Imines acids

The mechanism of (3-lactam formation has been investigated extensively. But the rationale for the observed diastereoselectivity in certain cases remains unknown. It has been demonstrated that the stereoselectivity depends on the structure of the imine, acid-chloride, order of addition of the reagents, solvent, temperature, bases, and many other conditions. In many cases, cis (3-lactam was found to be the exclusive or major product when acid chloride (equivalent) was added drop-wise at low-to-room temperature to the solution of imines and a base. However, a trans (3-lactam was the major or exclusive product obtained when a tertiary base was slowly added to the imine and acid chloride (equivalent) solution at high temperature. Georg and Ravikumar established a few rules regarding stereoselectivity in the formation of (3-lactam rings [122]. Computer-assisted calculations were advanced to explain the stereochemical preferences [140-144]. Cossio et al. [140-143] and... 

A new copper-catalyzed reaction involving imines, acid chlorides, and alkynes has been applied to the synthesis of propargyl amides 160 in a single operation by Arndtsen and co-workers. The same method allows the synthesis of N-carbamate-protected propargylamines [149]. a-Substituted amides 161 may also be prepared under palladium catalysis by substituting alkynes for vinyltin (Scheme 8.71) [150]. 

Nitriles A Grignard or organolithium reagent attacks the electrophilic cyano group to form the salt of an imine. Acidic hydrolysis of the salt (in a separate step) gives the imine, which is further hydrolyzed to a ketone (Section 18-9). 

The formation of the azetidin-one ring is by a [2 + 2] imine-acid chloride cycloaddition via the insitu formation of methoxy ketene. Other jS-lactams have been prepared using this route (1) as illustrated in Eq. 1. Spiro[3.5] jS-lactams have also been prepared in this manner and are discussed (2). 

Primary amines. Copper(I)-catalyzed Grignard reaction with the reagent gives (V-substituted imines. Acid hydrolysis releases the primary amines and the bis(trifluoromethyl)benzophenone. 

As in the furanol series, there is a problem of tautomerism with fura-namines. In general, aminofurans can exist to some extent as imines acid hydrolysis frequently eliminates ammonia. Meinwald and his colleagues have studied such 2-aminofuran hydrolyses and found them to give not the expected butenolides but dimers.215... 

The Palladium Catalyzed Synthesis of Carboxylate-Substituted Imidazolines A New Route Using Imines, Acid Chrloride, and Carbon Monoxide... 

This imidazoline-carboxylate synthesis involves the coupling of four separate cont5)onents (two imines, an acid chloride and carbon monoxide), and the generation of at least five separate bonds, all via a one-pot, palladium catalyzed process. From an analysis of the structure of the imidazoline carboxylate, the individual constituents can be seen (Figure 3). This stmcture might be considered to arise from the dipolar cycloaddition of an imine with a mesoionic l,3-oxazolium-5-oxide (5) intermediate, which itself could be generated from imine, acid chloride and carbon monoxide. Consistent with this potential formulation, performing the catalytic reaction with CO leads to the incorporation of the carbon-13 label into the carboxylate position of 4. 

Acid chlorides are also excellent precursors to 5-lactams when they react with an appropriate imine. Acid chlorides usually give a ketene under the reaction conditions. 

R. Dhawan, R. D. Dghaym, D. J. St. Cyr, B. A. Amdtsen, Org. Lett. 2006, 8, 3927-3930. Direct, palladium-catalyzed, multi-component synthesis of 3-lactams from imines, acid chloride, and carbon monoxide. 

K. Worrall, B. Xu, S. Bontemps, B. A. Amdtsen, J. Org. Chem. 2011, 76, 170-180. A palladium-catalyzed multicomponent synthesis of imidazolinium salts and imidazolines from imines, acid chlorides, and carbon monoxide. 

Scheme 6.48 Copper-catalyzed multicomponent coupling of imines, acid chlorides, and organoboron reagents, as described by Arndtsen and coworkers [67].

Comparison of this stmcture with that of the final product B shows that the amino nitrogen has become bonded to the carbonyl carbon to give a cyclic imine. Acid-catalyzed condensation of the amino with the carbonyl group (Section 17-9) provides a reasonable explanation for this... 

Among chemical methods for the separation of amines, those of Hinsberg (reaction with / -toluenesulfonyl chloride) and of Alexander (94) (reaction with 3-nitrophthalic anhydride) are most commonly used. Tertiary amines do not react with the reagents mentioned and they can be separated after the reaction — for example, by extraction. Derivatives of primary amines with p-toluenesulfonyl chloride are soluble in alkali hydroxide solutions, in contrast to sulfonamides of secondary amines this is utilized for their separation. When primary and secondary amines are separated by reacting them with 3-nitrophthalic anhydride, use is made of the fact that only phthal-imine acids derived from primary amines can be cyclized. Practical utilization of both procedures is demonstrated by the separated of a mixture of aniline, ethylaniline, and diethylaniline. However, it should be mentioned that in a number of cases the procedures fail or do not lead to a sufficiently sharp separation. Negatively substituted amines which do not react with / -toluenesulfonyl chloride can be separated with 3-nitrophthalic anhydride. Some p-toluenesulfonamides of primary amines are poorly soluble in alkali. The derivative of primary amine with 3-nitrophthalic anhydride is cyclized merely by boiling in benzene, and the phthalimide formed is soluble in benzene and can be isolated together with the tertiary amine. 

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