Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• anilines proceed through the formation of unisolable reactive intermediate, aryl N-thiocarbamoylbenzotriazole, which rapidly decomposes to the corresponding isothiocyanate in organic solvent [189]. The Štrukil and Friščić group successfully demonstrated the formation of aryl-N-thiocarbamoylbenzotriazole

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• 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

• -withdrawing group in the amine (lower nucleophilicity) and an electron-donating group in the isothiocyanate component (lower electrophilicity) led to prolonged grinding times necessary to achieve quantitative conversion. The reaction time in these cases was successfully reduced by LAG, providing N,N

• -type amine–isothiocyanate coupling reaction (Scheme 4). In the case of secondary amines (piperidine, morpholine and thiomorpholine) and sterically hindered amines (2,4- and 2,6-dimethylanilines), ball milling again resulted in ≥99% yields in 10 minutes, except for the reactions involving 4

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

• , although substitution at the 1-position prevails. For ethoxycarbonyl isothiocyanate, apart from the 1-substituted thioamide, 1,8-disubstituted thioamide and 2,7-di-tert-butylpyrene-1-carbonitrile are formed (especially at longer reaction times). Keywords: amide; Friedel–Crafts; isocyanate; isothiocyanate

• ). 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

• , for the reaction with p-methoxyphenyl isothiocyanate we were able to obtain, by crystallization, the major product, C(1)-substituted thioamide 3n, contaminated with only ≈5% of its C4-substituted counterpart. We tentatively explain this poorer regioselectivity by possible π–π interaction of pyrene

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• of the CD polymer and a reactive isothiocyanate–silane monolayer. Atomic force measurements of CD polymer decorated surfaces show enhanced supramolecular interaction energies which can be attributed to multiple inclusion complexes based on the rigidity of the polymer backbone and the regular

• well as the silicon AFM tip, were first functionalized by a polysiloxane monolayer bearing isothiocyanate groups, which smoothly react with amines forming stable thiourea links [48]. Monolayers of β-CD or β-CD-polymer were obtained by attachment of monoamino β-CD or amino-modified CD polymer 12

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

• iodine in ethyl acetate. Excellent yields of desired products were observed (Scheme 5). The mechanism shown in Scheme 6 was proposed for this transformation and comprises the following key steps: (i) the reaction of N-propargylamine 25 and isothiocyanate 26 forms the thiourea intermediate A, (ii

• towards thiazolidines of type 30, the group of Clausen has proposed a base-catalyzed protocol using t-BuOH in water at 20 °C for a quite efficient cyclization between secondary N-propargylamines 28 and fluorescein isothiocyanate 29 (Scheme 7) [89]. More recently, Beauchemin and co-workers reported the

• syntheses of a series of multiply substituted thiazolidines 33 via the cyclization reaction of secondary N-propargylamines 32 with blocked N-isothiocyanate precursors 31. The desired N-isocyanates A are produced in situ upon heating or treatment with a base, in acetonitrile under microwave irradiation

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• have been developed. Fenyvesi and Jicsinszky applied thioureido chemistry to attach fluoresceinyl isothiocyanate to randomly methylated 6-monoamino-β-CD as a possible sensor for soluble contaminants in groundwater [23]. In the conjugate obtained, the stability of the formed thioureido moiety also made

• possible its biological application and since the introduction of this strategy a wide variety of xanthene-dye-appended CDs have been developed [24][25] using the same methodology. However, the major drawbacks of this approach is the extremely high price of the isothiocyanate pre-modified xanthene starting

• -β-CD scaffold was achieved through amide-bond formation between the amino-CD and the carboxylic group of the xanthene dyes [26]. This strategy does not require the laborious isothiocyanate functionalization and it can be applied to all xanthene dyes having a carboxylic function. Encouraged by these

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

• from I followed by electron delocalization and the overall formation of cyclohexyl isothiocyanate (4) via C–S bond cleavage and the formation of quinazoline thiol anion II having a negative charge concerted on the nitrogen atom. The protonated cyclohexylamine in the previous step will transfer this

• extra proton to II to afford the quinazoline thione C2. On the other hand the free cyclohexylamine will add to cyclohexyl isothiocyanate (4) to form the thiourea 3. Similar results were obtained by Furumoto [40], and Sun [41] reported the application of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• (DSL5.6) can enter ASGPR-expressing cells, we examined the intracellular distribution of tetramethylrhodamine isothiocyanate (TRITC)-multi-Lac-β-CD (DSL5.6) in NPC-like HepG2 cells (ASGPR positive cells) Figure 5. The cellular uptake of TRITC-multi-Lac-β-CD (DSL5.6) was observed in NPC-like HepG2 cells 24

