Pyrrole dipole

Pyrrole is a five-membered aromatic heterocycle containing six n electrons. Five important resonance hybrid structures distribute the 7C-electron pair of the nitrogen atom over the four carbon atoms, and the dipole moment of pyrrole (1.84 daltons similar to water) in the gas phase is directed in a way to make the nitrogen atom the positive end of the dipole. Pyrrole carbon atoms are therefore extraordinarily rich in electrons (Gossauer, 1984). The H-NMR spectrum is of the expected AB type (Figure 6.2.1) the chemical shifts are similar to the ones of benzene. 

The dipole moment varies according to the solvent it is ca 5.14 x 10 ° Cm (ca 1.55 D) when pure and ca 6.0 x 10 ° Cm (ca 1.8 D) in a nonpolar solvent, such as benzene or cyclohexane (14,15). In solvents to which it can hydrogen bond, the dipole moment may be much higher. The dipole is directed toward the ring from a positive nitrogen atom, whereas the saturated nonaromatic analogue pyrroHdine [123-75-1] has a dipole moment of 5.24 X 10 ° C-m (1.57 D) and is oppositely directed. Pyrrole and its alkyl derivatives are TT-electron rich and form colored charge-transfer complexes with acceptor molecules, eg, iodine and tetracyanoethylene (16). 

Selenolo[3,2-6]pyrrole PE, 4, 1046 <77JOC2230> Selenolo[2,3-6]selenophene PE, 4, 1046 <77JOC2230) Selenolo[3,2-b]selenophene dipole moment, 4, 1049 (76AHC(19)123>... 

Ethylene, /3-(dimethylamino)-nitro-in pyrrole synthesis, 4, 334 Ethylene, dithienyl-in photochromic processes, 1, 387 Ethylene, furyl-2-nitro-dipole moments, 4, 555 Ethylene, l-(3-indolyl)-2-(pyridyl)-photocyclization, 4, 285 Ethylene, l-(2-methyl-3-indolyl)-l,2-diphenyl-synthesis, 4, 232 Ethylene, (phenylthio)-photocyclization thiophenes from, 4, 880 Ethylene carbonate C NMR, 6, 754 microwave spectroscopy, 6, 751 photochemical chlorination, 6, 769 synthesis, 6, 780 Ethylene oxide as pharmaceutical, 1, 157 thiophene synthesis from, 4, 899 Ethylene sulfate — see 2,2-dioxide under 1,3,2-Dioxathiolane... 

Pyrrole, 2-aeetyl-l-(2-hydroxyethyl)-5-nitro-cyelization, 4, 74 ipso substitution, 4, 243 Pyrrole, 2-aeetyl-l-methyl-dipole moment, 4, 194 photocyelization reaetions with 2,3-dimethylbut-2-ene, 4, 269 Pyrrole, 3-acetyl-4-methyl-Vilsmeier-Haaek formylation, 4, 222 Pyrrole, 2-aeetyl-3-nitro-reduction, 4, 297 Pyrrole, aeyl-basicity, 4, 207 isomerization, 4, 208 oximes... 

Pyrrole, 4-ethynyl-2-formyl-3-methyl-synthesis, 4, 222 Pyrrole, formyl-oxidation, 4, 289 reactions, 4, 292 with sulfoxides, 4, 293 synthesis, 4, 223, 274, 287 Pyrrole, 1-formyl-barrier to rotation, 4, 193 Pyrrole, 2-formyl-benzoylation, 4, 220 conformation, 2, 107 4, 193 diacetoxythallium derivative iodination, 4, 216 dipole moment, 4, 194 ketals, 4, 290 protonation, 4, 47 reactions... 

UV spectra, 4, 1044 Thieno[3,4-6]pyrroles reduction, 4, 1074 Thienop, 4- c]py rroles addition reactions, 4, 1060 dipole moment, 4, 1040 mass spectra, 4, 1045 oxidation, 4, 1063 reduction, 4, 1063... 

The electric dipole moments in units 1 X 10 18 e. s. u. of these molecules and their derivatives by hydrogenation measured19 in benzene solution are the following furan, 0.670 2,5-di-hydrofuran, 1.53 tetrahydrofuran, 1.68 pyrrole, 1.80 pyrroline, 1.42 pyrrolidine, 1.57 thiophene, 0.54 and tetrahydrothiophene, 1.87. We now give a very rough interpretation of these quantities based on the bond moments given... 

Pyrrole (68) also has 6n electrons in delocalised n orbitals, but here the nitrogen atom has to contribute two electrons to make up the six (thus becoming essentially non-basic in the process, cf. p. 73), and the dipole of pyrrole is found to be in the opposite direction to that of pyridine, i.e. with the positive end on nitrogen and the negative end on the nucleus ... 

Pagenkopf s group developed a novel domino process for the synthesis of pyrroles 4-183, which allows for the control over the installation of substituents at three positions and seems to be very suitable for combinatorial chemistry [62]. The process consists of a 1,3-dipolar cycloaddition of an intermediate 1,3-dipole formed from the cyclopropane derivative 4-181 with a nitrile to give 4-182 followed by dehydration and isomerization (Scheme 4.39). The yield ranges from 25 to 93 %, and the procedure also works well with condensed cyclopropanes. 

Arndtsen and coworkers [154] described the first Pd-catalyzed synthesis of miinchnones 6/1-318 from an imine 6/1-316, a carboxylic acid chloride 6/1-317 and CO. The formed 1,3-dipol 6/1-318 can react with an alkyne 6/1-319 present in the reaction mixture to give pyrroles 6/1-321 via 6/1-320, in good yields. The best results in this four-component domino process were obtained with the preformed catalyst 6/1-322 (Scheme 6/1.83). 

The reaction of 1 -phenyl-3-p-nitrophenylnitrile ylid (387) to methylenecyclo-propane 4 is the sole reported example of cycloaddition of this dipole type. The only product isolated from the reaction was the pyrrole 390, which arose via 389,... 

The reaction of 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

Note that the dipoles of furan and thiophene are opposite in direction to that in pyrrole. In furan and thiophene, there is a greater inductive effect opposing the resonance effect, whereas in pyrrole the resonance... 

Another nonclassical heterocycle, thienol3,4-cJpyrazole, was synthesized, utilizing the ability of mesoionic ring systems to act as 1,3 dipoles in cycloadditions. Condensation of IV-phenylsydnone (162) with dibenzoylacetylene formed 3,4-dibenzoyl-1-phenylpyrazole (163) (85%) with phosphorus pentasulfide in refluxing pyridine, this gave 85% of 2,4,6-triphenyIthieno[3,4-c]pyrazole (164) [Eq. (44)]. The synthesis of 5-methyl-l,3,4,6-tetraphenylthieno[3,4-c]pyrrole is also described. ... 

However, treatment of the precursor 74, where there is no substitution at C(4) (i.e., R = Me) led to a single [3+2] cycloadduct 75 with methyl acrylate. The unstable oxazolines 75, are considered to open spontaneously to their valence bond, 1,3-dipole tautomers 76, which are trapped in situ by the dipolarophile. Use of DMAD led to the formation of the expected 2,5-dihydropyrrole (77), but difficulties in isolation required DDQ aromatization to pyrrole 78 (Scheme 3.19). 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

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