Reactions at nitrogen

The nitrogen atom in a-ferrocenylalkylamines generally shows the same reaction pattern as that in other amines alkylation and acylation do not provide synthetic problems. Due to the high stability of the a-ferrocenylalkyl carbocations, ammonium salts readily lose amine and are, therefore, important synthetic intermediates. Acylation of primary amines with esters of formic acid gives the formamides, which can be dehydrated to isocyanides by the standard POClj/diisopropylamine technique (Fig. 4-16) [92]. Chiral isocyanides are obtained from chiral amines without any racemization during the reaction sequence. The isocyanides undergo normal a-addition at the isocyanide carbon, but could not be deprotonated at the a-carbon by even strong bases. This deviation from the normal reactivity of isocyanides prompted us to study the electrochemistry of these compounds, but no abnormal redox behaviour, compared with that of other ferrocene derivatives, was detected [93]. The isocyanides form chromium pentacarbonyl complexes on treatment with Cr(CO)s(THF) (Fig. 4-16) and electrochemistry demonstrated that there is no electronic interaction between the two metal centres. 

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The acylation of enamino ketones can take place on oxygen or on carbon. While reaction at nitrogen is a possibility, the N-acylated products are themselves acylating agents, and further reaction normally takes place. The first reported acylation of enamino ketones (72) was that of 129, prepared by acylation of the enamine (113), which was shown to have undergone O acylation because on mild hydrolysis the enol ester (130) could be isolated. A similar reaction took place with other aliphatic acid chlorides (80) and with dibasic acid chlorides [e.g., with succinyl chloride to give 118 above]. 

Steric effects. As expected, bulky groups on the mutagen as well as on the nucleophile have a significant impact on ease of SN2 reaction at nitrogen. 

Lack of reactivity towards SN2 reactions at nitrogen would in itself account for low mutagenic activity. However, the tert-butyl groups on 31c f and 32a,b are well removed from the reactive nitrogen and, as well, SN2 reactions of mutagens 31c e with A-methylaniline in methanol at 303 °C occur with relatively similar rate constants to that of unsubstituted 28a, and of mono tert-butylated systems 28i and 31 a,b (Table 18). 

S to N transfer of the nitroso group has also been postulated on a number of other occasions53,71 to explain enhanced reaction rates. Detailed kinetic studies on the nitrosa-tion of thioproline72 (12) and thiomorpholine73 (13) reveal that two pathways can exist, which depend on the reaction conditions, (a) a direct reaction at nitrogen and (b) a direct reaction at sulphur followed by S to N migration of the nitroso group. 

FIGURE 8. (a) Anomerically induced elimination (b) 8 2 reaction at nitrogen... 

Anchimeric assistance by the aUcoxyl oxygen lone pair promotes heterolytic S v 1 and reactions at nitrogen as well as homolysis of the N—Cl bond. A-Haloamides are also amidyl radical sources" but their heterolytic reactivity is known to involve positive, rather than negative, halogen ... 

In this configuration, the alkoxyl oxygen lone-pair involvement promotes not only heterolytic Sjvl and 8 2 reactions at nitrogen and homolysis of the A—OAcyl bond, but molecular rearrangements. 

Methylation of carbazole phenolic oxygen has been achieved using dimethyl sulfate without reaction at nitrogen. Demethylation of carbazole methyl ethers has been achieved with hydrobromic acid-acetic acid, boron trichloride,and pyridine hydrochloride. Selective demethylation of methoxyl ortho to an aldehydo function has been achieved using boron trifluoride. ° ° Partial demethylation of 1-methoxy-3-formylcarbazole occurred during Wolff-Kischner reduction." ... 

Oxidative Reactions at Nitrogen 1.09.2.2.1 Secondary alicyclic amines... 

A review75 of the SN reactions at neutral nitrogen, oxygen, and sulfur has been published. The substitution reactions at nitrogen and oxygen predicted by theory and found experimentally occur by an S 2 mechanism and are faster than the corresponding reactions at carbon. The SN reactions at sulfur, on the other hand, mostly occur by an addition-elimination mechanism, although some. S N2 mechanisms have been... 

Kinetic studies of nitrosation by aqueous nitrous acid have been carried out for reaction at nitrogen, carbon, oxygen, and sulphur. There are many similarities between the kinetic forms observed for reaction at the different centres it appears that nitrosation can involve the nitrosonium ion or a number of carriers of the nitrosonium ion depending on the acidity and the other species present. Some of the nitrosating agents that have been suggested are shown below in the expected order of reactivity ... 

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