Acetone pyrrole

If one heats acetone and pyrrole in the presence of catalytic amounts of acid, so-called acetone pyrrole is formed in over 80%i yield. This colorless, macrocyclic compound contains four pyrrole units which are connected by dimethylmethylene bridges, ft is formed by electrophilic-a-substitution of pyrrole by acetone, acid-catalyzed oligomerization, and spontaneous. 

The one-electron reduction of thiazole in aqueous solution has been studied by the technique of pulse radiolysis and kinetic absorption spectrophotometry (514). The acetone ketyl radical (CH ljCOH and the solvated electron e were used as one-electron reducing agents. The reaction rate constant of with thiazole determined at pH 8.0 is fe = 2.1 X 10 mole sec in agreement with 2.5 x 10 mole sec" , the value given by the National Bureau of Standards (513). It is considerably higher than that for thiophene (6.5 x 10" mole" sec" ) (513) and pyrrole (6.0 X10 mole sec ) (513). The reaction rate constant of acetone ketyl radical with thiazolium ion determined at pH 0.8 is lc = 6.2=10 mole sec" . Relatively strong transient absorption spectra are observed from these one-electron reactions they show (nm) and e... 

Pyrroles react with the conjugate acids of aldehydes and ketones to give carbinols (e.g. 67) which cannot normally be isolated but which undergo proton-catalyzed loss of water to give reactive electrophiles (e.g. 68). Subsequent reaction may lead to polymeric products, but in the case of reaction of pyrrole and acetone a cyclic tetramer (69) is formed in high yield. 

The precedent is strong for the involvement of oxetanes as Intermediates in carbonyl additions to pyrroles. " NMR evidence has been obtained far an oxetane adduct of acetone and N-methylpyrrole. The initial photoadduct was shown to rearrange readily on workup to the 3-(hydroxyalkyl)pyrrole derivative. 

The unsaturated tetraoxaquaterene (accompanied by linear condensation products) was first synthesized in 18.5% yield by the acid-catalyzed condensation of furan with acetone in the absence of added lithium salts. Other ketones also condensed with furan to give analogous products in 6-12% yield.A corresponding macrocycle was also prepared in 9% yield from pyrrole and cyclohexanone. The macrocyclic ether products have also been obtained by condensation of short linear condensation products having 2, 3, or 4 furan rings with a carbonyl compound. ... 

Solubility - The oxidized polymer (VIII) has a greater solubility than the original polymer (VII). It was found to be soluble in acetone, chloroform, benzene, DMF and DMSO. Unlike the polymer (VII), (VIII) was not soluble in formic acid or trifluoroacetic acid that was expected since the pyrrole moiety is less basic than pyrrolidine. In the oxidized polymer, the pair of unshared electrons on the nitrogen atom are contributing to the pyrrole ring aromaticity, therefore, unavailable for protonation as in the case of polymer (VII). A comparison of the solubilities is given in Table I. 

The /3-electrophilic additions of pentaamineosmium(ll) complexes bearing various 4,5-tf -coordinated pyrroles to carbonyl compounds have been reported by Harman and co-workers (Scheme 78). 1 1-Methylpyrrole complex, when reacted with benzaldehyde or its dimethylacetal in the presence of /-butyldimethylsilyl triflate (TBSOTf), afforded the corresponding aldol adduct 177 as a 1 1 ratio of diastereoisomers. Pyrrole, 1-methylpyrrole, or 2,5-dimethylpyr-role osmium complexes reacted with an excess of acetone in the presence of TBSOTf to give the O-silylated 377-pyrrolium aldol adducts 178, which may serve as intermediates for various other reactions. 

Unsubstituted acetone resists condensation with 2,3-diformylthiophene (71BSF1437) but, surprisingly, reacts with 3,4-diformylfuran, -thiophene, and -pyrrole or 1,2-diformylferrocene (Table II). The reactivity of hydroxy-acetone allows the preparation of heterocycle-fused tropolones. 

Thus, pyrrole and acetone react as shown above. This involves pyrrole acting as the nucleophile to attack the protonated ketone in an aldol-like reaction. This is followed by elimination of water, facilitated by the acidic conditions. This gives an intermediate alkylidene pyrrolium cation, a highly reactive electrophile that reacts with another molecule of nucleophilic pyrrole. We then have a repeat sequence of reactions, in which further acetone and pyrrole molecules are incorporated. The presence of the two methyl substituents from acetone forces the growing polymer to adopt a planar array, and this eventually leads to a cyclic tetramer, the terminal pyrrole attacking the alkylidene pyrrolium cation at the other end of the chain. 

