Simple Direct Synthesis of New 1-Heterocyclamino-3-Carbonylaminopyrroles by Reaction of Heterocyclic Azoalkenes with β-Ketoamides

Pyrrole and several its derivatives have been subjected to extensive chemical investigations, while substituted 1-aminopyrroles remain a class of compounds about which relatively little is known due to the far from trivial problem sposed by their syntheis. In fact, 1-aminopyrroles appear to be prepared mainly by direct reactionfrom conjugated azoalkenes,2 that unfortunately represent a class of relatively little     

An efficient synthesis of 2-aminopyrroles from enaminone-amidine adduct and phenacyl/benzyl/heteroalkyl-halides

Herein, we report an efficient and facile synthesis of substituted 2-aminopyrroles from the reaction of enaminone-amidine adduct and various phenacyl, benzyl, or heteroalkyl halides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in good to excellent yields. The reaction proceeds through an intramolecular 5-exo trig cyclization resulting into diversely substituted 2-aminopyrroles.     

The synthesis of 5-arylpyrrolo[3,2-b]pyridines and 7-arylpyrrolo[3,2-b]pyridines: Addition of 3-aminopyrroles to aryl enaminones

A series of 5-arylpyrrolo[3,2-b]pyridines 1 was synthesized by addition of 3-aminopyrroles to aryl enaminones. One example of a 7-arylpyrrolo[3,2-b]pyridine 2 was obtained as a minor product along with the 5-aryl isomer, by a modification of the reaction sequence.     

An effective new synthesis of 2-aminopyrrole-4-carboxylates

Efficient syntheses of 2-aminopyrroles are presented starting from β-dicarbonyl compounds, bromoacetonitrile, and amines. Alkylation of β-dicarbonyl compounds with bromoacetonitrile furnished α-cyanomethyl-β-dicarbonyl compounds. The condensation reaction of α-cyanomethyl-β-dicarbonyl compounds with amines catalyzed by p-TsOH affords the corresponding enamines in good yields. Base catalyzed cyclization via the addition of an amine moiety to the carbon-nitrogen triple bond of nitrile furnished 2-aminopyrroles in high yields.     

Synthesis of Water-Soluble α-Aminopyrroles, 1-(2-Amino-1H-pyrrol-3-yl)pyridinium Chlorides

Russian Journal of General Chemistry - A method for the synthesis of water-soluble α-aminopyrroles, 1-(2-amino-1H-pyrrol-3-yl)pyridinium chlorides, by the reaction 1-(cyanomethyl)pyridinium...     

The first example of tautomerism in 2-aminopyrroles: effect of structure and solvent

Amino/imino tautomerism is observed in secondary 2-aminopyrroles when an electron-withdrawing group is on the amino group. The amino tautomer was favored in solvents that were hydrogen bond acceptors.     

Rearrangement of O-vinyl-α-(amino-carbonyl)acetamidoximes to 2-aminopyrroles and 2-pyrrolinones

Rearrangement and cyclization of O-vinyl-α-(aminocarbonyl)acetamidoximes gives two isomeric 2-aminopyrroles and/or 2-pyrrolinones and this depends on the rearrangement route. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1328–1334, September, 2007.     

Facile,eco-friendly,catalyst-free synthesis of polyfunctionalized 2-aminopyrroles

Simple and eco-friendly synthesis of polyfunctionalized 2-aminopyrroles from vinyl azides and α-cyano derivatives has been accomplished with a good to excellent yield. The reaction was performed in ethanol/water co-solvent system without catalyst and the workup was facile. A plausible mechanism has been proposed.     

‘Interrupted’ diazotization of 3-aminoindoles and 3-aminopyrroles

‘Interrupted’ diazotization of 3-aminoindoles and 3-aminopyrroles, achieved by quenching with cold water immediately after the addition of nitrite, led, in good yields, to stable compounds whose structures were identified to be the diazonium species with nitrate as the counter ion, which show no saline character.     

Effect of the leaving group on the reaction of 2-aminopyrroles with electron deficient heteroaromatic azadienes: substitution by addition-elimination versus cycloaddition

When a good leaving group is present in the heteroaromatic azadiene, reaction with 2-aminopyrroles occurs by substitution by addition-elimination instead of cycloaddition. This novel reaction is sensitive to steric effects and takes place in 2-amino-1-methylpyrrole at C-5 and the exo amino group but at C-3 in 2-amino-1-t-butylpyrrole.     

