C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• cyclization of aryl hydrazones with aryl isothiocyanates promoted by elemental sulfur [70]. In the course of their studies for the thiocyanation of ketene dithioacetals, Yang, Wang and co-workers developed an electrochemical oxidization-based synthetic strategy to circumvent the need for external oxidants. In

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• mechanism. In the case of tertiary alkanethiols and arylmethanethiols, the corresponding imidoyl radicals 2 decompose to give tertiary alkyl and benzylic radicals, respectively, to form isothiocyanates 5. On the other hand, we have investigated the radical addition of diphenyl disulfide to isocyanides under

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• , product 17a shows cytotoxic activity against Hep G2 hepatocellular carcinoma and MCF-7 breast carcinoma cell lines. The synthesis of 3,5-bis(arylamino)pyrazoles 21 involves the preparation of bisarylthioamides 22 via nucleophilic addition and double retro-Claisen condensation of isothiocyanates 19 and

• acetylacetonate 20. Extension of the sequence by cyclization with hydrazine leads to the pyrazole products 21 (Scheme 5) [53]. The method works best with acetylacetonates, since deprotonation of other diketones with NaOEt leads to deactivation of the isothiocyanates. A limitation of the method is the formation of

• three different regioisomers when employing different isothiocyanates 19. However, easy separation by LC–MS could be achieved, as demonstrated for one-pot process generated pyrazoles 21a–f. The reaction demonstrates high tolerance to steric hindrance and electronic factors, enabling the synthesis of

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• to provide spirocarbamates 70a,b in moderate yields. Alternatively, spiro 2-alkylamino- and 2-arylamino-4,5-dihydro-1,3-oxazoles 72a,b were obtained by treating aminoalcohols 68a,b with isothiocyanates in the presence of triethylamine. The resulting thioureas 71a,b underwent cyclodesulfurization

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• suitably N-3-functionalized (thio)hydantoins 4a–r. aDCM was utilized as solvent with isothiocyanates 3a–f, while bEtOH was utilized with isocyanates 3g,h. Substrate scope of the iron(III)-catalyzed synthesis of functionalized heterocyclic N,O-aminals 5a–r and hemiaminals 6a–p. Proposed mechanism for the

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• 2020, Pedrosa and co-workers devised a chiral heterogenous thiourea catalyst that was applied in an enantioefficient aza-Friedel–Crafts process. A series of heterogenous catalysts were prepared by condensation between alkaloids and polystyrene-derived isothiocyanates. These polymer-supported materials

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

• triphenylbismuth dichloride (Ph3BiCl2) to act efficiently in desulfurization reactions (Scheme 1-I and II). In 2018, we reported the preparation of 2-aminobenzoxazoles by the Ph3BiCl2-mediated cyclodesulfurization of thioureas, which were obtained from 2-aminophenols and isothiocyanates [34]. In 2019, Doris et al

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• protocol towards the synthesis of 4H-3,1-benzothiazines was established by using a P(NMe2)3-mediated C–N/C–S bond formation reaction of 2-aminobenzyl alcohol with isothiocyanates under aerobic conditions [21]. Despite of the above achievements, the development of new efficient methods for the synthesis of

• obtained (compounds 8s, NR4R5 = NPh2). The aza-Wittig reaction of iminophosphoranes 5 with an excess of CS2 took place smoothly at 40 °C to produce isothiocyanates 9, which were allowed to react with secondary amines to generate thiourea intermediates 10. In the presence of K2CO3 in CH3CN at refluxing

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• formamides [11] and reduction of isothiocyanates to thioformamides [12] by its means. There have also been some catalytic protocols developed for the reduction of amides to imines. The most notable examples incorporate iridium complexes and silanes [13][14]. Cheng and Brookhart showed that the chlorobis

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• RNA in a highly selective and efficient way. The more traditional strategies rely on reaction of isothiocyanates or NHS esters with aliphatic amines [13][14], or on addition of thiols to the α,β-unsaturated carbonyl face of maleimides [15]. Over the past years, the copper catalyzed alkyne–azide

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• studied in detail only with the very active dipolarophiles: N-arylmaleimides, dialkyl fumarates, dicyanoethylene, diphenylcyclopropenone, aryl isocyanates, and aryl isothiocyanates [18][19][20][21][22]. Another approach to the generation of unstable AMIs from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes is based

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• -triazine-2,4-diamines in 44–72% yields that employed the reaction of isothiocyanates with sodium hydrogen cyanamide and amidines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and heating at 75 °C for 3 h. Recently, Ma et al. [33] described a one-pot two step procedure for

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• chemistry demands. Several methods were reported for the synthesis of triazinethione analogs. One of the most popular methods involved the reaction of a carboximidamide [16], or urea [17] with isothiocyanates. The C=S bond in the latter is highly polar, with the carbon atom always positive and therefore

• being susceptible to nucleophilic attack. The resulting substituted thioureas underwent a cyclization reaction providing the desired triazinethiones (Scheme 1a and 1b). However, this method required the preparation of the starting isothiocyanates, which limited its synthetic applications. In another

Recent synthesis of thietanes

• Jiaxi Xu

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

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• differential scanning calorimetry (DSC). Results and Discussion Synthesis In order to generate molecular structural diversity in thioureas, three sets of amines carrying 5-membered isoxazolines/isoxazoles (see Scheme 1) were employed and condensed with acyl isothiocyanates, as outlined in Scheme 2. Amines 3, 4

