Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• polymer undergoes a hydrogen radical abstraction, followed by radical coupling and finally chain scission (Scheme 3) [23]. Polyaddition polymerisation Another common form of polymerisation is polyaddition polymerisation, an example is the formation of polyurethane from a reaction between an isocyanate and

• depicts the screw configuration employed and each reaction. Adapted from [16]. Proposed mechanism for the branching of polylactide. Adapted from [23]. Chemical reaction between isocyanate and an alcohol to form polyurethane. Generic polycondensation reaction to produce polyamides. Synthesis of HKUST-1

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• is that the iminophosphorane reagents can be generated either from a phosphine such as 1 or from a phosphine oxide such as 2, by reaction with either an azide or isocyanate reagent, respectively. Thus, two possible strategies for catalytic aza-Wittig reactions exist, one using a phosphorous(V

• seems that the required isocyanate or azide group containing precursors are readily synthesized from simple starting materials. Conclusion While great advances have been reported regarding the development of catalytic Wittig and aza-Wittig reactions, it remains to be seen how widely these methods will

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• Minosaminomycin by Kondo et al.: The only total synthesis of minosaminomycin (9) to date was reported in 1977 by Kondo et al. (Scheme 14) [69]. Enduracididine (1) was prepared using the method reported by Shiba et al. [54] and was coupled with the isocyanate formed in situ from protected leucine 74 affording urea

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• reaction followed by a retro-aza-ene reaction and subsequent nucleophilic reaction of the in-situ generated imidazo[1,2-a]pyridines bearing an isocyanate functional group. Keywords: Groebke–Blackburn–Bienaymé reaction; imidazo[1,2-a]pyridines; multi-component reaction; one-pot reaction; Introduction

• species from 2-aminopyridine and isatin which then undergoes a formal [4 + 1] cycloaddition with isocyanide to generate a spiro intermediate b. The spiro compound then undergoes a retro-aza–ene reaction via a [1,5]-hydride shift resulting in an aromatic imidazo[1,2-a]pyridine having an isocyanate

• functional group. A further intramolecular nucleophilic reaction of the imidazole and the newly generated isocyanate provides the final product 1. Noteworthy, the benzodiazepinone-fused imidazo[1,2-a]pyridine 5 was not observed which may be due to the strain of the seven-membered ring. Conclusion In

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

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• suitably functionalized urea substrates 15 or 19. Inspired by a work of Garcia [39], we initially intended to use isocyanate for both, the introduction of the urea motif and for the functionalization of the terminal homoallylic alcohol. Consequently, we evaluated the conversion of 14 to 15. The required

• . Therefore, a stepwise approach towards 19 was pursued instead. This involved either a coupling of 12 first with isocyanate to give 16 followed by a cross-metathesis or starting with the cross-metathesis to 18 and subsequent installment of the urea motif. As shown in the table inserted in Scheme 3 for

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

• preliminary study on sonochemical Staudinger-aza-Wittig tandem reactions [20] proving that isocyanate and urea formation is strongly favored. However, the applied power must be optimised for the best conversions of azido-CD into urea to be obtained and if lower efficiency in the second step is to be avoided

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

• . We have previously reported urethane-crosslinked CD polymers, which were prepared by reacting heptakis(2,6-di-O-methyl)-β-cyclodextrins (DM-β-CDs) with aromatic diisocyanates such as 4,4’-methylenebis(phenyl isocyanate) (MDI) and 1,4-phenylene diisocyanate (PDI) [18]. Although MDI- or PDI-crosslinked

Urethane tetrathiafulvalene derivatives: synthesis, self-assembly and electrochemical properties

• Xiang Sun,
• Guoqiao Lai,
• Zhifang Li,
• Yuwen Ma,
• Xiao Yuan,
• Yongjia Shen and
• Chengyun Wang

