Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• of 5-unsubstituted dihydropyrimidinones from β,γ-unsaturated ketoesters in low melting ʟ-(+)-tartaric acid–N,N-dimethylurea mixtures is reported. This solvent-free method is very general and provides easy access to 5-unsubstituted dihydropyrimidinone-4-carboxylate derivatives in good yields

• ][3][4]. The dihydropyrimidinone structure is found in calcium channel blockers [5][6][7], α1a adrenoceptor-selective antagonists [8][9], antihypertensive [10][11][12][13] and anti-inflammatory agents [14][15]. An interesting example is a rather simple DHPM derivative, monastrol, which specifically

• -unsubstituted 3,4-dihydropyrimidinone-4-carboxylate derivatives by employing oxalacetic acid as a β-ketoester equivalent in the presence of TFA via a Biginelli reaction [23]. Lam and Fang reported the same synthesis under microwave conditions [24]. Very recently, Kambappa and co-workers reported a one-pot

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• . The obtained results are summarized in Table 6. Benzaldehyde (2a) underwent the reaction with ethyl acetoacetate (4) and urea (5) to obtain the corresponding dihydropyrimidinone 7a in 97% yield (Table 6, entry 1). Benzaldehyde derivatives bearing electron-donating groups, such as 4-Me (2b), 4-OMe (2e

• conditions.a Effect of the catalyst loading.a Effect of the temperature.a NDL-catalyzed synthesis of 2-aryl-1-arylmethyl-1H-benzo[d]imidazoles 3.a NDL-catalyzed synthesis of dihydropyrimidinone/-thione derivatives 7.a NDL-catalyzed synthesis of 2-amino-4-(hetero)aryl-3,5-dicarbonitrile-6-sulfanylpyridines 11.a

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

• ][133] in which the component aldehyde and catalytic amount of acid were generated in situ for the final step of dihydropyrimidinone synthesis. Benzyl alcohols were oxidized by a reagent combination of oxone (0.6 equiv), KBr (10 mol %) and 2,2,6,6-tetramethylpiperidin-1-yloxy radical (TEMPO, 1 mol %) to

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• then react with Cu(II) to provide species such as Q or iminium ion S. Either of them would aromatize to generate the desired product 90. The alternate proposal involved a ligand exchange between Cu(II)X2 and dihydropyrimidinone 88 providing compound T, which gets oxidized in the presence of TBHP to

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• aminopyrazoles and amides [41][42]. In our previous studies, dihydropyrimidinone was synthesized through the condensation of 5-aminopyrazole-4-carbonitrile and ketones [29][30]. 5-Aminopyrazole-4-carbonitrile was prepared from the reaction of ethoxymethylenemalononitrile with phenylhydrazine in a step-wise

Efficient synthesis of dihydropyrimidinones via a three-component Biginelli-type reaction of urea, alkylaldehyde and arylaldehyde

• Haijun Qu,
• Xuejian Li,
• Fan Mo and
• Xufeng Lin

Beilstein J. Org. Chem. 2013, 9, 2846–2851, doi:10.3762/bjoc.9.320

• chiral spirocyclic SPINOL-phosphoric acids. Keywords: Biginelli-type reaction; chiral phosphoric acid; dihydropyrimidinone; iodine; multicomponent reaction; Introduction The dihydropyrimidinones (DHPMs) have exhibited interesting and multifaceted biological activities, such as antiviral, antitumor

• , antibacterial, and antiflammatory properties as well as calcium channel modulating activity [1][2]. As a consequence, the synthesis of dihydropyrimidinone derivatives bearing diverse substitution patterns has attracted significant attention since its discovery 120 years ago in 1893 by the Italian chemist Pietro

• developed to be carried out in the presence of a Lewis or protic acid. It is still highly valuable to develop new direct approaches for the efficient synthesis of DHPMs due to the continued importance of the dihydropyrimidinone core in organic and medicinal chemistry. Recently, molecular iodine has emerged

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• flow instruments, transfer well to our de novo microwave flow cell and from there can be scaled up using a commercial microwave flow reactor for mesoscale production [45]. The basic design of our microwave flow cell has been adapted by Kappe for the synthesis of dihydropyrimidinone 8 in a 3-component

• Biginelli reaction and for the preparation of N3-substituted dihydropyrimidinone 10 by Dimroth rearrangement of 1,3-thiazine 9 [46]. In these studies, the 10 mL flow cell was loaded with glass beads and irradiated at 120 or 200 °C, respectively, to give the target heterocycle in yields that compared very

• favourably with microwave-heated batch experiments. For dihydropyrimidinone 8, a flow rate of 2 mL min–1 delivered a very respectable processing rate of 25 g h–1. Following the success of this reactor design in delivering pyridine and pyrimidine heterocycles, albeit from very different processes, and the

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

• ,SC)-19 when the catalyses were conducted under identical conditions (Table 1, entries 2 and 3). Racemic dihydropyrimidinone 20 was obtained in 32% and 30% yields, respectively. Next, we focused on the application of thioureas (S)-12 and (S)-13 having a more rigid benzene linker (Table 1, entries 4

• leading to a dihydropyrimidinone. In the future we aim to expand the scope of the chiral sulfonimidoyl-containing thiourea framework and hope to find more applications of these interesting molecules in asymmetric organocatalysis. General structure of sulfoximines 1 and one of the enantiomers of S-methyl-S

• . Synthesis of the sulfonimidoyl-containing thioureas (S)-12 and (S)-13. Syntheses of ethylene-linked sulfonimidoyl-containing thioureas (SS,SC)-18 and (RS,SC)-19. Evaluation of the sulfonimidoyl-containing thiourea organocatalysts in the asymmetric Biginelli reaction to afford scalemic dihydropyrimidinone (S

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• are used as common intermediates for post-condensation modifications such as cycloaddition, Liebeskind–Srogl reaction and Suzuki coupling to form biaryl-substituted dihydropyrimidinone, dihydropyrimidine, and thiazolopyrimidine compounds. The high efficiency of the diversity-oriented synthesis is

• ; Introduction Dihydropyrimidinone and dihydropyrimidine derivatives have broad biologically activities. Many synthetic samples have been studied as antibacterial, antiviral, antihypertensive, and anticancer agents [1], and the natural products containing these heterocyclic moieties have been studied as new

• diversity-oriented synthesis of biaryl-substituted dihydropyrimidinone 5, thiazolopyrimidine 6, and dihydropyrimidine 7 compounds (Scheme 1). The perfluorooctanesulfonyl-attached benzaldehydes 1 were used as a key component for the Biginelli reactions [6]. The Biginelli products 4 were used as a common

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• while the C2-atom and the pseudoaxial C2-phenyl group are situated above the plane (Figure 1). In order to convert the iodinated dihydropyrimidinone 10 into the fully saturated tetrahydropyrimidinone (R)-4, selective hydrodehalogenation and reduction of the double bond had to be accomplished