Pyrroles preparation from

Representatives of Pyrroles Prepared from Dialkyl Ketoximes... 

Representatives of Condensed Pyrroles Prepared from Oximes of Cyclic Ketones... 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

A mild and effective method for obtaining N- acyl- and N- alkyl-pyrroles and -indoles is to carry out these reactions under phase-transfer conditions (80JOC3172). For example, A-benzenesulfonylpyrrole is best prepared from pyrrole under phase-transfer conditions rather than by intermediate generation of the potassium salt (81TL4901). In this case the softer nature of the tetraalkylammonium cation facilitates reaction on nitrogen. The thallium salts of indoles prepared by reaction with thallium(I) ethoxide, a benzene-soluble liquid. 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Pyrroles and indoles can be protected with the r-butyldimethylsilyl group by treatment with TBDMSCl and n-BuLi or NaH. Triisopropylsilyl chloride (NaH, DMF, 0°-rt, 73% yield) has been used to protect the pyrrole nitrogen in order to direct electrophilic attack to the 3-position.It has also been used to protect an indole.This derivative can be prepared from the silyl chloride and The silyl protective group is cleaved with Bu4N F , THF, rt or with CF3COOH. 

Pyrrolealdehyde has been prepared from pyrrole, chloroform, and potassium hydroxide from pyrrolemagnesium iodide and ethyl, propyl, or isoamyl formate and, by the method here described, from pyrrole, phosphorus oxychloride, and dimethylformamide. Smith has suggested a possible intermediate in this process. The method has also been applied to substituted pyrroles and is similar to that described in this series for the preparation of -dimethylaminobenzaldehyde from di-methylaniline. ... 

Pyrryl)selenazole is protected for the same purpose, by another patent. This is stated to be prepared from 2-chloroacetyl-pyrrole with selenoamides by analogy with the corresponding thiazole. No concrete example of the reaction is given. 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

A similar synthesis starting with l-(2-nitrobenzyl)pyrrol-2-aldehyde used ethanol-ethyl acetate as solvent (62). Indoles are prepared in excellent yield by hydrogenation of o-nitrobenzyl ketones over Pd-on-C (i). Azaindoles are correspondingly prepared from nitropyridines (97). 

Benzoisobacteriochlorin 14 can be prepared from nickel(II) chlorin 12 by vinylogous Vilsmeier reaction to give 13 and subsequent acid-induced cyclization.22 The chlorin 12 is, as expected, alkylated in a meso position adjacent to the reduced pyrrole ring. 

The pyrrolotriazines 32 were prepared from 3,4-dihydro-5-ethoxy-2//-pyrrole 31 by sequential reaction with hydrazine hydrate and a-oxoesters (85GEP3340026). They are useful as selective herbicides (Scheme 10). 

Most 2,5-unsubstituted pyrroles and thiophenes, and most anilines can be polymerized by electrochemical oxidation. For pyrroles, acetonitrile,54 or aqueous55 electrolyte solutions are normally used, while the polymerization of thiophenes is performed almost exclusively in nonaqueous solvents such as acetonitrile, propylene carbonate, and benzonitrile. 0 Polyanilines are generally prepared from a solution of aniline in aqueous acid.21 Platinum or carbon electrodes have been used in most work, although indium-tin oxide is routinely used for spectroelectrochemical experiments, and many other electrode materials have also been employed.20,21... 

The synthesis of N-phenyl-1,3,4,6-tetrahydrothieno(3,4-c)-pyrrole-2,2-dioxide (II) was carried out by reacting aniline with 3,4-bis(bromomethyl)-2,5-dihydrothiophene-l,1-dioxide (I). The latter compound was synthesized by the bromination of the cycloaddition product, prepared from 2,3-dimethyl-l,3-butadiene and sulfur dioxide (17). 

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

In 1988, Ono and Maruyama reported a very simple synthesis of octaethylporphyrin (OEP) from 3,4-diethylpyrrole-2-carboxylate, as shown in Eq. 10.44 49 Reduction of this pyrrole with LiAlH4 gives 2-hydroxyethylpyrrole, which is converted into OEP on treatment with acid and an oxidizing agent. This route is very convenient for synthesis of porphyrins. This method is now used extensively for synthesis of P-substituted porphyrins.50 For example, a highly conjugated porphyrin, shown in Eq. 10.45, has been prepared by this route.51 The requisite pyrroles are prepared from nitro compounds or sulfones thus, various substituents are readily introduced into porphyrins. 

Nitrogen-containing carbon replicas of SBA-15 and MLV prepared from pyrrole as carbon precursor... 

The most efficient synthesis is based on the reaction of phthalic anhydride with the sodium salt of the pyrrole the intermediate acid after cyclization generally provides high yields of 206 and/or its substituted derivatives. Tetrachloro derivative 212 was prepared from tetrachlo-rophthalic anhydride via acid 211 by this procedure [90JCS(P 1) 1463 ]. 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

The pyrrole-3-boronic acid 67 has been prepared from the 3-iodopyrrole by Muchowski and subjected to a range of Suzuki couplings to afford 2-arylpyrroles 68 [59]. Subsequent fluoride deblocking to give 69 occurs in excellent yield. 

Muchowski has utilized Af-TIPS-3-iodopyrrole to prepare a series of 3-alkynyl pyrroles 119 using standard Sonogashira conditions [59]. Pyrroles 120 were obtained after fluoride cleavage of the TIPS group. Similarly, 3,4-bis(alkynyl)pyrroles were prepared from N-TIPS-3,4-diiodopyrrole [59]. 

To make tryptophan analogs, Gronowitz and coworkers conducted a pyrrole annulation from an aminoiodopyrimidine utilizing the Larock indole synthesis conditions (see Section 1.10.) [80]. They prepared heterocondensed pyrrole 115 by treating 4-amino-5-iodopyrimidine 114 with trimethylsilyl propargyl alcohol under the influence of a palladium catalyst The regiochemical outcome was governed by steric effects. 

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

There is a case where the resnlts of the electrode and chemical oxidation coincide (see Scheme 2.20). Calix[8]pyrrole was prepared from 3,3, 4,4 -tetraethyl-2,2 -bipyrrole during oxidative electrolysis in dichloromethane nsing platinum anode, tetrabutylammonium hydrogen sulfate as the... 

In connection with the synthesis of cytohalasin B, a pyrrole derivative 13 was prepared from methyl (5)-3-aminophenylbutyrate (78JA7775). In connection with the synthesis of l,2,4-triazolo[4,3-a]pyrazine derivatives with human Renin inhibitor activity, a /3,y-diamino acid derivative was transformed into a pyrrolidin-2-one (91JMC151). 

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