Beilstein J. Org. Chem. 2015, 11, 2343–2349, doi:10.3762/bjoc.11.255

• commercially available starting materials according to the reported methods. Compound 8 [18][21] was obtained by the reaction of 7 with 2-chloroethyl isocyanate in dry and degassed toluene. Finally, the TTF derivative T1 was obtained in acceptable yield (72%). For the synthesis of T2, urethane groups were

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• other hand understanding the behaviour of non-rigid molecules may also be useful and a challenging task. Experimental Synthesis Compound 1 was obtained by heating urea (1.0 g, 16.7 mmol) and n-butyl isocyanate (3.3 g, 33.4 mmol, 1:2 molar ratio) for 24 h under reflux in pyridine (20 mL). Then pyridine

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• that with X = CO, i.e., the bis(isocyanate) (see below). Once we have developed high-yielding routes to 8 and 9, we plan to apply them to the preparation of the isomeric tetraamines 10 and 11 from the corresponding, already available tetraacids [22][23]. Results and Discussion Preparation and

• at room temperature provided the isolable azidocarbonyl derivative 15 in 90% yield; for its analytical data see Supporting Information File 1. Compound 15 can even be purified by silica gel column chromatography although it was noted that Curtius rearrangement to the bis(isocyanate) 16 slowly set in

• . Hence 15 was employed in the Curtius step (toluene, reflux) without further purification and at about 95 °C the evolution of nitrogen gas could be clearly seen. The bis(isocyanate) 16 was isolated in quantitative yield and characterized by its spectroscopic and analytical data (see Supporting

Molecular cleft or tweezer compounds derived from trioxabicyclo[3.3.1]nonadiene diisocyanate and diacid dichloride

• Gert Kollenz,
• Ralf Smounig,
• Ferdinand Belaj,
• David Kvaskoff and
• Curt Wentrup

Beilstein J. Org. Chem. 2015, 11, 1–8, doi:10.3762/bjoc.11.1

• ability to extract some alkali, alkaline earth and rare earth metal ions. Keywords: carbamates; crown ethers; diisocyanate; isocyanate; ureas; Introduction The synthesis of the surprisingly stable, monomeric diisocyanate 1 (Figure 1) was reported recently [1]. This and several other derivatives of the

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• –15 were obtained and tested for their gelation properties. General procedure for the synthesis of ureas The urea library was synthesized by mixing compound 3 and the corresponding isocyanate in stoichiometric quantities in anhydrous THF. The solution was stirred at room temperature for 3–5 h. Then

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

• triaminoguanidinium salts underwent a threefold carbamoylation with aryl isocyanates to furnish 1,2,3-tris(ureido)guanidinium salts, while p-toluenesulfonyl isocyanate led only to a mono-ureido guanidinium salt. With aryl isothiocyanates, 3-hydrazino-1H-1,2,4-triazole-5(4H)-thione derivatives were obtained. Compounds

• 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

• with isocyanates When 1,2,3-tris(benzylamino)guanidinium salts 3 and 5-OTs were combined with three mol equivalents of aryl isocyanates 6a–c, triply carbamoylated salts 7a–f were obtained in good to high yields (Scheme 2). As was expected on the basis of the Hammett σp values [20], p-tolyl isocyanate

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

• sugar urea to the corresponding isocyanate intermediate, accompanied by the loss of ammonia, was postulated to be the key step of the reaction cascade. Another approach to nucleoside analogs bearing a nucleobase derived from benzo[e][1,3]oxazine was developed by Rai and Singh (Scheme 47) [124]. The

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• ) with t-butyl isocyanate as described elsewhere (Scheme 1) [24]. A higher scale of reaction improved the yield if compared to the literature data. Vinyl group modifications Oxidation of the vinyl group of quinine can be carried out in two different manners to give homologous aldehydes. The one-carbon

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• –ene [28], thiol–isocyanate [29] and others are used. Thereby most studies have in common that synthesis of the polymer with thermo-responsive properties is preferably accomplished by either living anionic polymerization, or controlled radical polymerization [18][21][22][24][29][30][31][32][33][34

