New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• Abstract A new efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reaction has been developed. The three-component Passerini reactions of 2-azidobenzaldehydes 1, benzoic acid (2), and

• isocyanides 3 produced the azide intermediates 4, which were treated sequentially with triphenylphosphine, isocyanates (or CS2), and secondary amines to give polysubstituted 3,4-dihydroquinazolines 8 and 4H-3,1-benzothiazines 11 in good overall yields through consecutive Passerini/Staudinger/aza-Wittig

• /addition/nucleophilic substitution reactions. Keywords: aza-Wittig reaction; 3,4-dihydroquinazoline; 4H-3,1-benzothiazine; nucleophilic substitution; Passerini reaction; Staudinger reaction; Introduction The chemistry of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines is of constant interest owing to

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• reaction promoted by trimethylsilyl polyphosphate (PPSE) is also proposed on the basis of literature data and our experimental observations. Keywords: cyclodehydrations; dihydroquinazolines; microwaves; nitrilium ions; PPSE; SNAr; Introduction Dihydroquinazolines (DHQs) represent heterocyclic cores of

• involve oxidation or reduction of related heterocycles (quinazolinones, quinazolines or tetrahydroquinazolines) [23][24][25][26][27][28]. Dihydroquinazolines can also be synthesized by heterocyclization of 2-aminobenzylamines (2-ABAs) with different C2 donors [3][16][17][29][30][31][32][33][34][35][36

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

• -pot synthesis of substituted dihydroquinazolines 35 from a variety of o-aminobenzylamines with appropriate aldehydes and alkylnitrates. The initial condensation of substituted o-aminobenzylamines with aldehydes afforded the substituted tetrahydroquinazoline 34, which was subsequently treated with a

• to generate the desired substituted dihydroquinazolines 35 in moderate to excellent yields (Scheme 9) [44]. In another example commercially available sodium hypochlorite (NaOCl) was used as an oxidant, under mild conditions in a highly efficient oxidative dehydrogenative coupling of o

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• Risorgimento 4, 40136 Bologna, Italy 10.3762/bjoc.13.145 Abstract A straightforward strategy for the synthesis of dihydroquinazolines is presented, which allows for the preparation of 3,4- and 1,4-dihydroquinazolines with different substitution patterns from 2-aminobenzylamine (2-ABA) as common precursor. The

• -assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE). Keywords: dihydroquinazolines; microwaves; N-acylations; N-alkylations; PPE; Introduction Nitrogen heterocycles are part of many drugs and represent structures with wide therapeutic potential. Therefore, much

• analogues, dihydroquinazolines, also represent heterocyclic cores of pharmacological interest. Some derivatives containing this motif have shown antimicrobial [11] and antifungal properties [12]. Their activity as selective T-type calcium channel blockers [13][14][15] and as inhibitors of β-secretase (an

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• , also a partial oxidation towards 3,4-dihydroquinazolines is possible for the case that the oxidation is promoted either by Cu(AcO)2 or by a mixture of elemental iodine and BuLi. These methods allow the synthesis of the partially unsaturated alkaloids vasicine or deoxyvasicine in good yields [22][28

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• to affect the selective oxidation of ring-fused aminals to dihydroquinazolines and quinazolinones, respectively. These methods enable the facile preparation of a number of quinazoline alkaloid natural products and their analogues. Keywords: aminal; copper; oxygen; tert-butylhydroperoxide

• , known as the Niementowski reaction [3][27][28][29][30] (Figure 2). The availability, or lack thereof, of the corresponding lactam can determine the length and efficiency of the route. Access to the sometimes more biologically active dihydroquinazolines, such as deoxyvasicine (2), from quinazolinones

• dihydroquinazolines vasicine (1) and deoxyvasicine (2) can be synthesized from their corresponding aminals by using an iodine-promoted oxidation [34]. While resulting in good yields, these oxidations have the drawback of requiring large amounts of a strong oxidant for the permanganate oxidation and the necessity of