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Review

Hemetsberger–Knittel and Ketcham Synthesis of Heteropentalenes with Two (1:1), Three (1:2)/(2:1) and Four (2:2) Heteroatoms

by
Zita Tokárová
1,*,
Renáta Gašparová
1,
Natália Kabaňová
1,
Marcela Gašparová
1 and
Róbert Balogh
1,2
1
Department of Chemistry, Faculty of Natural Sciences, University of St. Cyril and Methodius in Trnava, 917 01 Trnava, Slovakia
2
Polymer Institute, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 41 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
Reactions 2023, 4(2), 254-273; https://doi.org/10.3390/reactions4020015
Submission received: 7 March 2023 / Revised: 4 April 2023 / Accepted: 28 April 2023 / Published: 8 May 2023
Browse Figures
Versions Notes

Abstract

:
The synthetic methods leading to furo[3,2-b]pyrroles and thiazolo [5,4-d]thiazoles are reviewed herein. Furo-, thieno- and seleno [3,2-b]pyrroles are related to heteropentalenes, containing two heteroatoms in the entire structure, one each per core. The synthetic approach follows the Hemetsberger–Knittel protocol covering three reaction steps—the nucleophilic substitution of halogen-containing aliphatic carboxylic acid esters, Knoevenagel condensation and, finally, thermolysis promoting the intramolecular cyclocondensation to O,N-heteropentalene. The Hemetsberger–Knittel reaction sequence is also known for the preparation of O,N-heteropentalenes with three heteroatoms (2:1) and their sulphur and selen heteroatoms containing structural analogues and bispyrroles. The synthetic approach towards thiazolo [5,4-d] thiazoles represents a more straightforward route, according to the Ketcham cyclocondensation. Proceeding with the Ketcham process is more challenging since it occurs stepwise and the formation of by-products is obvious. Thiazolo [5,4-d]thiazole is a representative of the aromatic heteropentalene with four heteroatoms in the structure—twinned N and S, two for each of the five-membered rings. The synthetic approaches towards those particular heteropentalnes have been chosen as a consequence of our ongoing research dealing with the design, synthesis and applications of substituted furo [3,2-b]pyrroles and thiazolo [5,4-d]thiazole-based derivatives. While the furopyrroles are known for their pharmacological activity, thiazolothiazoles have become of interest to materials science. We are aware that from a “bank” of existing compounds/procedures not all are presented in this review, and we apologise to respective groups whose research have not been objectively included.

1. Introduction

Annelated [5+5] heterocyclic systems that consist of two-fused, five-membered rings represent a family of heteropentalenes (HPs) [1]. HPs are isoelectronic to pentalenyl dianion (PnDa, Figure 1) [2] with the preserved 10π-electron system since the electron pair/s of heteroatom/s are involved in the conjugation. In combination with the structural planarity and bicyclic motif, HP scaffolds are aromatic [3]. Since the first Ramsden’s classification of HPs into four general types (I–IV, Figure 2) in 1977 [4,5], the number of identified 5-5 bicyclic regioisomers with two heteroatoms, one for each core (1:1), has increased dramatically [1,6]. The presence of four heteroatoms in a structure, two per core (2:2), has led to the rise of basic structural prototypes up to sixteen [7]. Undoubtedly, through the addition of more heteroatoms into the bicyclic system and by variations in modes of fusion altogether, including the non-classical heteropentalenes and betaines, the number of possible isoconjugates has reached an uncountable number. Generally, oxygen, sulphur, nitrogen, selenium and tellurium are the most commonly employed as heteroatoms [1,2,3,4,5,6,7], but a few reports on HPs with phosphorus [8], boron [9] or silicon [10] in the position of heteroatom have recently been published.
For a structural description in combination with the HPs’ nomenclature, the general Formula (1) can be applied for recognising the appropriate hetarene [11] according to:
hetaryl[m,n-p]hetarene
where m,n are numbers of carbon atoms shared by both rings, the p-junction mode reveals the shared bond, hetaryl is the name of a five-membered heterocycle in a prefix, and hetarene is the name of a superior five-membered heterocycle [1,4,6,7,11].
Although there is a plethora of HPs permutations, at the same time they represent a small-organic-type compounds with an advantage of being easily prepared. The ring closure reactions, cyclisations and cycloadditions are obviously performed to obtain a particular HP derivative [12,13,14]. With their synthetic availability, in combination with a variety of advantageous optoelectronic, physicochemical and pharmacological properties, HPs are of significant interest in the fields of both academic research and industry.
With respect to our research aims [15,16], together with taking into account the enormous number of existing derivatives, herein we have highlighted the synthesis of furo [3,2-b]pyrroles (V, Figure 3) using a three-step Hemetsberger–Knittel procedure, and thiazolo [5,4-d]thiazoles (VI, Figure 3) as representative products of the Ketcham reaction. While the furo [3,2-b]pyrroles come from a category of O,N-two heteroatoms containing HPs with applications in pharmaceuticals, the thiazolo [5,4-d]thiazole scaffold consists of two thiazole rings containing a combination of four heteroatoms, nitrogen and sulphur in each annelated core and are very important in applied science for the development of optoelectronic devices such as organic photovoltaic cells (OPV and organic field-effect transistors (OFETs).

2. Furo-, Thieno- and Selenopheno [3,2-b]pyrroles

Furo [3,2-b]pyrroles (V, Figure 3) and their thieno- and selenopheno- analogues are isosteres of the indole ring system in which the benzene ring is replaced by the furan, thiophene or selenophene rings. Efficient synthetic routes to these heterocycles are of great interest [17,18,19] because of their significant biological activity. 4H-Furo [3,2-b]pyrrole derivatives have been screened for their analgesic and anti-inflammatory activity [20], or antituberculotic [21] activity. 4H-Furo [3,2-b]pyrrole-5-carboxylic acid showed inhibitory activity against D-amino acid (DAO) oxidase, which is important for the treatment of schizophrenia [22]. 2,3,5,7-Tetrabromobenzofuro [3,2-b]pyrrole, isolated from a marine Pseudoalteromonas sp., displayed significant antimicrobial activity against methicillin-resistant Staphylococcus aureus [23]. Furo [3,2-b]pyrrole derivatives are also used as fluorescent dyes [24]. Thieno [3,2-b]pyrroles has shown anti-tumorous [25] and antiviral [26] activity. Thieno [3,2-b]pyrrole dimers have promising semiconductive properties [27].

2.1. Hemetsberger–Knittel Synthesis of Furo [3,2-b]pyrroles and Related Compounds

The first preparation of various aromatic or heteroaromatic pyrrole-fused heterocycles was accomplished by H. Hemetsberger and D. Knittel in 1972 [28]. The Hemetsberger–Knittel reaction is a versatile method for the synthesis of functionalised indoles [29,30,31] or azaindoles [32]. The Hemetsberger process has been extended to include the synthesis of many heterocyclic compounds from 2-azido-3-heteroaromatic-acrylates, including nitrogen-containing heteropentalenes [33,34,35].
Hemetsberger–Knittel synthesis requires readily available starting materials with a wide variety of functional groups and often induces good overall yields. The overall process involves three steps: the initial synthesis of an alkyl azidoacetate 3, followed by a base-promoted Knoevenagel condensation of alkyl azidoacetate 3 and an aromatic aldehyde 4 to form 2-azido-3-arylacrylate 5, and finally the thermolysis of the 2-azido-3-arylacrylate 5 in an intramolecular cyclisation to form the fused pyrrole skeleton 1 (Scheme 1). The major limitation of the Hemetsberger–Knittel process emerged from the use of sodium azide and two potentially explosive intermediates, 3 and 5, in sequence [36].

2.2. Behaviour of the Hemetsberger–Knittel Procedure

Alkyl azidoacetates 3 can be synthesised from an alkyl haloacetate 2 and sodium azide, usually by heating in DMF [35], aceton/H2O [37] or methanol [38], producing high yields (85–87%).
The second step of the Hemetsberger–Knittel procedure involves the Knoevenagel condensation of aromatic aldehydes 4 with alkyl azidoacetate 3 to form 2-azido-3-arylacrylates 5 in relatively low yields. Typical yields of 5 have been reported to range from 12% to 65% when five-membered heteroaromatic aldehydes were used [28,39].
The low yields of 5 could be explained [36] due to two primary reasons. First, alkyl azidoacetates 3 decompose in the presence of base, and the decomposition competes with the desired condensation process.
The second reason lies in the hydrolysis of the ester functionality of the alkyl azidoacetate reagent 3, the azido alcohol intermediate and the 2-azido-3-arylacrylate product 5, which is promoted by the hydroxide by-product from the condensation. In the case of the Knoevenagel condensation of furan-2-carbaldehyde and ethyl azidoacetate, the undesired ester hydrolysis product of the azido alcohol intermediate (2-azido-3-hydroxy-3-(furan-2-yl)propanoic acid) 6 has been identified as a side product in yields as high as 40%. In this particular case, this acidic by-product did not undergo dehydration to afford 2-azido-3-(furan-2-yl)acrylic acid (Figure 4) [36].
The third step of the Hemetsberger–Knittel reaction is the thermolysis of the 2-azido-3-arylacrylate 5 in an intramolecular cyclisation to form a fused pyrrole skeleton (Scheme 1). The typical solvents that are used are toluene [18], xylenes [28] or mesitylene [38].