One-pot multicomponent synthesis of diversely substituted 2-aminopyrroles. A short general synthesis of rigidins A, B, C, and D

Privileged medicinal scaffolds based on the structures of tetra- and pentasubstituted 2-aminopyrroles were prepared via one-pot multicomponent reactions of structurally diverse aldehydes and N-(aryl-, hetaryl-, alkylsulfonamido)acetophenones with activated methylene compounds. This methodology was used in a four-step synthesis of alkaloids rigidins A, B, C, and D in overall yields of 61%, 58%, 60%, and 53%, respectively. Of these, rigidins B, C, and D were synthesized for the first time.     

Aromatic ring synthesis by N-aminopyrrole Diels-Alder reaction. Characterization of the heteroatom fragment

Aminonitrenes are produced on reaction of $\text{N}$-aminopyrroles with dimethyl acetylenedicarboxylate; a new reaction of dialkyl aminonitrenes is described.     

Reactivity of aminopyrroles: Protonation

The behaviour of 2- and 3-aminopyrroles towards protonation is similar. In dimethyl sulphoxide/trifluoroacetic acid they are protonated at the exocyclic nitrogen, whereas in pure trifluoroacetic acid, protonation at the 5- and/or 3-position of the ring takes place.     

Unexpected behavior of the reaction between 1,2-diaza-1,3-butadienes and 3-dimethylaminopropenoates: a useful entry to new pyrrolines, pyrroles, and oxazolines

We observed a nucleophilic attack by the ene-amino carbon of 3-dimethylaminopropenoates at the terminal carbon of the azo-ene system of 1,2-diaza-1,3-butadienes. In tetrahydrofuran at 65 degrees C, this attack produced 1-aminopyrrolines with a high degree of cis-stereoselectivity by means of an unusual zwitterionic adduct intermediate followed by intramolecular ring closure. In toluene under reflux, 1-aminopyrrolines produced oxazoline-fused 1-aminopyrrolines. Oxazoline-fused 1-aminopyrrolines were directly obtained by reaction of 1,2-diaza-1,3-butadienes with 3-dimethylaminopropenoates in toluene under reflux. The ring opening of oxazoline-fused 1-aminopyrrolines in acidic or basic media provides highly substituted 1-aminopyrroles. 5-Unsubstituted 1-aminopyrrole derivatives were obtained from 1-aminopyrrolines under basic conditions by loss of dimethylamino and ester groups. We discuss the plausible mechanisms of the ring closure and opening.     

Beneficial effect of carboxylic acid additives on the Pd-catalyzed intramolecular N-arylation of 2-amino-3-(2-chlorophenylsulfonyl)pyrroles

Carboxylic acid additives have been shown to significantly improve the yield of the Pd-catalyzed intramolecular N-arylation of 2-aminopyrroles containing a 2-chlorophenylsulfonyl group at the 3-position to give a novel tricyclic ring system. Pivalic and phenylacetic acid provided the best yield enhancement, while acetic acid showed moderate enhancement. Other acids showed limited to no enhancement or even a detrimental effect on the reaction.     

Polyfluorobicyclo[2,2,2]octanes. Part III. Syntheses and reactions of new mono- di- and trihydrides and derived compounds

Fluorobicyclo[2,2,2]octanes as follows were made by fluorination with cobaltic fluoride :- 1H- and 2H- tridecafluoro- ; 1H,2H-, 1H,3H-, 2H,2H-, 2H,3H-, and 1H,4H- dodecafluoro-; 1H,2H,3H-, 1H,2H,4H-, and 1H,3H,3H- undecafluoro-; 2H,2H,3H,3H- decafluoro-. These afforded, by the appropriate dehydrofluorinations, dodecafluoro-; 1H- and 2H- undecafluoro-; 1H,2H-, 1H,3H-, and 1H,4H- decafluoro- bicyclo[2,2,2]oct-2-ene. Self-consistent nmr data confirmed all structures. 1H-Trideca- and 1H,4H-dodeca- fluorobicyclo[2,2,2]octanes possess acidic bridgehead hydrogens, which are reactive under basic conditions, and may be replaced by various functional groups. 1-Lithiotridecafluorobicyclo[2,2,2]octane, a remarkably stable perfluoroalkyl lithium derivative, survived many hours in refluxing ether, but slowly decomposed to 1- substituted undecafluorobicyclo[2,2,2]oct- 2-enes, via a transient intermediate, a bridgehead ‘olefin’ ‘violating’ Bredt's rule.     

Nuclear magnetic resonance studies of cytochalasin E and its decomposition product

The proton and carbon-13 nuclear magnetic resonance signals of cytochalasin E (1) were assigned with the aid of 1H-1H, 1H-13C and 1H-13C long-range chemical shift correlation spectroscopy spectra, and the structure of the decomposition product (2) generated under neutral conditions was determined.     

