Secondary and tertiary amides

This procedure, which is based on the work of Ishii and co-workers, affords a mild and general method for converting a wide variety of esters to primary, secondary, and tertiary amides (Table 1). While the preparation of the tertiary amide, N,N-dimethylcyclohexanecarboxamide, described here is carried out in benzene, aluminum amides derived from ammonia and a variety of primary amines have been prepared by reaction with trimethylaluminum in dichloromethane and utilized for aminolysis in this solvent. Although 1 equivalent of the dimethylaluminum amides from amines was generally sufficient for high conversion within 5-48 hours, best results were obtained when 2 equivalents of the aluminum reagent from ammonia was used. Diethyl-aluminum amides can also effect aminolysis, but with considerably slower rates. 

A series of palmitoylethanolamine-derived inhibitors has been described in the literature as FAAH inhibitors [77, 78]. This study explored the effect of shortening the chain length and replacement of the ethanolamine head group with primary, secondary and tertiary amide alternatives. Of the compounds synthesised and tested, two compounds gave reasonable affinities for FAAH inhibition, palmitoyl-isopropylamide (63) (IC50 = 13/rM) and palmitoyl-allylamide (64) (IC50 = 3.4/rM). Both these compounds had little affinity for either CBi or CB2 receptors. 

Our investigations showed that in mixed melts of eutectic composition carbamide-NH4(K)Cl, the oxidation and reduction of melt constituents take place mainly independently of each other. The anodic process at platinum electrodes in the range of potentials below 0.9V is associated with the direct oxidation of carbamide to secondary and tertiary amide compounds, accumulation of ammonium ions in the melt, and evolution of the same gaseous products as in carbamide electrolysis [8], The cathodic process is accompanied by the formation of ammonia, CO, and C02, i.e. of the same products as in pure- carbamide electrolysis. In contrast to carbamide melt, a large amount of hydrogen appears in the cathode gases of the mixed melt, and in the anode gases of the carbamide-KCl melt, the presence of chlorine has been established at potentials above 0.9V. In the... 

The microwave-assisted thionation of amides has been studied by Ley and coworkers using a polymer-supported thionating reagent [115]. This polymer-supported amino thiophosphate serves as a convenient substitute for its homogeneous analogue in the microwave-induced rapid conversion of amides to thioamides. Under microwave conditions, the reaction is complete within 15 min, as opposed to 30 h by conventional reflux in toluene (Scheme 7.95). The reaction has been studied for a range of secondary and tertiary amides and GC-MS monitoring showed that it proceeded almost quantitatively. More importantly, this work was the first incidence of the use of the ionic liquid l-ethyl-3-methylimidazolium hexafluorophosphate... 

Another example of microwave-assisted PSR chemistry involves the rapid conversion of amides to thioamides by use of a polystyrene-supported Lawesson-type thio-nating reagent. By use of microwave irradiation at 200 °C in sealed vessels (monomode reactor), a range of secondary and tertiary amides was converted within... 

The conjugate hydrosilylation of a,/S-unsaturated amides can be carried out in high yields with PhSiH3/Mo(CO)6 (Eq. 297)450 or Ph2SiH2/ZnCl2/Pd(PPh3)4.436 Primary, secondary, and tertiary amides are equally reactive 450 The reduction of a J3 -tribu ty I s (annyl-a, /3 -unsaturatcd tosylamide is also reported 469... 

The following sections examine the hydrolysis of amides originating from aliphatic acids. The presentation is organized according to the degree of substitution on the amide nitrogen - i.e., primary, secondary, and tertiary amides. 

Base hydrolysis of secondary and tertiary amides is less readily achieved than with primary amides, and may require stronger basic conditions. 

The most powerful classes, for several reasons, comprise carboxylic acid and carbonate-derived functions containing both nitrogen and oxygen secondary and tertiary amides, ... 

A large number of polymer materials are based on nitrogen containing monomers, such as urea and related compounds, various amides, amines etc. The most frequent nitrogen forms found in polymers are primary, secondary and tertiary amides, respectively, the later usually being a part of the network structure. Since the... 

Two 15N-enriched urea-formaldehyde resins with different crosslink density were studied by tfie solid state CP MAS 15N NMR. Despite at least six expected 15N chemical shifts arising from tertiary, secondary and primary amides in the different structural moieties, both resins exhibit only two major peaks. The lower field resonance is more pronounced in the highly cured resin, suggesting its origin in the tertiary amides. A DD experiment, which would confirm this assumption, does not result in clearly separated secondary and tertiary amides. Thus, from the analytical point of view, it seems that 13C NMR spectra are more useful than 15N NMR spectra, although 1SN resonance data provide a useful supplement 252). 

