Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• ][52][53][54][55][56][57][58] (Scheme 9). Thioketones, thiochalcones, and tertiary thioamides react as C=S super dipolarophilic agents. Jasiński et al. reported that these thiocarbonyl compounds react with trifluoromethylated hydrazonoyl halides to give trifluoromethylated 1,3,4-thiadiazoles via

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• molecules that attack and destroy lipids and protein membranes of weed cells [10]. Fipronil is an inhibitor of GABA receptors and affects the nervous system of insects as a broad-spectrum insecticide [11][12]. On the other hand, thioamides are an important class of organic compounds. 6-Thioguanine and

• molecule cyano- and thioamide groups, as well as a fragment of enamine, each in principle being capable of interaction with hydrazine (3a) (Figure 2). First, we have studied the reaction of thioamides 1a–c with hydrazine (3a). It was found that the reaction proceeds smoothly in ethanol at 80 °C to form 3,5

• the data given in the current work. The formation of 3,5-diaminopyrazoles 4a–c occurs, presumably, as a result of a sequential attack of electrophilic carbon atoms of the cyano- and thioamide groups of thioamides 1a–c by nucleophilic nitrogen atoms of hydrazine (3a) and is accompanied by the

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• calculations for enaminone synthesis from iodonium ylides and thioamides. Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143][144]. Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); and, reaction between 6 and HCl to give 7, as

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• synthesis; isoquinolin-4-ones; primary thioamides; structure–reactivity relationships; Introduction During several past years, we have developed [1][2] a novel synthetic approach toward (Z)-3-[amino(phenyl/methyl)methylidene]-1,3-dihydro-2H-indol-2-ones and have demonstrated [3][4] its application

• potential in the synthesis of various tyrosine kinase inhibitors, including hesperadin and the approved drug nintedanib. The key step of the synthesis involves the Eschenmoser coupling reaction (ECR) between a substituted 3-bromooxindole 1 and appropriate primary, secondary or tertiary thioamides which

• -bromoxindole) have not been used in ECR before, only α-haloketones and α-haloesters. Finally, the use of primary thioamides (R3, R4: H) in ECR was quite unique – there are only two other examples [5][6] described in the literature starting from thioacetamide or 3-phenylpropanethioamide. In existing literature

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• -tethered thioamide and amide conjugates. The thioamides were generated by employing a three-component reaction of diverse pyrazole C-3/4/5 carbaldehydes, secondary amines, and elemental sulfur in a single synthetic operation. The advantages of this developed protocol refer to the broad substrate scope

• ; pyrazole carbaldehydes; sulfur insertion; thioamides; Introduction During the past years, the significance of pyrazole chemistry has been notably escalated which is attributed to the discovery of their amazing biological properties. Among the heterocyclic molecules, pyrazoles are considered as privileged

• reagent for the generation of thioamides owing to its nontoxic, odorless nature and versatile reactivity profile [65][66][67][68][69][70][71][72][73][74][75][76]. To the best of our knowledge, the syntheses of pyrazole C-3/4/5-linked thioamide and amide conjugates have not been reported. Herein, we report

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzazole derivatives is of interest as they are biologically active substances. Herein, a simple method for the synthesis of 2-aryl- and 2-alkyl-substituted benzazoles is described. The reaction of 2-aminophenols with thioamides at 60 °C in the presence of triphenylbismuth dichloride in 1,2-dichloroethane

• benzimidoyl chloride from thioamides by desulfurization and chlorination, as well as its application to the synthesis of 2-substituted benzazoles. Keywords: benzazole; bismuth; cyclization; desulfurization; thioamide; Introduction In the production of pharmacologically active compounds, 2-substituted

• reaction of o-alkoxythiobenzamides with iodine in the presence of sodium hydride as the base [11]. Sugita et al. reported an unstable iodoalkyne, pentafluoro(iodoethynyl)benzene, which catalyzed the cyclization of thioamides with 2-aminophenol [12]. These approaches have some drawbacks, such as low yields

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• respective hydrazonoyl bromides 8 and smoothly undergo [3 + 2]-cycloadditions with both electron-rich C=C dipolarophiles [27][28][29] and arynes [30], yielding the corresponding pyrazole derivatives. Unexpectedly, they reacted also with electron-deficient polyfluorinated thioamides to give the desired 1,3,4

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• scaling up the preparation of two pincer-type thioamides, we have successfully developed a convenient process with ethylene glycol to replace ethanol during the workup, including a traditional phase separation, extraction, and recrystallization. The newly developed chromatography-free procedure did not

• potential large-scale preparations. Thioamides are highly attractive molecules in pharmaceuticals, agrochemicals, electronic chemicals, and materials sciences [17][18][19][20][21][22][23][24][25][26][27]. In coordination chemistry, pincer-type ligands containing a thioamide motif were shown to exhibit

