Hydrazines polymer-supported

As mentioned before for other azolide reactions, acylations can be carried out with polymer-supported azolides as acylating reagents. For example, acetic acid hydrazide can be prepared with a polymer of l-acetyl-4-vinyl-imidazole/divinylbenzene (96 4) and hydrazine (no diacylation occurs when this method is used) [122]... 

Polymeric hydrazides are obtained in quantitative yield by the reaction of hydrazine with polymer-supported benzotriazolides.[172] (R may be H or CH3, X preferably CONH(CH2)5 or COQH4) ... 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

Thiamine-catalyzed transformations are reversible, thus TV,/V-dialkyl hydrazones were selected as alternative acyl anion equivalents that were reported to react with electrophiles without acidic activation.41 One especially reactive example, formaldehyde hydrazone resin 13, was constructed from polymer-supported hydrazines and was employed in the first polymer-supported, uncatalyzed acyl anion additions (Fig. 8).38 As test substrates, nitroalkenes (as Michael acceptors) and activated aldehydes were selected. Reactivity of these acyl anion equivalents depended critically not only on the nature of the starting hydrazine, but also on the protocol for hydrazine formation. 

A robust catch, cyclize, and release preparation of 3-thioalkyl-1,2,4-triazoles mediated by the polymer-bound base P-BEMP has been described <02TL5305>. Reaction of solid-supported hydrazides 103 with isocyanates or isothiocyanates followed by base-induced cyclization/cleavage afforded 1,2,4-trisubstituted urazoles and thiourazoles 104 <02JCO491, 02TL3899>. Polymer-supported V-acyl-1 //-benzotriazole- 1-carboximidamides 105 reacted with hydrazines followed by acidic cyclizative release to give 3-alkylamino-l,2,4-triazoles 106 <02OL1751>. 

Generation of a-ketoenamines (Table 8, entry 8) [456] Spivey et al. [456] performed a pyrazole synthesis with a polymer-supported acetophenone and a germanium-based traceless linker. The support-bound acetophenone was allowed to react with dimethylformamide dimethyl acetal (Bredereck s reagent) [498]. Subsequent reaction of the resulting a-ketoenamine with aryl hydrazine hydrochlorides gave the pyrazoles. 

Hydrazine, DMF, 2 h, 100% yield. This method was used to remove the TCP group from polymer supported peptides. 

In the dehydration of aldehydes to form nitriles, Ley and colleagues used a polymer-supported hydrazine (Scheme 6.3). The immobilized hydrazine was reacted with aldehydes to give a hydrazone. Subsequent oxidation with mCPBA (meta-chloroperoxybenzoic acid) rendered the corresponding N-oxide, which spontaneously eliminated to form the desired nitrile [10]. Polyvinylpyridine was used as a scavenger for excess mCPBA. 

For deava of the peptide fi-om the polymer three methods were su te (1) Hydro i bromide in trifluoroacetic add with the suspended polymer support, (2) hydro n bromide in a benzene solution of the carrier, and (3) anhydrous hydrazine in dimethylformamide with heating. The method was illustrated by the syntheds of Ala-He-Arg-Ser-Ala and the authors emphasize the much greater flexibility of the liquid-phase method in terms of the coujding techniques which can be used. 

This multi-step, one-pot process was taken further by integration of a third supported reagent for the sequential preparation of 3,5-diphenylpyrazole (Scheme 2.17). Following the previously established procedure, acetophenone was deprotonated and acylated to afford the 1,3-dicarbonyl species. This intermediate was easily separated from the spent polymers by filtration and passed without isolation into a suspension of the resin bound hydrazine salt (9), affording the desired pyrazole in 91% yield. In a subsequent publication, the authors reported that the depleted polymeric reagents from the first step of the conversion (i.e. (7) and (8)) were recovered and separated via a selective flotation procedure, enabhng them to... 

The polymer-bound p-nitrobenzophenone oxime (71d) has been found to be a suitable support for stepwise peptide synthesis. Protected peptides can be assembled on 70d by coupling and deprotection steps similar to those employed in the usual Merrifield solid-phase procedures (Scheme 39). Cleavage of peptides from 71d can be accomplished with hydrazine and amino acid esters under mild conditions, which do not affect benzyl ester side-chain protecting groups. 

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