Amide functional types

The tertiary amines 303 and the acid chlorides 304 (X = Cl) initially formed acylammonium salts 305, which underwent a von Braun type degradation by an attack of the nucleophilic chloride ion at the allyl system to give allyl chlorides 306/307 and carboxylic acid amide functions. 

The cycloaddition of Weinreb amide functionalized nitrile oxide with a range of dipolarophiles has been studied. N-Methoxy-N-methylcarbonocyanidic amide, nitrile oxide 207 (i.e., a nitrile oxide of Weinreb amide type derivative) was generated from 2-chloro-2-(hydroxyimino)-N-methoxy-N-methylacetamide as intermediate and used in situ. Thus, addition of 3-bromo-l-propyne as dipolarophile to this precursor of 207, followed by quenching with triethylamine, gave 5-(bromo-methyl)-N-(methoxy)-N-methyl-3-isoxazolecarboxamide 208 in 55% to 60% yield (367). 

Systems which can react by either 5-exo or 6-endo cyclization normally produce the five-membered ring system. Exceptions result when equilibration of the initially formed five-membered ring is facile and substitution electronically favors the 6-endo mode of cyclization. Several examples have been found in amidoselenation reactions.41158 216 216 232 For example, halocyclization of thioimidate (17) produced only the pyrrolidone product,217b 217c 233 while selenocyclization of amide (18) produced only the piperi-done product.232 Note that the cyclization of (18) to a piperidone also involves regioselectivity in the cyclization of an amide functionality to a lactam rather than an imidate. Both the ring size and type of product can be explained by equilibration. 

There are three amide functions of the type CNH2, two of which belong to side chains of asparagine and glutamine, respectively. The third amide belongs to the C-terminal amino acid, glycine, O O... 

A useful property of hyper valent iodine reagents is their ability to react first as an electrophile and then to be transformed into an excellent leaving group. This particular aspect has been used in different rearrangements for the construction of highly functionalized molecules. Various iodine(III) reagents have been employed in Hofmann-type rearrangements [136-139]. The presence of a nucleophile in the ortho position of aromatic amides of type 72 can lead to direct cyclizations and to the formation of heterocyclic compounds 73 as shown in Scheme 33 [140]. 

Crystallographic analysis of the 3 C1 complex (Fig. 3a,b) verified the proposed structure where chloride anion is held almost symmetrically by the amidic functions (Cl...HN=2.45 and 2.52 A). It is also evident that there are several close contacts with the aromatic hydrogens of calixarene (ArH...Cl= 3.05, 3.15 A) and metallocene (CH...C1=2.75, 2.95 A) moieties. As the whole structure creates a dimeric form of head-to-tail type, the chloride anion is held by additional HBs of the metallocene unit from the second molecule (CH... Cl= 2.77,2.93 A). 

This type of receptor is represented by compounds 16a,b bearing ruthenium ) bipyridine moieties. Both calixarenes [18] exhibit 1 1 binding of chloride and bromide anions (DMSO-d6), and they are especially suitable for the complexation of H2POj (X16a=2.8-104 M-1 K16b=5.2 103 M"1). On the other hand, if we compare these results with those for similar non-calixarene receptors, where the bipyridine unit is substituted by alkyl, aryl or ethylene glycol substituents, the introduction of calixarene does not bring any substantially new features into the complexation abilities of these derivatives. As shown by X-ray analysis, the anion is encapsulated within the cavity formed by amidic functions with the contributions of CH...anion interactions from the bipyridine unit. 

Uracil-type compounds are insoluble in common organic solvents. Radicals R4 in 168 have been used to permit a more facile allylation or rearrangement to 167, as shown in Scheme 37). Further transformation into the amide functional group permits preparation of 169, and finally 170 (93ACS72). 

Arylsulfonyl chlorides are pivotal precursors for the preparation of many diverse functional types including sulfonate esters,8 amides,4 sulfones,9 sulfinic acids,10 and others.11 Furthermore, sulfonyl fluorides are best prepared from sulfonyl chlorides.12 The sulfonyl fluorides have many uses, among which is their utilization as active site probes of chymotrypsin and other esterases.13 The trifluoromethyl group also plays valuable roles in medicinal chemistry.14... 

So far the reactivity of epoxides has involved their use as an electrophile. However, oxtranyl anions can serve as functionalized nucleophiles in their own right. Thus, the sulfonyl substituted epoxide 107 can be deprotonated with -butyllithium to provide a stabilized anion which engages in facile Sn2 reaction with triflate 108 <03JOC9050>. Other examples of such stabilized epoxide anions include those derived from oxazolinyloxiranes (e.g., 110), which react with nitrones to provide the spirotricyclic heterocycles of type 112, Hydrolysis provides the epoxy amino acids 113, in which the carboxylic acid moiety was provided by the oxazoline nucleus and the amine functionality was derived from the nitrone <03OL2723>. A recent report has demonstrated that oxiranyl anions can also be stabilized by the amide functionality <03H(59)137>. 

Very diverse routes have been followed in the preparation of perhydro-oxazolo[3,2-a]pyridines, particularly those incorporating amide functions. Systems of type 226 have been obtained by the reaction between substituted A -oxazolines with diketene (66FRPI441937) and of 228, from the oxazoline (227) with azidoketene (77MII). 

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