• preparation. Indeed, with this improvement, various thioamides were conveniently synthesized and isolated in good to excellent yields after column chromatography (Table 1). Although the synthesis of the thioamides at a 1 mmol scale was successful, the required purification by column chromatography is a major

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• of all products was confirmed by NMR techniques. Keywords: 3-bromooxindoles; Eschenmoser coupling reaction; thioamides; tyrosin kinase inhibitors; (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones; Introduction 3-(Aminomethylidene)-1,3-dihydro-2H-indol-2-ones (3-(aminomethylidene

• ) through the intermediary (and in most cases isolable) 2-aryl-5-(2-aminophenyl)-4-hydroxy-1,3-thiazoles 8aa–ad formed from 3-bromooxindole (1a) and various substituted primary aromatic thioamides (e.g., thiobenzamides 2a–d) in acetonitrile (Scheme 2). Although the overall yields of such a two-step

• /or crystallization. Aliphatic thioamides Although our concern was mainly dedicated to the synthesis of 3-[amino(aryl)methylidene]oxindoles many of which display a significant tyrosin kinase inhibiting activity, we also verified the versatility of our method for the analogous oxindoles 10a–c carrying

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

• commonly used methods to prepare these compounds include the Cu-catalyzed multicomponent reaction of alkynes, sulfonyl azides and amines [23][24][25][26][27][28][29][30][31], the reaction of thioacetamide derivatives and cyclic thioamides with sulfonyl azides [22][32][33], the chlorophosphite-mediated

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , carboxylic acids [16][17][18][19][20], acyl anhydrides [21][22][23], acyl chlorides [24][25][26][27], esters [28], thioamides [29][30][31], dithionates [32][33], or thiocarbamates [34] are employed as electrophilic components, but oxidative cyclocondensations with aldehydes have also been showcased [35][36

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• accompanied by elimination reactions. 3. Synthesis via cycloadditions Cycloadditions, especially the photochemical [2 + 2] cycloaddition (thia-Paternò–Büchi reaction) of thiones and thioamides with olefins [15][16][17][18], and formal cycloadditions are alternative routes for the construction of thietane

• alkyl-2-enoyl)thiobenzamides 355. Some thioamides 355, (i.e., R = CHMe2), formed R2CH=CR1CONHCMe2CSPh via a β-H abstraction of the thiocarbonyl group. Substituents at the α-position to the alk-2-enoyl moiety led to a preference for the [2 + 2] cyclization over the β-H abstraction. The reaction was shown

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• -hydroxybutyl)thioamides promoted by PPA esters. The preparation of these acyclic precursors is not straightforward, as it involves a selective thionation step. We present herein a novel method for the synthesis of seven-membered cyclic iminothioethers from commercially available 4-aminobutanol. The sequence

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• heterocycles; thioamides; Introduction Omnipresent among natural compounds and drugs, the indole core is a privileged scaffold for library design and drug discovery [1]. Its dioxo derivative, isatin (1H-indole-2,3-dione), is an important building block for the construction of diverse indole-based compounds

• serve for a catalyst-free C–H functionalization of thioacetamide and mild introduction of this fragment in other molecules, which is valuable in terms of synthetic organic chemistry. Approaches to the synthesis of the 5-azaisatin core. Our previous work on the interaction of PBTs 2 with thioamides

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , scalable and environmentally friendly reaction conditions than the traditional methods employed for making these highly substituted heteroaromatics. Access to the saturated oxazolines and thaziolines from amides and thioamides, respectively, has been described by Nicewicz who used acridinium salt

• drugs. The Yadav research group have also published the homocoupling of primary thioamides for the formation of symmetrical 1,2,4-thiadiazoles, using visible light and Eosin Y as the photocatalyst, in air at room temperature (Scheme 19) [64]. The immediately obvious limitation of this reaction is the

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• groups [23][27][28], C=C double [24][25][26], or C≡C triple [29][30][31][32] bonds in the structure of the initial molecule (Scheme 1). Intermolecular reaction of metal carbenes with thioamides usually generates thiocarbonyl ylides which leads for example to enaminones [14][33][34][35] or, in the

• thioamides 1a–e of cyanoacetic acid (differing in the structure of substituents in the amino fragment) and diazoesters of three types: acyclic diazomalonates 2a,b, their cyclic analogue, 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dione (diazo Meldrum’s acid, 2c), as well as α-cyanodiazoacetic ester 2d were used in

• the study (Figure 1). Dirhodium carboxylates [Rh2(OAc)4, Rh2(Oct)4 and Rh2(Piv)4] which were found to be the most effective catalysts in reactions of diazo carbonyl compounds with different substrates [46][47], were employed in this research. At first, we studied reactions of thioamides 1 with