• , Japan). Lactose monohydrate was purchased from Wako Pure Chemical Industries (Osaka, Japan). Tetramethylrhodamine isothiocyanate (TRITC) was obtained from Funakoshi (Tokyo, Japan). Biotinylated-peanut agglutinin (PNA) and bovine serum albumin (BSA) were purchased from Cosmo Bio (Tokyo, Japan) and

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• ) [92]. Moderate to good yields (60–90%) of the desired heterocyclic phosphonates 262 and 264 were obtained. The same group has also reported another Reissert-type reaction for the synthesis of 1,2-dihydroisoquinolin-1-ylphosphonates via activation of isoquinoline with isocyanate or isothiocyanate. In

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• -aminoethylamino)-β-CD was obtained by in situ conversion of the terminal amino group of the fluorophore into isothiocyanate group. To summarize, fluorescein has been connected to CDs through an ester bond by performing the reaction in water or DMF. Although the synthetic procedure is well described, the

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• isocyanates and isothiocyanate gave ureido and thioureido persubstituted β-CD derivatives in a MW oven at 85 °C for 4 h (see Scheme 9). A multivalent azido-scaffold such as persubstituted 6-azido-6-deoxy-α-, β- or γ-CD with conformational constraints can be efficiently perfunctionalized in a MW- and ligand

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

• = 0.25) was assigned to π–π aggregates, the presence of which was revealed by single-crystal X-ray diffraction analysis. Keywords: amide; fluorescence; isothiocyanate; phosphonate; pyrene; thioamide; X-ray structure; Introduction Friedel–Crafts-type reaction of arenes with isothiocyanates constitutes a

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels

• Shintaro Kawano,
• Toshiyuki Kida,
• Mitsuru Akashi,
• Hirofumi Sato,
• Motohiro Shizuma and
• Daisuke Ono

Beilstein J. Org. Chem. 2015, 11, 2355–2364, doi:10.3762/bjoc.11.257

• method. The CD nanogel was labeled with fluorescein isothiocyanate (FITC) in the aqueous phase before emulsification. A Pickering emulsion was prepared by mixing the aqueous dispersion containing FITC labeled-CD nanogels (0.1 wt %) with n-dodecane (Φoil = 0.1) and subsequent shaking for 1 min. After

• to use. Anhydrous N,N-dimethylformamide (DMF) and 1,4-phenylene diisocyanate (PDI) were purchased from Wako Pure Chemical Industries, Ltd. (Japan). Toluene and n-dodecane were purchased from Kanto Chemical Co., Ltd. (Japan). Fluorescein-4-isothiocyanate was purchased from Dojin Chemical Co. Ltd

• homogenized for 1 min using a homogenizer (DIAX 900; Heidolph) at 8000 rpm (25 °C). The resulting emulsion was allowed to stand at 25 °C for 24 h. To confirm the adsorption of the CD nanogels at the oil–water interface in the emulsion, the CD nanogel (0.1 wt %) was labeled with fluorescein-4-isothiocyanate

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• whether Lac-β-CyD can associate with ASGPR-expressing cells, we examined the cellular uptake of tetramethylrhodamine isothiocyanate (TRITC)-labeled Lac-β-CyD after treatment for 24 h in U18666A-treated HepG2 and NPC-like ASGPR-expressing cells, by a flow cytometric analysis (Figure 4). As a result, TRITC

• Pharmaceuticals (Tokyo, Japan) and Nichirei (Tokyo, Japan), respectively. Tetramethylrhodamine isothiocyanate (TRITC) was obtained from Funakoshi (Tokyo, Japan). The cell counting kit was purchased from Wako Pure Chemical Industries (Osaka, Japan). The cholesterol cell-based detection assay kit was purchased from

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• assembled from acyclic starting materials by methods such as i) reaction of lithiated 1-alkynes or allenes with substituted phenyl isothiocyanates [20], ii) treatment of N-allylbenzotriazole with substituted phenylisothiocyanates [21] and iii) reaction between phenyl isothiocyanate and electron-deficient

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• did not result in a satisfactory yield and demonstrates a current limitation of the automated glycan assembly approach. Recently, placement of an isothiocyanate moiety on the C5 position was reported to be an effective method to construct alpha linkages [22] and may prove useful for solid-phase

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• . Fluorescent labeling of the β-CD polymer based on the reaction between the amino moieties and the isothiocyanate form of the dye (rhodamine or fluorescein). As an example of the first strategy we report the fluorescent labeling of β-CD polymer with rhodamine isothiocyanate (Scheme 2). 1) Introduction of the

• kDa (1.4% of the starting weight). 3) Fluorescent labeling The coupling between rhodamine isothiocyanate (RBITC) and compound 2 was performed in pyridine and the addition of an extra base (DBU) contributed to the progression of the reaction (Scheme 2). As in the case of the fluorescent labeling of