2.3. Mechanism of the Hemetsberger–Knittel Synthesis

The mechanism [40] of the Hemetsberger–Knittel reaction proceeds via an azirene intermediate 8. The first step is the thermal degradation of 2-azido-3-arylacrylate 5, generating molecular nitrogen and nitrene 7. Nitrene 7 is believed to be in equilibrium with the azirine intermediate 8. The subsequent step is the insertion of the nitrene into the cyclic ring followed by a final [1,5] hydrogen shift that is accompanied by the final re-aromatisation, forming the pyrrole core of the fused aromatic system 1 (Scheme 2).

2.4. Application of the Hemetsberger–Knittel Synthesis towards a Variety of [3,2-b]HPs

Hemetsberger and Knittel [28] also reported the synthesis of nitrogen-containing heteropentalenes (Hemetsberger). Furo- thieno- and 4-methyl-4H-pyrrolo [3,2-b]pyrrole-5-carboxylates 1 were synthesised in 85–97% yields by the condensation of appropriate aldehyde 10 with ethyl azidoacetate 3 and the subsequent thermal cyclisation of 2-azido-3-arylacrylate 5 in xylene (Scheme 3). The first synthesis of ethyl seleno [3,2-b]pyrrole-5-carboxylate 12c was later accomplished with an 82% yield by Soth et al. [41].

2.5. Structural Modifications to [3,2-b]HPs through Subsequent Treatment

The synthesis of various substituted furo [3,2-b]pyrrole derivatives was developed by Krutošíková [42,43]. Formylation, nitration, the Mannich reaction and copulation were accomplished. Vilsmeier formylation should preferably take place at the C-2 position of furo- or thieno [3,2-b]pyrrole-5-carboxylate 1, affording aldehydes 16 at an ambient or moderately elevated temperature (Scheme 4).
The reaction of the aldehydes 16 with azidoacetate 3 in the presence of sodium methoxide was found to proceed smoothly to give azide 17, which upon thermolysis in boiling toluene gave diethyl 1,7-dihydrofuro [3,2-b:4,5-b’]dipyrrole-2,6-dicarboxylates 18 in 43 and 45% yields, respectively [44] (Scheme 5).
The condensation reaction of thiophene-2,5-dicarbaldehyde 19 with ethyl azidoacetate 3 generated compound 20, which was further subjected to cyclisation by heating in toluene to form the thienodipyrrole derivative 21 in an 85% yield (Scheme 6). Compound 21 was used as the starting material for the synthesis of thiophene polymers [45]. Compound 21 can be oxidised with an HOF.CH3CN complex to give sulphone 22 with a 95% yield (Scheme 6) [46].
Further applications of the Hemetsberger reaction were also reported in the 1990s [47,48]. The intermediate nitrene I was inserted into a п-deficient heterocycle. The versatility of this approach is shown in the synthesis of pyrrolo [3,2-d]thiazoles or selenazoles 24 (Scheme 7). The thermolysis of the 3-thiazolyl- or 3-selenazolyl-2-azidoacrylates 23 produces these bicyclic heterocycles in high yields (85–90%).
A series of substituted pyrrolo [3,2-d]imidazoles 28 were synthesised by Shaffiee and Hadizadeh [49]. The starting imidazole 25 was converted into the appropriate aldehydes 26 in two steps—the alkylation of the thiol group, and the subsequent oxidation of alcohol with manganese dioxide. The Knoevenagel condensation of aldehydes 26 with ethyl azidoacetate 3 produced acrylates 27, which then underwent thermal cyclisation in boiling xylene to give pyrrolo [3,2-d]imidazoles 28. Compounds 28 were oxidised with m-chloroperbenzoic acid (m-CPBA) to the desired sulphones 29 (Scheme 8).
Schaffie et al. [50] later synthesised substituted pyrrolo [2,3-d]imidazole-5-carboxylates 34 and isomeric pyrrolo [3,2-d]imidazole-5-carboxylates 35 (Scheme 9). The alkylation of 2-alkylimidazole-4-carbaldehyde 30a (or 5-carbaldehyde 30b) with methyl 4′-bromomethylbiphenyl-2-carboxylate 31 gave a 30:70 mixture of aldehydes 32a and 32b, respectively. Both aldehydes 32a and 32b were separated by column chromatography. Further condensation of compounds 32a and 32b with methyl azidoacetate 3 produced acrylates 33a and 33b, and their subsequent cyclisation into the desired compounds 34 and 35 was accomplished through heating in xylene in 32–39% yields (Scheme 9).
2-(Trimethylsilyl)ethoxymethyl- (SEM)-protected pyrazole-2-carbaldehyde 36 was used for the preparation of pyrrolo [3,2-c]pyrazole 38 under Hemetsberger–Knittel conditions. Knoevenagel condensation, followed by the thermal cyclisation of azidoacrylate 37, produced 38 [22] (Scheme 10).
Recently, Sartori et al. [51] described the Hemetsberger–Knittel synthesis of various heteropentalenes. (Scheme 11). The appropriate heterocyclic aldehydes 39 were converted into azido derivatives 40 through the reaction with ethyl azidoacetate 3 and potassium ethoxide in ethanol. The subsequent cyclisation of 40 occurred by refluxing in xylene. The yields of all products 41 were reported to range from 91% to 99%, except for ethyl 1-methyl-4H-pyrrolo [3,2-b]pyrrole-5-carboxylate (54%) and ethyl 1-methyl-6H-pyrrolo [2,3-c]pyrazole-5-carboxylate (18%).

2.6. Application Potential of Seleno-, Thieno- and Pyrrolo [3,2-b]pyrroles as HP Related to Furo[3,2-b]pyrroles

Generally, furo [3,2-b]pyrrole (V, Figure 3), as representative for the category of (1:1), (1:2)/(2:1) heteropentalenes and their derivatives, are known as effective antimicrobial [23], anti-inflammatory [20] and antituberculotic agents [21]. Their thieno-and seleno [3,2-b]pyrrole-type analogues have gained interest due to possessing antivirotic activity [52,53,54], and in the field of proteomics [55,56]. In particular, the derivatives 6-[2-(N,N-dimethylamino)ethyl]-4H-thieno [3,2-b]pyrrole (42, Figure 5) are bioisosteric analogues of the hallucinogen and the serotonine agonists and have become leading derivatives in such fields of medicinal research since their discovery [57].
Thieno [3,2-b]pyrroles, beyond their biological activities, have been investigated as the donor-moieties in a variety of organic semiconductors. Recently, the importance of seleno [3,2-b]pyrrole-type compounds in materials chemistry has been highlighted. In some studies, it has been proposed that through the replacement of the thieno [3,2-b]pyrrole segment by selenophene [3,2-b]pyrrole in a particular compounds such as 43 and 44 (Figure 6), there could be an improvement in the performance of organic field effect transistors (OFETs) [58]. However, the results are not clearly understood since some studies explain the converse trend [59]. Contrary to this, S,N and Se,N-heteroatoms containing HPs, and their N,N-azanalogues, have been always investigated and applied as electron-acceptor units and chromophores in organic photovoltaic devices [59,60,61]. In a novel study, the deep red emission for B/N-doped, ladder-type pyrrolo [3,2-b]pyrroles 45a/45b (Figure 7) has been developed [62]. Such a novel type of dye underwent a fully reversible first oxidation, located on the diphenylpyrrolo [3,2-b]pyrrole core, directly to the di(radical cation) stage.

3. Thiazolo [5,4-d]thiazoles

Thiazolo [5,4-d]thiazole (TzTz) is a conjugated (π)-heterocyclic scaffold containing two fused thiazole rings presenting a rigid planar structure (46, Figure 8) [63]. Unsubstituted TzTz is a white powder containing two nitrogen, two sulphur and four carbon atoms, and without a wide range of utilisation, but its derivatives have attracted enormous attention.
According to ScienceDirect® 490 and Scopus®, 289 peer-reviewed papers/articles on TzTz compounds were published between 1959 and 2021 (Figure 9). The first papers published by Johnson and Ketcham presented only the preparation of TzTz and provided some other general information, such as UV–Vis spectra, mass spectra and IR characterisation [64]. The number of papers showed a slight increase until 2004, when the first TzTz based donor–acceptor–donor molecules were presented [65,66]. Since 2008, the trend has been for a rapid increase in research works focusing on intensive studies of applications of TzTz in organic electronics. In particular, since the first n-type thiazolo [5,4-d]thiazole-based organic field-effect transistor (OFET) was presented [67], reports on TzTz-containing materials have increased almost exponentially [68]. Although the applications of TzTz-type materials in the development of OFETs [69], organic-light emitting diodes (OLEDs) [70], optical sensors [71] and organic redox flow batteries [72] have already been described, TzTz-based organic photovoltaics (OPVs) [73], including dye-sensitised solar cells (DSSCs) [74], bulk heterojunction solar cells (BHJ) [75], perovskite solar cells [76], hybrid solar cells [77] and polymer solar cells [78] with high values of power conversion efficiency (PCE), ranging from 3% up to a maximum of 17%, have been presented in a vast number of research works. Concerning the structure of the heterocyclic core, the functionalisation of thiazolo [5,4-d]thiazole-based derivatives towards materials with efficient charge transfer, [79] intense absorption and strong fluorescence, [80] as well as higher solubility, is due to the lack of free positions handled mainly through the substituents at C2 and C7 (46, Figure 8) [81].

