The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• , Světlik et al. studied the Biginelli-type condensation of 2-hydroxybenzaldehyde with urea (thiourea) and dialkyl acetone-1,3-dicarboxylates as active methylene components [16]. Unexpectedly, the reaction with salicylaldehyde furnished two different products depending on the ester alkyl group (Scheme 2

• derivatives from salicylaldehyde, various dicarbonyl compounds, and urea (thiourea) using PdO as a catalyst (Scheme 2). Heterocyclizations involving both, salicylaldehyde and aminoazoles, are intriguing as well. Thus, for example in the course of the study on the application of 3-amino-1,2,4-triazole and

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

• Main, Germany 10.3762/bjoc.10.317 Abstract A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea

• ://www.ccdc.cam.ac.uk/data_request/cif. The reagent used herein is a convenient one to prepare carbodiimides from thiourea derivatives [11][12][13]. Therefore, the reaction mechanism is envisioned to proceed via the initial formation of one carbodiimide unit in 3 (Scheme 2). The (N=C=N) unit experiences an

• intramolecular nucleophilic attack at its central, highly electrophilic carbon by the adjacent -NH- of the yet unreacted thiourea unit to produce 4 in a first cyclization step (cyclization-I). The second ring closure to generate the 1,2,4-thiadiazole ring may be assisted by one equivalent of methansulfonyl

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• volatilities of BrCCl3 and CHCl3 by removing them under vacuum and replacing the solvent. A solvent switch was also reported when photoredox activation of 4a was combined with thiourea-catalysed enantioselective alkylation [37]. The enantioselectivity of the thiourea-catalysed alkylation was optimal in non

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

• 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

• Scheme 6. We assume that the reaction starts with the thiocarbamoylation of one of the benzyl-substituted amino functions of 3. Cyclization of the formed intermediate with participation of the thiourea-NH nitrogen gives rise to 1,2,4-triazole-5(4H)-thione 12 from which the major reaction product 10 is

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• reaction furnished olefins 2a and 2b after acetylation in quantitative yield (Scheme 1). In the gluco-case a yield of 70% for 2c was obtained owing to incomplete consumption of the starting material 1c. Ozonolysis of the olefins 2 was performed using thiourea as reducing agent. Subsequently the generated 2

• , biologically active octodioses are now accessible from compounds 7b and 7c, which is subject of ongoing research. Functionalization of carbohydrates; reagents and conditions: (a) In, allyl bromide, EtOH/H2O, ultrasound, 2.5–7 h, then Ac2O/pyridine, DMAP, rt, 16 h, quant.; (b) O3, CH2Cl2, −78 °C then thiourea

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• have excellent catalytic activities and enantioselectivities, only a few acyclic phosphines were effective. In this context, inspired by polyfunctional chiral small-molecule catalysts, particularly amino acid and thiourea-based systems [31][32], multifunctional chiral phosphines were constructed by

• to excellent yields. N-Alkyl-substituted maleimides were converted to cyclopentenes in high ee, while N-aryl-substituted maleimides underwent the reaction with low to moderate enantioselectivity. Using the multifunctional chiral phosphine G6, featuring a binaphthyl skeleton and bearing a thiourea

• imines. Based on thiourea-based catalyst systems, they developed the multifunctional catalyst H3 containing a phosphine fragment, a thiourea moiety, and an amino acid residue [67]. In the presence of 10 mol % of catalyst H3, with the assistance of triethylamine (5 mol %) and water (20 mol %), a wide

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• greatest stabilizing effect by disodium ethylenediamine (EDTA) (96.2%), followed by thiourea (88.2%), methylparaben (86.4%), DL-methionine (76.3%), sodium thiosulfate (72.9%), ribonucleic acid (59.3%) and reduced glutathione (26.2%). When RF solutions were exposed to a 40 W fluorescent light (Sylvania

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

• ) consists in the three-component condensation of a 1,3-dicarbonyl compound, an aldehyde, and a nitrogen component, i.e., urea (X = O, R3 = H) or thiourea (X = S, R3 = H) [29]. The use of N-substituted derivatives of urea or thiourea (R3 ≠ H) has also been reported. Recently numerous advances in the

• system (Scheme 27) [98][99]. Attempts to replace the aldehyde 73a with its 3,4,6-hydroxylated counterpart failed to give the expected product [99]. Dwivedi et al. showed that the isopropylidene-protected sugars 75 reacted efficiently with urea (or thiourea) and 1,3-dicarbonyl compounds in diethylene