Synthesis and Structure of Novel Cyclohistidinopeptide Box

A novel tetra-histidine cyclopeptide was prepared through multi-step reactions from histidine and naphthalene diamine (Scheme 1). All new compounds were characterized by 1H, 13C, 1H-15N and 1H-13C HETCOR spectra.     

Low-lying excited states and nonradiative processes of the adenine analogues 7H- and 9H-2-aminopurine

We have investigated the UV vibronic spectra and excited-state nonradiative processes of the 7H- and 9H-tautomers of jet-cooled 2-aminopurine (2AP) and of the 9H-2AP-d(4) and -d(5) isotopomers, using two-color resonant two-photon ionization spectroscopy at 0.3 and 0.045 cm(-1) resolution. The S(1) ← S(0) transition of 7H-2AP was observed for the first time. It lies ～1600 cm(-1) below that of 9H-2AP, is ～1000 times weaker and exhibits only in-plane vibronic excitations. In contrast, the S(1) ← S(0) spectra of 9H-2AP, 9H-2AP-d(4), and 9H-2AP-d(5) show numerous low-frequency bands that can be systematically assigned to overtone and combinations of the out-of-plane vibrations ν(1)', ν(2)', and ν(3)'. The intensity of these out-of-plane bands reflects an out-of-plane deformation in the (1)ππ?(L(a)) state. Approximate second-order coupled-cluster theory also predicts that 2-aminopurine undergoes a "butterfly" deformation in its lowest (1)ππ? state. The rotational contours of the 9H-2AP, 9H-2AP-d(4), and 9H-2AP-d(5) 0(0)(0) bands and of eight vibronic bands of 9H-2AP up to 0(0)(0) + 600 cm(-1) exhibit 75%-80% in-plane (a∕b) polarization, which is characteristic for a (1)ππ? excitation. A 20%-25% c-axis (perpendicular) transition dipole moment component may indicate coupling of the (1)ππ? bright state to the close-lying (1)nπ? dark state. However, no (1)nπ? vibronic bands were detected below or up to 500 cm(-1) above the (1)ππ? 0(0)(0) band. Following (1)ππ? excitation, 9H-2AP undergoes a rapid nonradiative transition to a lower-lying long-lived state with a lifetime ≥5 μs. The ionization potential of 9H-2AP was measured via the (1)ππ? state (IP = 8.020 eV) and the long-lived state (IP > 9.10 eV). The difference shows that the long-lived state lies ≥1.08 eV below the (1)ππ? state. Time-dependent B3LYP calculations predict the (3)ππ? (T(1)) state 1.12 eV below the (1)ππ? state, but place the (1)nπ? (S(1)) state close to the (1)ππ? state, implying that the long-lived state is the lowest triplet (T(1)) and not the (1)nπ? state.     

Synthesis and NMR spectral studies of some 2,6-diarylpiperidin-4-one O-benzyloximes

Variously substituted 2,6-diarylpiperidin-4-one O-benzyloximes were synthesized by the direct condensation of the corresponding 2,6-diarylpiperidin-4-ones with O-benzylhydroxylamine hydrochloride. All the synthesized compounds are characterized by IR, Mass and NMR spectral studies. NMR spectral assignments are made unambiguously by their one-dimensional (1H NMR and 13C NMR) and two-dimensional (1H-1H COSY, NOESY, HSQC and HMBC) NMR spectra. All the synthesized compounds are resulted as single isomer, i.e., exclusively E isomer (9-14). The conformational preference of 2,6-diarylpiperidin-4-one oxime ethers with and without alkyl substituents at C-3 and C-5 has also been discussed using the spectral studies. The observed chemical shifts and coupling constants suggest that compounds 8-13 adopt normal chair conformation with equatorial orientation of all the substituents while compound 14 contributes significant boat conformation along with the predominant chair conformation in solution. The effect of oximination on ring carbons, their associated protons, alkyl substituents and ipso carbons are studied. Every proton in the piperidone ring of the oxime ether is observed as distinct signal due to oximination. The order of chemical shift magnitude in compound 8 is H-2a>H-6a>H-5e>H-3e>H-3a>H-5a. For 9-12, the order is H-6a>H-5e>H-2a>H-3a>H-5a, for 13, H-6a>H-2a>H-5e>H-3a>H-5a and for 14, the order is H-2a>H-6a>H-5e>H-3a>H-5a while the 13C chemical shift magnitude for 8-14 due to oximination is C-2>C-6>C-3>C-5.