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• (cyano)(methoxycarbonyl)methanide with episulfides [14] or thioamides [15]. Also, methyl cyanoacetate was reported to undergo both chemical (using (NH4)2Ce(NO3)6 = CAN in methanol) or electrochemical oxidation (Ce(NO3)3, HNO3 in acetonitrile) yielding selectively E-1b in 68 and 77% yield, respectively

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• the tolerance of reducible functional groups like a nitro group and a triple bond in the reaction which cannot be used in the reported methods. A hypothetical mechanism (Scheme 2) for this conversion was believed to involve, in analogy with the thionation of nitriles to thioamides [20], initial

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• photophysical properties [4][10][13][14][15][16][17][18][19][20], we thought it would be of interest to study its reactivity in the above reaction (and to extend its scope for isocyanates). An additional reason for such a study was the fact that thioamides (and amides) are versatile starting materials in the

• , whereas a 7-day reaction afforded 5 in a moderate (54%) isolated yield. Attempts to separate the regioisomeric bis-thioamides failed, but repeated chromatography and recrystallization from dichloromethane/hexane allowed isolation of the practically pure main regioisomer, 1,8-dithioamide 4. Its structure

• into 5, but to our knowledge this reaction, which must involve cleavage of the C–N bond, has no precedent in the literature (in contrast to the well-known formation of nitriles from primary thioamides, involving formal elimination of H2S [24]). Encouraged by the above results, we decided to check

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• ]. As a consequence, many routes for the synthesis of thiazole derivatives are reported in the literature [26][27][28][29][30][31][32][33]. Among them, the Hantzsch thiazole synthesis (condensation of α-haloketones with thioamides) is the most efficient and straight forward procedure [34][35][36][37][38

• conditions (Scheme 8). The reaction tolerated a variety of functional groups such as fluoro, cyano, hydroxy, and methoxy, allowing a further derivatization of the products [90]. 3 From N-propargyl thioamides The first example of a thiazole synthesis from N-propargyl thioamides has been reported by Short and

• reaction is based on the formation of β-oxo-N-propargyl thioamides A as intermediates, followed by their spontaneous ring closure. This reaction was run in refluxing ethanol and provided in all cases the desired thiazolidines 42 in high to excellent yields (Scheme 10) [93]. In 2009, Yarovenko and co

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• , Faculty of Science, Masaryk University, Brno, Czech Republic 10.3762/bjoc.13.20 Abstract In this paper, we introduce a novel and convenient method for the transformation of heterocyclic amides into heteocyclic thioamides. A two-step approach was applied for this transformation: Firstly, we applied a

• chlorination of the heterocyclic amides to afford the corresponding chloroheterocycles. Secondly, the chloroherocycles and N-cyclohexyl dithiocarbamate cyclohexylammonium salt were heated in chloroform for 12 h at 61 °C to afford heteocyclic thioamides in excellent yields. Keywords: heterocyclic amides

• ; heterocyclic thioamides; N-cyclohexyl dithiocarbamate cyclohexylammonium salt; novel thiating agent; thiation; Introduction Transforming heterocyclic amides into thioamides is an important task in organic synthesis. Earlier reports for this type of O/S conversions were achieved by several thiating reagents

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• -chloroacrylamides; cascade reactions; flow chemistry; Introduction Since the efficient and highly stereoselective transformation of α-thioamides to the corresponding α-thio-β-chloroacrylamides derivatives was first reported [1][2], the considerable synthetic utility of these heavily functionalized acrylamide

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• oxazolones and pyrazinediones [150][153][154], which are found alongside thioamides in these molecules (Figure 11). These post-translational modifications are critical for copper binding but the mechanisms of these heterocyclisation steps have not yet been determined for any pathway, despite the

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• useful method for the synthesis of aromatic secondary thioamides [1][2][3][4][5][6]. Our group [7] and others [8] have recently described an efficient modification of this method by using trifluoromethanesulfonic (triflic) acid as a promoter. Furthermore, we reported a simple procedure for the oxidative

• desulfurization of thioamides to amides via reaction with Oxone®. Now we want to apply this approach to the synthesis of N-thioacyl- and acyl derivatives of 1-aminoalkylphosphonates from arenes and 1-(isothiocyanato)alkylphosphonates. 1-Aminoalkylphosphonates and their derivatives are compounds of biological

• isolated in 87% yield. Photophysical properties of 3a–d and 4 As expected, thioamides 2a–d were nonfluorescent (thioamide group is a well-known fluorescence quencher [31]). In contrast, the corresponding amides 3a–d showed strong fluorescence emission in solution and in the solid state. We studied the