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• diphenylphosphine to a range of nitroalkenes 56 has been described using a bifuntional Cinchona alkoid/thiourea catalyst 58 [132]. The catalyst 58 is able to simultaneously activate both the electrophilic and nucleophilic reagents. On one hand the thiourea presumably binds the nitro group while on the other hand

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

• protons of the bipyridine moiety that would indicate successful binding of the silver(I) ions to the nitrogen atoms. Thus, we conclude that the soft silver(I) ions rather bind to one of the sulfur atoms of the thiourea groups. This, however, does not cause the necessary conformational change of the

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• couplings [16][23], the classical formation of ester [12][17], amide [25][26] or imide [27] bonds between CDs or amino CDs and acid- or anhydride-linkers, and finally urea/thiourea bonds [28][29]. However, the obvious advantages of the Staudinger ligation (high reaction rates, absence of a catalyst, aqueous

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• ] and enaminones [34]. On the other hand, as frequently utilized building blocks in organic synthesis, alkynes have been known to possess versatile reactivity in the synthesis of small molecules. For example, a previous protocol employing aryl alkynes, aldehydes and urea/thiourea has been found to

• use of the activation effect of a secondary amine to alkynes (Scheme 1) [37]. Results and Discussion The work began from the three-component model reaction of p-chlorobenzaldehyde (1a), thiourea (2a) and ethyl propiolate (3a). The optimization results are outlined in Table 1. Firstly, parallel studies

• higher yields than those containing an electron donating group (EDG) (Table 2, products 5a–5e, 5i–5k). A similar tendency occurred in the experiments using N-methyl thiourea (Table 2, products 5f–5h). Attempts on employing EDG-substituted aldehydes such as p-tolylaldehyde to react with N-substituted

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• reaction of methyl acrylate with benzaldehyde the substituted triamide catalysts show a comparable or an even superior activity relative to the thiourea analogue. Recently, Gale et al. demonstrated that the same phosphoric triamides effectively act as anion transporters by hydrogen bonding [19]. These

• the nitro moiety with a bonding energy (ΔE) of 5.2 kcal/mol and a mean bond length NHurea–Onitrobenzene of 2.31 Å. Thiourea complex Ib forms slightly stronger hydrogen bonds to the NO2 moiety with a bonding energy of 6.5 kcal/mol, which is also reflected in the shorter mean bond length of NHthiourea

• –Onitrobenzene (2.19 Å). This is in accordance with the experimentally observed higher acidity [27] of thiourea over urea. Squaramide complex II forms the strongest hydrogen bonds of all computed motifs. The bond lengths NHsquaramide–Onitrobenzene are shortest with 2.11 Å while the bonding energy is highest (8.3

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• DDS 1 and thioglycosides 2–7 are required. The large scale synthesis of DDS 1 was achieved according to a published procedure [26]. The required β-thioglycosides 2–7 were prepared via their corresponding glycosyl bromides followed by SN2 displacement of the anomeric bromide with thiourea [41] or Na2S

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

• chromium(VI) oxide yielded the aldehyde 1.67 required for the previously described Knoevenagel condensation. The five membered heterocycle 2,4-thiazolidinedione (1.68) is readily available commercially, but can be easily prepared at scale via a simple cyclocondensation between thiourea and chloroacetic

• (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

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• . Enantioselective reactions have been controlled by asymmetric metal-centred Lewis acids; chiral hydrogen bond donors, in particular by the use of asymmetric thiourea organocatalysts, chiral Brønsted acids, phase-transfer catalysts and Brønsted base catalysts [3][15][25][26][27][28][29][30][31][32][33][34][35][36

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• which has received less attention are isothiocyanates. These species are widely utilised as valuable starting materials for many thiourea-based organocatalysts [24][25][26], numerous heterocyclic entities [27][28][29] as well as important entry points towards other key functional groups such as

• ], both reagents causing safety concerns due to the formation of toxic, malodorous and/or extremely corrosive byproducts (Scheme 1a). An underutilised alternative sequence is the 1,3-dipolar cycloaddition reaction between a nitrile oxide and a thiourea compound which initially generates an unstable 1,4,2

• weak base and a functionalised thiourea) placed as a 1:1-mixture within a single glass reactor cartridge (Scheme 2). The immobilised base affects the in situ formation of the reactive nitrile oxide from the chloroxime which is immediately captured by the local tethered thiocarbonyl dipolarophile

