Other N-Substituted Derivatives

N-Nitroso compounds (13) have been obtained by the action of nitrous acid64-66 on tetrahydrooxazines (3 R3 = H). Compounds 13 

Urea derivatives (Id) were obtained from 3-unsubstituted tetra-hydro-l,3-oxazines and aryl isocyanates.68 

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Reaction between diethyl piperidyl-1,2-carboxylate and hydrazine gives amino derivative 115 (71AP216), and the synthesis of other N-substituted derivatives with pesticidal properties is illustrated by the preparation of 118. The hydantoin (116) is treated with formaldehyde followed by hydrogen bromide to give 117, which reacts with 5-ammonium-0,0-dimethylphosphorothioate to give 118 (7IBRP1337269). 

Reference 10 lists eight other N-substituted derivatives. 

Because of the high-energy LUMO, nucleophilic substitution at the carbonyl is greatly slowed down compared to other X -substituted derivatives [205]. If the geometric constraints of the molecular framework force the nitrogen to be distorted from planarity, the n -n interaction is reduced. As a consequence, reactivity of the carbonyl toward nucleophilic attack is increased [206], as is the nucleophilicity of the nitrogen atom [207]. 

Several compds, some of them explosive, were patented recently by Swedish inventors. For their prepn, polynitro-alcohols(having all N02 groups attached to the same C atom and the OH group or groups attached to the adja-cent C atom) were treated with ammonia(or an N-substitution deriv thereof) in aq or other solns... 

The synthesis of isoquinolinones by amidoalkylation may also be achieved from other starting materials. N-Substituted derivatives were synthesized by the reaction of arylacetyl chlorides and azomethines in the presence of A1C13 to obtain a number of new compounds, such as 48 (Scheme 13) [75MI1 78ACH(98)315 81MI1 82S216]. 

Picramide and its N-substituted derivatives introduce the added complication that proton loss may occur from the amino-group to give the Bronsted bases 23 (R = H, alkyl, phenyl). Green and Rowe (1913) found support for this formula from the alkali metal analyses of the solids formed from many polynitroanilines with bases. In fact picramide itself has been frequently used as an indicator for establishing H-acidity scales in basic media on the assumption that its indicator behaviour is due to proton loss (Schaal, 1955 Stewart and O Donnell, 1962 Stewart et al., 1962). The most likely other alternatives for the products of 1 1 interaction of picramides with bases are 24 and 25 (R = H, alkyl, phenyl R =R = H, alkyl). Formula 24, the analogue of Meisenheimer s formula for the adducts of picryl ethers, was suggested by Busch and... 

In neutral and alkaline media, pyrazoles unsubstituted in the 1-position undergo hydroxymethylation at that position.653,667 Polymeric material of unknown structure is obtained in acid media, but from 3,5-dimethylpyrazole a small yield of l,4-bis(hydroxy-methyl)-3,5-dimethylpyrazole was isolated.653 Hydroxymethylation was used in the synthesis of the naturally occurring pyrazolyl-alanine.657 When the reaction is carried out in hydrochloric acid on 1 -phenylpyrazole,350 1,1, 5,5 -tetraphenyl-3,3 -dipyrazolyl,219 and other N-substituted pyrazoles,656 it is found that W-alkylpyrazoles give hydroxymethyl, and iV-arylpyrazoles chloromethyl derivatives. The 4-position is always the site of substitution. A side reaction is the linking of pyrazoles by methylene bridges.656... 

Related 1,3-oxazepines have been obtained from irradiation of many other heterocyclic A-oxides including pyndine N oxides, isoquinohne A oxides, qumoxalme IV-oxides, quinazohne A-oxides, phenanthndine N-oxides, benzophenazine iV-oxides, and acridine A-oxides However, the reported yields are variable and have generally been higher for phenyl and other aryl-substituted derivatives... 

It is interesting to compare the endo selectivities of two closely related types of dipoles. The ylides 47, derived by an imine-azomethine ylide tautomerism of the imines of a-amino esters (Section II,C), are typical dipoles that exhibit high endo selectivity in cycloadditions to cyclic olefins. On the other hand, N-substituted derivatives 79, derived by the deprotonation route (Section II,D) from N-substituted a-amino esters and aldehydes, are very poor in endo selectivity. The N-unsubstituted dipoles 47 are involved in the cycloadditions as ( , )-ylides (or syn-ylides), while the N-substituted dipoles 79 as ( ,Z)-ylidic forms (or anti -ylides). However, the difference in ylide geometry is not the only reason for the lowered endo selectivity of 79, since the anti forms of heteroaromatic N-ylides undergo exclusive endo-selective cycloadditions with cyclic cis-olefins (83H1907 84CL465 85BCJ3137). 

Numerous N-alkylnorcodeines have been prepared, and these can be nitrated, acetylated and chlorinated like codeine [361], Other N-substituted norcodeines have also been prepared [362-7], and of these N-aflylnorcodeine and other /3 y-unsaturated derivatives have an action antagonistic to that of morphine [364, 368], A dimolecular derivative results from the interaction of norcodeine and trans A2 3-l 4-dibromo-butene [369]. Spirocyclic quaternary salts such as [li] result from the treatment of norcodeine with pentamethylene iodide, o-xylyldibromide, and /3 /3 di-iododiethyl ether, and these suffer degradation in alkaline solution with fission of the codeine heterocyclic ring [370] (see Chap. VI). 

In N-substituted derivatives, the nature of the electronic environment of the pyrrole-type nitrogen is different from that of its pyridine-type counterpart. Each of these pyrrole-type nitrogens is bound covalently to three neighboring atoms, and supplies two electrons to the delocalized 7r-bond system. In this case, the component, which is oriented radially with the bond N-R (R = H, alkyl, metal), is dominated by a o n-c- transition. The 22 component, which is dominated by a aN R--7r transition, is approximately tangential to the aromatic ring. In other words, the tangential component ( t) is dominated by an h-tt (lone-pair) transition for a pyridine-type nitrogen. 

Nuclear magnetic resonance spectroscopy has been used to determine the isomer distribution in reaction products,98-135 to determine substituent positions,277 and generally to study structural problems.109-156-201 NMR data for a number of 2- and 5-aminooxazoles and their N-substituted derivatives have also been recorded.107-136-198-201 The observed proton chemical shifts of oxazole and other heteroaromatic compounds have been used to obtain qptimates of the electron distribution in these systems.278... 

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