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• [7], insecticides (cartap) [8], and herbicides [9]. They are also used as key intermediates in the generation of carbonyl sulfide/hydrogen sulfide [10], the synthesis of isothiocyanates [11], asymmetric thioureas [12], and thiazolidine/thiaoxazine [13]. Therefore, as a result, numerous synthetic

• methods for carbamothioates have been reported. These include reactions of chlorothioformates with amines [14], thiocarbonyl benzotriazoles with alcohols [15], copper-catalyzed reactions of α-substituted stannanes with carbamothioates [16], reactions of isothiocyanates with alcohols [6][17], and reactions

• of xanthate esters with amines [18]. Furthermore, many methods have also been reported for the synthesis of cyclic thiocarbamates, and these include reactions of isothiocyanates with aldehydes in the presence of organocatalysts [19][20], reactions of vicinal diols with potassium thiocyanate [21

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• isothiocyanates, as valuable building blocks from isocyanides and sulfur is proposed, as well. The synthetic procedure suits the demand of a modern organic chemist, as it tolerates a wide range of functional groups, it is atom economic and easily scalable. Keywords: ditihiocarbamate; elemental sulfur

• isothiocyanate [48][49][50][51][52] showing better atom economy. Nonetheless, only a few examples can be found in the literature starting from thiocyanates, and regarding the isothiocyanates the preparation of the reagent is required as an additional reaction step before. The synthesis of isothiocyanates

• afford isothiocyanate and harmless urea [63][64][65], but one should note that the instability of the nitrile oxides leads to many byproducts, turning this approach less attractive. The synthesis of isothiocyanates starting from isonitriles involves sulfur-containing reagents such as thallium

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• already been achieved by the intramolecular aldol-type condensation of N,S-acetal 7a (Figure 2C). Subsequently, we investigated the scope of the reaction using our optimized conditions (Scheme 1). As shown in Scheme 1, various isothiocyanates containing aryl and alkyl groups were applied, and the desired

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• a result of their direct heterocyclization involving various single-carbon electrophilic reagents [15][16][20]. A similar one-pot aza-Staudinger reaction of 3-(azidomethyl)pyridazines with isothiocyanates in the presence of PMe3 also results in imidazopyridazines [17]. In the synthesis of imidazo

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• rather than an electrophilic trifluoromethylating reagent (Scheme 3). A similar behavior was recently reported by Schoenebeck [37] who showed that isothiocyanates are formed in reactions of primary amines with the (Me4N)SCF3 salt (through a different mechanism). Interesting differences in the NMR spectra

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• the reactivity of gaseous and solid amines with solid isothiocyanates was described [30]. The authors carried out gas–solid reactions via vapour digestion and solid–solid reactions by means of ball milling. To ensure that the investigated reactions were genuine solid-state processes, in some cases the

• milling was performed at low temperatures (−30 °C) using an in-house ball mill equipped with a cooling jacket. As isothiocyanate component, liquid phenyl isothiocyanate and solid methyl, 1-naphthyl, 4-bromophenyl and 4-nitrophenyl isothiocyanates were screened. While ammonia, methylamine and dimethylamine

• -and-pestle synthesis of 14 diarylthioureas by reacting 4-ethoxy-, 4-chloro- and 4-bromophenyl isothiocyanates with several anilines. After manual grinding for 5–40 min, the crude products were recrystallized from ethanol or acetone, and dried under vacuum to afford the thioureas in 89–98% yield [31

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

• reported an efficient method for the synthesis of pyrene-1-carbothioamides via reaction of pyrene with isothiocyanates in the presence of trifluoromethanesulfonic (triflic) acid (TfOH) [11][12]. Since 2 was used as a starting material in the syntheses of various pyrenyl fluorophores exhibiting unique

• syntheses of various products (especially heterocycles) [21][22]. Furthermore, aromatic amides undergo a variety of directed C–H bond functionalizations [23]. Herein we report that the reaction of 2 with aliphatic isocyanates and isothiocyanates proceeds regioselectively at the 1-position (Scheme 1

• ). Results and Discussion The reaction was carried out at room temperature in dichloromethane using 1.7 equiv of isocyanate or isothiocyanate and 3.3 equiv of TfOH. For the isocyanates, the reaction was completed in less than 5 min, whereas the reaction with isothiocyanates required ≈30 min for completion

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

• high yields (Scheme 2b) [82]. 2 From N-propargylamines and isothiocyanates The first example of a synthesis of thiazole derivatives from N-propargylamines and isothiocyanates was reported in 1964 by Easton et al. The authors obtained 2-iminothiazolidines 11 in good yields by the treatment of secondary

• α,α-disubstituted N-propargylamines 9 with isothiocyanates 10 through a catalyst-free thiourea formation/intramolecular thia-Michael cyclization in ether (Scheme 3a). They also showed that the treatment of primary α,α-disubstituted N-propargylamines with isothiocyanates led to the corresponding N

• -propargylthioureas that converted to the cyclic forms upon standing for several days at room temperature [83]. Thirteen years later, Arya and co-workers applied this method for the synthesis of 3-thia-1-azaspiro[4,5]decane ring systems [84]. In 1993, U. Urleb extended the scope of the reaction from isothiocyanates

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

• , TCT) as a desulfurylation reagent in the synthesis of carbodiimides or alkyl isothiocyanates from thioureas under mild conditions. Conclusion Several synthetic procedures related to thiation of heterocyclic amides have been reported to date. The drawback of the existing methods is the use of expensive