Secondary amides lateral

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (—78 °C). N,N-Dimethyl, diethyl (495) and diisopropyl amides have all been laterally lithiated with aUcyllithiums or LDA, but, as discussed in Section I.B.l.a, these functional groups are resistant to manipulation other than by intramolecular attack" . Clark has used the addition of a laterally lithiated tertiary amide 496 to an imine to generate an amino-amide 497 product whose cyclization to lactams such as 498 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures (Scheme 194) ". The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures. ... 

The usual directing groups such as secondary amides will also successfully direct lateral lithiation at the 2-methyl group of a pyrrole (Scheme 226/° . 

The secondary amide can also attack intramolecularly an additional ester function to form a cyclic imide, although only in moderate yields [67], Finally, the palladium-catalysed intramolecular reaction with an alkyne, resulting in a hydro-amination of the latter, will be described later (Fig. 17) [68]. 

Amines may also behave as nucleophiles (Lewis bases). Primary amines are stronger nucleophiles than secondary amines, which, in turn, are stronger nucleophiles than tertiary amines. As nucleophiles, amines attack acid chlorides to form amides. Later in this chapter you see that they re important in the formation of sulfonamides. 

The earliest report on such lactim ether formation was from Sammes [72JCS(P1)2494], who converted piperazine-2,5-dione to 2,5-diethoxy-3,6-dihydropyrazine (173) with an excess of triethyloxonium fluoroborate. Subsequently, Rajappa and Advani (73T1299) converted proline-based piperazine-2,5-diones into the corresponding monolactim ethers. The starting material was a piperazinedione in which one of the amino acid units was the secondary amino acid proline, and the other a primary amino acid. This naturally led to the regiospecific formation of a monolactim ether (169) (on O-alkylation) from the secondary amide, whereas the tertiary amide remained intact. This was later extended to piperazine-2,5-diones in which the secondary amino acid was sarcosine [74JCS(P 1)2122], leading to the monolactim ethers (170). 

So far [234], we have limited ourselves to unreactive neutral functional groups following the historic evolution in functionalisation of NHC that confined itself to tertiary amines like pyridine [235], ester, keto and ether functionalities [236], oxazolines [237] and phosphines [238], We will later see that recently researchers have discovered the suitability of stronger nucleophiles such as alcoholates [239] and secondary amides [240], But, as in phosphine chemistry the golden rule of functionalised carbenes is to introduce the functional group first and generate the carbene (phosphine) last [237],... 

Much later, an alternate synthesis of naphthyridinones and quinoli-nones was discovered. Palladium-catalyzed amidation of halo aromatic rings with an ortho carbonyl group with primary or secondary amides to from substituted naphthyridinones and quinolinones (Scheme 97) (04OL2433). 

Substituted Amides. Monosubstituted and disubstituted amides can be synthesized with or without solvents from fatty acids and aLkylamines. Fatty acids, their esters, and acid halides can be converted to substituted amides by reaction with primary or secondary aLkylamines, arylamines, polyamines, or hydroxyaLkylamines (30). Di- -butylamine reacts with oleic acid (2 1 mole ratio) at 200—230°C and 1380 kPa (200 psi) to produce di-A/-butyloleamide. Entrained water with excess -butylamine is separated for recycling later (31). 

ControUed-potential oxidations of a number of primary, secondary, and tertiary alkyl bromides at platinum electrodes in acetonitrile have been investigated [10]. For compounds such as 2-bromopropane, 2-bromobutane, tert-butyl bromide, and neopentyl bromide, a single Ai-alkylacetamide is produced. On the other hand, for 1-bromobutane, 1-bromopentane, 1-bromohexane, 1-bromo-3-methylbutane, and 3-bromohexane, a mixture of amides arises. It was proposed that one electron is removed from each molecule of starting material and that the resulting cation radical (RBr+ ) decomposes to yield a carbocation (R" "). Once formed, the carbocation can react (either directly or after rearrangement) with acetonitrile eventually to form an Al-alkylacetamide, as described above for alkyl iodides. In later work, Becker [11] studied the oxidation of 1-bromoalkanes ranging from methyl to heptyl bromide. He observed that, as the carbon-chain length is increased, the coulombic yield of amides decreases as the number of different amides increases. 

Deacetylvinblastine acylazide (62) was later shown to be an exceptionally versatile intermediate for the preparation of C-3 amides. Since nucleophilic displacement of azide occurs at relatively low temperatures under mild conditions, a wide variety of C-3 derivatives have been prepared (Scheme 1, Table III). This observation is in contrast to the direct amino-lysis of vinblastine which usually fails when the amine employed is substituted (e.g., p-hydroxyethylamine) or secondary (dimethylamine). The reactions can be conveniently followed by the disappearance of the CO—N, infrared band at 2135 cm" with the concomitant appearance of the CO—NHj band in the region 1665-1675 cm". Acetylation of the... 

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... 

Surprisingly, 43 was consistently isolated as the C12-05 diene, as opposed to a system in conjugation with the amide carbonyl. That this was in fact the kinetic product was revealed by isomerization of 43 to 44 upon exposure to sodium methoxide. However, 44 was unstable and difficult to purify, not surprising, considering its functionality. If this problem could be resolved later, secondary amine 43 would represent a... 

The frequency of the amide I peak observed in the lens is sensitive to protein secondary structure. From its absolute position at 1672 cm-1, which is indicative for an antiparallel pleated 3-sheet structure, and the absence of lines in the 1630-1654 cm-1 region, which would be indicative of parallel (1-sheet and a-helix structures, the authors could conclude that the lens proteins are all organized in an antiparallel, pleated 3-sheet structure [3]. Schachar and Solin [4] reached the same conclusion for the protein structure by measuring the amide I band depolarization ratios of lens crystallins in excised bovine lenses. Later, the Raman-deduced protein structure findings of these two groups were confirmed by x-ray crystallography. 

We have already discussed primary structure in terms of the general character of amino acids and some specific examples of amino acid sequences in certain proteins will be discussed later. Our attention now is focused on secondary structure, or conformation as we called it when we discussed synthetic polymers. There are a number of factors that afreet the conformation of a polypeptide chain and a lot can be learned initially by just focusing on two of these steric restrictions on bond rotations and the strong driving force for amide groups to hydrogen bond to one another. 

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