3.1. Ketcham’s Cyclocondensation Reaction

Pioneering synthesis of TzTz-based compounds was performed by John Johnson and Roger Ketcham, who published their work in 1960. The goal of the authors was to monitor the condensation of dithiooxamide (48) with different aromatic carbaldehydes (47) [64]. A condensation experiment (Scheme 12) was carried out in different solvents (benzyl chloride, phenol, benzene and chloroform) at boiling point temperature. The most commonly used solvents were N,N-dmiethylformamide (DMF), nitrobenzene, chlorbenzene and phenol, or a solvent-free method was applied. The presented TzTz derivatives were formed in moderate to good yields (7–78%). A curiosity concerning the synthesis was that the first condensation between the aromatic aldehyde with rubeanic acid was performed by Ephraim in 1891 [82], but in that period the structure of the products was primarily misstated as 2,2’-diaryl-4,4’-bisthiazetine (49, Scheme 12) [83]. Later, the correct structure of TzTz-based derivatives was confirmed.
Ketcham cyclocondensation is the most widely utilised process for the synthesis of TzTz-based derivatives, mainly symmetrically substituted by aromatic and heteroaromatic rings (Scheme 12). On the one hand, the reaction represents a very available process since it represents a single step, one-pot method which does not require an inert atmosphere or cooling [84] and can be performed under solvent-free conditions using microwave irradiation [85]. Moreover, dithiooxamide and a broad range of aldehydes are widely affordable at good prices. Still, such an elegant synthetic approach is accompanied by a few drawbacks, such as long reaction times, high reaction temperatures and the formation of products in poor to average yields [86,87,88,89,90]. The formation of by-products, as a consequence of the stepwise process, probably contributes the most to lowering the yield of the desired products.

3.2. Mechanism of the Ketcham Reaction

In our previous work [16], we presented the completed mechanism of the Ketcham stepwise process. The proposal was based on our experimental observation, and the structural characterisation of the main products and by-products [16]. Our proposal was supported by data from the literature [91,92], where the authors proposed a shortened version of the mechanism or highlighted the formation of by-products 51 and 54 (Figure 10) resulting from the process’ behaviour. In detail, according to Scheme 13 the condensation of two equivalents of substituted furan-2-carbaldehyde (50) produced the stable imine-type derivative 51. Such iminie-type derivatives are formed during the early stage of the reaction that is followed by a ring-closing reaction, producing the non-isolable dihydro intermediate 52. The process is completed by double intramolecular rearrangement of the dihydro intermediates 52, 53, ending up with oxidative cyclisation to furan-substituted TzTz 55. Some improvements to the oxidation step were presented by the use of SeO2 as an oxidising agent [93]. This approach shows oxidation from the cyclised 2,3-dihydrothiazolo [5,4-d]thiazole (Scheme 13, Pathway B). The free amino group of the initially formed single thiazole ring allows condensation with another amount of aldehyde. The intermediate bearing the -SH moiety, possibly dimerize, forms the bisthiol-type compound 54 in which the S-S bond is subsequently cleaved. The unsaturated TzTz core is oxidised further. In spite of that, the presented proceeding could be taken as being hypothetical, according to two independent research works previously published in [16,93]. It has to be mentioned that the formation, isolation and identification of intermediate bis-thiol type derivative 54 (Figure 10) was possible only if the presence of the oxygen atom of the substituent stabilised the nitrogen of the imine bond by intramolecular effects. Such a phenomenon, nevertheless, has not been discussed as of yet.

3.3. Synthesis of Asymmetrical Thiazolo [5,4-d]thiazoles by Ketcham’s Reaction

It is quite surprising to achieve an asymmetrically substituted TzTz-based compound through simple cyclocondensation. To the best of our knowledge, there have only been two examples of such phenomenon in the literature presented until now.
The first example was presented in the literature very recently, in 2022, and it shows the use of two different carbaldehydes, pyrene-1-carbaldehyde 55 and 4-pyridinecarboxaldehyde 56, in a ratio of 1:1 in cyclocondensation with dithiooxamide (48) towards C2-pyrene and C7 p-pyridine-substituted thiazolo [5,4-d]thiazole 57 (Scheme 14) [94]. Interestingly, the authors report only the sole asymmetric product; however, the character of this reaction would possibly enable the formation of symmetrical products as well.
Another example of the achievement of asymmetrical TzTz derivative 56 using a direct Ketcham procedure was presented recently [95]. The reaction of ferrocenyl aldehyde (58) with protochatecuic aldehyde (59) produced thiazolo [5,4-d]thiazole 60 (Scheme 15).

3.4. Cyclopolymerisations Following Ketcham’s Reaction Protocol

Recently, a very promising way to achieve a TzTz-based oligomer or polymer directly was offered by the simple Ketcham’s synthetic protocol. Instead of a small-molecule thiazolo [5,4-d]thiazole-type derivative, the compound had approximately two to seven repeating TzTz units in the final oligo- or polymer. Such types of reactions are rather rare, but this seems to be very promising for the construction of organic materials with enhanced π-conjugation and the required electronic properties. Reports on Ketcham-type polycondensation have recently garnered interest. At the moment, there are on average only ten reports [96,97,98,99,100,101,102,103,104,105] presenting the direct Ketcham reaction approach towards TzTz-based oligomers and polymers.
  • The first report, published in 2016 [96], presented the synthesis of a 9-hexyl-9H-carbazole-unit bearing a TzTz-based oligomer 61 with seven repeating units (Figure 11a). A similar product geared towards the same oligomer was presented in 2021 [97].
  • The polycondensation reaction of the Ketcham-type of dithiooxamide with triethylamine and carbazole-based aldehydes was published by Dabuliene at al. in 2022 [98]. GPC analysis showed the average molecular weights of triphenylamine-based compounds (62) (Figure 11b) between 2980 and 3080, while in the case of carbazole containing derivatives (63) it was from 1640 to 3290. The published GPC results indicated that the molecules contained approximately three to seven repeating units.
  • Zhu et al. (2014) [99] demonstrated the preparation of a porous cross-linked polymer 64 (Figure 11c) containing TzTz and phenyl units. Similar phenyl-based monomers with three carbaldehyde groups, such as tris(4-formylphenyl)-benzene and tetra(4- formylphenyl)-benzene, can be also condensed with dithiooxamide to give a cross-linked copolymer with a porous structure [100].
  • The polycondensation of 1,3,5−triformylfloroglucinol with 4,4′-(thiazolo [5,4-d]thiazole-2,5-diyl)dianiline gave a crosslinked copolymer 65 with a porous structure (Figure 11d) [101,102].
  • Cross-linked copolymer 66 was synthesised by the condensation of dithiooxamide with (1,3,5- tris(4-formylphenyl)-benzene) or with (2,4,6-tris(4-formylphenyl)-1,3,5-triazine (Figure 11e) [103].
  • Finally, the structure of cross-linked polymers 67 as products of Ketcham’s type polycondensation of dithiooxamide with different monomers containing multiple carbaldehyde groups was described according to [104] (Figure 11f).
  • The polycondensation approach following the Ketcham procedure was successfully used to achieve porous, cross-linked copolymer containing porphyrin-residues 68 (Scheme 16) [105].
With the final example presented in Scheme 16, it can be concluded that the utilisation of Ketcham’s ring-closure method significantly extends beyond its generally accepted potential. The polycyclocondensation approach is, moreover, a novel alternative way to achieve novel functional materials using a simple, one-step manner affecting significant cost-reduction and enhancement of the eco-friendliness of the entire process, from design through synthesis up to real-life application.

4. Conclusions

In combination with our several years of experience in the field of synthesis and applications of furo [3,2-b]pyrroles and thiazolo [5,4-d]thiazole-based derivatives with respect to published research work, the knowledge and current “state-of-the-art” of the Hemetsberger–Knittel synthesis regarding furopyrroles and their sulphur- and seleno- heteroatom containing derivatives and the Ketcham cyclocondensation methodology affording thiazolothiazoles is detailed herein. The primary interest is focused on the preparation processes, benefits and drawback of each method. The mechanism or the proposal of the mechanism is discussed. Both types of discussed heteropentalenes are very important in applied sciences. Furo [3,2-b]pyrroles exhibit a variety of pharmacological effects, and thiazolo [5,4-d]thiazole are targets of materials research, particularly in the field of optoelectronic materials. Both the Hemetsberger–Knittel approach and the Ketcham synthesis represent a versatile route towards a concrete type of heteropentalenes. Under current review are insights into both methodologies with the ambition of the further design and synthesis of a novel type of heteropentalenes with two (1:1); three (1:2)/(2:1) and four (2:2) mainly O, S,N heteroatoms. Both series of compounds are of prospective interest for pharmacological sciences (furopyrroles) and for materials research (thiazolothiazoles). Current applications of thieno-, selenopheno, pyrrolo [3,2-b]pyrroles are included as well, mainly focusing on fields of materials chemistry.

