Cyclization, caprolactam

Under forced conditions, the reductive cyclization of a 6-oximeester at 150 °C gave a simple c-caprolactam in about 60% yield [5a]. A preliminary chemoen-... 

Activated carboxylic acids served as versatile precursors in lactam synthesis. Robl described some a-amino-c-alkyl-c-caprolactam syntheses, Eqs. (4-7)] [12]. Ring closure was induced after an EDC/HOBt activation of the acid function of 31 to form the 6-propyllactam 32 in 51 % yield, Eq. (4). The cyclization of... 

Dutton reported on the synthesis of an e-caprolactam analog of an anthelmintic cyclic peptide. The a-hydroxy-e-caprolactam 44 was generated in an ex chiral pool synthesis staring from malic acid. The a-hydroxy carboxylic acid unit was protected as a dioxolanone in 43. The protective group served simultaneously as the reactive function during cyclization lactam 44 formation succeeded by ring opening of the dioxolanone 43 by the nucleophilic attack of the amino function, Eq. (8) [14]. 

The ultimate greening of fine chemical synthesis is the replacement of multistep syntheses by the integration of several atom-efficient catalytic steps. For example. Figure 9.9 shows the new Rhodia, salt-free caprolactam process involving three catalytic steps. The last step involves cyclization in the vapor phase over an alumina catalyst in more than 99% conversion and more than 99.5% selectivity. 

A general route to azepinones is by intramolecular cyclization of e-aminohexanoic acids or their derivatives (80TL2443). For caprolactam, however, yields are low and superior preparative methods are available (70MI51600, B-75MI51601). Surprisingly few methods are known for the synthesis of C-substituted caprolactams. A useful summary of existing... 

Cyclization of a,abis(dimethylthiomethylene) ketones by phosphorus pentasulfide leads to 2,5-bis(methylthio)-l,6,6aA4-trithiapentalenes (equation 7) (71AHC(13)161, p. 185). Condensation of carbon disulfide with pyrrolidin-2-one in basic medium, followed by methylation of the reaction product, leads to methyl 3-(dimethylthiomethylene)-2-oxopyrrolidine-l-dithiocarboxylate. This compound, when treated with phosphorus pentasulfide and perchloric acid, yields the 2,5-bis(methylthio)-l,6,6aA4-trithia-2aA5-azacyclopenta[a/]pen-talen-2a-ylium cation. With e- caprolactam similar results are obtained (76BSF1200). 

Comparing the structure of the monomer with that of the polymer as shown in Table I, we see that the polymerization of the / -carboxy-methyl caprolactam must involve isomerization of the monomer ring system. This isomerization may be described by several possible processes, all of which are characterized by reaction between the amide and acid group of the / -carboxymethyl caprolactam. Based upon the results of our studies on the structure of this polymer (5) we may eliminate confidently those processes according to which the formation of the glutarimide moiety results either by intrachain cyclization or by trans-cyclization of certain intermediate polymer structures. The former would involve a polymer formed by a conventional ring opening polymerization ... 

ALTAM A process for making caprolactam from butadiene and carbon monoxide. Developed by DSM in the late 1990s and subsequently improved by Shell Chemicals, which contributed catalyst know-how. In the first two steps of the process, butadiene undergoes two hydroformylations with carbon monoxide, followed by reductive animation with ammonia and then cyclization to caprolactam. First commercialization was expected in Taiwan. A joint venture with Chiyoda Corporation, to further develop and commercialize the process, was announced in 2002. 

Cyclization. The two functional end groups of a monomer or polymer molecule might react with one another to form a cyclic compound [15,16]. An example is the formation of caprolactam as a by-product in condensation polymerization of 6-aminocaproic acid to Nylon-6 [5] ... 

The excellent properties of fiber melt spun from nylon 6,6 led to research by would-be competitive companies to produce similar polymers that did not infringe on the Du Pont patent. Nylon 6 was such a product developed by I.G. Farbenindustrie, a German company, who started production of this resin in 1940. Nylon 6 is a single monomer polyamide of the AB type made by the ring-opening cyclization of caprolactam (Eq. 21.8). Nylon 6,6 and nylon 6 were initially, and remain, the dominant commercial polyamides. 

DSM, working initially with DuPont and then later with Shell, have developed a process using butadiene and carbon monoxide feedstocks to make caprolactam without ammonium sulfate production in the mid-1990s. Called Altam, the process employs four steps - carbonylation, hydroformylation, reductive amination and cyclization. DSM claims cost reductions of 25-30%, simplified plant operations and lower energy consumption, but the process never reached commercial scale. 

The Techni-Chem. process (process 10, Figure 2.11) that started from cyclohexanone also did not develop beyond pilot plant operations [127]. It is characterized by the following reaction scheme entailing (1) acylation of cyclohexanone with ketene, (2) nitration of the resulting cyclohexenyl acetate with concurrent deacetylation to 2-nitrocyclohexanone, (3) hydrolytic cleavage to s-nitrocaproic acid, (4) hydrogenation to s-aminocaproic acid, and (5) cyclization to caprolactam ... 

Figure 16-1. Experimentally obtained equilibrium constants Kx of cyclization for bulk polymerizations at 110°C (e-caprolactam and cyclosiloxane) or at 50°C (1,3-dioxoIane). (From data by J. A. Semiyen, G. R. Walker, P. V. Wright, and J. M, Andrews.)...

Gupta et al. simulated polymerization of caprolactam including all important reactions reversible ROP, polycondensation, polyaddition, and cyclization reactions as well as the reaction with monoftinctional acids and found that reactions constituting the ring-chain equilibria influence the molar mass distribution of product. 

Caprolactam scaffold represents a bioactive moiety in many drugs [99]. Fox and coworkers have described the synthesis of 3-(acylamino)azepan-2-one derivatives as stable broad-spectrum chemokine inhibitors resistant to metabolism in vivo [100]. Azepan-2-ones are also reported as valuable inhibitors of metallic proteinase [101]. The synthesis of N-alkyl-2-(2-oxoazepan-l-yl)-2-arylacetamide derivatives is carried out by a three-component Ugi reaction in water. The reaction of 6-aminohexanoic acid 133, aromatic aldehydes 51, and isocyanide derivatives 134 in water under reflux without any catalyst affords N-alkyl-2-(2-oxoazepan-l-yl)-2-arylacetamides 135 (Scheme 45) [102]. The first step of the reaction leads to the formation of imines 136 by the reaction of 6-aminohexanoic acid 133 and aldehydes 51 (Scheme 46). The nucleophilic attack of the isocyanide 134 on protonated imine 137 leads to the formation of nitrilium carboxylate intermediate 138, which xmdergoes cyclization through attack of carboxylate on nytrilium carbon to give an intermediate cyclic product 139. The latter product undergoes a Mumm rearrangement to yield the final product 135 via the intermediate 140. 

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