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• additional scavenging of the unreacted amines with polystyrene-based isocyanate (PS-NCO) improved the purities of the final products (69–84%). It is noteworthy that the use of TMSN3 has several advantages, as it is less toxic and explosive than commercial derivatives and the byproduct (methoxytrimethylsilane

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• Curtius rearrangement, upon heating the intermediate isocyanate was trapped with EtOH to yield ethyl carbamate protected amine 141. Deprotection of the Alloc-group [126] and chloro carbamate formation furnished 142. Exposure of this compound to a silver source led to the formation of the five-membered

• (see Scheme 21), followed by the formation of an acid-azide. Shiori version [146][147] of the Curtius rearrangement with concomitant addition of MeOH to the intermediate isocyanate afforded carbamate 171. Oxetane 171 was then opened under Lewis-acidic conditions. The deprotected alcohol was protected

• underwent Curtius rearrangement upon heating. The intermediate isocyanate was intercepted by benzyl alcohol to provide secondary Cbz-protected amine 192. Bredereck’s reagent (193) [162] was used to generate enamine 194. The enol-form of the remaining carbonyl moiety was transformed into the corresponding

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• [1]. Isocyanates play a relevant role as chemical intermediates in the manufacturing of thermoplastic foams, elastomers, adhesives, agrochemicals and pharmaceuticals. The isocyanate group is also widely used as a precursor to several bioactive compounds and drugs that contain urea and carbamate

• large number of functional groups and therefore has various uses in organic synthesis and can also be exploited for the preparation of heterocyclic compounds. Isocyanate derivatives can be generally obtained in good yields. However, it is necessary to avoid the traditional triphenylphosphine to obtain

• the supported reagent to work in a friendly environment and, at the same time, facilitate the reaction outcome. In the first part of this work, we have focused on the development of a MW promoted protocol for isocyanate synthesis with the aim of reducing reaction time and decreasing the amount of

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

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• researchers have confirmed this finding [19][20]. Trichloromethylisocyanate [21] and tribromomethylisocyanate [22] react similarly with 3 equivalents of triethyl phosphite forming isocyanate 2, which was characterized by its IR and NMR spectra and also by its reaction products 3 and 4 (Scheme 2

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• purification by acid–base extraction afforded the amine-containing ligand 8 in 96% yield. Ligand 8 was connected to water-soluble DAB-Am dendrimers via a protocol described by Peerlings and Meijer (Scheme 3) [32]. First, a multi-isocyanate was prepared in situ by using di-tert-butyl tricarbonate (11). After

• perform compartmentalized catalysis. G3 catalyst 16 activity in dialysis device. G4 catalyst 17 activity in subsequent runs. Synthesis of water-soluble iridium catalyst 3. Synthesis of the desymmetrized bipyridine 8. Attachment of the adapted ligand 8 to the dendrimers via a multi-isocyanate coupling

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• -alkenyl carbamates. Results and Discussion Simple N-alkenyl ureas 1 were prepared by a reported method [2] entailing N-acylation of an acetophenimine with an isocyanate, followed by N-alkylation of the resulting urea. When urea 1a was treated with t-BuLi or s-BuLi in THF at −78 °C for one hour, followed

From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies

• Kevin S. Martin,
• Cristian Soldi,
• Kellan N. Candee,
• Hiromi I. Wettersten,
• Robert H. Weiss and
• Jared T. Shaw

Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31

• benzimidazole 3 with isocyanate 2 (Figure 2). We initially sought to avoid nitration, protection and deprotection steps and access this intermediate by performing a late-stage 3CR with benzimidazole 4, which would be available from nitrile 6 or acid 7 (Figure 2, A). Although synthesis of 4 proceeded without

• mixed anhydride followed by displacement with ammonia gas to produce 29 in 65% yield [22]. Final Boc deprotection of 29 with TFA (87%) and subsequent acylation of the free amine of 30 with isocyanate 2 (75%) provided the desired compound 1 in 11 total steps and 3% overall yield. Conclusion We have