Читать книгу Handbook of Aggregation-Induced Emission, Volume 2 - Группа авторов - Страница 15

Although TPP was found to be AIE‐active by Tang in 2015, its research dates back to the mid‐nineteenth century. The early synthesis of TPP was carried out by Laurent in 1845 and later by Erdmann in 1865 [40, 41]. The reaction was carried out by heating benzoin with ammonium chloride at 100 °C for four to six hours. Three main products formed after the reaction named as benzoinam (formula C₂₈H₂₄N₂O), benzoinimide (formula C₁₄H₁₁N), and lophine, respectively. In 1886, Japp and Wilson reinvestigated the reaction. They found that a yellow crystalline powder of benzoinimide formerly obtained was actually impure. After recrystallization with a large amount of alcohol, colorless, slender, and lustrous crystals were collected. Further elemental analysis study indicated that the formula of the compound agreed better with C₂₈H₂₀N₂ than with C₁₄H₁₁N. That is, the name of benzoinimide given by Erdmann is misleading. They thus renamed the compound as ditolane‐azotide and also gave the prototype structure of TPP in the text [42]. It is the first report of TPP.

Since that, the researches on TPP were burgeoning. In 1937, Davidson, Weiss, and Jelling studied the action of ammonia on benzoin [43]. Besides the generated TPP, an imidazole derivative of 2‐methyl‐4,5‐dipenylglyoxaline and tetraphenyldihydropyrazine was formed. It represented the most classical rudiment in the later preparation of TPP. The reaction mechanism was given as below: the carbonyl group of benzoin was possible to convert to imine in the presence of ammonia, followed by generating carbinamine by structural rearrangement, while the hydroxyl group nearby was converted to the carbonyl group. Two formed intermediates can undergo cyclization reaction by condensation and removal of water. After structural tautomerization, a resembling product of tetraphenyldihydropyrazine was formed to oxidize to TPP. On the other hand, the intermediate was also easy to react with the solvent of acetic acid by the amino group and then formed 2‐methyl‐4,5‐dipenylglyoxaline by cyclization (Scheme 1.1). The formation of tetraphenyldihydropyrazine was evidenced by the orange color of the reaction mixture soon after refluxing of the starting materials. Remarkably, oxygen plays a crucial role in the conversion of tetraphenyldihydropyrazine to TPP. It is proved that the yield of reaction solution bubbled with air is higher than that in the closed environment. Nevertheless, the total yield of TPP is in the range from 53 to 57%, and the tetraphenyldihydropyrazine cannot convert to TPP completely even in the presence of enough oxygen. After filtering out the formed crude TPP precipitates, the unreacted tetraphenyldihydropyrazine in the mother liquor can be further oxidized to TPP by adding nitric acid until the orange color of solution was discharged.

Tang also reported the synthesis of TPP by refluxing benzoin, ammonium acetate, and acetic anhydride in acetic acid for 3.5 hours, while the acetic anhydride acts as a dehydrating agent to remove the water after cyclization (Scheme 1.2, Route A, Condition 1) [33]. TPP shows the same polarity with the byproducts as monitored by the silica gel plate. The blue emission of TPP disappeared, while only the orange emission was observed on the plate. It is mainly due to energy transfer taking place from TPP to the byproducts, which dramatically quenches its emission. It implies that the purity of TPP after purification must be rather high because the trace of impurities in TPP will obviously affect its photo‐physical properties. TPP and its byproducts show different solubility in acetic acid. TPP is badly dissolved in acetic acid. It precipitates during the reaction, while most of the byproducts were still left in the solution. The crude TPP powder is collected by filtration and shows a yellow appearance due to the presence of trace impurities. However, repeated recrystallization of crude products in a larger amount of heat acetic acid can afford very pure TPP crystals. The yield (34%) is lower than the above studies, probably due to the loss of product during the purification. The convenience in preparation and purification of TPP makes it very promising for further deep investigations.

Scheme 1.1 Reaction mechanism of synthesizing TPP with benzoin and ammonia.

Scheme 1.2 Current synthetic routes to TPP.

This method not only affords TPP readily but is also useful for preparing its derivatives with diverse structures. For example, by using mono‐ or disubstituted benzoin, di‐ or tetrasubstituted TPP derivatives can be easily obtained. The reaction is less affected by the electronic effect of substituents. However, if the substituents are bulky, the crude products are difficult to purify by recrystallization. It is worth noting that two isomers are usually formed by using monosubstituted benzoin in the reaction. Such behavior is similar to that in the preparation of disubstituted TPE derivatives by the McMurry coupling reaction [44]. The presence of isomerization in TPP derivatives is proved by the fact that four resonance signals exist around 148 ppm in their ¹³C NMR spectra due to the four different chemical environments of carbon atoms in the pyrazine ring [33].

Tamaddon used SnCl₂·2H₂O as a catalyst to synthesize α‐amino ketones with benzoin and aniline as starting materials under solvent‐free conditions at either 80 °C or microwave irradiation [45]. Although the yields of reaction are high (up to 83%), the undesired byproduct of 1,4‐dibenzyl‐2,3,5,6‐tetraphenyl‐1,4‐dihydropyrazine is formed as examined by the NMR analysis, which is possibly due to the self‐condensation of the in situ formed α‐amino ketones. Further investigation indicated that under the same catalytic condition, a [2 + 1 + 1 + 2] four‐component reaction of benzoin and ammonium acetate can generate TPP in a high yield of 90% (Scheme 1.2, Route A, Condition 2). It provides a convenient strategy to prepare tetrasubstituted tetraphenylpyrazines in high yields. The substituents on benzoin are widely alternative. For example, by using methoxyl‐, methyl‐, bromine‐, chlorine‐, and fluorine‐substituted benzoins, the reactions can proceed smoothly. However, as the electron‐donating property of substituents increases, the yield of reactions slightly decreases.

