Pyrrole-2-carboxaldehydes

Reaction between [W(RC=C)Cl(CO)2(py)2] (R = Ph, Me) with the anionic chelating Schiff base pyrrole-2-carboxaldehyde methylimine yields the cationic complexes [NEt4][W(RCCO)(NN)2(CO)] (where NN is the dianion of the pyrrole ligand). These complexes react with methyltriflate, forming the neutral acetylenic complexes [W(NN)2(CO)(RC=COMe)] (87OM1503). One of the pyrrolic Schiff bases is coordinated via the pyrrole and imino nitrogen atoms, and another one only via the imino nitrogen atom. 

An interesting approach to the pyrrolizidine skeleton was devised wherein pyrrole-2-carboxaldehyde (70) underwent A-allylation under basic conditions and subsequent olefmation with ethyl p-tolylsulfinylmethanephosphonate to produce the pyrrolyl alkene 71 <00TL1983>. Intramolecular Heck reaction of the iodo species then produced the 1 -p-tolylsulfinyl-1,3-diene 72. 

The aziridine 101 derived from pyrrole-2-carboxaldehyde was found to undergo a further unusual transformation when treated with trifluoroacetic acid (TFA) at room temperature, giving the 5//-pyrrolo[l,2-r ]imidazole 102 in good yield. The cyclization is initiated by protonation of the carbonyl group (Scheme 10) <2000TL4991>. 

Dehydrative condensation of pyrrole-2-carboxaldehyde 77 and ethyl carbazate afforded carbethoxyhydrazone 78 in quantitative yield. Cyclization of 78 in the presence of a catalytic amount of sodium hydride (10mol%) in dimethyl-formamide (DMF) at 100°C led to the formation of pyrrolo[l,2-tf][l,2,4]triazin-4-one 27 in 75% yield (Scheme 8) <1999T13703>. 

Condensation of A-protected pyrrole-2-carboxaldehyde with ethyl a-amino-/3, -diethoxypropionate followed by reduction and cyclization in the presence of TiCU afforded the pyrrolo[2,3-c]pyridine derivative 70 in excellent yield (93T8139). 

Pyrrole units form part of the coordinating entities of Schiff base ligands derived from pyrrole 2-carboxaldehyde, for example in the iron(II) complex of the ligand derived from pyrrole 2-carboxaldehyde and trien, which is low-spin despite the feeble coordinating properties of the pyrrole—CH=N— units. The synthesis, structure, and spectroscopic and electrochemical properties of tris-ligand iron(III) complexes of phenyldipyrromethenate (dipyrrin, (129)), and its... 

As written, the reaction is endothermic by ca 30 kJmoD. Pyrrole and pyridine are both 6-71 nitrogen-containing heterocycles. However, the former is electron-rich while the latter is electron-deficient and so conjugative stabilization mechanisms are different for the two species. Furthermore, the former can form one more hydrogen bond per molecule than the latter, a feature that may account for pyrrole-2-carboxaldehyde being a solid while pyridine-2-carboxaldehyde is a liquid. We wonder if either difference accounts for the profound lack of thermoneutrality for the above reaction. 

In addition to the protected pyrroles mentioned above, the 1-azafulvene dimer formed by Mannich reaction of pyrrole-2-carboxaldehyde with di-methylamine has also been successfully lithiated adjacent to both pyrrole nitrogens (Scheme 10). Reaction with electrophiles and subsequent hydrolysis leads to 5-substituted pyrrole-2-carboxaldehydes in good yield [88TL777 92JOM(423)173]. 

Other examples of N-substituted 3-bromopyrroles that have been successfully derivatized at the 3-position include either 4- or 5-substituted-3-bromo-l-tosylpyrroles 5 (90TL6785 91T7615) 3-bromo-l-tritylpyrrole 6 (91UP1) and the bromo-azafulvene dimer , which leads to 4-substituted pyrrole-2-carboxaldehydes 8 after reaction with electrophiles and hydrolysis (88TL3215). 

Pyrrole-2-carboxylic acid esters have been prepared from ethyl chloroformate and pyrrolylmagnesium bromide1 2 or pyrrolyllithium,3 by hydrolysis and decarboxylation of dimethyl pyrrole-1,2-dicarboxylate followed by re-esterification of the 2-acid4 and by oxidation of pyrrole-2-carboxaldehyde followed by esterification with diazomethane.4... 

Pyrrole, 2-acetyl-1-ethyl Sd (roasted) Pyrrole, 2-acetyl-N-methyl Sd (roasted) Pyrrole, 2-carboxaldehyde Sd Hu ... 

In an effort to explore the chemistry of pyrrolodiazines and their quatemized salts (see Section 6.2.2.2), Alvarez-Builla and co-workers prepared a series of pyrrolo[l,2-c]pyrimidines via methodology developed in their laboratory <99JOC7788>. Cyclocondensation of tosylmethyl isocyanide with substituted pyrrole-2-carboxaldehydes 17 produced pyrimidine derivatives 18 sifter removal of the tosyl group. The key to this procedure was the use of tosylmethyl isocyanide, which provided a relatively easily removed tosyl group in comparison to the more problematic decarboxylation of a carboxylic acid functionality. 

