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

• . Keywords: green protocol; mild conditions; no additional catalyst; solvent free; triple role of melt; Introduction In recent years, dihydropyrimidinones (DHPMs) and their derivatives have attracted considerable attention due to the multifaceted pharmacological properties of this class of compounds [1][2

• (Mtb) [19]. Owing to the biological significance of 5-unsubstituted dihydropyrimidinones, a variety of multistep protocols has been reported for the synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones [20][21]. Typically, dihydropyrimidinones are obtained via a Biginelli reaction leading to an

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• anticancer activities (72, Figure 6) [66][67][68][69] prompted chemists to develop newer methodologies for the synthesis of pyrimidinones with atom economy and high yields. The Biginelli reaction is one of the frequently employed MCRs for the synthesis of dihydropyrimidinones. The classical Biginelli

• reduced yield of mere 18% in 16 h. A slight variation to the protocol with malononitrile (51) as the active methylene compound affords a series of substituted 4-aminopyrimidines 76 in moderate yields. The efficacy of the synthesized dihydropyrimidinones as antinociceptive was also established. The authors

• construction of dihydropyrimidinones 78 utilizing a three-component reaction of acyclic 1,3-diketones 54, urea/thiourea (77) and aldehyde 5 exploring La2O3 as catalyst under microwave irradiation under solvent-free conditions with good functional group tolerance and excellent yields (Scheme 28). The reaction

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

• , India Department of Physics, S.V.D. College, Kadapa-516003, Andhra Pradesh, India 10.3762/bjoc.16.156 Abstract Natural dolomitic limestone (NDL) is employed as a heterogeneous green catalyst for the synthesis of medicinally valuable benzimidazoles, dihydropyrimidinones, and highly functionalized

• : benzimidazoles; dihydropyrimidinones; highly substituted pyridines; natural dolomitic limestone; ultrasound irradiation; Introduction Nitrogen heterocycles are recognized as “privileged medicinal scaffolds” because these compounds are found in a wide variety of bioactive natural products and pharmaceuticals [1

• ][2][3]. Among them, benzimidazoles, dihydropyrimidinones, and pyridines have emerged as promising and valuable structural units in many pharmaceutical lead compounds (Figure 1) [4][5][6][7][8][9]. Hence, there is a great need for the development of a green and sustainable synthetic route to the

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• could be conducted under ultrasound irradiation using sodium ethoxide as catalyst, thus generating steroid ring A-fused 3,4-dihydropyrimidinones and 3,4-dihydropyrimidinthiones 44 in very good yields. Mohamed et al. [44] reported a 4CR for the synthesis of pyridopyrimidines fused to ring D of

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

• intermediate β-enaminone which further reacted with α-iodoketone following by a cyclo-condensation which resulted in the substituted pyrroles shown in Scheme 31. The Biginelli reaction is a well-known 3-component reaction for the synthesis of dihydropyrimidinones [124][125]. During the last few decades many

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

• intermediate R´ which undergoes aromatization to provide the desired 86 (Scheme 31). Yamamoto et al. demonstrated a mild oxidative dehydrogenation of dihydropyrimidinones 88 and dihydropyrimidines 89 via catalytic copper salts and K2CO3 as base along with TBHP as the terminal oxidant (Scheme 32). The desired

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• dihydropyrimidinones or the corresponding dihydropyrimidinethiones. Due to their general importance (e.g. as biologically active compounds) the development of efficient protocols for the preparation of functionalized pyridine [10][11][12][13][14][15][16][17][18][19][20] and pyrimidine derivatives [21][22][23][24][25

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

• aldehydes, electron deficient alkynes and ureas/thioureas have been smoothly performed to yield a class of unprecedented 3,4-dihydropyrimidinones and thiones (DHPMs). The reactions are initiated by the key transformation of an enamine-type activation involving the addition of a secondary amine to an alkyne

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

• Haijun Qu Xuejian Li Fan Mo Xufeng Lin Department of Chemistry, Zhejiang University, Hangzhou 310027, China 10.3762/bjoc.9.320 Abstract A one-pot three-component synthesis of dihydropyrimidinones via a molecular iodine-catalyzed tandem reaction of simple readily available mono-substituted urea

• , alkylaldehyde, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give highly diverse dihydropyrimidinones in reasonable yields under mild reaction conditions. Moreover, the first catalytic enantioselective version of this reaction was also realized by using

• 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

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

• Bruno Piqani Wei Zhang Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA 10.3762/bjoc.7.150 Abstract Dihydropyrimidinones and dihydropyrimidinethiones generated from the Biginelli reactions of perfluorooctanesulfonyl-attached benzaldehydes

• leads for AIDS therapies [2]. The Biginelli reaction of a β-keto ester, an aldehyde, and urea is considered as one of the most efficient ways to synthesize dihydropyrimidinones [3]. This acid-catalyzed reaction can be conducted under conventional or microwave heating [4][5]. Reported in this paper is a

• from the reaction mixtures by F-SPE eluted with fluorophobic 80:20 MeOH/H2O and then fluorophilic 100% MeOH or acetone [7]. The fluorous Biginelli products were collected from the MeOH fraction to give dihydropyrimidinones 4a–d and dihydropyrimidinethiones 4e,f in 85–95% yields (Table 1). The Biginelli