Three-Component Reaction toward Polyannulated Quinazolinones, Benzoxazinones, and Benzothiazinones

Abstract

An efficient conversion of readily accessible cyclic imines with acid chlorides, that are able to take part in nucleophilic aromatic substitution (SNAr) reactions is realized in a new three-component, one-pot reaction, giving at least tricyclic annulated quinazolinones, benzoxazinones, and benzothiazinones as a result of the employed nitrogen, oxygen, or sulfur nucleophiles, respectively. Especially in the case of quinazolinones, this convenient strategy enables the access to heterocycles of heightened diversity, which offer the development of efficient derivatizations of the elaborated heterocyclic scaffolds. In a subsequent Heck or Ullmann cyclization, further annulations to the mentioned quinazolinones can be carried out.

Four-Component Reaction for the Synthesis of Dithiocarbamates Starting from Cyclic Imines

“…The CN double bond enables multiple conversions to different type of amides, 19,20 bisamides, 21 and polycyclic structures. 22 We started our investigation with a one-pot, four-component reaction of cyclic imine 1{1}, acetyl chloride 2{1}, allylamine 3{1}, and carbon disulfide as a model reaction to examine the optimal reaction conditions for the preparation of dithiocarbamates 4{1,1,1} (Table 1). Water is a nonqualified solvent in the planned synthesis because of the hydrolysis-sensitivity of the in situ generated α-chloroamide intermediate (see Scheme 2).…”

“…9,10,23 Whereas carbonate bases did not lead to satisfactory results in acid chloride addition reactions. 22 First we tested DCM, MeCN, and DMF (Table 2, entries 1−3) as solvents. The use of all three solvents led to the formation of the product, even though the yield was not satisfactory.…”

The Concept of Sequential Multicomponent Reactions: A Short Synthesis of Thiazolo- and Oxazolo[1,4]benzodiazepine-2,5-diones

“…The syntheses of 2,2,5,5-tetramethyl-1,3-thiazoline (1a), 2,2,5,5-tetramethyl-1,3-oxazoline (1b), 2,2-dimethyl-1-thia-4azaspiro [4,5]dec-3-ene (1c), 2,2-dimethyl-1-oxa-4-azaspiro [4.5]dec-3-ene (1d) and 7-thia-14-azadispiro[5.1.5 8 .2 6 ]pentadec-14-ene (1e) were recently reported by us. 17 Allyl isocyanide, 20 4-methoxybenzyl isocyanide 21 and 3-bromo-2-fluoro-5-nitrobenzoic acid 17 were prepared according to published procedures.…”

“…18 According to our proposed synthetic route (Scheme 1), we devoted our initial efforts into the Asinger 4CR, expecting that the reaction of a ketone, an α-chloro aldehyde, ammonia and sodium hydrogen sulfide or sodium hydroxide would result in a rapid synthesis of known heterocyclic imines 1. 17 Indeed, the reproduction of this known multicomponent reaction proceeded effectively, independently of the structural nature of the carbonyl compounds, and we obtained smoothly various types of thiazolines and oxazolines 1 in one-pot procedures; the substitution patterns are depicted in Table 1. One advantage of this transformation is the direct generation of the reactive iminic bond, which enables a straightforward conversion of the precursors 1 in the intended sequence of multicomponent reactions.…”

“…Very recently, our group described classical nucleophilic substitutions at electron-deficient aromatic compounds with high efficiency. 16,17 The processes proceeded quickly at room temperature and avoided harsh conditions and cost-intensive reagents, while the waste materials were non-toxic ammonium salts. Our findings that displacement of the fluorine in 2-fluoro-5-nitro-substituted aromatic compounds can be quite facile suggests that such structural properties offer a benign strategy for the synthesis of thiazolo-and oxazolo-fused benzodiazepinediones 3.…”