The higher stability of the N(H),0-ds form has also been reported for pyrrole-2-carboxaldehyde (63JA3886 74BSF2677 74JST(23)93 ... 

Pyrroles are found in the volatiles of most heated foods [29], although they have received less attention than some other classes of aroma volatiles. Some pyrroles may contribute desirable aromas, e.g. 2-acetylpyrrole has a caramel-like aroma, and pyrrole-2-carboxaldehyde is sweet and corn-like, but alkylpyrroles and ac-ylpyrroles have been reported to have unfavourable odours [22]. Many more volatile pyrroles have been found in coffee than in other foods [30], and they are common products of amino acid-sugar model systems. Pyrroles are closely related in structure to the furans, and they are probably formed in a related manner from the reaction of a 3-deoxyketose with ammonia or an amino compound followed by dehydration and ring closure (cf Scheme 12.2). 

For the preparation of the Gly analogue 8 (R1 = H) pyrrole-2-carboxaldehyde was reacted with bromoacetic acid followed by reduction with NaCNBH3 as described above mp 170-172 °C.[1141... 

Pyrrolo[2,1 -d][ 1,5]benzothiazepine-6-carboxylic acid (27) was obtained via base-catalyzed cyclization of pyrrole-2-carboxaldehydes 26 and 28, each synthesized by Vilsmeier-Haack formylation of their respective pyrroles 24 and 25, prepared in turn by condensation of 18, respectively, with ethyl bromoacetate and chloroacetonitrile in the presence of sodium ethylate at room temperature. When treated with piperidine in refluxing benzene for 48 hours, 26 and 28 afforded ester 29 and nitrile 31 from which, in an alkaline medium, acid 27 could be obtained. Under similar experimental conditions, acid 27 was also formed from amide 30 (Scheme... 

Triphenylphosphine was employed as a nucleophilic catalyst for the umpolung addition of azoles (225) to the electron-deficient allenes (226 R1 = H, R2 = OEt, R3 = H, Et) to afford the addition products (227). This organocatalytic methodology has been extended to addition-cyclization reactions between electron-deficient allenes or alkynes and pyrrole-2-carboxaldehyde in the presence of a catalytic amount of tri-butylphosphine, giving the substituted indolizine-7-carboxylates (228 R2 = OEt, Me R3 = H, Et).265... 

In 2011, Singh et al. have reported the synthesis of meso-functionalized dipyrromethanes (11SC3491) 261 (X = NH) (Scheme 101) as well as unsym-metrical bis(heterocyclyl)methanes through Grignard addition of various aliphatic and aromatic halides on pyrrole-2-carboxaldehyde, followed by BF3 OEt2-catalyzed condensation of pyrrole-2-carbinols with pyrrole, etc. 

Some pyrrole derivatives have pleasant flavor. For example, pyrrole-2-carboxaldehyde gives a sweet and corn-like odor and 2-acetylpyrrole has caramel-like flavor. However, some pyrroles have been found to contribute to off-flavor of food products (24). Pyrroles have not received as much attention as flavor components as other heterocyclic Maillard reaction products such as pyrazines and thiazoles even though the number of derivatives identified is almost the same as that of pyrazines (Figure 1). Proposed formation mechanisms of pyrroles in the Maillard reaction systems are similar to those of thiophenes (Figures 2). 

Yanagimoto el a/.458 examined the antioxidative activity of heterocyclic MRPs in inhibiting the oxidation of hexanal by air. Of the three pyrroles, three furans, two thi-azoles, three thiophenes, and two pyrazines tested, pyrrole-2-carboxaldehyde was by far the most active, closely parallelling BHT in giving about 100% inhibition at 50 fig mL 1 and about 90% at 5 fig ml.. ... 

Although the Schiffbase (pyrol)3tren) (17) formed by condensation of pyrrole-2-carboxaldehyde with 2,2, 2"-tris(ethylamino)amine is potentially heptadentate the neutral low-spin complex [Fe (py-rol)3 tren ] has a six-coordinate (trigonally distorted octahedral) structure, the distance between the metal atom and the central tertiary aliphatic nitrogen being greater than the van der Waals contact... 

Although the 2,3,4,6-tetrahydro-l,l -methylene-2,2 -pyrromethen-5[l-//]-one (190) is not strictly a perhydropyrrolo[l,2-c]pyrimidine, it carries the essential features of this ring system. Synthesis was effected by treatment of pyrrole-2-carboxaldehyde (186) with diiodomethane in the presence of a base to give 187 which was oxidized to 188 by w-chloroper-benzoic acid. Intramolecular condensation of 188 gave 189 which was... 

Pyrrok[IJ-i -as-triaziae. This IO -heteroaromatic system (2) has been synthesized by the base-catalyzed cyclodehydration of pyrrole-2-carboxaldehyde formyl-hydrazone (I) in refluxing xylene in 56% yield. 

From the methylated pectin, the main pyrolysis compound seems to be 4-(hydroxymethyl)-butyrolactone. Two main nitrogenous compounds are formed from amidated pectin, hydroxypyridine and pyrrol-2-carboxaldehyde. Their formation can be explained by the foilowing reactions ... 

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