Secondary amine naming

The thioxotetrazinoquinazoline 7 was reacted with paraformaldehyde and secondary amines, namely diethylamine and piperidine (Mannich reaction), to afford the corresponding derivatives (Equation 2) <1999IJB850>. 

This possible mechanism is applicable only to compounds having a hydrogen atom attached to the nitrogen atom, yet Kuhn and Birkofer found that mutarotation occurs in pyridine solutions of derivatives of secondary amines, namely, n-glucosylpiperidine and iVjiV -dibenzyl-D-glucosylamine, where no such hydrogen atom is available. To explain mutarotation in such cases they postulated the formation of an acyclic imonium ion by expulsion of a proton from a substituted ammonium ion. 

Liebermann discovered the reaction between nitrous acid and phenols and secondary amines named after him. He prepared amino-naphthols from nitro-naphthols, synthesised the dihydroxyanthraquinones anthrarufin and chrysazin, and studied the reduction of anthraquinone. Another dihydroxy-anthraquinone, quinizarin, was discovered by F. Grimm by heating hydro-quinone with phthalic anhydride. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

The mechanism of H02 formation from peroxyl radicals of primary and secondary amines is clear (see the kinetic scheme). The problem of H02 formation in oxidized tertiary amines is not yet solved. The analysis of peroxides formed during amine oxidation using catalase, Ti(TV) and by water extraction gave controversial results [17], The formed hydroperoxide appeared to be labile and is hydrolyzed with H202 formation. The analysis of hydroperoxides formed in co-oxidation of cumene and 2-propaneamine, 7V-bis(ethyl methyl) showed the formation of two peroxides, namely H202 and (Me2CH)2NC(OOH)Me2 [16]. There is no doubt that the two peroxyl radicals are acting H02 and a-aminoalkylperoxyl. The difficulty is to find experimentally the real proportion between them in oxidized amine and to clarify the way of hydroperoxyl radical formation. 

Substituent effects have been interpreted in another way (213), namely, by considering the aqueous uncorrected pKa values of the parent secondary amine HNR, R2 as a measure of the inductive effects of the Rt and R2 substituents. It has been argued that the greater the pKa, the more favored the limiting form 2 S2C=NR2 is. This form has been associated with diminished covalency in the Fe—S bond and high-spin behavior (213). 

The concept of proton-transfer to the base leads to an important generalisation (18, 52), namely, this type of polymerisation may be initiated not only by aprotic bases but also by primary or secondary amines. The latter may then act in a dual way — as proton "acceptors as well as proton donors. Hence, the initiation by primary or secondary... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

The other major class of fatty imidazoline derived amphoteric surfactants is the amphopropionates. Again, the ampho portion of the name indicates that they are derived from imidazolines but, rather than being alkylated with sodium chloroacetate, they are carboxy-lated with an acrylate via the Michael reaction. A primary or secondary amine is added across the double bond of the acrylate to yield the beta-alanine derivative. 

The review starts with a discussion of the mechanism of keto-enol tautomerisation and with kinetic data. Included in this section are results on stereochemical aspects of enolisation (or enolate formation) and on regioselec-tivity when two enolisation sites are in competition. The next section is devoted to thermodynamic data (keto-enol equilibrium constants and acidity constants of the two tautomeric forms) which have greatly improved in quality over the last decade. The last two sections concern two processes closely related to enolisation, namely the formation of enol ethers in alcohols and that of enamines in the presence of primary and secondary amines. Indeed, over the last fifteen years, data have shown that enol-ether formation and enamine formation are two competitive and often more favourable routes for reactions which usually occur via enol or enolate. 

Although the term enamine was coined in 1927 (to emphasize the structural analogy with enols)1, it wasn t until 1936 that a general synthesis for enamines was published, namely the condensation between aldehydes and secondary amines developed by Mannich and Davidsen2. That method was improved in the early 1950s by Herr and Heyl who employed the azeotropic removal of water to facilitate formation of a wider variety of enamines than had been available3. As described by Haynes, many other preparations were subsequently devised4. 

Even though zincation of secondary amines was already studied by Frankland in 1856 and 1867, it is only in the past few decades that some efforts were made to isolate and characterize the products. Numerous compounds of the type RZnNR2 or Zn(NR2)2 can now be prepared nsing two principal procedures, namely the zincation of amines with simple dialkylzinc compounds " (equation 26) and the metathesis reaction of alkali metal amides with anhydrons zinc dihalide (equation 27). 

Metabolites derived by loss of an alkyl or arylalkyl group from ethers [Eq. (4)], thioethers [Eq. (5)], amines [Eq. (6)], and amides [Eq. (7)] represent common biotransformation pathways (R, R" = H, alkyl or aryl). These processes involve oxidation on carbon adjacent to the heteroatom. The intermediates are generally unstable and readily decompose to the corresponding alcohol, thiol, amine, or amide and an aldehyde. Intermediates formed from amides [Eq. (7)] are more stable and may be detected as excreted metabolites. If a secondary carbon atom is adjacent to the heteroatom, then this portion of the molecule is released as a ketone. The heteroatom may also be located in a cyclic structure (e.g., morpholine, piperazine). Two processes have been adopted for amines, namely, N-dealkylation or deamination, that are essentially the same event. In general, which of the two terms applies depends on the... 

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