Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• molecules, contributing significantly to sustainability, innovation and economic growth across various sectors. In this study, we present an efficient and rapid method for synthesizing a variety of heteroannulated pyrimidones using cyanoacetamide-based multicomponent reaction (MCR) chemistry. By utilizing

• structure was obtained, revealing certain geometrical features. Keywords: 2-amino-substituted heterocycles; cyanoacetamide; Gewald reaction; multicomponent reaction (MCR); pyrimidine; Introduction The term “net-zero carbon” is becoming increasingly common as we consider a future marked by a rising global

• installed amino group and a disubstituted amide group at the 2- and 3-positions, respectively, and reacting them with formamide (Scheme 1B). Those synthetic hubs can be rapidly accessed by cyanoacetamide-based MCRs, which is an interesting reaction type that gives access to privileged cores and has been

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• pyridine-3,5-carbonitriles 6–9 were synthesized starting with 4-bromobenzaldehyde (1) (Scheme 1 and Scheme 2). Thus, piperidinium 3,5-dicyano-6-hydroxy-4-(4-bromophenyl)pyridin-2-olate (2) was prepared by cyclocondensation of 1 with cyanoacetamide in methanol in the presence of piperidine. The conversion

• melting point analyzer” (Fisher), and the results are given without correction. Reagents and solvents were purchased from common vendors such as ACROS, Fluorochem, ABCR, and others. Piperidinium 3,5-dicyano-6-hydroxy-4-(4-bromophenyl)pyridin-2-olate (2). A mixture of cyanoacetamide (10.51 g, 0.125 mol

• duration 6 ns. b) Electric field dependence of electron mobility for the layer of 7 at room temperature (295 K). Synthesis of dicyanocarbazole 6. Reaction conditions: a) cyanoacetamide, piperidine, methanol, 40 °C, 48 h; b) POBr3, 170 °C, 1 h; c) 3,6-di(tert-butyl)carbazole, NaH, THF, DMF, 0 → rt, 3 h; d

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• repeated attempts [14]. TLC and NMR analysis consistently indicated no conversion of 4, even after stirring at 80 °C in MeCN for 48 hours. We therefore proposed an alternative route to 5, directly from reaction of a C6 nitrile with NaN3, obviating the need for intermediate cyanoacetamide formation (Scheme

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• work used preformed β-aminocarbonyl compounds. The classification we propose is based on the molecularity of the reaction (two, three, or four components), calculated based on preformed β-aminocarbonyl species and the use of cyanoacetic esters or cyanoacetamide as the cyanocarbonyl reagent. We suggest

• Guareschi pyridine synthesis is a modified two-component version, mechanistically similar to the Biginelli pyrimidine synthesis [33] and based on the condensation of cyanoacetamide and a β-dicarbonyl derivative [45][46]. This is the most famous Guareschi pyridine synthesis, both in textbooks and in other

• cyanoacetamide (and not a cyanoacetic ester) with a carbonyl derivative (aldehyde or ketone) was further investigated by the British chemist Jocelyn Fred Thorpe (1872–1940), a decade after the original studies by Guareschi [52]. In Thorpe’s modification, the reaction takes place in the presence of a secondary

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

• the phospha-Michael adducts were converted to new phosphorylated heterocycles through intramolecular cyclization reactions. The phospha-Michael adduct 149 resulting from the three-component reaction of 6-methyl-3-formylchromone with malononitrile 145 or 2-cyanoacetamide 148 and diethyl phosphite is

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

• associated with the lack of regioselectivity and difficult isomer separation [23]. Other methods for the synthesis of 2,3-disubsituted thiophenes include the reactions of (i) 1,4-dithiane-2,5-diol with nitroalkenes [24], activated nitriles [25] and cyanoacetamide [26]; (ii) 3-nitrothiophene with Grignard

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

• to the thiazolidinedione moiety as experienced using other reducing systems. As an aside the synthesis of 2-pyridones (i.e. 1.42) can be achieved via a number of methods. For example the classical Guareschi–Thorpe condensation in which cyanoacetamide reacts with a 1,3-diketone delivers highly

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• central problem we wished to address was the preparation of the 3-alkyl-2-pyridone moiety of 36 by an unusual [3 + 3] construction developed in our laboratory [80]. This chemistry (Scheme 7) promotes the condensation of a cyanoacetamide 37, with an enone or enal 38, in the presence of t-BuOK in DMSO

• . Under anoxic conditions, a series of events, culminating in the elimination of HCN from a presumed dianion intermediate, leads to the formation of pyridones 39a, wherein R3 may be H, alkyl, or aryl. Conduct of the reaction with plain cyanoacetamide (cf. 37, R3 = H) under an oxygen atmosphere produces

• more electrophilic quinolyl ketone would direct an initial conjugate addition of the anion of a suitable cyanoacetamide to its own β-position. A particularly direct way to produce 41 seemed to be the oxidative cleavage of the furan ring in 42, which thus became the first subgoal of our study. In that

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• the range of 25–85%, whereas the decarboxylation step gives the corresponding glutaric acids in 60–80% yield [19][33]. Variations of Method 1B involve the use of cyanoacetamide [34][35][36] or Meldrum’s acid [19][37] instead of malonate diester. For the former, the condensation with aldehyde is

• -carboxylic acid (entry 9). It appears that the most economical way to prepare simple 3-alkyl-1,5-dibromopentanes is by using the aldehyde/malonate or aldehyde/cyanoacetamide method (Method 1B, Scheme 1), while the glutaconate method (Method 1C) is the simplest and most efficient. For the preparation of 3

• overall yields (Method 2B, Scheme 2). Attempts at conserving the alkylating reagent by using a stoichiometric Wittig olefination rather than conjugate addition of excess Grignard reagent to glutaconate did not give the expected result. It is possible that the aldehyde/cyanoacetamide method (Method 1B) [36

The tert- amino effect in heterocyclic chemistry: Synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives

• Dipak Prajapati and
• Kalyan Jyoti Borah

Beilstein J. Org. Chem. 2007, 3, No. 43, doi:10.1186/1860-5397-3-43

• malononitrile and cyanoacetamide followed by cyclisation using anhydrous zinc chloride. Background The N-phenyl-3-substituted 5-pyrazolone derivatives are organic compounds that have been known since 1883; they are very useful as intermediates for pharmaceuticals and are used as anti-inflammatory agents and

• conditions. Similarly, when cyanoacetamide was reacted in place of malonodinitrile and the Knoevenagel product 4b thus obtained was further heated in the presence of zinc chloride, the corresponding pyrazolinoquinolizine 6a was obtained in 60% yield. The structures of the end products obtained were

• good yields. Reagents and conditions: (a) DMF, POCl3; (b) piperidine, ethanol, triethylamine; (c) malonodinitrile, cyanoacetamide; (d) ZnCl2, toluene, reflux. Mechanism for the formation of pyrazolinoquinolizines 6. Physical characteristics of pyrazolinoquinolizines and 1,4-oxazinopyrazolines 6