolonging the reaction. The formation of diisopropylamine anions from LDA, which act as nucleophiles on the cyano group of the phthalonitrile, is suggested as the key step of the reaction mechanism, which is similar to that of alkoxy nucleophiles. The proposed mechanism of the reaction, involving nucleophilic attacks, cyclization, reduction and acidification steps, was further verified with DFT calculations, from which an activation energy as low as 13.16 kcal/mol was estimated. Typically, a reaction with an activation energy of less than approximately 20 kcal/mol is considered accessible at room temperature. Therefore, the formation of phthalocyanine at ambient or even lower temperatures is reasonable due to the low activation energy involved. Figure 8 displays the structures of the phthalocyanines whose synthesis is described in this paragraph.

Phthalocyanines synthesized with solution-based room temperature methods.
3 E-factor Calculations



Entry |
Phthalocyanine |
Quantity of reactant (g) |
Methodology |
Reaction time |
Yield (%) |
E factor [without water] |
Ref |
---|---|---|---|---|---|---|---|
1 |
PcH2[a] |
0.128 |
IL/MW |
5 min |
80 |
TMGT 2870,9 [249,5] TBAB 2871,8 [250,4] |
|
2 |
PcH2[a] |
0.128 |
IL/MW |
3 min |
88 |
TMGT 2612.3 [223.0] TBAB 2612.6 [223.2] |
|
3 |
PcH2[a] |
0.128 |
IL/MW |
5 min |
70 |
TMGT 3287.3 [287.3] TBAB 3288.3 [288.3] |
|
4 |
PcH2 |
0.128 |
DES |
60 min |
32 |
4796.9 [424.2] |
|
5 |
CoPc |
0.25 |
IL |
5 min |
63 |
1633.2 [225.5] |
|
6 |
CoPc |
0.256 |
DES |
25 min |
72 |
958.4 [83.5] |
|
7 |
CoPc |
1.0 g |
benign solvent (Anisole,DBU) |
3 h |
72 |
105.3 [55.5] |
|
8 |
CuPc |
1.0 g |
benign solvent (Anisole, KOH) |
3 h |
76 |
98.9 [52.1] |
|
9 |
CuPc |
1.0 g |
benign solvent (Glycerol/anisole, DBU) |
3 h |
73 |
103.6 [54.9] |
|
10 |
CuPc |
0.25 |
IL |
5 min |
76 |
1358.1 [187.5] |
|
11 |
CuPc |
0.256 |
DES |
15 min |
83 |
824.6 [71.7] |
|
12 |
ZnPc |
1.0 g |
benign solvent (Anisole, DBU) |
3 h |
56 |
133.2 [69.9] |
|
13 |
ZnPc |
0.25 |
IL |
10 min |
59 |
1799.2 [296.1] |
|
14 |
ZnPc |
0.25 |
IL |
10 min |
59 |
1799.2 [296.1] |
|
15 |
FePc |
0.25 |
IL |
5 min |
58 |
1803.9 [249.2] |
|
16 |
FePc |
0.256 |
DES |
40 min |
60 |
1157.0 [101.3] |
|
17 |
PdPc |
5.0 |
solid state |
2 h |
93 |
78.3 [42.6] |
|
18 |
PtPc |
1.0 |
MW |
5 min |
93 |
95.6 [64.4] |
|
19 |
(NO2)4-PcH2[a] |
0.173 |
IL |
25 min |
74 |
TMGT 2301.5 [200.2] |
|
20 |
(NO2)4-CoPc |
0.25 |
IL |
10 min |
43 |
1213.4 [344.7] |
|
21 |
(NO2)4-CoPc[b] |
1.73 |
solid state |
5 h |
44 |
585.2 [500.9] |
|
22 |
(NO2)4-ZnPc |
0.25 |
IL |
10 min |
40 |
1293.4 [366.7] |
|
23 |
(NO2)4-PdPc |
6.5 |
solid state |
3 h |
81 |
94.3 [51.3] |
|
24 |
(NO2)4-PtPc |
1.0 |
MW |
5 min |
90 |
106.0 [71.4] |
|
25 |
(t-bu)4-CoPc |
0.203 |
benign solvent (1,2-propane diol/anisole, DBU) |
6 h |
33 |
1124.0 [1008.0] |
|
26 |
(t-bu)4-CuPc |
0.200 |
benign solvent (1,2-propane diol, DBU) |
3 h |
55 |
316.5 [233.1] |
|
27 |
(t-bu)4-ZnPc |
0.200 |
benign solvent (1,2-propane diol, DBU) |
3 h |
51 |
696.7 [624.7] |
|
28 |
MW1 |
1.0 |
MW |
8 min |
75 |
290.0 [160.1] |
|
29 |
MW2 |
0.8 |
MW |
8 min |
80 |
276.3 [151.3] |
|
30 |
MW3[c] |
0.31 |
MW |
10 min |
75 |
156.9 [116.0] |
|
31 |
MW4 |
1.0 |
MW |
8 min |
85 |
245.8 [134.7] |
|
32 |
MW5 |
0.7 |
MW |
8 min |
75 |
329.0 [179.7] |
|
33 |
MW6 |
0.7 |
MW |
