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

• chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream. Keywords: chloroxime; dipolar cycloaddition; flow chemistry; flow synthesis; immobilised reagents; isothiocyanate; nitrile oxide; Introduction Flow based chemical

• -oxathiazoline intermediate that readily rearranges into urea and eliminates the desired isothiocyanate product [37][38] (Scheme 1b). Whilst this approach appears on initial inspection to be very attractive it is somewhat hampered by the requirement to access the reactive nitrile oxide species, which once formed

• for trapping even the small quantities of polar impurities within the matrix thus allowing for the isolation of the desired isothiocyanate product in high purity after only simple solvent removal. Results and Discussion Initially a set of batch experiments was performed using (4-bromophenyl)chloroxime

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

• . Apparently, the reason for this can be attributed to the retardation of the nucleophilic attack of the amines on the isothiocyanate due to the steric effect (Figure 2) in the former, and decrease of the nucleophilicity of the amines by the electron-withdrawing group in the latter, thus not affording the

• of the nucleophilic attack of amines on the isothiocyanate due to the steric effect. Possible regio/stereoisomeric products. Stereoselectivity of the reaction directed by A1,3 strain. Plausible mechanism. Regioselective cyclization in 2-iminothiazolidin-4-one synthesis directed by allylic strains

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• negative βX values for less basic anilines are not ascribed to (i) a desolvation step prior to the rate-limiting nucleophilic attack, because the aniline nucleophile is neutral and the MeCN solvent is dipolar aprotic; and to (ii) a TS imbalance phenomenon, because the leaving group of isothiocyanate is too

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• of the glycopolymers 11 with TBAF yielded the amino-terminated monotelechelic glycopolymers 12. The complete disappearance of the TMS protons in 1H NMR (Figure 1, top spectrum) confirmed the successful and complete deprotection. Subsequent conjugation of 12 with the pyrene isothiocyanate 15, prepared

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

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• -Diaminocyclohexane (1) and (R)-1-phenylethyl isothiocyanate (2) were employed for the synthesis of primary amine-thiourea 3 [36][38][40][54]. Subsequent treatment of 3 with a guanidinylation reagent, N,N′-di-Boc-N″-triflylguanidine (4) [54][55], gave the intermediate 5 in 98% yield. The next step involved cleavage

• -Methylbenzyl isothiocyanate (2): To a solution of (R)-1-phenylethylamine (3.000 g, 3.151 mL, 24.76 mmol, 1.0 equiv) in anhydrous diethyl ether (20 mL), cooled to 0 °C and under a nitrogen atmosphere, carbon disulfide (12.065 g, 158.46 mmol, 9.6 mL, 6.4 equiv) and N,N′-dicyclohexylcarbodiimide (5.109 g, 24.76

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• a very straightforward approach: Enantiopure (S)-S-methyl-S-phenylsulfoximine [(S)-2] was added to 3,5-bis(trifluoromethyl)phenyl isothiocyanate to provide product (S)-3 (Scheme 1). This kind of addition was first described by Wehr in 1965 who allowed a number of isothiocyanates to react with

• racemic sulfoximines have been applied, and the reactions were performed at elevated temperatures, such as 80 °C, or in a steam bath. The protocol introduced here is most simple: After addition of the isothiocyanate to a solution of sulfoximine (S)-2 in dichloromomethane (DCM) the mixture was stirred at

• [35][59][60], two isothiocyanates, namely phenyl isothiocyanate and 3,5-bis(trifluoromethyl)phenyl isothiocyanate, were added. Both thiourea formations went very well, and the desired products (S)-12 and (S)-13 were obtained in almost quantitative yields (98% and 99%, respectively). In (S)-12 and (S

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• organocatalyst 2 was prepared from quinine, via the azide, in a two-step sequence by using the Bose–Mitsunobu reaction followed by Staudinger reduction, as described by others [15]. Thiourea Cinchona organocatalyst 3 was easily obtained from catalyst 2 by reaction with the appropriate aromatic isothiocyanate [15

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

• Nan Sun,
• Bin Li,
• Jianping Shao,
• Weimin Mo,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2012, 8, 61–70, doi:10.3762/bjoc.8.6

• generation of a dithiocarbamate salt from the amine substrate by reacting with CS2 followed by elimination to form the isothiocyanate product with cyanuric acid as the desulfurylation reagent. The choice of solvent is of decisive importance for the successful formation of the dithiocarbamate salt

• which are abundant in many cruciferous vegetables. Recently, it has been found that naturally occurring isothiocyanates play a significant role in the cancer chemopreventive activity of these plant species [1][2], and thus, many of such analogues containing the isothiocyanate motif have been synthesized