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• a small amount of THF to dissolve the starting material). The oxy-Michael addition with chiral thiourea and phenylboronic acid proceeded to give a single diastereomer; however, after 48 h at 50 °C, only 17% of the syn diol was formed, and 56% of the starting material was re-isolated. Under the

• carry out the reaction with diisopropylamine as a substitute for the thiourea catalyst. This modification afforded both the syn and anti diols in roughly a 1:1 ratio and a combined yield of 40–45%, albeit without recovery of starting material. The syn and anti diastereomers could be separated by

Structures of the reaction products of the AZADO radical with TCNQF₄ or thiourea

• Hideto Suzuki,
• Yuta Kawahara,
• Hiroki Akutsu,
• Jun-ichi Yamada and
• Shin’ichi Nakatsuji

Beilstein J. Org. Chem. 2013, 9, 1487–1491, doi:10.3762/bjoc.9.169

• reaction of AZADO (2-azaadamantane N-oxyl) with TCNQF4 (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane), the reaction of AZADO with thiourea provided an inclusion compound, in which AZADO molecules are incorporated in cylindrical channels formed by thiourea molecules. Keywords: adduct; inclusion

• compound; nitroxide radical; TCNQF4; thiourea; Introduction TEMPO radical (2,2,6,6-tetramethylpiperidinyl-N-oxyl) (1) is a typical nitroxide radical and is persistent because of the steric hindrance of the four neighboring methyl groups of the NO moiety protecting it from attack by various reagents

• acceptor. Moreover, we tried to prepare a supramolecule from 2 with thiourea (4), as structurally similar 1-bromoadamantane was reported to form an intriguing inclusion compound with thiouea [9]. There are some reported examples of inclusion compounds derived from TEMPO and related nitroxide radicals with

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• -Leopoldshafen, Germany 10.3762/bjoc.9.158 Abstract A variety of organocatalysts were screened for the catalysis of the naphthoquinone monoketal Diels–Alder reaction. In this study we found that Schreiner's thiourea catalyst 10 and Jacobson's thiourea catalyst 12 facilitate the cycloaddition of the sterically

• hindered naphthoquinone monoketal dienophile 3 with diene 4. The use of thiourea catalysis allowed for the first time the highly selective synthesis of the exo-product 2a in up to 63% yield. In this reaction a new quaternary center was built. The so formed cycloaddition product 2a represents the ABC

• tricycle of beticolin 0 (1) and is also a valuable model substrate for the total synthesis of related natural products. Keywords: beticolin 0; Diels–Alder reaction; natural product; organocatalysis; thiourea catalysis; total synthesis; Introduction In the past few years, many different types of

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• from purple to brown (d). (a) Ozonolysis of a series of alkenes using ozone in a bottle-reactor; (b) Glaser–Hay coupling using oxygen gas in the second-generation reactor. Cartridges containing polymer supported (PS) reagents are used to scavenge residual reagents: thiourea (TU) sequesters copper, and

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• halide or acetate with thiourea or thioacetate and hydrolysis of the resulting intermediates [26][27]; (b) reaction of hydrogen sulfide gas with glycosyl halides in hydrogen fluoride [39]; (c) treatment of the glycosyl hemiacetal derivatives with Lawesson’s reagent [40] and (d) treatment of 1,6-anhydro

A facile, rapid, one-pot regio/stereoselective synthesis of 2-iminothiazolidin-4-ones under solvent/scavenger-free conditions

• Murugan Sathishkumar,
• Sangaraiah Nagarajan,
• Poovan Shanmugavelan,
• Murugan Dinesh and
• Alagusundaram Ponnuswamy

Beilstein J. Org. Chem. 2013, 9, 689–697, doi:10.3762/bjoc.9.78

• the formation of the carboxylate anion of one the starting materials viz. chloroacetic acid or the thiourea-chloroacetic acid coupled product. This may retard the direct amine–carboxylic acid coupling, thus decreasing the yield of the product. In view of the above perception, the solvent-free protocol

• expected thiourea. Having established the new protocol for the synthesis of 2-iminothiazolidin-4-ones, the method was extended to the rapid synthesis of a library of thiazolidinone derivatives (Table 4). Further, it is pertinent to mention here the interesting regio/stereoselectivity noted in the synthesis

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• consequence, the development of new methodologies for CAr–S bond formation still represents a challenge in organic chemistry (Figure 1). Nucleophilic substitution of aryl halides by a variety of sulfur anions, such as PhS−, 1-naphthylS−, S2−, thiourea anion (−SCNH(NH2)), thioacetate anion (MeCOS−) and

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39