Pyrrole with hydroxylamine

The chemical consequences of /3-protonation are illustrated further by the ring-opening reactions of furans with methanolic hydrogen chloride and of (V-substituted pyrroles with hydroxylamine hydrochloride (Scheme 11) (82CC800). 

Problem 20.16 Give the sequence of steps for the formation of the open-chain products from reaction of (a) 2,S-diethylfuran with acid (b) pyrrole with hydroxylamine, NHjOH Cl. ... 

The 2H- and 3Af-pyrrolium cations are essentially iminium ions and as such are electrophilic they play the key role in polymerisation (see 16.1.8) and reduction (16.7) of pyrroles in acid. In the reaction of pyrroles with hydroxylamine hydrochloride, which produces ring-opened 1,4-dioximes, it is probably the more reactive 37f-pyrrolium cation that is the starter. Primary amines, RNH2, can be protected, by conversion into l-R-2,5-dimethylpyrroles (16.16.1.1), recovery of the amine being by way of this reaction with hydroxylamine." ... 

The most useful general method for the C-acylation of pyrroles is the Vilsmeier-Haack procedure in which pyrrole is treated with the phosphoryl chloride complex (55a, b) of an AiA-dialkylamide (54). The intermediate imine salt (56) is hydrolyzed subsequently under mildly alkaline conditions to give the acylated pyrrole (57). On treatment of the imminium salt (56 R =H) with hydroxylamine hydrochloride and one equivalent of pyridine and heating in DMF, 2-cyanopyrrole (58) is formed (80CJC409). 

The major development in the Knorr pyrrole synthesis has been access to the amine component. For example, use of preformed diethyl aminomalonate with 1,3-diketones affords much higher yields of pyrroles 14. Reaction of 6-dicarbonyl compounds with hydroxylamine 0-sulfonic acid gives pyrroles 15 in one step. Weinreb a-aminoamides have found use in the Knorr pyrrole synthesis of a wide variety of pyrroles 16. °... 

General synthesis of pyrroles and 1-vinylpyrroles by the reaction of ketoximes with acetylenes and their synthetic equivalents (vinyl halides and dihaloethanes) in the presence of the strongly basic KOH/DMSO system (Trofimov reaction) has been reviewed ° in recent years. Therefore, in the present work this reaction will be described very shortly. In principle, pyrrole (51) synthesis can be carried out as a one-pot procedure by treating ketones (49) with hydroxylamine and then reacting the ketoximes (50) formed with acetylenes (equation 22). 

The fused pyrrole ring system (204) has been obtained by the reaction of 17/3-hydroxy-17-methylandrosta-l,4-dien-3-one with tosylmethyl isocyanide in the presence of sodium hydride in DMSO,92 and 17/3-hydroxy-17-methyl-7-oxa-5o -androstano-[3,2-c]- (205) or -[2,3-d]-isoxazoles (206 X = O) have been prepared by treating 7-oxa-2-(hydroxymethylene)-17/3 -hydroxy-17-methyl-5 a -androstan-3-one with hydroxylamine hydrochloride.93 In the presence of pyridine, the isox-azole (206 X = O) is formed, but when the reaction is catalysed by sodium acetate in acetic acid the isomeric steroid (205) results. Cycloaddition of hydrazine hydrate to the same 2-hydroxymethylene-7-oxa-steroid results in the [3,2-c]pyrazole (206 X = NH). A similar addition is encountered in the reactions between 3/3-hydroxy-16-(hydroxymethylene)-5a-androstan-17-one and the substituted hydrazines RNHNH2 (R = H, o-COC6H4NH2, or p-COQHUNH ,) when the corresponding [17,16-c]pyrazoles (207) are formed after cyclization of the intermediate hydrazones.94... 

In principle, the synthesis can be realized as a one-pot process treatment of ketones with hydroxylamine in KOH-DMSO following interaction of the formed ketoximes with acetylene. Various pyrroles with alkyl, cycloalkyl, aryl and hetaryl substituents, as well as pyrroles condensed with aliphatic macrocycles, terpenic and steroid structures, together with their vinyl derivatives now become available. 

Amino-3-(pyrrol-2-yl)isoxazoles 348 were selectively prepared by treatment of cyano-ethylthio-ethenylpyrroles 347 with hydroxylamine in methanol, probably through replacement of their SEt group with a hydroxylamino moiety. With carbamoyl derivatives 347 (R = CONH2), minor amounts of regioisomers 349 were also isolated and their formation was increased (12-48%) operating in the presence of aqueous NaOH (Scheme 84) <2005T4841>. 

