Amides Experimental Procedures

The technical production of poly(benzimidazole) (PBI) is also carried out in two steps. In the first step an aromatic tetramine is condensed with the diphenyl ester of an aromatic dicarboxylic acid at 220-260 °C, yielding a poly(amino amid) with elimination of phenol. Ring closure with elimination of water occurs in the second step (solid-phase polycyclocondensation), conducted at 400 °C and yielding the polybenzimidazole (experimental procedure, see Table 2.3). 

All enthalpy of solution measurements were carried out with an LKB 8700-1 precision calorimetry system. The experimental procedure and tests of the calorimeter have been reported previously (3, 4, 5). The purification of the solvent DMF (Baker Analyzed Reagent) and of all solutes used has been described in the same papers. The solvent mixtures were prepared by weighing and the mole fraction of water in the DMF-water mixtures was corrected for the original water content of the amide as measured by Karl Fischer titration. 

The facile reduction of amides by borane[67 69 was used for the reduction of the carbonyl group of the peptide bond.159 This reduction procedure is compatible with Boc, Z, OMe, and OBzl protecting groups. Generally, yields are relatively low. The following experimental procedure describing a dipeptide reduction, is the one which produces the best results/57 ... 

The p-sulfanyl amides 28 are synthesized from N-protected amino acids 24 via amino alcohols 25, which are converted into (5-acetylsulfanyl amides 26 by a Mitsunobu reaction. The (5-amine disulfide 27 is subsequently coupled with a variety of carboxylic acids, followed by reduction with tributylphosphine in aqueous THF in the presence of pyridine to produce the free thiol 28 (Scheme 5).1211 Detailed experimental procedures for these compounds have not been reported. 

The condensation of aldehydes and ketones with ethyl chloroacetate in the presence of sodium ethoxide or sodium amide produces a,/3-epoxy esters (Darzens). The scope, limitations, typical experimental procedures, and examples have been given. Briefly, aliphatic and aromatic ketones, and aromatic aldehydes react satisfactorily, whereas aliphatic aldehydes give poor yields. a-Halopropionic and a-halobutyric... 

The experimental procedure for performing the kinetic measurements is the following a known amount of alkali metal is introduced into the reaction cell in the presence of argon. The cell is attached to the vacuum line, cooled below the boiling point of ammonia (—33.5°C.) and dry ammonia is introduced. Alkali amide is prepared in situ. Beforehand traces of a ferrous salt have been allowed to be absorbed on the cell walls and serve as a catalyst for the reaction... 

It was shown that amide formation can be suppressed by the appropriate choice of reaction conditions, such as homogeneous solutions, e.g. in DMF, DMSO, HMPA, high acidity and low temperatures (-30 to -5°C). If the peptide hydrazide contains acid-labile protecting groups, e.g. trityl, 2-(4-biphenyl)propyloxycarbonyl, tert-butyloxycarbonyl, tert-butyl esters and ethers, the temperature has to be kept below -20 °C. Generally, tert-butyl or butyl nitrite is used as the organic nitrite, and for sterically hindered peptides amyl nitrite is employed. The time required for full conversion of the hydrazide into the azide may vary between 5 to 30 min and can be monitored by spray reagents (see experimental procedure below). 

Reactions involving a variety of terpene-derived, chiral acrylic amides and esters at least partly lead to equally remarkable yields and diastereoselectivities (Table 2). A more detailed discussion including experimental procedures is available. ... 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

Regarding the control of the temperature it was observed that the exotherm ceased after addition of the first drops of the nitrate to the reaction mixture. Afterwards the nitrate could be added at a fast rate. The experimental procedure is simple and is as follows the ketone is added to potassium amide in liquid ammonia at -33 and the suspension stirred for 30 min. Then the nitrate ester is added dropwise over 10 min, the mixture stirred for 30 min, and the ammonia gradually replaced by ether. Filtration gives then the nitro salt. 

The experimental procedure for the synthesis of N,N-diethyl- n-toluamide (21) nicely illustrates a common method for preparing amides. In the first step, m-toluic acid (19) reacts with thionyl chloride to give the acid chloride 20 (Eq. 20.8). The acid chloride is treated directly with an excess of diethylamine to give N,N-diethyl-TH-toluamide and diethylammonium hydrochloride (Eqs. 20.9,20.10). 

A qualitative test for an amide group (Eq. 25.68) is the same as that for an ester, as given in Section 25.16A. Follow the experimental procedure provided there. The colors observed with amides are the same as those with esters. 

In a natural compound of rather high complexity, namely ictor P4301435 from methanogenic bacteria, the amide and lactam functions are converted into the dinitrile 1436 by dehydration with phosphoryl chloride [1091]. In a detailed evaluation of the experimental procedure, Eschenmoser and Pfaltz found that 2,6-luti-dine works much better than pyridine as an auxiliary base (84% yield of dinitrile instead of 54%). 

Amides can also serve as nucleophilic partners. The amidation of sterically hindered aryl chlorides with bulky amides proceeds with a new bulky ligand as demonstrated by the Paradies group (Experimental Procedure below). ... 

Experimental procedure for the thermolysis of aryliodonium ylides. Preparation of 40 (Scheme 18.31) A suspension of 133 (1 mmol) and benzyl amine (1 mmol) in CH2CI2 (15 mL) was refluxed for 4-7 hours until a clear solution resulted and TLC showed the disappearance of the starting ylide. The solution was concentrated in a vacuum to half its volume, hexanes (10 mL) were added, and the precipitated yellow solid was filtered and washed repeatedly with hexanes. The amide 140 (mp 144-146°C) was obtained in 84% yield. An analytical sample was obtained by recrystalUzation from CH2Cl2-hexanes. 

Typical experimental procedure for (S)-3-(l,3-dioxo-l,3-dihy-dro-isoindol-2-yl)-3-fluoro-2-oxo-piperidin-l-carboxylic acid tert-butyl ester (precursor of 3S-fluorothalidomide) using the dihydroquinine/NFSI combination with TMEDA Lithium bis (trimethylsilyl)amide solution l.OM in THF (0.087mL, 0.087 mmol) was added to the solution of 3-(l,3-dioxo-l,3-dihydro-iso-indol-2-yl)-2-oxo-piperidin-l-carboxylic acid tert-hutyl ester (20 mg, 0.058 mmol) and tetramethylethylenediamine (0.013 mL, 0.087 mmol) in THF (l.OmL) at -80°C under Ar. After being stirred for 0.5 hours, the suspension of the dihydroquinine/NFSI combination [the solution of dihydroquinine (28.4 mg, 0.087 mmol) and N-fluorobenzenesulfonimide (27.4 mg, 0.087 mmol) in THF (2.0 mL) was stirred for 1 hour at room temperature under Ar] was dropwise and then stirred for overnight at -80 °C. The reaction was quenched with IN hydrochloric acid, extracted with ethyl acetate, washed with brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by silica-... 

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