Subsequently, Tamaddon found that the multicomponent reaction can be carried out without SnCl₂·2H₂O as catalyst (Scheme 1.2, Route A, Condition 3) [46]. That is, SnCl₂·2H₂O is not necessary in the reactions. By directly heating the solid mixture of benzoin and ammonium acetate at 80 °C, the product can be obtained in a very high yield. Overall, this reaction is very close to the original one reported by Laurent, Erdmann, Japp, and Wilson, except that the ammonium chloride has been replaced by ammonium acetate. This optimal reaction condition was confirmed by the author after evaluation of the influence of ammonium salt, solvent, and reaction temperature on the reaction efficiency. The yields remain high in the reaction of benzoin derivatives regardless of the electron effect of the substituents. The reaction mechanism was similar to the previous one. Ammonium acetate releases the ammonia by heating to react with benzoin to generate an intermediate. Because the ammonium acetate is subtly excess, few acetic acid is formed, which can hardly react with the intermediate to produce 2‐methyl‐4,5‐dipenylglyoxaline. On the other hand, the solid‐state reaction allows the full contact of reactant with air. Both the factors may decide a high yield of reaction.

Khafizova reported a new one‐pot synthesis of tetrasubstituted TPP derivatives based on the reaction of nitriles with EtAlCl₂ catalyzed by metallic Mg and Cp₂TiCl₂ (Scheme 1.2, Route B) [47]. The reaction is efficient, and the product can be obtained in good yields of 60–90%. The catalytic system of Ti and Zr complexes such as Cp₂TiCl₂, Ti(PrⁱO)₄, TiCl₄, Cp₂Ti(PMe₃)₂, Ti(acac)₂Cl₂, Ti(Net₂)₄, and Cp₂ZrCl₂ is investigated to examine the influence on the reaction. Only Cp₂TiCl₂ and Ti(Pr_iO)₄ display superior catalytic activity and selectivity. Besides, the reaction has a wide universality of nitriles. For example, by using the starting materials of 2‐methyl‐, 3‐methyl‐, 4‐methyl‐, 4‐isopropyl‐, 3,5‐dimethyl‐, and 4‐methoxy‐substituted benzonitriles, different TPP derivatives with the tetrasubstituents can be obtained efficiently. The probable mechanism of this reaction was also given. Cp₂TiCl₂ was first reduced to the coordinatively unsaturated Cp₂Ti(II) complex by activated Mg. Then, two nitriles can coordinate with the Cp₂Ti(II) complex to form titanium‐nitrile π‐complexes, followed by transforming to diazatitanacyclopentadiene intermediate A. Subsequently, two additional nitrile molecules are inserted into the active Ti–N bonds of the intermediate, which gives rise to ring expansion to form the unsaturated tetraaza derivative B. The excess EtAlCl₂ reacts with B to replace the metal center to generate intermediate C, which further results in TPP by skeletal isomerization after elimination of aluminadiazirine (Scheme 1.3).

Catalytic system based on ruthenium chemistry has been widely investigated because it plays an important role in arene hydrogenation, hydrogenation of carbonyl compound, click reaction, and so on. Leeuwen employed ligand‐modified ruthenium nanoparticles (RuNPs) to catalyze the transfer hydrogenation of α‐diketone. Interestingly, the unexpected product of TPP was produced by reacting the mixture of benzyl and ammonium formate in dimethyl formamide (DMF) at 85 °C with dbdocphos‐stabilized RuNPs as catalyst (Scheme 1.2, Route 3) [48]. A very high yield (>98%) of product was monitored by GC analysis, and the byproducts are water, carbon dioxide, and dihydrogen. However, the reaction affords another product of triphenyloxazole in a yield of 30% in the absence of catalyst, proving that the Ru‐based catalyst is indispensable in the reaction process. Besides dbdocphos, other phosphines such as dppp, DPEphos, and Xantphos are also used to prepare RuNPs. Among these, Xantphos‐supported RuNPs behave similarly to the dbdocphos‐based catalyst in activity and selectivity. The influence of nitrogen source on the reaction was studied. By replacing ammonium formate with ammonium acetate, ammonium chloride, and aqueous ammonia solution, no product of TPP can form, whereas, in the first case, only triphenyloxazole in a 30% conversion is obtained. The efficient catalytic system also has good group tolerance to provide tetrasubstituted TPP derivatives with different structures. The proposed mechanism of the reaction assumes that the benzyl first undergoes reductive amination under transfer hydrogenation conditions to generate α‐amino ketone with RuNPs as catalyst. Then, the molecule self‐condenses by removing the water, followed by tautomerization and oxidation to give TPP (Scheme 1.4).

Scheme 1.3 Proposed mechanism of synthesizing TPP catalyzed by Mg and Cp₂TiCl₂.

Scheme 1.4 Proposed mechanism of preparing TPP catalyzed by RuNPs.

Different from the above reactions, benzil can directly react with dipenylethylenediamine in acetic acid under reflux for four hours to afford TPP (Scheme 1.2, Route 4) [33]. The product was obtained in a satisfactory yield of 47% after recrystallization. A large amount of benzil derivatives with mono‐ or disubstituents can be prepared readily or purchased at low cost. However, the synthesis and purification of dipenylethylenediamine derivatives are difficult. Thus, this method is very helpful to prepare mono‐ or disubstituted tetraphenylpyrazines.