Abstract:SummaryThe amidine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) display nucleophilic behaviour towards highly electrophilic p-nitrophenyl carbonate derivatives with ring opening of the bicyclic ring to form corresponding substituted ε-caprolactam and γ-lactam derived carbamates. This simple method presents a unified strategy to synthesize structurally diverse ε-caprolactam and γ-lactam compounds with a large substrate scope.
“…In fact, the activation energy of ammonium ion formation is very low, [67] and thus we suppose a dynamic equilibrium between the quaternization of the terminal and the middle nitrogens. The nucleophilicity of DBU and related amidines DBN, TBD and MTBD has been used in their reactions with aldehydes, [68] carbonates, [69] imidazolides, [70] methyl-pyrazoles [71] and benzoxazinones [72] as electrophiles leading to caprolactams or substituted tetrahydropyrimidinones. Notably, cyclic amidines undergo ring-opening in the presence of water yielding aminopropyl lactams and pyrimidinones that readily react with halobenzenes [73][74][75] and esters.…”
The development of a new three-component chromatographyfree reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.
“…In fact, the activation energy of ammonium ion formation is very low, [67] and thus we suppose a dynamic equilibrium between the quaternization of the terminal and the middle nitrogens. The nucleophilicity of DBU and related amidines DBN, TBD and MTBD has been used in their reactions with aldehydes, [68] carbonates, [69] imidazolides, [70] methyl-pyrazoles [71] and benzoxazinones [72] as electrophiles leading to caprolactams or substituted tetrahydropyrimidinones. Notably, cyclic amidines undergo ring-opening in the presence of water yielding aminopropyl lactams and pyrimidinones that readily react with halobenzenes [73][74][75] and esters.…”
The development of a new three-component chromatographyfree reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.
“…A number of processes gathered in this review could most probably be extended to reactions with 1,5‐diazabicyclo[4.3.0]non‐5‐ene (DBN). Indeed, DBN display properties similar to those of DBU, and reports describing similar results are already available …”
Section: Conclusion and Remarksmentioning
confidence: 58%
“…p-Nitrophenyl carbonates, which are highly electrophilic species, underwent ring opening of DBU giving ε-caprolactam derived carbamates (Scheme 28a). [55] The reaction occurs via nucleophilic addition of DBU to the carbonate affording 28A which suffers attack of water leading to 28B (Scheme 28b). Subsequent ring opening gives the product.…”
Section: Other Carbonyl Compoundsmentioning
confidence: 99%
“…Indeed, DBN display properties similar to those of DBU, [8] and reports describing similar results are already available. [13,18,20,30,34,40,43,44,46,49,50,51,55,62,70,73,[75][76][77][78]…”
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is traditionally considered to be a non-nucleophilic base. Nevertheless, DBU possesses nucleophilic properties which mediate organic reactions and may lead to the formation of compounds containing the DBU scaffold. Participation of water to the processes affords there-component products. The review covers the reactions leading to DBU derivatives showing that the interest of this sterically hindered amidine is not limited to its basic role. Proposed mechanisms are described with, in some cases, personal comments.
“…The role of DBN or DBU as a sterically hindered, weakly nucleophilic amidine-type strong base and catalyst is well-known, especially in dehydrohalogenation reactions, but some reports in the literature revealed their ability to act as nucleophiles . Their capacity to act as nucleophile led to some unexpected results, as revealed by the ring opening of the bicyclic amidine reported for the first time by Lammers in 1994 and followed by a few others involving as ultimate product, ε-caprolactam derivatives. − The nucleophilic character of DBU and DBN was observed in the reaction with carbonyl electrophilic species, namely, methyl esters, p -nitrophenyl carbonate, imidazolides, and benzoxazinones, on the hydrolysis of amide carbonyls or even in palladium-catalyzed carbonylation reactions, in all cases leading toward lactams resulting from the ring opening of the cyclic amidine. , …”
For
the first time, 1,2-dimethyl-3-ethylimidazolium iodide (1a) catalyzes the ring opening of the bicyclic amidine system
of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or DBN (1,5-diazabicyclo[4.3.0]non-5-ene)
on reaction with aldehydes. The mechanism here proposed involves an
N-heterocyclic olefin (NHO) catalytic species that acts as a nucleophile
to promote the cyclic amidine ring opening. The resulting ε-caprolactam-
and γ-lactam-derived imines were obtained in moderate to excellent
yields (28–99%) and reduced to the corresponding amines by
sodium borohydride. Confirmation of the imine product was achieved
via single-crystal X-ray diffraction studies.
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