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• dimensions 0.08 × 0.10 × 0.60 mm) was measured on a Siemens SMART 1K CCD diffractometer at a temperature of about −87 °C. General procedure for the preparation of dithiourea 1a–c. A solution of o-phenylenediamine (2.00 g, 18.5 mmol) and the corresponding isothiocyanate (37.0 mmol) in tetrahydrofuran (100 mL

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• isothiocyanate-labeled 1-adamantylamine (Figure 3). The characteristic confocal microscopy images revealed red fluorescence upon excitation at λex = 568 nm, as well as green fluorescence upon excitation at 488 nm. Following superimposition of the two fluorescence channels it could be concluded that PpIX

• ΄), 34.4 (C3), 27.1 (C2) ppm; MS (MALDI–TOF) m/z: 1685.2 (100%, [M + Νa]+), 1798.18 (89%, [M’ + Na]+); exact mass calculated for C66H119N9O39 ((1)2-CD = M): 1661.76 and for C71H126N10O41 ((1)3-CD = M’): 1774.808. Complexation of fluorescein isothiocyanate-labeled 1-adamantylamine with 2. The conjugate, 2

• (1 mM solution, with respect to ALA content) in phosphate buffer saline (pH 7.4) was mixed with fluorescein isothiocyanate-labeled 1-adamantylamine (0.2 mM) [21] and the dispersion was stirred for 20–30 min until a clear solution was obtained. This solution was subsequently used for cell incubation

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• 7a and 8 show interesting solid-state structures with intra- and intermolecular hydrogen bonds. Keywords: aryl isocyanate; aryl isothiocyanate; carbamoylation; sulfonyl isocyanate; triaminoguanidinium salt; 1H-1,2,4-triazole-5(4H)-thione; Introduction The 1,2,3-triaminoguanidinium ion, [C(NHNH2)3

• as a spectrum taken in acetone-d6 at 295 K) showed only two of them. Reaction of salt 3 with isothiocyanates We thought that when salt 3 was combined with at least three molar equivalents of an isothiocyanate instead of an isocyanate, likewise a threefold sulfonylcarbamoylation, with formation of a

• tris(thiourea) derivative, could result. With phenyl isothiocyanate and its 4-nitro derivative, however, 3-hydrazinyl-1H-1,2,4-triazole-5(4H)-thiones 10a,b were obtained as major products in 57 and 68% yield, respectively (Scheme 5). In the case of (4-nitrophenyl) isothiocyanate, the bis(arylthiourea

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• irradiation-assisted condensation of sugar hydrazine 115, 4-chlorobenzothioamide and an aromatic aldehyde in the presence of (diacetoxyiodo)benzene (Scheme 48) [125]. The conversion of 4-chlorobenzothioamide to 4-(chlorophenyl)isothiocyanate intermediate by (diacetoxyiodo)benzene was suggested to initiate the

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• glycocalixarenes “Click Chemistry” [23] reactions are extensively used to conjugate (oligo)saccharides to macrocyclic structures due to the mild conditions and the high yields [24]. For the synthesis of glycocalixarenes the amino–isothiocyanate condensation [25][26][27][28][29][30] or the 1,3-dipolar cycloaddition

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• synthetic lectin HisHis is able to selectively bind to NANA immobilized on a substrate which serves as a model for a cell surface. To this end, we prepared a set of simple carbohydrate microarrays as well as fluorescein-isothiocyanate labeled HisHis (FITC-HisHis) and studied the selectivity and affinity of

• previously [39]. Fluorescein-labeled FITC-HisHis was obtained by labeling of Cys-His-Cys with fluorescein isothiocyanate, which was achieved by using an Fmoc-protected oligo(ethylene glycol) spacer synthesized in four steps from commercially available ethylenediamine (see Supporting Information File 1). The

• Wilhelms-Universität Münster). Milli-Q water was prepared from distilled water using a PureLab UHQ deionization system (Elga). Tetramethylrhodamine isothiocyanate-labeled concanavalin A (TRITC-ConA) was purchased from Sigma Aldrich. Fluorescein isothiocyanate-labeled peanut agglutinin (FITC-PNA) was

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• . Results and Discussion Synthesis The synthesis of 1–3 requires the three different 2,2’-bipyridines that carry isothiocyanate functions and a monoaminated β-cyclodextrin that could be coupled with each other via two-fold nucleophilic addition. Symmetrically 4,4’- and 6,6’-disubstituted 2,2’-bipyridines

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• complete the syntheses of pioglitazone as outlined in the previous schemes several procedures for the installation of the thiazolidinedione ring system have been reported [50]. For instance the α-bromoester of intermediate 1.82 will render the desired heterocycle upon treatment with sodium isothiocyanate

• (Scheme 16, A). Alternatively, the α-amino acid portion of 1.81 can be diazotised under standard conditions and will subsequently deliver the same product when treated with lithium isothiocyanate (Scheme 16, B). Finally, α-bromonitrile 1.77 can be condensed with thiourea to give pioglitazone after aqueous