The first example involving a rhodium catalyst in an ene reaction was reported by Schmitz in 1976. An intramolecular cyclization of a diene occurred to give a pyrrole when exposed to rhodium trichloride in isobutanol (Eq. 2) [15]. Subsequently to this work, Grigg utilized Wilkinson s catalyst to effect a similar cycloisomerization reaction (Eq. 3) [16]. Opplozer and Eurstner showed that a n -allyl-rhodium species could be formed from an allyl carbonate or acetate and intercepted intramolecularly by an alkene to afford 1,4-dienes (Eq. 4). Hydridotetrakis(triphenylphosphine)rhodium(l) proved to be the most efficient catalyst for this particular transformation. A direct comparison was made between this catalyst and palladium bis(dibenzylidene) acetone, in which it was determined that rhodium might offer an additional stereochemical perspective. In the latter case, this type of reaction is typically referred to as a metallo-ene reaction [17]. 

Similarly, methylation of pyrrolo-benzothiazepines 172 (Scheme 34, Section 2.3.1 (1994MI283)) and 307 (Scheme 66, Section 3.3.1.2 (2005FES385)) with methyl iodide in acetone in the presence of potassium carbonate proceeds regioselectively and produces N-methyl pyrrole derivatives as sole products. Methylation on the thiazepine ring nitrogen requires stronger base, i.e. potassium ferf-butoxide, to give dimethyl 174 and 311, respectively. 

The Knovenagel condensation under basic conditions was first investigated with D-glucosamine chlorhydrate (28.HC1) as the sugar. The condensation of this reducing amino sugar with pentane-2,4-dione 1 in aqueous acetone in the presence of sodium carbonate afforded the pyrrole derivative 29 in 85% yield [99] (Scheme 5). The reaction was extended to other 2-amino-2-deoxy-aldose and carbon nucleophiles [100-104]. 

Pyrrole reacts with aldehydes and ketones and an acid catalyst to form resins, probably linear polymers however, surprisingly, from an entrop-ic point of view, with acetone (propanone) and hydrochloric acid the product is a cyclic tetramer. Possibly the two methyl groups in the developing side chains force it to bend and thus bite its own tail (Scheme 6.7). 

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

It has been found that l,3-di(ethoxycarbonyl)allene reacts readily with such heterocyclic dienes as furan, pyrrole, and pyrone derivatives. The furan adduct 383, obtained in 87% yield, was hydroxylated, and after acetonation, was cleaved251 with ozone, to afford intermediate 384. An approach to the conversion of 384 into C-glycosyl compounds by hydride-promoted scission of the C-5-C-6 bond was disclosed.255... 

The quantitative assay for PBG and ALA (Bio Rad, Hercules, CA, USA) that is based on the classical method by Mauzerall and Granick may be used for determination of the porphyrin precursors. PBG is absorbed by the anion-exchange column and ALA by the cation-exchange column interferences are washed out. After elution from the column, ALA is derivatized by acetyl acetone to form a pyrrole. Both ALA and PBG are determined colorimetrically with the modified Ehrlichs reagent. Instead of this broadly used standard method ALA, but not PBG may be detected and quantified using amino acid chromatography. However, our experience has shown that this method is only valid for detecting massively increased concentrations of ALA. 

Figure 5. Profiles of volatiles for low-quality peanuts with contaminants, raw and roasted (I) ethanol (2) pentane (3) 2-propanol (4) acetone (5) methylene chloride (6) methyl acetate (7) 2-methylpropanal (8) chloroform (9) diacetyl (10) benzene (11) 3-methylbutanal (12) 2-methylbutanal (13) 2,3-pentanedione (14) fl-methyl-pyrrole (15) pyridine (16) toluene (17) hexanal (18) 2-methylpyrazine (19) 2-methylpyrrole (20) 2-heptanone (21) styrene (22) 2,5-dimethylpyrazine (23) 2-ethyl-5-methylpyrazine (24) 2-ethyl-3,6-dimethylpyrazine (25) phenylacetalde-hyde.

In their studies of the effect of solvent upon the N—H stretching frequency in pyrrole, Fuson and Josien [1] have shown the distinction between the solvent-solute interaction which is a function of dielectric constant alone [2, 3] and that which is more specific, involving N—H hydrogen bonding. The most pronounced frequency shifts are those caused by pyridine [4] (K—M N bonding) and by acetone (N—H 0 bonding). The choice of pyrrole for these studies was presumably partly governed by convenience since the N—H band in pyrrole is considerably more intense than in the more basic secondary amines. We have attempted an extension of this work in two directions ... 

The correlation with basicity will only appear in so far as there is an inverse correlation between proton-acceptor and proton-donor character in the amines concerned. (Zezyulinski [7] has suggested a converse correlation between the shifts in the N—It frequency of pyrrole and the basicity of acceptors, as solvents, from acetone to pyridine.)... 

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