Author Contributions

Conceptualisation, Z.T.; methodology: Z.T. and R.G.; validation, M.G. and N.K.; investigation, Z.T. and R.G.; resources, Z.T. and R.G.; data curation, M.G. and N.K.; writing—original draft preparation, Z.T.; writing—review and editing, Z.T.; visualisation, N.K. and M.G.; supervision, Z.T.; project administration, Z.T.; funding acquisition, Z.T. and R.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Slovak Scientific Grant Agency VEGA 1/0086/21(UCM Trnava) is gratefully acknowledged. Research was co-financed by the APVV-19-0338 project (PI, SAV).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Stecko, S.; Gryko, T.G. Multifunctional Heteropentalenes: From Synthesis to Optoelectronic applications. J. Am. Chem. Soc. 2022, 2, 1290–1305. [Google Scholar] [CrossRef] [PubMed]
  2. Katz, T.J.; Rosenberg, M. The pentalenyl dianion. J. Am. Chem. Soc. 1962, 84, 865–866. [Google Scholar] [CrossRef]
  3. Alkorta, I.; Blanco, F.; Elguero, J. Heteropentalenes aromaticity. J. Mol. Struct. 2008, 851, 75–83. [Google Scholar] [CrossRef]
  4. Ramsden, C.A. Mesomeric betaine derivatives of heteropentalenes. Tetrahedron 1977, 33, 3193–3202. [Google Scholar] [CrossRef]
  5. Molander, G.A.; Shaumann, E.; Thomas, E.J.; Aitken, R.A.; Ameduri, B.; Braverman, S.; Brønsded Nielsen, M.; Cherkinsky, M.; Heydt, H.; Meehan, A.; et al. Product class 21: Five-five fused heteroarenes with one heteroatom in each ring. In Science of Synthesis: Knowledge Updates 2014/3, 1st ed.; Barnet, A., Nielsen Brønsded, M., Drabowicz, J., Joule, J.A., Schaumann, E., Weinreb, S.M., Eds.; Thieme: Delaware City, DE, USA, 2014; Volume 3. [Google Scholar]
  6. Kruotšíková, A. Bicyclic 5-5 Systems: Two heteroatoms. In Comprehensive Heterocyclic Chemistry II, 1st ed.; Katrizky, A.R., Reeds, C., Scriven, E.F.V., Eds.; Elsevier: Amsterdam, The Netherlands, 1996; Volume 7, pp. 1–47. [Google Scholar]
  7. Katrizky, A.R.; Ramsden, C.; Scrive, E.; Taylor, R.; Neuville, L.; Zhu, J. Bicyclic 5-5 Systems with one Bridgehead (Ring Junction) Nitrogen Atoms: Four Extra Heteroatoms 2:2. In Comprehensive Heterocyclic Chemistry II, 1st ed.; Katrizky, A.R., Ramsden, C., Scriven, E.F.V., Taylor, R.J.K., Eds.; Elsevier: Amsterdam, The Netherlands, 2008; Volume 11, pp. 1–13718. [Google Scholar]
  8. Panova, Y.S.; Khristolyubova, A.V.; Sushev, V.V.; Zolotareva, N.V.; Baranov, E.V.; Fukin, G.K.; Kornev, A.N. Rearrangements and reductive cleavage of 3a,6a-diaza-1,4-diphosphapentalenes. New J. Chem. 2021, 45, 18491–18496. [Google Scholar] [CrossRef]
  9. Kashida, J.; Shoji, Y.; Ikabata, Y.; Taka, H.; Sakai, H.; Hasobe, T.; Nakai, H.; Fukushima, T. An Air-and Water-stable B4N4-Heteropentalene serving as a Host Material for Phosphorescent OLED. Angew. Chem. Int. Ed. 2021, 60, 23812–23818. [Google Scholar] [CrossRef]
  10. Su, B.; Kostenko, A.; Yao, S.; Driess, M. Isolable Dibenzo[a,e]disilylpentalene with a Dichotomic reactivity toward CO2. J. Am. Chem. Soc. 2020, 142, 16935–16941. [Google Scholar] [CrossRef]
  11. Stanforh, S.P. Product class 21: Five-five-Fused Hetarenes with One Heteroatom in Each ring. In Science of Synthesis: Knowledge Updates 2014/3, 1st ed.; Barnet, A., Nielsen Brønsded, M., Drabowicz, J., Joule, J.A., Schaumann, E., Weinreb, S.M., Eds.; Thieme: Delaware City, DE, USA, 2014; Volume 3. [Google Scholar]
  12. Katrizky, A.R.; Rachwal, S. Synthesis of Heterocycles Mediated by Benzotriazole. 2. Bicyclic Systems. Chem. Rev. 2011, 111, 7063–7120. [Google Scholar] [CrossRef]
  13. Zlatoidský, P.; Martinelli, E.; Svensson, E.; Pruvost, A. A Facile Access to Novel (5+5)Annellated Heterocycles: Synthesis of a Furopyrrole, an Imidazoimidazole and a Pyrroloimidazole. Synthesis 2019, 51, 3491–3498. [Google Scholar] [CrossRef]
  14. Musicki, B. Synthesis and 1,3-Dipolar Cycloaddition Reactions of Novel Heteropentalene Mesomeris Betaines, Pyrrolo[1,2-c]Imidazole Mesomeric Betaines. J. Org. Chem. 1990, 55, 910–918. [Google Scholar] [CrossRef]
  15. Zemanová, I.; Gašparová, R.; Boháč, A.; Maliar, T.; Kraic, F.; Addová, G. Synthesis and antibacterial activity of furo[3,2-b]pyrrole derivatives. ARKIVOC 2017, v, 204–215. [Google Scholar] [CrossRef]
  16. Tokárová, Z.; Eckstein-Andicsová, A.; Balogh, R.; Tokár, K. Survey of the Ketcham reaction for series of furan-substituted thiazolo[5,4-d]thiazoles. Tetrahedron 2021, 89, 132155. [Google Scholar] [CrossRef]
  17. Milkiewicz, L.K.; Parks, J.D.; Lu, T. Synthesis of a novel series of tetrasubstituted furan[3,2-b]pyrrols. Tetrahedron Lett. 2003, 44, 4257–4260. [Google Scholar] [CrossRef]
  18. Gajdoš, P.; Pavlíková, S.; Bureš, F.; Krutošíková, A. 2-[3-(Trifluoromethyl)phenyl]furo[3,2-b]pyrroles: Synthesis and reactions. Cent. Eur. J. Chem. 2005, 3, 311–332. [Google Scholar] [CrossRef]
  19. Ilyin, A.P.; Dmitrieva, I.G.; Kustova, V.A.; Manaev, A.V.; Ivachtchenko, A.V. Synthesis of Heterocyclic Compounds Possessing the 4H-Thieno[3,2-b]Pyrrole Moiety. J. Comput. Chem. 2007, 91, 96–106. [Google Scholar]
  20. Kawashima, Y.; Amanuma, F.; Sato, M.; Okuyama, S.; Nakashima, Y.; Sota, K.; Moriguchi, I. Structure-activity studies of 4,6-disubstituted 2-(morpholinocarbonyl)furo[3,2-b]indole derivatives with analgesic and antiinflammatory activities. J. Med. Chem. 1986, 29, 2284–2290. [Google Scholar] [CrossRef]
  21. Garzan, A.; Willby, M.J.; Green, K.D.; Tsodikov, O.V.; Posey, J.E.; Garneau-Tsodikova, S. Discovery and Optimization of Two Eis Inhibitor Families as Kanamycin Adjuvants against Drug-Resistant M. tuberculosis. ACS Med. Chem. Lett. 2016, 7, 1219–1221. [Google Scholar] [CrossRef]
  22. Sparey, T.; Abeywickrema, P.; Almond, S.; Brandon, N.; Byrne, N.; Campbell, A.; Hutson, P.H.; Jacobson, M.; Jones, B.; Munshi, S.; et al. The discovery of fused pyrrole carboxylic acids as novel, potent d-amino acid oxidase (DAO) inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 3386–3391. [Google Scholar] [CrossRef]
  23. Fehér, D.; Barlow, R.; McAtee, J.; Hemscheidt, T.K. Highly Brominated Antimicrobial Metabolites from a Marine Pseudoalteromonas sp. J. Nat. Prod. 2010, 73, 1963–1966. [Google Scholar] [CrossRef]
  24. Umezawa, K.; Matsui, A.; Nakamura, Y.; Citterio, D.; Suzuki, K. Bright, color-tunable fluorescent dyes in the VIS/NIR region: Establishment of new „Tailor-Made“ multicolor fluorophores based on borondipyrromethene. Chem. Eur. J. 2009, 15, 1096–1103. [Google Scholar] [CrossRef]
  25. Jiang, K.J.; Boxer, M.B.; Vander Heiden, M.G.; Shen, M.; Skoumbourdis, A.P.; Southall, N.; Veith, H.; Leister, W.; Austin, C.P.; Park, H.W.; et al. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of tumor cell specific M2 isoform of pyruvate kinase. Bioorg. Med. Chem. Lett. 2010, 20, 3387–3393. [Google Scholar] [CrossRef] [PubMed]
  26. Sindac, J.A.; Yestrepsky, B.D.; Barraza, S.J.; Bolduc, K.L.; Blakely, P.K.; Keep, R.F.; Irani, D.N.; Miller, D.J.; Larsen, S.D. Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis. J. Med. Chem. 2012, 55, 3535–3545. [Google Scholar] [CrossRef]
  27. Jones, C.; Boudinet, D.; Xia, Y.; Denti, M.; Das, A.; Facchetti, A.; Driver, T.G. Synthesis and Properties of Semiconducting Bispyrrolothiophenes for Organic Field-Effect Transistors. Chem. Eur. J. 2014, 20, 5938–5945. [Google Scholar] [CrossRef] [PubMed]
  28. Hemetsberger, H.; Knittel, D. Syntheses and Thermolyzen von α-Azidoacrylestern. Monatsh. Chem. 1972, 103, 194–204. [Google Scholar] [CrossRef]
  29. Bingul, M.; Kumar, N.; StCBlack, D. The Hemetsberger reaction: A new approach to the synthesis of novel dihydroindoloindole systems. Arkivoc 2020, vii, 16–26. [Google Scholar] [CrossRef]
