Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• -3-methyl-pyrazole, aromatic aldehydes and dimedone under controlled microwave irradiation at 150 °C involves the participation of C3-H of the pyrazole ring in such a cyclocondensation reaction, this is not favoured in our case. In addition two signals were assigned to two CH2 groups and three methyl

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• pyrazoles in a consecutive fashion from terminal alkynes, acid chlorides, and hydrazine derivatives. Classical approaches to these valuable compounds are notably based on the cyclocondensation of hydrazine derivatives with 1,3-disubstituted three-carbon units, including α,β-unsaturated ketones, and

• group 31, which will undergo addition–intramolecular cyclocondensation processes leading to the formation of pyrrole derivatives. For instance, a series of (hetero)aryl-, alkynyl-, and cycloalkyl acid chlorides were cross-coupled with N-Boc-protected propargylamine at room temperature, and the resulting

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

• effort was to convert them to thiazolopyrimidine through cyclocondensation with chloroacetone [16][17]. The reaction was performed in water under microwave heating at 120 °C for 30 min to afford thiazolopyrimidines 8a and 8b in 89% and 85% yields, respectively, after F-SPE. Suzuki reactions of 8a and 8b

• Initiator microwave synthesizer at 140 °C for 30 min. The resulting mixture was purified by flash chromatography to give 5a (24 mg) in 67% yield. Typical procedure for cyclocondensation of 4e,f. Synthesis of methyl 3,7-dimethyl-5-(3-(perfluorooctylsulfonyloxy)phenyl)-5H-thiazolo[3,2-a]pyrimidine-6

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• - and pyrazolylazulenes through the use of glyoxylation–decarbonylative alkynylation–cyclocondensation sequences starting from azulene or guaiazulene as substrates, gives rise to the formation of the target compounds in moderate to good yields. Keywords: azulenes; catalysis; decarbonylation

• [48]. Our retrosynthetic analysis (Scheme 3) suggests that a wide range of N-heterocycle-substituted azulenes should be accessible through Michael addition–cyclocondensation of azulenylynones with binucleophiles. Azulenylynones in turn could be simply disconnected by our glyoxylation–decarbonylative

• relatively low yields were achieved. With this versatile three-component synthesis of azulenylynones in hand, the stage was set to expand the sequence to a four-component access to pyrimidyl- and pyrazolyl-substituted azulenes. Hence, the conditions for the terminating Michael addition–cyclocondensation step

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• chains in the 2- and 6-positions is described. The presented two-step process utilizes a multicomponent reaction of alkoxyallenes, nitriles and carboxylic acids to provide β-methoxy-β-ketoenamides which are transformed into 4-hydroxypyridines in a subsequent cyclocondensation. The process shows broad

• , we reported a new synthesis of pyridines based on the trimethylsilyl trifluoromethanesulfonate (TMSOTf) induced cyclocondensation reaction of β-ketoenamides [29][30][31][32][33][34]. This cyclocondensation step can be rationalized as a 6π-electrocyclization of the disilylated intermediate 5 to

• cyclocondensation must be induced or completed by treatment with TMSOTf and an amine base in a suitable solvents at elevated temperatures. In order to minimize the operational effort, the process can be performed as quasi-one-pot procedure without purification of the intermediary β-ketoenamide. Scope and

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• concentration (MIC) of 25 μg/mL against Aspergillus niger [33]. Unsubstituted and 3-substituted-7-aryl-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazoles were designed by Sztanke et al. and obtained from biologically active 1-aryl-2-hydrazonoimidazolidines by cyclocondensation reactions with triethyl orthoformate

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• less effective. The use of methanol as solvent helped suppress the formation of the undesired furan by-product. This study provides yet another example of the advantages of gold catalysis in the activation of alkyne π-systems. Keywords: alkynes; cyclocondensation; cycloisomerization; gold-catalyzed

• 5,5-spiroketals, including cyclocondensation of ketone diols [6][7], the cycloisomerization of alkyne diols (Scheme 1) [8][9][10][11][12][13][14][15][16], oxidative spirocyclization of tetrahydrofuryl propanols [17][18][19][20], and others. Cyclocondensation of ketone diols is perhaps the most

• cyclocondensation of alkyne diols to give substituted furans (Scheme 3, Reaction 3) [35]. Our objective, laid out in Scheme 4, was to initiate cycloisomerization with a 5-endo-dig cyclization of the homopropargyl alcohol 6, followed by 5-exo-trig cyclization onto the resulting dihydrofuran, whilst avoiding

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

• synthetic approach was based on the classical Paal–Knorr cyclocondensation of a highly substituted 1,4-diketone with a primary amine bearing a masked aldehyde functionality. The 1,4-diketone component, which can be accessed via a 3-step sequence [5] starting from aniline, was refluxed with 3

• since benzodiazepines lead to a higher tolerance as well as physical dependence. The standard route to this scaffold is the cyclocondensation of a functional 2-aminopyridine with an α-bromo-carbonyl compound [67][68]. In the case of zolpidem, the amide moiety in the 3-position of the ring system is

