With lactams, high pressure

When thioamides 24f-h were irradiated in benzene with a high-pressure mercury lamp, iV-isopropyl-P-thiolactam 26 and 1,3,5-dithiazine 28 were obtained (Scheme 15 and Table 10, entries 1,3, and 5). Considerably different photochemical behavior was observed between that in solution and in the solid state. Powdered thioamide 24f was irradiated in the solid state at 0 °C until 19% conversion, because the solid changed to amorphous at around 20% conversion. In this case, only dithiazine 28f was obtained as the sole photoproduct (entry 2). On the contrary, photolysis of 24g gave a new type of p-lactam 27g as a main product in 88% yield in addition to dithiazine 28g (12%) the P-lactam 26g was not detected at all (entry 4). Photochemical ( ,Z) isomerization of (Z)-24g was also observed in the early stage of the reaction, where the ratio of the photostationary state was ZIE=1.9. In the case of 24h, P-thiolactam 27h was ob-... 

Aoyama et al. in relation to their studies on photochemical synthesis of (3-lactams [91] reported the synthesis of 4-spirocyclopropylazetidin-2-one [92] via photocycloaddition of 4-thioxoazetidin-2-one to alkenes followed by subsequent desulfurization. A solution of 1-isopropyl-3-phenyl-4-thioxoazetidin-2-one 70 and 1,1-diphenylethylene in benzene on irradiation with a high pressure mercury lamp afforded a [2 + 2] adduct 72 (R = Ph), in 67% yield which, on desulfurization with Raney-nickel [93] in anhydrous ethanol gave two isomeric... 

The 5-7V-tosylamino substituted a-diazo-P-keto carbonyl compounds 101 were obtained from the reaction between diazo ketone 100 and the tosylimine 99 in the presence of TiCU in dichloromethane. The diazo ketone 101 underwent Wolff rearrangement in benzene upon irradiation with a high-pressure Hg lamp to afford 102, which subsequently cyclized to give the expected y-lactam derivatives. ... 

Another example is the purification of a P-lactam antibiotic, where process-scale reversed-phase separations began to be used around 1983 when suitable, high pressure process-scale equipment became available. A reversed-phase microparticulate (55—105 p.m particle size) C g siUca column, with a mobile phase of aqueous methanol having 0.1 Af ammonium phosphate at pH 5.3, was able to fractionate out impurities not readily removed by hquid—hquid extraction (37). Optimization of the separation resulted in recovery of product at 93% purity and 95% yield. This type of separation differs markedly from protein purification in feed concentration ( i 50 200 g/L for cefonicid vs 1 to 10 g/L for protein), molecular weight of impurities (<5000 compared to 10,000—100,000 for proteins), and throughputs ( i l-2 mg/(g stationary phasemin) compared to 0.01—0.1 mg/(gmin) for proteins). 

The previously reported preparations of N-benzyl-2,3-azetidinedione involve either high-pressure lactamization with carbon monoxide and lead(ll) acetate, Pd(OAc)2, in the presence of triphenylphosphine,2 or construction of the p-lactam from an isoxazolidine precursor.3 The present approach uses the readily available methyl... 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

Ikeda et al. [80] have reported a photochemical entry to spiro-(3-lactams 27 (Scheme 8) by the irradiation of a solution of 2 - (/V - ac y I - /V-al k y I a m i n o) eye I o h e x -2-enone 26 in acetone with a 300 W high pressure mercury lamp in a pyrex vessel under nitrogen. The reaction occurred with the intervention of the 1,4-diradical intermediate formed via abstraction of a hydrogen on the N-acyl group by the (3-carbon atom of the ot,(3-enone system. 

One of the most facile methods for construction of the (i-lactam skeleton would be [2 + 2] cyclo additions of isocyanates to alkenes. However, the [2 + 2] cycloadditions of alkyl or aryl isocyanides with either 2,3-dihydrofuran or vinyl ethers often fails under normal conditions. High pressure can surmount this difficulty in certain cases. For instance, alkyl isocyanates 125 underwent [2 + 2] cycloadditions with such cyclic vinyl ethers as 126 to produce the P-lactams 127 (Scheme 34) [80]. 

The racemic acid 399 was treated with oxalyl chloride to afford an acyl chloride 401, which on reaction with anhydrous hydrazine yielded the hydra-zide 402. The latter was converted to the azide 403 by treatment with nitrous acid. Photolysis of 403 which a high-pressure mercury lamp afforded the lactam 404. This lactam was synthesized earlier by Japanese chemists by an entirely different method (187). 

Homogenous lactam polymerizations usually proceed with a decrease of volume. At atmospheric pressure the value of the pAV term is negligible and the heat of polymerization can be considered as a measure of the difference in internal energy between the linear and cyclic monomer unit. At very high pressures, however, the effect of volume contraction during polymerization on the monomer-polymer equilibrium cannot be neg-... 

In contrast to the complete regioselectivity observed in the 1,3-dipolar cycloaddition of nitronate 16b and methyl crotonate 42 or methyl cinnamate 44 shown in Scheme 9.14, the [3 -t 2] cycloaddition of yS-nitrostyrene (15a) and nitronate intermediate 16a was not completely regioselective. Regio-isomers 46 and 47 were formed in 83 % yield, as mixtures of diastereomers, in a 7 3 ratio after the high pressure-promoted domino cycloaddition of enol ether 14 with 2 equiv. fi-nitrostyrene (15a) (15 kbar, RT, 18 h, Scheme 9.15). The formation of regio-isomer 46 as major product was rather unexpected, since comparable 1,3-dipolar cycloadditions of nitrones and nitroalkenes [25] showed the opposite regio-isomer to be formed predominantly. This nitroso acetal (46) was converted to )S-lactam (48) via a base-catalyzed rearrangement (Scheme 9.16). This conversion appeared applicable to different hi- and tricyclic nitroso acetals and led to the formation of a novel class of bi- and tricyclic yS-lactams [26]. 

Lactam polymerizations usually imply a volume contraction and, at very high pressures, the effect of the PAV term on equilibrium carmot be neglected. Lactams that have a low or are prevented from polymerizing at normal pressure for thermodynamic reasons can polymerize at high pressures. Tc increases with pressure in accordance with the Clausius-Clapeyron equation. ... 

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