  30. Bingul, M.; Arndt, G.M.; Marshall, G.M.; Cheung, B.B.; Kumar, N.; Black, D.S. Synthesis, characterization and biological evaluation of novel dihydropyranoindoles improving the anticancer effects of HDAC inhibitors. Molecules 2020, 25, 1377. [Google Scholar] [CrossRef]
  31. Ranasinghe, N.; Jones, G.B. Extending the versatility of the Hemetsberger–Knittel indole synthesis through microwave and flow chemistry. Bioorg. Med. Chem. Lett. 2013, 23, 1740–1742. [Google Scholar] [CrossRef]
  32. Roy, P.J.; Dufresne, C.; Lachance, N.; Leclerc, J.-P.; Boisvert, M.; Wang, Z.; Leblanc, Y. The Hemetsberger-Knittel Synthesis of Substituted 5-, 6-, and 7-Azaindoles. Synthesis 2005, 16, 2751–2757. [Google Scholar] [CrossRef]
  33. Bobošík, V.; Krutošíková, A. Synthesis of N-phenylsulfonyl protected furo[3,2-b]pyrroles. Collect. Czech. Chem. Commun. 1994, 59, 499–502. [Google Scholar] [CrossRef]
  34. Eras, J.; Galvez, C.; Garcia, F. Reactivity of thienopyrroles. Synthesis of isomeric nitro and bromothienopyrroles. J. Heterocycl. Chem. 1984, 21, 215–217. [Google Scholar] [CrossRef]
  35. Welch, M.; Phillips, R.S. Improved Syntheses of [3,2-b]- and [2,3-b]-fused Selenolo- and Thienopyrroles, and of Furo[3,2-b]pyrrole. Heterocycl. Commun. 1999, 5, 305–310. [Google Scholar] [CrossRef]
  36. Heaner, W.L., IV; Gelbaum, C.S.; Gelbaum, L.; Pollet, P.; Richman, K.W.; DuBay, W.; Butler, J.D.; Wells, G.; Liotta, C.L. Indoles via Knoevenagel–Hemetsberger reaction sequence. RSC Adv. 2013, 3, 13232–13242. [Google Scholar] [CrossRef]
  37. Jacobs, L.; Kock, C.; Taylor, D.; Pelly, S.C.; Blackie MA, L. Synthesis of five libraries of 6,5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity. Bioorg. Med. Chem. 2018, 26, 5730–5741. [Google Scholar] [CrossRef]
  38. Roy, P.; Boisvert, M.; Leblanc, Y. Preparation of substituted 5-azaindoles: Methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate. Org. Synth. 2007, 84, 262–271. [Google Scholar]
  39. O’Brien, A.G.; Lévesque, F.; Seeberger, P.H. Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates. Chem. Commun. 2011, 47, 2688–2690. [Google Scholar] [CrossRef] [PubMed]
  40. Hemetsberger, H.; Knittel, D.; Weidmann, D. Thermolyzen von α-Azidoacrylestern: Synthese von Indole-derivaten. Monatsh. Chem. 1970, 101, 161–165. [Google Scholar] [CrossRef]
  41. Soth, S.; Farnier, M.; Paumier, C. Recherches en série hétérocyclique. XXIX. Sur des voies dàccès à des thiéno, sélénolo, furo et pyrrolopyrroles. Can. J. Chem. 1978, 56, 1429–1434. [Google Scholar] [CrossRef]
  42. Kralovičová, E.; Krutošíková, A.; Kováč, J.; Dandárová, M. Electrophilic substitution reactions of furo[3,2-b]pyrrole derivatives. Collect. Czech. Chem. Commun. 1986, 51, 106–111. [Google Scholar] [CrossRef]
  43. Krutošíková, A.; Kováč, J.; Dandárová, M.; Leško, J.; Ferík, S. Synthesis and reactions of furo[3,2-b]pyrrole derivatives. Collect. Czech. Chem. Commun. 1981, 45, 2564–2572. [Google Scholar] [CrossRef]
  44. Krutošíková, A.; Dandárová, M.; Chýlová, J.; Végh, D. Condensed O-, N-heterocycles by the Transformations of Azidoacrylates. Monatsh. Chem. 1992, 123, 807–815. [Google Scholar] [CrossRef]
  45. Nguyen, H.Q.; Rainbolt, E.A.; Sista, P.; Stefan, M.C. Synthesis and Polymerization of Fused-Ring Thienodipyrrole Monomers. Macromol. Chem. Phys. 2012, 213, 425–430. [Google Scholar] [CrossRef]
  46. Shefer, N.; Rozen, S. Synthesis of Oxidized Thienopyrroles using HOF.CH3CN. J. Org. Chem. 2011, 76, 4611–4616. [Google Scholar] [CrossRef]
  47. Shafiee, A.; Mazloumi, A.; Cohen, V.I. Selenium heterocycles. XXVIII. Synthesis of pyrrolo[3,2-d]selenazole and pyrrolo[3,2-d]thiazole. Two novel heterocycles. J. Heterocycl. Chem. 1979, 16, 1563–1566. [Google Scholar] [CrossRef]
  48. Athmani, S.; Farhat, M.F.; Iddon, B. Azoles. Part 9. Synthesis of Derivatives of Thieno[2,3-d]thiazole, 4H-Pyrrolo-[2,3-d]thiazole, 2H- Pyrazolo[3,4-d]thiazole and lsoxazolo [3,4-d]thiazole from Thiazolidine-2,4-dione. J. Chem. Soc Perkin Trans. 1992, 1, 973–977. [Google Scholar] [CrossRef]
  49. Shaffie, A.; Hadizadeh, F. Synthesis of sbstituted pyrrolo[3,2-d]imidazoles. J. Heterocycl. Chem. 1997, 34, 549–550. [Google Scholar] [CrossRef]
  50. Shafiee, A.; Mojarrad, J.S.; Jalili, M.A.; Adhami, H.R.; Hadizadeh, F. Syntheses of substituted pyrrolo[2,3-d]imidazole-5-carboxylates and substitued pyrrolo[3,2-d]imidazole-5-carboxylates. J. Heterocycl. Chem. 2002, 39, 367–373. [Google Scholar] [CrossRef]
  51. Sartori, L.; Mercurio, C.; Amigoni, F.; Cappa, A.; Fagá, G.; Fattori, R.; Legnaghi, E.; Ciossani, G.; Mattevi, A.; Meroni, G.; et al. Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 1: High-Throughput Screening and Preliminary Exploration. J. Med. Chem. 2017, 60, 1673–1692. [Google Scholar] [CrossRef] [PubMed]
  52. Ching, K.-C.; Kam, Y.-W.; Merits, A.; Ng, L.F.P.; Chai, C.L.L. Trisubstituted thieno[3,2-b]pyrrole 5-carboxamides as potent inhibitors of alphaviruses. J. Med. Chem. 2015, 58, 9196–9213. [Google Scholar] [CrossRef]
  53. Gholap, S.S. Pyrrole: An emerging scaffold for construction of valuable therapeutic agents. Eur. J. Med. Chem. 2016, 110, 13–31. [Google Scholar] [CrossRef]
  54. Peng, W.; Peltier, D.C.; Larsen, M.J.; Kirchhoff, P.D.; Larsen, S.D.; Neubig, R.R.; Miller, D.J. Identification of thieno[3,2-b]pyrrole derivatives as novel small molecule inhibitors of neurotropic alphaviruses. J. Infect. Dis. 2009, 199, 950–957. [Google Scholar] [CrossRef]
  55. Welch, M.; Phillips, R.S. Enzymatic syntheses of 6-(4H-selenolo[3,2-b]pyrrolyl)-L-alanine, 4-(6H-selenolo[3,2-b]pyrrolyl)-L-alanine, and 6-(4H-furo[3,2-b]pyrrolyl)-L-alanine. Bioorg. Med. Chem. Lett. 1999, 9, 637–640. [Google Scholar] [CrossRef]
  56. Bae, J.-H.; Alefelder, S.; Kaiser, J.T.; Friedrich, R.; Moroder, L.; Hubert, R.; Budisa, N. Incorporation of β-selenolo[3,2-b]pyrrolyl-alanine into proteins. J. Mol. Biol. 2001, 309, 925–936. [Google Scholar] [CrossRef]
  57. Blair, J.P.; Maruna-Lewicka, D.; Kanthasamy, A.; Lucaites, V.L.; Nelson, D.L.; Nichols, D.E. Thieno[3,2-b]pyrrole and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltraptamine. J. Med. Chem. 1999, 42, 1106–1111. [Google Scholar] [CrossRef]
  58. Gamage, P.L.; Gedara, C.M.U.; Ma, Z.; Bhadran, A.; Gunawardhana, R.; Biewer, H.C.; Stefan, M.C. Incorporation of selenopheno[3,2-b]pyrrole into benzothiadiazole-based small molecules for organic field effect tranzistors. ACS Appl. Electron. Mater. 2021, 3, 5335–5344. [Google Scholar] [CrossRef]
  59. Gedara, C.M.U.; Ma, Z.; Talukder, M.M.; Gunawardkana, R.; Biewer, M.C.; Stefan, M.C. Siloxane side-chain-modified diketopyrrolopyrrole and thienopyrrole containing small molecules for organic field effect tranzistors. ACS Appl. Electron. Mater. 2022, 4, 5340–5350. [Google Scholar] [CrossRef]
  60. Domínguez, R.; Montcada, N.F.; de la Cruz, P.; Palomarez, E.; Langa, F. Pyrrolo[3,2-b]pyrrole as the central core of the electron donor for the solution-processed organic solar cells. Chem. Plus. Chem. 2017, 82, 1096–1104. [Google Scholar] [CrossRef] [PubMed]
  61. Song, S.; Ko, S.-J.; Shin, H.; Jin, Y.; Kim, I.; Kim, J.Y.; Suh, H. Pyrrolo[3,2-b]pyrrole small molecules as donor materials for OPVs. Sol. Energy Sol. Cells 2013, 112, 120–126. [Google Scholar] [CrossRef]
  62. Tasior, M.; Kowalczyk, P.; Przybyl, M.; Cichy, M.; Janasik, P.; Bousquel, M.H.E.; Lapkowski, M.; Rammo, M.; Rebane, A.; Jacquemin, D.; et al. Going beyond borders: Pyrrolo[3,2-b]pyrroles with deep red emission. Chem. Sci. 2021, 12, 15935–15946. [Google Scholar] [CrossRef] [PubMed]
  63. Woodward, A.N.; Kolesar, J.M.; Hall, S.R.; Saleh, N.A.; Jones, D.S.; Walter, M.G. Thiazolothiazole Fluorophores Exhibiting Strong Fluorescence and Viologen-Like Reversible Electrochromism. J. Am. Chem. Soc. 2017, 139, 8467–8473. [Google Scholar] [CrossRef]