8 min |
75 |
434.0 [248.8] |
|
34 |
MW7 |
0.8 |
MW |
8 min |
80 |
455.6 [288.9] |
|
35 |
MW8[d] |
2.1 |
MW |
7 min |
83 |
61.0 [57.2] |
|
36 |
MW11 |
34.58 |
MW |
5 min |
90 |
158.0 [69.3] |
- [a] 10 mL of water were estimated to be used to wash the phthalocyanine after precipitation from sulfuric acid/water. [b] The catalytic amount of (NH4)6Mo7O24 ⋅ 4H2O required to perform the reaction was estimated to be 0.035 g (2 % by weight). [c] The amount of water:methanol 1 : 3 mixture employed in the workup was estimated to be 20 mL for each step. [d] 10 mL of methanol were estimated to be used to precipitate the phthalocyanine during the workup.
The methanol used for the Soxhlet extraction is not considered in the calculation, as the same batch can be reused many times.
The first observation upon examining the table is the magnitude of the numbers presented. In many cases, E-factors exceed 1000. These values, pertaining to single synthetic steps, are notably high when compared to other reference values on a laboratory scale. Syntheses considered environmentally sustainable typically score values up to a few hundreds, depending on the number of steps involved.151, 152 According to data reported in the table, there is not a methodology that stands out among the others. Microwave-assisted syntheses on average show the best results. E-factors look quite consistent, with only a few exceptions above 300 including water. Instead, for syntheses based on ionic liquids and deep eutectic solvents, E-factors above 1000 are frequently achieved, which is surprisingly high considering that the reaction media are reusable. A comparison between the values with and without water, the latter lower even by an order of magnitude, reveals that the biggest issue lies in its use in the workup and purification steps. Although we have already pointed out that water may not present critical environmental issues, such significant discrepancies deserve to be highlighted. E-factor values for benign solvents suffer great fluctuations, ranging from 98.9 to 1124.0, mostly depending on reaction yields and isolation of some target products using chromatography. Generally speaking, workup and purification steps appear to be materials-demanding in phthalocyanine synthesis and it is likely that their optimization has not yet been addressed as much as the synthetic procedures. For instance, the two reported syntheses of (NO2)4-CoPc (entries 20 and 21 in Table 1) exhibit very different E-factors despite having the same yields. We highlight that working with small reaction batches, as in the case of entry 20, can significantly amplify the E-factor compared to larger reaction batches. However, as a general criterion, meticulously attending to details in purification processes can help in reducing waste production and improve the environmental (and economic) quality of a synthesis. Lastly, the reaction time is indeed a significant parameter that is worth highlighting in a dedicated column. While not considered in the calculation of the E-factor, the energy consumption of a synthesis conducted on a hot plate for several hours is inherently more impactful than one performed in a microwave reactor for just a few minutes. When comparing different synthetic procedures, this information should therefore be considered.