• desulfurylation affords the desired isothiocyanate with proper desulfurylation reagent. Although many desulfurylating reagents for this strategy were developed [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59], most of them were efficient only for alkyl and

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• The bisureido- and bisthioureido-substituted dibenzobarrelene derivatives 1e–i were synthesized by the reaction of the known bis(diaminomethyl)-substituted derivative of dibenzobarrelene 1d [45] with a slight excess of the corresponding isocyanate or isothiocyanate (Scheme 3). The resulting products

• in front of the lamp. General procedure for the preparation of bisurea- and bisthiourea derivatives of dibenzobarrelene (GP1): The isocyanate or isothiocyanate derivative (1.1 molar equiv) was added to a stirred solution of 11,12-bis(aminomethyl)-9,10-dihydro-9,10-ethenoanthracene (1d, 0.45–10.0 mmol

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• -component, two-step “catch and release” solid-phase synthesis of 3,4,5-trisubstituted pyrazoles was reported which involved a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (29 or 33) with an isothiocyanate and in situ immobilization of the resulting thiolate anion (30

• -benzoyl-3,5-diamino-1-(2-cyanoethyl)pyrazole 147 (Scheme 40) [82]. 2-Cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide (148) was utilized for the synthesis of the 5-aminopyrazole 150. Treatment of 148 with phenyl isothiocyanate in DMF in the presence of potassium hydroxide at room

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

• Xiao-bo Zhou,
• Yuk-Wang Yip,
• Wing-Hong Chan and
• Albert W. M. Lee

Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11

• -trimethylbenzene with sodium azide in DMSO afforded the corresponding bis-azide. Transformation of the crude bis-azide into bis-isothiocyanate 3 was achieved by treatment with triphenylphosphine in the presence of CS2. The “fluorophore–spacer–receptor” sensing motif for carboxylate was incorporated into the

• guests, an additional binding site must be introduced. Thus, (S)-phenylalaninol (obtainable from L-phenylalanine) was reacted with isothiocyanate 4 to give sensor 2 in 40% yield. We envisaged that the additional alcohol functionality present in 2 could provide a binding site for the α-amino group of

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• using functionalized monomers or copolymers with additional functionality that do not participate in the polyaddition, in this case, e.g., amino, carboxylic, hydroxy, epoxide, isocyanate, or isothiocyanate. Such capsules could be used to encapsulate contrast agents (Magnevist®, Gadovist®) for magnetic

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• Lewis base catalysis are known to be involved in the catalytic cycle, the latter possibly involving the isothiocyanate counterion [52]. Despite their many favourable properties, there is one drawback associated with catalysts 1 and 2; they exhibit highest activity and highest enantioselectivity in

• came from 51V NMR studies of complex 2 (Figure 5). The spectrum of complex 2 in CDCl3 shows a resonance at −580 ppm (Figure 5a). It is known from X-ray crystallography that the isothiocyanate unit in complex 2 is directly bound to the vanadium ion through the nitrogen atom. Thus, the vanadium ion is

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• analogue 37 with an isothiourea group instead of an isourea group, which is also a potent trehalase inhibitor [66][67]. D-Gluco trehazolin analogues have also been synthesised by means of novel methodology based on the coupling of O-unprotected β-D-glucopyranosyl isothiocyanate with different aminosugars

• carbodiimides via a tandem Staudinger-aza-Wittig type reaction with triphenylphosphine and an isothiocyanate, followed by the addition of a nucleophile (H2O, H2S, NH3, amines) (Figure 14). Although this second methodology is more straightforward and versatile than the first, only a few examples of

• longer thiourea-linked glycooligomers with linear dendritic and branched architectures, our group has recently reported an efficient synthetic strategy based on the use of AB, AB2 and ABC-type monosaccharide building blocks containing isothiocyanate (A), azido (B) or carbamate groups (C) (Scheme 4) [85

The first organocatalytic carbonyl- ene reaction: isomerisation- free C-C bond formations catalysed by H-bonding thio- ureas

• Matthew L. Clarke,
• Charlotte E. S. Jones and
• Marcia B. France

Beilstein J. Org. Chem. 2007, 3, No. 24, doi:10.1186/1860-5397-3-24

• isothiocyanate in 52% yield and has recently been reported by another group.[19] This catalyst was tested in the α-methyl styrene ene reaction to ethyl trifluoropyruvate with ultimately disappointing results. This catalyst did allow us to demonstrate the first asymmetric organocatalytic carbonyl ene reaction