  64. Johnson, J.R.; Ketcham, R. Thiazolothiazoles. I. The Reaction of Aromatic Aldehydes with Dithiooxamide. J. Am. Chem. Soc. 1960, 82, 2719–2724. [Google Scholar] [CrossRef]
  65. Ando, S.; Nishida, J.; Inoue, Y.; Yamashita, Y. Synthesis, physical properties, and field-effect transistors of novel thiophene/thiazolothiazole co-oligomers. Science 2004, 14, 1787–1790. [Google Scholar] [CrossRef]
  66. Ando, S.; Nishida, J.; Fujiwara, E.; Tada, H.; Inoue, Y.; Tokito, S.; Yamashita, Y. Characterization and Field-Effect Transistor Performance of Heterocyclic Oligomers Containing a Thiazolothiazole Unit. Chem. Lett. 2004, 33, 1170–1171. [Google Scholar] [CrossRef]
  67. Ando, S.; Nishida, J.-I.; Tada, H.; Inoue, Y.; Tokio, S.; Yamashita, Y. High performance n-type organic field-effect transistors based on pi-electronic systems with trifluoromethylphenyl groups. J. Am. Chem. Soc. 2005, 127, 5336–5337. [Google Scholar] [CrossRef] [PubMed]
  68. Osaka, I.; Zhang, R.; Sauvé, G.; Smiligies, D.-F.; Kowalewski, T.; McCullough, R.D. High-Lamellar Ordering and Amorphous-Like π-Network in Short-Chain Thiazolothiazole−Thiophene Copolymers Lead to High Mobilities. J. Am. Chem. Soc. 2009, 131, 2521–2529. [Google Scholar] [CrossRef] [PubMed]
  69. Lim, D.-H.; Jang, S.-Y.; Kang, M.; Lee, S.; Kim, Y.-A.; Heo, Y.-J.; Lee, M.-H.; Kim, D.-Y. A systematic study on molecular planarity and D–A conformation in thiazolothiazole- and thienylenevinylene-based copolymers for organic field-effect transistors. J. Mater. Chem. C 2017, 5, 10126–10132. [Google Scholar] [CrossRef]
  70. Zhang, Z.; Chen, Y.-A.; Hung, W.-Y.; Tang, W.-i.-F.; Hsu, Y.-H.; Chen, C.h.-L.; Meng, F.-Y.; Chou, P.-T. Control of the Reversibility of Excited-State Intramolecular Proton Transfer (ESIPT) Reaction: Host-Polarity Tuning White Organic Light Emitting Diode on a New Thiazolo[5,4-d]thiazole ESIPT System. Chem. Mater. 2016, 28, 8815–8824. [Google Scholar] [CrossRef]
  71. Jung, J.Y.; Kang, M.; Chun, J.; Lee, J.; Kim, J.; Kim, J.; Kim, Y.; Kim, S.-J.; Lee, C.; Yoon, J. A thiazolothiazole based Cu2+ selective colorimetric and fluorescent sensor via unique radical formation. Chem. Commun. 2013, 49, 176–178. [Google Scholar] [CrossRef]
  72. Luo, J.; Hu, B.; Debruler, C.; Liu, T.L. A π-Conjugation Extended Viologen as a Two-Electron Storage Anolyte for Total Organic Aqueous Redox Flow Batteries. Angew. Chem. Int. Ed. 2018, 57, 231–235. [Google Scholar] [CrossRef]
  73. Ma, L.; Zhang, S.; Wang, J.; Xu, Y.; Hou, J. Recent advances in non-fullerene organic solar cells: From lab to fab. Chem. Commun. 2020, 56, 14337–14352. [Google Scholar] [CrossRef]
  74. Dessi, A.; Calamante, M.; Mordini, A.; Peruzzini, M.; Sinicropi, A.; Basosi, R.; de Biani, F.F.; Taddei, M.; Colonna, D.; di Carlo, A.; et al. Organic dyes with intense light absorption especially suitable for application in thin-layer dye-sensitized solar cells. Chem. Commun. 2014, 50, 13952–13955. [Google Scholar] [CrossRef]
  75. Zhang, Z.G.; Min, J.; Zhang, S.; Zhang, J.; Zhang, M.; Li, Y. Alkyl chain engineering on a dithieno[3,2-b:2′,3′-d]silole-alt-dithienylthiazolo[5,4-d]thiazole copolymer toward high performance bulk heterojunction solar cells. Chem. Commun. 2011, 47, 9474–9476. [Google Scholar] [CrossRef] [PubMed]
  76. Nazim, M.; Ameen, S.; Akhtar, M.S.; Nazeeruddin, M.K.; Shin, H.S. Tuning electronic structures of thiazolo[5,4-d]thiazole-based hole-transporting materials for efficient perovskite solar cells. Sol. Energy Mat. Sol. Cells 2018, 180, 334–342. [Google Scholar] [CrossRef]
  77. Wu, J.; Li, G.; Fang, J.; Guo, X.; Zhu, L.; Guo, B.; Wang, Y.; Zhang, G.; Arunagiri, L.; Liu, F.; et al. Random terpolymer based on thiophene-thiazolothiazole unit enabling efficient non-fullerene organic solar cells. Nat. Commun. 2020, 11, 4612. [Google Scholar] [CrossRef] [PubMed]
  78. Hwang, Y.-J.; Earmme, T.; Subramaniyan, S.; Jenekhe, S.A. Side chain engineering of n-type conjugated polymer enhances photocurrent and efficiency of all-polymer solar cells. Chem. Commun. 2014, 50, 10801–10804. [Google Scholar] [CrossRef] [PubMed]
  79. Zhou, W.; Wu, D.; Xiao, H.; Song, J.; Qu, L.; Wang, L.; Zhou, X.; Xu, Z.-X.; Xiang, H. Syntheses and photophysical properties of axially chiral thiazolothiazoles: Multi-stimuli-responsive fluorescence and circularly polarized luminescence. Dye. Pigment. 2022, 197, 109906–109916. [Google Scholar] [CrossRef]
  80. Sayresmith, N.A.; Saminathan, A.; Sailer, J.K.; Patberg, S.M.; Sandor, K.; Krishan, Y.; Walter, M.G. Photostable Voltage-Sensitive Dyes Based on Simple, Solvatofluorochromic, Asymmetric Thiazolothiazoles. J. Am. Chem. Soc. 2019, 141, 18780–18790. [Google Scholar] [CrossRef]
  81. Huang, X.; Zeng, T.; Liu, Y.A.; Hu, W.; Yang, H.; Zhang, Y.-B.; Wen, K. Thiazolo[5,4-d]thiazole-based donor-acceptor covalent organic framework for sunlight-driven hydrogen evolution. Angew. Chem. Int. Ed. 2021, 61, 1869–1874. [Google Scholar] [CrossRef]
  82. Ephraim, J. Ueber die Einwirkung von Aldehyden auf Thioamide I. Eur. J. Inorg. Chem. 1891, 24, 1026–1031. [Google Scholar] [CrossRef]
  83. Tokárová, Z.; Biathová, A. Synthesis and structure-physicochemical properties relationship of thiophene substituted bis(5,4-d)thiazoles. Nova Biotech. Chim. 2018, 17, 193–200. [Google Scholar] [CrossRef]
  84. Osaka, I.; Sauvé, G.; Zhang, R.; Kowalewski, T.; McCullough, R.D. Novel thiophene-thiazolothiazole copolymers for organic field-effect transistors. Adv. Mater. 2007, 19, 4160–4165. [Google Scholar] [CrossRef]
  85. Papernaya, L.K.; Shatrova, A.A.; Sterkhova, I.V.; Levkovskaya, G.G.; Rozentsveig, I.B. Microwave-Assisted Synthesis of 2,5-Diarylthiazolo[5,4-d]thiazoles from benzaldehydes and dithioxamide. Russ. J. Org. Chem. 2015, 51, 389–393. [Google Scholar] [CrossRef]
  86. Nazim, M.; Ameen, S.; Akhtar, M.S.; Seo, H.K.; Shik, H.; Shin, H.S. Novel liquid crystalline oligomer with thiazolothiazole-acceptor for efficient BHJ small molecule organic solar cells. Synth. Met. 2014, 187, 178–184. [Google Scholar] [CrossRef]
  87. Schneider, J.A.; Black, H.; Lin, H.P.; Perepichka, D.F. Polymorphism in new thienothiophene-thiazolothiazole organic semiconductors. ChemPhysChem 2015, 16, 1173–1178. [Google Scholar] [CrossRef] [PubMed]
  88. Zhang, X.; Kang, M.; Choi, H.; Jung, Y.; Swamy, K.M.K.; Kim, S.; Kim, D.; Kim, J.; Lee, C.; Yoon, J. Organic radical-induced Cu2+ selective sensing based on thiazolothiazole derivatives. Sens. Actuators B Chem. 2014, 192, 691–696. [Google Scholar] [CrossRef]
  89. Ziessel, R.; Nano, A.; Heyer, E.; Bura, T.; Retailleau, P. Rational design of new thiazolo-thiazole dyes as input energy units in molecular dyads. Chem.—A Eur. J. 2013, 19, 2582–2588. [Google Scholar] [CrossRef] [PubMed]
  90. Liu, Y.; Wang, B.; Sui, Y.; Lei, Y.; Jin, Y.; Wu, Y. Imidazole-thiazolo[5,4-d]thiazoles as corrosion inhibitors for mild steel in acidic media: Experimental and theoretical investigation. J. Mater. Sci. 2022, 35, 16904–16922. [Google Scholar] [CrossRef]
  91. Bevk, D.; Marin, L.; Lutsen, L.; Vanderzande, D.; Maes, W. Thiazolo[5,4-d]thiazoles-promising building blocks in the synthesis of semiconductors for plastic electronics. RSC Adv. 2013, 3, 11418–11431. [Google Scholar] [CrossRef]
  92. Reginato, G.; Mordini, A.; Zani, L.; Calamante, M.; Dessì, A. Photoactive Compounds Based on the Thiazolo[5,4-d]thiazole Core and Their Application in Organic and Hybrid Photovoltaics. Eur. J. Org. Chem. 2016, 2016, 233–251. [Google Scholar] [CrossRef]
