Halogeno-amides

A-Halogeno-amides are familiar and convenient sources of positive halogen for the organic chemist, and the 2 1 complex formed in benzene between diazabicyclooctane (DABCO) and /V-bromsuccinimide (NBS) [48] (the numbers are the observed interatomic distances in angstroms) in effect shows one such reagent in action (Crowston et al., 1984). The N-Br-N angle is close to linear [175.1(2) A], and the bromine is poised almost midway between the two nitrogen atoms, which are of similar basicity. The... 

The trianionic ligand 53a has been discussed in Section 4.3.4 in the context of Ce ", Ce" and mixed valence Ce /Ce amides and halogeno-amides." Reactions of the less bulky hgand 53b (as a Li salt) with LnCls (Ln = Nd or Y) led to polynuclear clusters, which included or ps-O and p2-OCH=CH2 ligands. 5 The dinuclear tripodal triamido... 

The halogeno amide becomes in effect an oxidizing agent. This behaviour is exemplified by the treatment of the divalent metal amides (Si le5)2 [2)21 (M = Mn, Fe or Co) with... 

Halogenopurines are generally most usefully prepared by direct halogenation of the purine (62JOC986) with halogens or halogeno amides. 

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

Ring expansion of haloalkyloxiranes provides a simple two-step procedure for the preparation of azetidin-3-ols (Section 5.09.2.3.2(f)) which can be extended to include 3-substituted ethers and O-esters (79CRV331 p. 341). The availability of 3-hydroxyazetidines provides access to a variety of 3-substituted azetidines, including halogeno, amino and alkylthio derivatives, by further substitution reactions (Section 5.09.2.2.4). Photolysis of phenylacylamines has also found application in the formation of azetidin-3-ols (33). Not surprisingly, few 2-0-substituted azetidines are known. The 2-methoxyazetidine (57) has been produced by an internal displacement, where the internal amide ion is generated by nucleophilic addition to an imine. 

Simple isothiazole-4-carboxylic acids have been made from the corresponding nitriles, which are available in turn from the halogeno derivatives, or directly by the olefin route.5-Aminoiso-thiazole-4-esters and -nitriles are readily obtained by the thioamide route. The 4-acids behave normally and form acid chlorides, esters, amides, and hydrazides. In contrast to the 5-series... 

Action of alkali amides and alkyl- and aryl-lithiums on mono-halogeno aromatic compounds,... 

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

Note Aminolysis of halogeno esters may be accompanied by amide formation, depending on the amine and conditions employed. 

The nature of the leaving halogeno atom. It has been observed that reaction of mono-labeled 6-fluoro-, 6-chloro-, and 6-iodo-4-phenyl[l(3)- Njpyrimidine with potassium amide/liquid ammonia leads to 6-amino-4-phenylpyrimidine in which the exocyclic amino group is N-labeled the percentages, however, strongly depend on the nature of the halogen atom, i.e., F (73 5%), Cl (93 5%), Br (83 5%), I (13 5%) (Scheme 11.12) (72RTC1414). 

Extensive investigations have been carried out in order to establish the intermediary occurrence of didehydro-1,5-, -1,6-, -1,7-, and -1,8-naphthyri-dines in aminations of halogenonaphthyridines with potassium amide in liquid ammonia. These studies have definitively proved that 3,4-didehydro-1, X-naphthyridines (X = 5, 6, 7, 8) are intermediates in aminations of the 3-and 4-bromo (chloro) derivatives of the I. X-naphthyridines.22,24-48-50 No evidence has been found for the occurrence of 2,3-didehydro-1,X-naphthyridines in these reactions. Also, in the reaction of the 2-halogeno-l,X-naphthyridines no evidence for these 2,3-didehydro intermediates was obtained. 

One example has been reported of the occurrence of an even tele substitution within one ring of the 1,7-naphthyridine system. Amination of 5-halogeno-l,7-naphthyridines (27) with potassium amide gave 8-amino-1,7-naphthyridine (54).28 This reaction bears a close analogy to the formation... 

Note Potassium amide in liquid ammonia can be used for aminolysis of halogeno-1,7-naphthyridines, but it also induces fe/e-aminolysis.54 For example, 2-chloro-l,7-naphthyridine gave a separable mixture of 1,7-naphthyridin-2-amine and both the 4- and 8-isomers (KNH2, NH3, Et20, —33°C, 4 h 70% yield of the mixture) from which each product was isolated in low yield 834 also analogous examples.332 808 834... 

The reactivity of halogen atoms in position 2 of oxazoles is considerably enhanced by quaternization. This is best illustrated by the synthetic utility of the salt (141) which, like other Ar-alkyl-2-halogeno-azolium and -azinium salts, effects a number of condensation reactions but it far surpasses these other salts in activity (79AG(E)707). Thus it activates carboxylic acids and it dehydrates formamides to isocyanides (Scheme 6). Amides are similarly converted into cyanides, ketones (RCH2COAr) into alkynes (RC=CAr), and cyanohydrins (RCH(OH)CN) are transformed into the corresponding chloro compounds <79CL1117>. 

N—C—O + C—C. The construction of the oxazole ring by the condensation of a-halogeno ketones with primary amides (equation 122) is the Bliimlein-Lewy synthesis (1884/1888). The method succeeds best when the resulting oxazole contains one or more aryl substituents. The use of formamide leads to oxazoles with a free 2-position and in this case it is possible that the reaction proceeds as in equation (113). 2-Aminooxazoles are produced by the action of a-halogeno ketones on urea and its derivatives (equation 123) or on cyanamide (80ZOR2185). The mercury(II) sulfate-catalyzed condensation of alkynic alcohols or their esters with primary amides leads to trisubstituted oxazoles (equation 124). 

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