Tertiary 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 labile tertiary amide groups described in Section I.B.l.a are also applicable to lateral lithiations the piperazine-based amide 511 has been used to direct lateral lithiation before being methylated and cleaved to the acid 512 (Scheme 198). ... 

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). 

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... 

In a later development by Bedenbaugh et methylamine was used as solvent and lithium as electron donor. No proton donor was required, suggesting that the lithium salt (28) of hemiaminal (27) is stable under the reaction conditions (both aldehydes and aldimines are reduced by the reagent cf. the analogous reduction of carboxylic acids, Section 1.12.2 and Scheme 2). Yields of aldehydes produced by this method are shown in Table 8. It is notable that only tertiary amides are reduced satisfactorily. A major limitation of the reaction is the substantial formation of side products resulting from transamid-ation by the methylamine solvent (/. e. RCONHMe from RCONR 2). 

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. 

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],... 

When saturated alkyl halides were used in place of allyl compounds, a zinc/cop-per couple or zinc dust/copper iodide promoted the 1,4-addition to a-enones or a-enals. Sonication enhanced the efficiency of the process leading to the 1,4-adducts in very good yields [166]. This reaction was later extended to various a,j3-unsaturated compounds such as esters, amides and nitriles [167]. The reactivity of the halide followed the order tertiary > secondary primary and iodide > bromide > chloride making the assumption of a radical process highly probable [168]. 

Later, Heck also reported the synthesis of amide from various aryl, heterocyclic, and vinylic halides and primary or secondary amines in the presence of a palladium catalyst.The reaction was carried out under an atmosphere of carbon monoxide, and a tertiary amine was generally added to neutralize the hydrogen halide formed in the reaction. The reaction is also highly stereospecific with cis- and trans-winyl halides (Table 3). 

Alkyl halides in the presence of a zinc-copper couple, as a mixture of zinc dust and copper(i) iodide, reacted smoothly with a-enones and a-enals in aqueous media (Scheme 4.7). Sonication enhanced the efficiency of the process, leading to 1,4 adduct in good yields (Petrier et al, 1986). Such a conjugate addition was later extended to various electron-deficient alkenes, including a,P-unsaturated esters, amides, nitriles (Dupuy et al., 1991) or phosphine oxides (Pietrusiewicz and Zablocka, 1988). It appeared that the reactivity of the halide (RX) followed the order tertiary > secondary primary and iodide > bromide chloride. The preferred solvent system was aqueous ethanol, but the parameter of highest importance was the solvent composition (Luche and Allavena, 1988a). 

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