  93. Biswal, B.P.; Becker, D.; Chandrasekhar, N.; Seenath, J.S.; Paasch, S.; Machill, S.; Hennersdorf, F.; Brunner, E.; Weigand, H.; Berger, R.; et al. Exploration of Thiazolo[5,4-d]thiazole Linkages in Conjugated Porous Organic Polymers for Chemoselective Molecular Sieving. Chem. Eur. J. 2018, 24, 10868–10875. [Google Scholar] [CrossRef]
  94. Kumar, V.; Sony, S.; Kaur, N.; Mobin, S.M.; Kaur, P.; Singh, K. Thiazolothiazole based donor-π-acceptor fluorophore: Protonation/deprotonation triggered molecular switch, sensing and bio-imaging applications. Anal. Chim. Acta 2022, 1206, 339776. [Google Scholar] [CrossRef]
  95. Flores, E.; Muñoz-Osses, M.; Torrent, C.; Vásquez-Martínez, Y.; Gómez, A.; Martin, M.C.; Vega, A.; Martí, A.A.; Godoy, F.; Mascayano, C. Design, Synthesis and Biological Evaluation of Ferrocenyl Thiazole and Thiazolo[5,4- d]thiazole Catechols as Inhibitors of 5-hLOX and as Antibacterials against Staphylococcus aureus. Structural Relationship and Computational Studies. Organometallics 2020, 39, 2672–2681. [Google Scholar] [CrossRef]
  96. Sathiyan, G.; Sakthivel, P.; Thangamuthu, R.; Thangamuthu, R.; Sakthivel, P. Synthesis of carbazole-based copolymers containing carbazole-thiazolo[5,4-d]thiazole groups with different dopants and their fluorescence and electrical conductivity applications. RSC Adv. 2016, 6, 69196–69205. [Google Scholar] [CrossRef]
  97. Li, Z.; Li, L.; Wang, Y.; Yang, Y.W. Pillararene-enriched linear conjugated polymer materials with thiazolo[5,4-d]thiazole linkages for photocatalysis. Chem. Commun. 2021, 57, 6546–6549. [Google Scholar] [CrossRef] [PubMed]
  98. Dabuliene, A.; Dainyte, A.; Andruleviciene, V.; Lygaitis, R.; Punniyakoti, S.J.; Tomkeviciene, A.; Velasco, D.; Obushak, M.; Grazulevicius, J.V. Low-molar-mass and oligomeric derivatives of carbazole and triphenylamine containing thiazolo[5,4-d]thiazole moieties. Polym. Bull. 2023, 80, 1477–1493. [Google Scholar] [CrossRef]
  99. Zhu, X.; Tian, C.; Jin, T.; Wang, J.; Mahurin, S.M.; Mei, W.; Xiong, Y.; Hu, J.; Feng, X.; Liu, H.; et al. Thiazolothiazole-linked porous organic polymers. Chem. Commun. 2014, 50, 15055–15058. [Google Scholar] [CrossRef]
  100. Huang, Q.; Guo, L.; Wang, N.; Zhu, X.; Jin, S.; Tan, B. Layered Thiazolo[5,4-d] Thiazole-Linked Conjugated Microporous Polymers with Heteroatom Adoption for Efficient Photocatalysis Application. ACS Appl. Mater. Interfaces 2019, 11, 15861–15868. [Google Scholar]
  101. Biswal, B.P.; Vignolo-González, H.A.; Banerjee, T.; Grunenberg, L.; Savasci, G.; Gottschling, K.; Nuss, J.; Ochsenfeld, C.; Lotsch, B.V. Sustained Solar H2 Evolution from a Thiazolo[5,4-d]thiazole-Bridged Covalent Organic Framework and Nickel-Thiolate Cluster in Water. J. Am. Chem. Soc. 2019, 141, 11082–11092. [Google Scholar] [CrossRef] [PubMed]
  102. Wang, Y.; Li, X.; Dong, X.; Zhang, F.; Lang, X. Triazine-based two dimensional porous materials for visible light-mediated oxidation of sulfides to sulfoxides with O2. J. Colloid Interface Sci. 2022, 616, 846–857. [Google Scholar] [CrossRef]
  103. Wang, Y.; Liu, H.; Pan, Q.; Ding, N.; Yang, C.; Zhang, Z.; Jia, C.; Li, Z.; Liu, J.; Zhao, Y. Construction of Thiazolo[5,4-d]thiazole-based Two-Dimensional Network for Efficient Photocatalytic CO2 Reduction. ACS Appl. Mater. Interfaces 2020, 12, 46483–46489. [Google Scholar] [CrossRef]
  104. Sami, M.M.; Mekhemer, I.M.A.; Mohamed, M.G.; Elsayed, M.H.; Lin, K.; Chen, Y.; Wu, T.; Chou, H. Conjugated microporous polymers incorporating Thiazolo[5,4-d]thiazole moieties for Sunlight-Driven hydrogen production from water. Chem. Eng. J. 2022, 446, 137158. [Google Scholar]
  105. Samal, M.; Valligatla, S.; Saad, N.A.; Rao, M.V.; Rao, D.N.; Sahu, R.; Biswal, B.P. A thiazolo[5,4-d] thiazole-bridged porphyrin organic framework as a promising nonlinear optical material. Chem. Commun. 2019, 55, 11025–11028. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Resonance structures of the pentalenyl dianon (PnDa) as a leading structure for a class of heteropentalenes.
Figure 1. Resonance structures of the pentalenyl dianon (PnDa) as a leading structure for a class of heteropentalenes.
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Figure 2. Structure of general types of HPs containing two heteroatoms, one per core, according to Ramsden’s classification [4,11]: I—hetaryl [3,2-b]hetarene (1,4-diheteropentalene), II—hetaryl [2,3-c]hetarene = hetaryl [3,4-b]hetarene (1,5-diheteropentalene), III—hetaryl [2,3-b]hetarene (1,6-diheteropentalene), IV—hetaryl [3,4-c]hetarene (2,5-diheteropentalene). In combination with the Formula (1), the distinguishing strategy can be applied for a whole class of HPs. A,X,Y = heteroatoms (O,S,N, rarely Se, Te); a, b, c—condensed bond positioning.
Figure 2. Structure of general types of HPs containing two heteroatoms, one per core, according to Ramsden’s classification [4,11]: I—hetaryl [3,2-b]hetarene (1,4-diheteropentalene), II—hetaryl [2,3-c]hetarene = hetaryl [3,4-b]hetarene (1,5-diheteropentalene), III—hetaryl [2,3-b]hetarene (1,6-diheteropentalene), IV—hetaryl [3,4-c]hetarene (2,5-diheteropentalene). In combination with the Formula (1), the distinguishing strategy can be applied for a whole class of HPs. A,X,Y = heteroatoms (O,S,N, rarely Se, Te); a, b, c—condensed bond positioning.
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Figure 3. Structure of furo [3,2-b]pyrrole (V) as representative of two heteroatoms containing HPs (1:1, each core), achievable through the Hemetsberger–Knittel procedure, and thiazolo [5,4-d]thiazole (VI) from the category of four heteroatom-containing HPs (2:2, two per core) as a product of Ketcham’s process, respectively.
Figure 3. Structure of furo [3,2-b]pyrrole (V) as representative of two heteroatoms containing HPs (1:1, each core), achievable through the Hemetsberger–Knittel procedure, and thiazolo [5,4-d]thiazole (VI) from the category of four heteroatom-containing HPs (2:2, two per core) as a product of Ketcham’s process, respectively.
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Scheme 1. Three steps of the Hemetsberger–Knittel reaction as following: (a) synthesis of alkylazidoacetate, (b) condensation towards azidoarylacrylate, (c) cyclization.
Scheme 1. Three steps of the Hemetsberger–Knittel reaction as following: (a) synthesis of alkylazidoacetate, (b) condensation towards azidoarylacrylate, (c) cyclization.
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Figure 4. Chemical structure of the by-product of Knoevenagel condensation between furan-2-carbaldehyde and ethylazidoacetate [36].
Figure 4. Chemical structure of the by-product of Knoevenagel condensation between furan-2-carbaldehyde and ethylazidoacetate [36].
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Scheme 2. Proposed mechanism of the Hemetsberger–Knittel synthesis of heteropentalenes.
Scheme 2. Proposed mechanism of the Hemetsberger–Knittel synthesis of heteropentalenes.
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Scheme 3. Synthesis of [3,2-b]-fused heteropentalenes 12 with O, S, Se and NH/N-CH3 heteroatoms.
Scheme 3. Synthesis of [3,2-b]-fused heteropentalenes 12 with O, S, Se and NH/N-CH3 heteroatoms.
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Scheme 4. Vilsmeier–Haack formylation of furo [3,2-b]pyrroles.
Scheme 4. Vilsmeier–Haack formylation of furo [3,2-b]pyrroles.
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Scheme 5. Synthesis of diethyl 1-alkyl-1,7-dihydrofuro [3,2-b:4,5-b’]dipyrrole-2,6-dicarboxylates 18.
Scheme 5. Synthesis of diethyl 1-alkyl-1,7-dihydrofuro [3,2-b:4,5-b’]dipyrrole-2,6-dicarboxylates 18.
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Scheme 6. Synthesis of diethyl 1,7-dihydrothieno [3,2-b:4,5-b’]dipyrrole-2,6-dicarboxylate 21 and -4,4-dioxide 22.
