Naphthamides

Siddall and his co-workers (46) have examined the barriers to rotation of a series of 2,6-disubstituted anilides. Af-Ethyl-A/-(2,6-xylyl)formamide (9) was recrystallized as a uranyl nitrate complex, and one isomer, which at equilibrium was favored by a factor of 3 1, was enriched up to a 30 1 ratio. The kinetics of rotation were examined at 0 to 29°C. The Arrhenius activation energy was 26 3 kcal/mol and log A was 18.5 2.4 hr-1. Siddall and Gamer (47) were able to obtain an almost pure isomer (which also predominated at equilibrium 1.3 1 for the ethyl compound and 1.1 1 for the methyl compound) of Ar-alkyl- V-(2-methyl-4,6-dibromophenyl)-l-naphthamide (10). The half-lives of... 

The deuterium kinetic isotope effect has been used to protect the 2-position of (80) from deprotonation and thereby force an organolithium to add to the naphthamide ring of (81). °... 

Most benzylic organolithiums, unless they bear an a heteroatom, are configurationally unstable over a period of seconds or more" , so any stereoselectivity in lateral lithiation is rarely detectable. However, as implied above, the lateral lithiation of tertiary 1-naphthamides 570 is stereoselective, and yields a single diastereoisomeric atropiso-mer of the organolithium 571 Both diastereoisomers of 571 were characterized by... 

The absolute configuration of all chiral amines prepared was determined by comparison with literature rotation values to be S. The (S)-enantiomers possess a positive rotation and the derived a-naphthamides elute, as in other cases, after the (//(-enantiomer on a chiral Pirkle column. 

Bis(a- naphthyl)-succinamide( called Bernstei n-saure-bis-a-naphthamid or N.N -Di-a-naphthyl -succinamid in Ger),... 

Two mechanisms (i.e. direct hydrolysis and alternatively a path via an unstable acyl phosphate intermediate) are involved in the hydrolysis in phosphate buffer of N-arylsulfonyl / -lactams such as (130).107 The acyl phosphate intermediate can be trapped with hydrazine. The alkaline hydrolysis of some torsionally distorted lactams, i.e. the bridged benz[rfe]isoquinolin-l-ones (131), in 70% (v/v) DMSO-water has been compared under the same conditions with the hydrolysis of AvA-dimethyl-1 -naphthamide (132). The relative rates of reaction and activation parameters indicate the effect of torsional distortion.108 The reaction of the tricyclic azetidinones (133) with trifluoroacetic acid gives the bicyclic thioesters (135). The mechanism may involve acid-catalysed elimination of methanethiol to give an azetinone intermediate (134) which, after nucleophilic attack of the thiol, is converted into (135).109... 

Attempts to induce asymmetry in the cyclisation of 57 using the chiral lithium amides, which had worked well with simple benzamides, were frustrated by the inherent chirality, at low temperature, of the naphthamide itself. This feature is common to all 2-substituted tertiary aromatic amides, which may become atropisomeric at low temperature due to slow rotation about the Ar-CO bond.48 We therefore sought to... 

This was our initial plan, and we set about making the starting materials 37 or 87. We used the cumyl group as a readily removable bulky protecting substituent, but we found that while the amide 85 could be readily, if slowly, benzylated, it was surprisingly much harder to alkylate with a p-methoxy substituted benzyl halide than its naphthamide... 

The dimerization of thioformylketene was investigated by B3LYP and G3MP2B3 methods. The 4 + 4-pathway has the lowest energy barrier and calculations suggest that the reaction is pseudopericyclic.231 The stereospecific intramolecular 4 + 4-cycloaddition reaction between cyclohexadiene iron tricarbonyl complex and appended dienes (198) generates cyclooctadiene tricyclic adducts (199) (Scheme 56).232 The first example of an asymmetric intermolecular 4 + 4-photocycloaddition reaction in solution between 9-cyanoanthracene and chiral 2-methoxy-l-naphthamides has been reported. The frozen chirality is effectively transferred to the optically active product.233... 

The solid-state structure of the species DMG = CH2NMe2 is a tetramer in which each Li atom is associated with three carbanion carbons and one nitrogen atom. Similar analysis of N,N-diisopropylbenzamide and 1-naphthamide shows that in the solid state the bulky amide substituent, being unable to bridge the amide carbonyl O with ortho-C via a single Li atom, escapes into bridged dimer structures in which one Li is planar with the amide and the other is planar with the aromatic ring. 

Figure 4. Acid dependence of 1-naphthamide fluorescence intensity protonated form (O) unprotonated form ( ) (Watkins, 1972b).

Schulman and co-workers have invoked non-fluorescent H30 + exciplexes to interpret similar breaks in the titration curves of 1- and 2-ethyl naphthoate (Kovi and Schulman, 1972), 1-naphthoic acid and methyl-l-naphthylketone (Capomacchia et al., 1973). It is difficult to explain why in some cases only the 1-isomer shows this behaviour. It has also been suggested (Capomacchia et al., 1973) that the fluorescence titration curve reported by Watkins (1972b) for 2-naphthamide is an example of the same phenomenon although the B and BH+ curves seem to be complementary at lower acidities in this case (see Fig. 4). 

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