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

• enter clinical trials [13] (Figure 1). Besides the importance of 5-aminopyrazoles as biologically active agents, they are also useful synthons and building blocks for many heterocyclic products and can act as a binucleophile [14][15][16][17][18]. Cyclocondensation of 5-aminopyrazoles with 1,3

• chloride, which affords, again after Fmoc removal, the diglycylpyrazole 142 (Scheme 38) [80]. A new synthetic route [81] to 5-amino-1-aryl-4-benzoyl pyrazole derivatives 144 involves the reaction of β-ketonitriles with N,N’-diphenylformamidine to give initially the cyclocondensation precursors 143 which is

A new and facile synthetic approach to substituted 2-thioxoquinazolin-4-ones by the annulation of a pyrimidine derivative

• Nimalini D. Moirangthem and
• Warjeet S. Laitonjam

Beilstein J. Org. Chem. 2010, 6, 1056–1060, doi:10.3762/bjoc.6.120

• condensation with ethyl orthoformate to give the condensation products, 5-ethoxymethylene-1,3-diaryl-2-thiobarbituric acids 1. These condensation products possess three electrophilic centers and can undergo cyclocondensation with various nucleophiles to give a number of fused heterocyclic systems that contain

• catalyst afforded 7-hydroxy-2,3-dihydro-2-thioxo-1,3-diarylquinazolin-4(1H)-ones 3 in 76–87% overall yields (Scheme 3) [32][33] and these results are listed in Table 4. Conclusion The cyclocondensation of ethoxymethylene thiobarbituric acids with active methylene compounds under the above noted catalytic

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

• . In the course of this study, an L-asparagine derivative was condensed with benzaldehyde and subsequently converted to orthogonally protected (R)-β2-homoaspartate. Keywords: β2-amino acids; cyclocondensation; diastereoselective alkylation; N,N-acetals; peptidomimetics; ring opening; self-regeneration

• , this structural modification would facilitate a final release of the β2-amino acid by hydrogenolysis of all remaining benzyl-type N-protective groups. Results and Discussion Cyclocondensation of benzaldehyde and β-amino acid amides to 2-phenyl-tetrahydropyrimidine-4(1H)-ones is problematic, since

• of cyclising stabilised benzyl imines. Cyclocondensation was successfully carried out under two different reaction conditions (Scheme 2). On the one hand, 3 was reacted with benzaldehyde or with the corresponding dimethylacetal in refluxing toluene in the presence of a catalytic amount of p-TsOH. The

Silica- bound benzoyl chloride mediated the solid- phase synthesis of 4H-3,1-benzoxazin- 4-ones

• Kurosh Rad-Moghadam and
• Somayeh Rouhi

Beilstein J. Org. Chem. 2009, 5, No. 13, doi:10.3762/bjoc.5.13

• ], photoisomerization of 2-arylisatogen [25], and cyclocondensation of anthranilic acid with orthoesters [26]. Meanwhile, the cyclodehydration of N-acylanthranilic acids in refluxing acetic anhydride has been the prevalent method used for production of 4H-3,1-benzoxazin-4-ones. However, use of traditional dehydrating

Zeolite catalyzed solvent- free one-pot synthesis of dihydropyrimidin- 2(1H)-ones – A practical synthesis of monastrol

• Mukund G. Kulkarni,
• Sanjay W. Chavhan,
• Mahadev P. Shinde,
• Dnyaneshwar D. Gaikwad,
• Ajit S. Borhade,
• Attrimuni P. Dhondge,
• Yunnus B. Shaikh,
• Vijay B. Ningdale,
• Mayur P. Desai and
• Deekshaputra R. Birhade

Beilstein J. Org. Chem. 2009, 5, No. 4, doi:10.3762/bjoc.5.4

• monastrol, a potent inhibitor of kinesin Eg5. Keywords: Biginelli reaction; DHPMs; neat; MCR; zeolite; Introduction The Biginelli reaction is a well-known multicomponent reaction involving a one-pot cyclocondensation of an aldehyde, β-ketoester and urea/thiourea [1][2][3]. Multicomponent reactions (MCRs

• diverse important biological activities like antiviral, antitumor, antibacterial and antiinflammatory properties [11][12][13]. The first report of the Biginelli reaction dates back to 1893. This involved a very simple and straightforward procedure for the synthesis of DHPMs. A one-pot cyclocondensation of

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• , many pyrimidine derivatives have been used for various medicinal applications (Figure 1) [1][2][3]. Synthesis of pyrimidine rings most commonly involves cyclocondensation reactions of amidine, guanidine or thiourea derivatives with either 1,3-diketone or 1,3-diester systems [4][5]. However, many of

Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones

• Aboul-Fetouh E. Mourad,
• Ashraf A. Aly,
• Hassan H. Farag and
• Eman A. Beshr

Beilstein J. Org. Chem. 2007, 3, No. 11, doi:10.1186/1860-5397-3-11

• . Analysis of the 1H NMR spectra of 4a-d provided answers on the chemoselectivity of the cyclocondensation. The δ values of the most carbon signals could be determined and assigned to the corresponding carbon atoms. For example, the 13C NMR spectrum of compound 4b revealed fourteen distinctive carbon signals