Scheme 6. Synthesis of diethyl 1,7-dihydrothieno [3,2-b:4,5-b’]dipyrrole-2,6-dicarboxylate 21 and -4,4-dioxide 22.
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Scheme 7. Synthesis of fused azoles 24.
Scheme 7. Synthesis of fused azoles 24.
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Scheme 8. Synthesis of pyrrolo [3,2-d]imidazoles 28 and 29.
Scheme 8. Synthesis of pyrrolo [3,2-d]imidazoles 28 and 29.
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Scheme 9. Synthesis of pyrrolo [2,3-d]imidazole-5-carboxylates 34 and pyrrolo [3,2-d]imidazole-5-carboxylates 35.
Scheme 9. Synthesis of pyrrolo [2,3-d]imidazole-5-carboxylates 34 and pyrrolo [3,2-d]imidazole-5-carboxylates 35.
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Scheme 10. Synthesis of methyl 1-SEM-protected 1,4-dihydropyrrolo [3,2-c]pyrazole-5-carboxylate 38.
Scheme 10. Synthesis of methyl 1-SEM-protected 1,4-dihydropyrrolo [3,2-c]pyrazole-5-carboxylate 38.
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Scheme 11. Application of Hemetsberger–Knittel synthesis in order to produce three- and four-heteroatom-containing heteropentalenes.
Scheme 11. Application of Hemetsberger–Knittel synthesis in order to produce three- and four-heteroatom-containing heteropentalenes.
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Figure 5. 6-[2-(N,N-dimethylamino)ethyl]-4H-thieno [3,2-b]pyrrole (42) as the representative compound from the category of S,N-heteroatom containing (1:1) HPs [57].
Figure 5. 6-[2-(N,N-dimethylamino)ethyl]-4H-thieno [3,2-b]pyrrole (42) as the representative compound from the category of S,N-heteroatom containing (1:1) HPs [57].
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Figure 6. Derivatives of thieno [3,2-b]pyrrole 43 and seleno [3,2-b]pyrrole 44 as representatives of the S,N and Se,N (1:1) HPs for interests in organic semiconducting materials [58].
Figure 6. Derivatives of thieno [3,2-b]pyrrole 43 and seleno [3,2-b]pyrrole 44 as representatives of the S,N and Se,N (1:1) HPs for interests in organic semiconducting materials [58].
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Figure 7. Pyrrolo [3,2-b]pyrrole-based dyes/emitters 45a/45b possessing deep red emission [62].
Figure 7. Pyrrolo [3,2-b]pyrrole-based dyes/emitters 45a/45b possessing deep red emission [62].
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Figure 8. Structure of a thiazolo [5,4-d]thiazole scaffold with atom numbering.
Figure 8. Structure of a thiazolo [5,4-d]thiazole scaffold with atom numbering.
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Figure 9. Dramatic increase in publications presenting the synthesis and application of TzTz derivatives between 1958 and 2022, according to Scopus® and ScienceDirect®.
Figure 9. Dramatic increase in publications presenting the synthesis and application of TzTz derivatives between 1958 and 2022, according to Scopus® and ScienceDirect®.
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Scheme 12. Representative synthesis of symmetrical thiazolo [5,4-d]thiazoles (46) by Ketcham/Johnson [64], also showing the misstated structure of Ephraim (49) [82].
Scheme 12. Representative synthesis of symmetrical thiazolo [5,4-d]thiazoles (46) by Ketcham/Johnson [64], also showing the misstated structure of Ephraim (49) [82].
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Scheme 13. Proposed mechanism of the Ketcham reaction according to [16,91,92,93], including the formation of imines 51 as isolable and stable types of by-products (Pathway A) and the possible formation of an unstable and unique intermediate of bis-thiol type 54 (Pathway B).
Scheme 13. Proposed mechanism of the Ketcham reaction according to [16,91,92,93], including the formation of imines 51 as isolable and stable types of by-products (Pathway A) and the possible formation of an unstable and unique intermediate of bis-thiol type 54 (Pathway B).
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Figure 10. Chemical structure of Ketcham’s reaction by-products—the common imine-type derivative 51 and unusual bis-thiol type 54, evidenced only twice according to [16,93]. The possible intramolecular effects are proposed—the dipole–dipole interactions (red arrow) and hydrogen bonds (red dashed line) as a probable interpretation of the stabilisation of this unusual by-product.
Figure 10. Chemical structure of Ketcham’s reaction by-products—the common imine-type derivative 51 and unusual bis-thiol type 54, evidenced only twice according to [16,93]. The possible intramolecular effects are proposed—the dipole–dipole interactions (red arrow) and hydrogen bonds (red dashed line) as a probable interpretation of the stabilisation of this unusual by-product.
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Scheme 14. Example of the synthesis of unsymmetrically substituted thiazolo [5,4-d]thiazole 53 by the use of a mixture of two different aldehydes 55 and 56 with dithioxamiede [94].
Scheme 14. Example of the synthesis of unsymmetrically substituted thiazolo [5,4-d]thiazole 53 by the use of a mixture of two different aldehydes 55 and 56 with dithioxamiede [94].
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Scheme 15. Synthesis of monoferrocenyl-substituted TzTz-derivative 60 [95].
Scheme 15. Synthesis of monoferrocenyl-substituted TzTz-derivative 60 [95].
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Figure 11. Chemical structure of oligo- and copolymers prepared by simple Ketcham’s reaction protocol. (a) 9-hexyl-9H-carbazole-unit bearing a TzTz-based oligomer 61; (b) triphenylamine-based TzTz-type oligomers 62,63; (c) TzTz-based star-shaped oligomer 64; (d) TzTz-based porous cross-linked polymer 65; (e) trisbenzene and triazine cross-linked TzTz-based oligomers 66; (f) aromatic and heteroaromatic polycondensed thiazolo[5,4-d]thiazoles 67.
Figure 11. Chemical structure of oligo- and copolymers prepared by simple Ketcham’s reaction protocol. (a) 9-hexyl-9H-carbazole-unit bearing a TzTz-based oligomer 61; (b) triphenylamine-based TzTz-type oligomers 62,63; (c) TzTz-based star-shaped oligomer 64; (d) TzTz-based porous cross-linked polymer 65; (e) trisbenzene and triazine cross-linked TzTz-based oligomers 66; (f) aromatic and heteroaromatic polycondensed thiazolo[5,4-d]thiazoles 67.
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Scheme 16. Synthesis of porphyrin-centred TzTz-based copolymer achieved by simple Ketcham’s synthetic protocol according to [105].
Scheme 16. Synthesis of porphyrin-centred TzTz-based copolymer achieved by simple Ketcham’s synthetic protocol according to [105].
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Tokárová, Z.; Gašparová, R.; Kabaňová, N.; Gašparová, M.; Balogh, R. Hemetsberger–Knittel and Ketcham Synthesis of Heteropentalenes with Two (1:1), Three (1:2)/(2:1) and Four (2:2) Heteroatoms. Reactions 2023, 4, 254-273. https://doi.org/10.3390/reactions4020015

AMA Style

Tokárová Z, Gašparová R, Kabaňová N, Gašparová M, Balogh R. Hemetsberger–Knittel and Ketcham Synthesis of Heteropentalenes with Two (1:1), Three (1:2)/(2:1) and Four (2:2) Heteroatoms. Reactions. 2023; 4(2):254-273. https://doi.org/10.3390/reactions4020015

Chicago/Turabian Style

Tokárová, Zita, Renáta Gašparová, Natália Kabaňová, Marcela Gašparová, and Róbert Balogh. 2023. "Hemetsberger–Knittel and Ketcham Synthesis of Heteropentalenes with Two (1:1), Three (1:2)/(2:1) and Four (2:2) Heteroatoms" Reactions 4, no. 2: 254-273. https://doi.org/10.3390/reactions4020015

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