Substituents aminoethyl

Chapters 9, 10 and 11 describe methods for substitution directly on the ring with successive attention to Nl, C2 and C3. Chapters 12 and 13 are devoted to substituent modification as C3. Chapter 12 is a general discussion of these methods, while Chapter 13 covers the important special cases of the synthesis of 2-aminoethyl (tryptaminc) and 2-aminopropanoic acid (tryptophan) side-chains. Chapter 14 deals with methods for effecting carbo cyclic substitution. Chapter 15 describes synthetically important oxidation and reduction reactions which are characteristic of indoles. Chapter 16 illustrates methods for elaboration of indoles via cycloaddition reactions. 

One of the virtues of the Fischer indole synthesis is that it can frequently be used to prepare indoles having functionalized substituents. This versatility extends beyond the range of very stable substituents such as alkoxy and halogens and includes esters, amides and hydroxy substituents. Table 7.3 gives some examples. These include cases of introduction of 3-acetic acid, 3-acetamide, 3-(2-aminoethyl)- and 3-(2-hydroxyethyl)- side-chains, all of which are of special importance in the preparation of biologically active indole derivatives. Entry 11 is an efficient synthesis of the non-steroidal anti-inflammatory drug indomethacin. A noteworthy feature of the reaction is the... 

The nonaromatic character of oxepins makes this structure susceptible to the reduction of one or more double bonds. 10-[(2-Aminoethyl)sulfanyl]-substituted dibenz[b,/]oxepins with various substituents in position 2 smoothly react to give the 10,1 l-dihydrodibenz[b,/]oxepin system 1 on treatment with magnesium in methanol.71 202 The advantage of this method is the possibility of reducing dibenz[b,/]oxepins with various heteroatoms such as sulfur, oxygen or nitrogen in the side chain. 

With both diastereomers (S,R)-9 and (R,R)-9 the same enantiomer is predominantly formed. Therefore, the enantioselectivity of the addition reactions is induced by the chirality of the fcrrocenyl moiety rather than by the chirality of the aminoethyl substituent. 

Allyl p-tolyl sulphoxide 535 reacts with sodium methoxide in methanol by initial prototropic isomerization and subsequent addition of methanol to give 536 (equation 333). Protic solvents are photochemically incorporated by the open chain olefinic bond of trans methyl )S-styryl sulphoxide 537 in a Markovnikov regiospecificity (equation 334). Mercaptanes and thiophenols add to vinyl sulphoxides in a similar manner (compare also Reference 604 and Section IV.B.3) to give fi-alkylthio(arylthio)ethyl sulphoxides 538 (equation 335). Addition of deuteriated thio-phenol (PhSD) to optically active p-tolyl vinyl sulphoxide is accompanied by a low asymmetric a-induction not exceeding 10% (equation 336) . Addition of amines to vinyl sulphoxides proceeds in the same way giving )S-aminoethyl sulphoxides in good to quantitative yields depending on the substituents at the vinyl moiety When optically active p-tolyl vinyl sulphoxides are used in this reaction, diastereoisomeric mixtures are always formed and asymmetric induction at the p- and a-carbon atoms is 80 20 (R = H, R = Me) and 1.8 1 (R = Me, R = H), respectively (equation 337) ... 

Substituent effects on the -(aminoethyl)cyclohexenone photochemistry were carried out to study the relative kinetic acidities of the tertiary aminium radical47. The ease of the methylene hydrogen to be removed as H+ increased in the order of X = alkyl < Si(CH3)3 < C=CH (equation 13). 

It is noteworthy that 4,5-dihydro-1,2,4-oxadiazoles with a nucleophilic j6-aminoethyl substituent in the 3-position undergo ring transformation to cyclic amide oximes (48) by nucleophilic attack on C(5) (Scheme 17) <92JCS(Pi)3069>. 

Specific substrates such as diethyl a -acetylglutarate, 2-ethoxycarbonylcyclopentanone and 3-carboxypiperidone are useful for the synthesis of special classes of functionally substituted indoles, as shown in Scheme 10. When cyclization is followed by hydrolytic decarboxylation of the C-2 substituent, these cyclizations provide indoleacetic acids, indolepropionic acids and tryptamines, and 3-(2-aminoethyl)indoles, respectively <72HC(25-1)236). 

Triazasilatranes are hydrolytically less stable than silatranes4083,414. However, it is of interest that 1-aminotriazasilatrane (185) is stable to solvolysis by EtOH in CgDg at room temperature312. Methanolysis of triazasilatranes 169, 172 and 176 at room temperature does not proceed by an initial displacement of an axial substituent but by attack on the tricyclic structure to afford tris(2-aminoethyl)amine and the corresponding trimethoxysilanes (equation 188)414. 

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