Tamura, Y., Kato, S., Ikeda, M. One-Step Knorr pyrrole synthesis with hydroxylamine 0-sulfonic acid. Chem. Ind. 1971,767. 

Potassium carbonate One-step pyrrole ring synthesis with hydroxylamine-O-sulfonic acid... 

For general remarks regarding these reactions see p. VII. It is interesting to notice that among them are the small number of instances of nucleophilic attack upon the pyrrole nucleus the reductions to pyrrolines and the reactions with sodium bisulphite and with hydroxylamine. 

Liquid pyrrole and its derivatives can be cleaved by reaction with hydroxylamine in alkaline medium, leading to the oxime of succinic acid dialdehyde (107) this method was also used for the study of the structure of pyrrole homologs (108). Reduction of pyrrole and its homologs with... 

In this case, 3-aminoisoxazoles are likely formed due to the opening of the pyr-rolizine ring that leads to 2-(l-ethylthio-2-carbamoyl-2-cyanovinyl)pyrroles with the di-configuration of nitrile and NH groups and (after reaction with hydroxylamine) intermediates B, which further cyclize to the isoxazoles (Scheme 2.116). 

The only pathway of the reaction of pyrrolizines bearing a nitrile group, 3-imino-2-pyrrolizinecarbonitriles, with hydroxylamine in methanol is the substitution of an ethylthio moiety for hydroxylamine to deliver l-hydroxylamino-3-imino-2-pyrro-lizinecarbonitriles (Scheme 2.119, Table 2.13) [582]. The latter are unstable in DMSO solutions and gradually transform to 2-(l-hydroxylamino-2,2-dicyanovinyl)pyrroles. 

Reactions of Pyrrole-2-carbaldehydes with Hydroxylamine, Semicarbazide, Thiosemicarbazide, and Aminoguanidine... 

It has been found [648] that such route of N-vinylpyrroles hydrolysis can be realized only in the dilute solutions if the released acetaldehyde is coupled (e.g., by the reaction with hydroxylamine). Under normal conditions, however, complex acid-catalyzed and oxidative condensation reactions of the initial and formed pyrroles with acetaldehyde as well as between pyrroles themselves take place. Consequently, mixtures of deeply colored oligomers, the composition of which depends on the hydrolysis and isolation conditions, are formed. On the basis of the literature data [1,2,627], spectral (IR, NMR, and ESR) characteristics, and the results of elementary analysis, it has been assumed [648] that these mixtures contain fragments A-D (Scheme 2.189). 

Complete Synthesis of Succindialdehyde. JACS, 68, 1608 (1946). In a 2 liter 3 necked flask equipped with a stirrer, reflux condenser, and an addition funnel, is mixed 1 liter of ethanol, 67 g of freshly distilled pyrrole, and 141 g of hydroxylamine hydrochloride. Heat to reflux until dissolved, add 106 g of anhydrous sodium carbonate in small portions as fast as reaction will allow. Reflux for 24 hours and filter the mixture. Evaporate the filtrate to dryness under vacuo. Take up the residue in the minimum amount of boiling water, decolorize with carbon, filter and allow to recrystallize in refrigerator. Filter to get product and concentrate to get additional crop. Yield of succinaldoxime powder is a little over 40 g, mp is 171-172°. 

In the course of redox pyrrolization of the oxime 39 with X = OH, the hydroxyl group in position 5 is vinylated to a slight extent to form 1-vinyl-5-vinyloxy-4,4,6,6-tetramethyl-4,5,6,7-tetrahydro-5-azaindole (40, X = OCH=CH2). This was the first example of nucleophilic addition of hydroxylamine to a triple bond not activated by strong electron-withdrawing substituents. x... 

Reduction of T [l-(2-nitrophenyl)-l//-pyrrol-2-yl]sulfonyl -acetone or -1-phenylethan-l-one with sodium borohy-dride and 5% palladium on carbon, a reagent known to convert aromatic nitro compounds to hydroxylamines, triggers intramolecular interaction and gives pyrrolo[l,2- ][3,l,6]benzothiadiazocine derivatives 90 (Equation 11 <2001MI1405, 2004T8807>). This method was further successfully applied to the reductive cyclization of 2- [l-(2-nitrophenyl)-17/-pyrrol-2-yl]sulfanyl acetonitrile. 

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