A strong carbonyl absorption is evident in the spectra of all amides, although the frequency of absorption varies somewhat with the structure of the amide. Thus primary amides generally absorb near 1680 cm 1, whereas secondary and tertiary amides absorb at slightly lower frequencies. The N—H stretching frequencies of amides are closely similar to those of amines and show shifts of 100 cm-1 to 200 cm 1 to lower frequencies as the result of hydrogen bonding. Primary amides have two N—H bands of medium intensity near 3500 cm 1 and 3400 cm 1, whereas secondary amides, to a first approximation, have only one N—H band near 3440 cm 1. However, a closer look reveals that the number, position, and intensity of the N—H bands of mono-substituted amides depend on the conformation of the amide, which can be either cis or trans ... 

Primary amides react under Swern conditions, producing the corresponding nitriles213 and minor amounts of iminosulfurans.210 Nonetheless, there is some report depicting the selective oxidation of alcohols in the presence of primary amides.214 Secondary and tertiary amides remain unaffected. 

We will see that this technique can be used to demonstrate the importance of the principle of stereoelectronic control in tetrahedral intermediates derived from amides. Primary, secondary, and tertiary amides as well as N — H and N-alkyllactams will be examined. 

Reduction of esters, nitriles, and amides. These groups are rapidly reduced by horanc-dimcthyl sulfide in refluxing THF (b.p. 67°) if the dimethyl sulfide (b.p. 38°) is removed as liberated. Under these conditions, the reagent is comparable to uncomplexed diborane. Reduction of secondary and tertiary amides is best effected in the presence of boron trifluoride etherate otherwise, excess reagent is utilized for formation of complexes with the products. 

New polymer-supported reagents for sulfide transfer have been developed to avoid exposure to malodorous and toxic sulfur reagents. Ley et al.15 prepared a stable aminothiophosphate polystyrene resin for the conversion of secondary and tertiary amides to thioamides in high conversion and purity (Table III, entry 11). This procedure is extremely clean and affords the desired product with short reaction times in comparison to Law-esson s reagent. In addition, the aminothiophosphate resin dehydrates primary amides to nitriles. 

Mechanisms of sodium borohydride reactions with primary, secondary, and tertiary amides have been investigated both at the B3LYP/6-31+- -G(d,p)//B3LYP/6-31G(d,p) and B3LYP/6-31++G(d,p)//HF/6-31G(d,p) levels of theory. The predicted structures of the key intermediates were then confirmed by experiment.317 For chemoselective reductions of a-substituted and aromatic esters with sodium borohydride, agreement between experimental results and theoretical computations at the B3LYP/6-31+-1-G(d,p)//HF/6-31G(d,p) levels of theory have been reported.318... 

Conformations of primary, secondary, and tertiary amides of (R,R)-tartaric acid, both symmetrically and asymmetrically substituted, have been studied ciys-tallographically [22, 24, 29, 30-40] Moreover, ab initio studies up to MP2 / 6-31G //RHF/6-31G level [41] for both the diamide and N,N,N ,N -tctramcthyl-diamide of (/ ,/ [-tartaric acid have been carried out [20, 22]. X-ray results have shown that primary and secondary amides of (R,R [-tartaric acid tend to adopt a conformation with the extended carbon chain - the Taa structure. In this Taa conformation both the a-hydroxy-amide moieties form planes and the structure gains stabilization from hydrogen bonding between donors, the NH, and acceptors, the proximal OH groups. Moreover, the Taa structure is favorably stabilized by the attraction of antiparallel local dipoles formed along distal C H and Csp2=0 bonds [18, 21, 22],... 

The regioseledivity of the last reaction in Scheme 5.13 is not only because of the greater acidity of the methylene group, but also because some secondary and tertiary amides (e.g. /3-arylamides, /3-vinylamides, or /3-(phenylthio)amides, or borane complexes of /3-phosphino propionamides [132, 133]) are deprotonated at the /3 position under kinetic control to yield chelate-stabilized carbanions [58, 134], Illustrative examples of such remarkable metalations are shown in Scheme 5.14. 

Helgen, C. Bochet, C. G. Preparation of secondary and tertiary amides under neutral conditions by photochemical acylation of amines. Synlett 2001, 1968—1970. 

Reduction Nitriles and amides can be easily reduced to alkylamines using lithium aluminium hydride (LiAlH4). In the case of a nitrile, a primary amine is the only possible product. Primary, secondary, and tertiary amines can be prepared from primary, secondary and tertiary amides, respectively. 

Secondary and tertiary amides would release the corresponding alkyl ammonium salts which, when neutralized, would yield the amine. 

The most powerful classes, for several reasons, comprise carboxylic acid and carbonate-derived functions containing both nitrogen and oxygen secondary and tertiary amides,104 oxazolines,140102 and carbamates.104 We have grouped these functional groups into the N+O class . Their importance stems firstly from their amphoteric nature they are all functional... 

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