4 Summary and Outlook
Green chemistry is a powerful tool to advance research in the synthesis of phthalocyanines towards improved economic and environmental sustainability. Given their widespread use in cutting-edge technologies such as clean energy production, rethinking their synthesis with sustainability in mind is of significant interest. Given the general requirements for their synthesis, such as high temperatures (>100 °C), alkaline reaction environment, absence of water, and the common use of problematic solvents, developing general protocols that are truly sustainable proves challenging. Therefore, we believe it is crucial to identify the strengths of each synthetic strategy that we have analyzed and synergistically combine them with one another. This body of work serves as a starting point for identifying new strategies that integrate various aspects discussed here, ultimately aiming to increase yields and purity of products while minimizing waste generation. Microwave radiation-assisted syntheses have been extensively explored and have demonstrated the highest tolerance towards substituents present on the precursor molecule. Undoubtedly, the possibility of working with minimal quantities of solvent entails a great advantage in terms of material consumption and simplicity of workup of the reaction crude. Scaling up optimized synthetic protocols could present challenges due to the need for considerably larger reactors capable of providing adequate homogeneity of irradiation. However, the results achieved on a laboratory scale are already notable. To reduce the E-factor values, which are less sensitive to the quantities of reaction materials compared to other procedures due to the modest or absent presence of solvents, the focus should be on improving the workup and purification processes where possible. As regards benign reaction media, we believe it is interesting to extend the study of low-impact solvents such as glycerol, propylene glycol and anisole also to other substrates, taking into consideration the favorable and unfavorable interactions with the metal ions used and the possible collateral reactions with functional-reactive groups present on the precursors. For example, nitro- and fluoride/chloride precursors may not efficiently react in OH-containing solvents, as the alkaline environment may favor concomitant aromatic nucleophilic substitution. Redesigning the synthesis of functionalized derivatives by leveraging micellar processes in aqueous or other environmentally benign media could open a field of investigation that is currently underexplored. The enormous number of studies on the topic to date allows to outline a plausible action plan, for example envisaging the synthesis of designer surfactants optimized for the synthesis of the phthalocyanine macrocycle. This would open up an entirely unexplored research field concerning the synthesis of phthalocyanines. Furthermore, their general poor solubility in water makes the reaction medium potentially recoverable and recyclable. In addition, it would be worth increasing the solvent portfolio to include significant materials such as poly-ethylene glycols (PEGs) and other benign reaction media. With the aim of synergistically combining two synthetic strategies, and based on what is reported in the literature, it could be extremely interesting to exploit UV irradiation in the first phases of reactions carried out in non-toxic hydroxy-based solvents to increase the number of reactive species capable of nucleophilically attacking the reactants and increasing the quantity of products obtained. The solvothermal approach is extremely useful for the synthesis of three-dimensional architectures with specific properties and large crystals. This latter option would pave the way both to the detailed study of the structural properties of a specific phthalocyanine and to the obtaining of highly ordered materials for technological applications. While interest in the use of ionic liquids for the synthesis of phthalocyanines appears to be on a downward trend, as deduced from the years of publication of the articles we have reviewed, deep eutectic solvents deserve more attention. Their sustainability and recyclability combined with their chemical characteristics make them excellent candidates as low-impact and very effective reaction media. Calculating the E-factor of a selection of phthalocyanine ring syntheses and establishing a database, however limited, of comparable data is a fundamental first step towards applying green chemistry metrics to these processes. While not exhaustive, it provides valuable insights into where strategies should be developed to minimize waste production during synthesis. The high values of the E-factors, along with the significant variability of values obtained for overall similar procedures, underscore the importance of evaluating this metric to swiftly assess whether a process demands improvements, and at which step. In this particular case, we believe that a significant effort should be directed towards minimizing the environmental impact of the purification processes. We are confident that such analysis, combined with the consideration of other parameters such as energy inputs, costs, and intrinsic toxicity of materials used, will contribute to making the synthesis of phthalocyanines significantly less impactful than it currently is.
Acknowledgments
G.Z. and V.R. gratefully acknowledge financial contribution from MUR under Grant PRIN2022 REPLACE (2022C4YNP8). F.P. gratefully acknowledges financial contribution from Regione Lazio's innovation ecosystem «Rome Technopole». Open Access publishing facilitated by Consiglio Nazionale delle Ricerche, as part of the Wiley - CRUI-CARE agreement.
Conflict of Interests
The authors declare no conflict of interest.