N-Alkylpyrroles

Alkylphenols Alkyl polyglycosides N-Alkylpyrroles Alkyl thiophenes Alkyltins Alkynes... 

N-Alkylpyrroles may be obtained by the Knorr synthesis or by the reaction of the pyrrolyl metallates, ie, Na, K, and Tl, with alkyl haUdes such as iodomethane, eg, 1-methylpyrrole [96-54-8]. Alkylation of pyrroles at the other ring positions can be carried out under mild conditions with allyhc or hensylic hahdes or under more stringent conditions (100—150°C) with CH I. However, unless most of the other ring positions are blocked, poly alkylation and polymerisation tend to occur. N-Alkylation of pyrroles is favored by polar solvents and weakly coordinating cations (Na", K" ). More strongly coordinating cations (Li", Mg " ) lead to more C-alkylation. 

Carbon tetrachloride was also found to react with pyrryl potassium to give 3-chloropyridine, however the mechanism is obscure and would justify further investigation. In a preparatively useful reaction, pyrrole and chloroform in the vapor phase at 500-550° gave 3-chloro-pyridine (33%) and a little 2-chloropyridine (2-5%). No interconversion of the isomers occurred under these conditions, though pyrolytic rearrangement of N-alkylpyrrole to 3-substituted pyridines is considered to involve 2-alkylpyrroles as intermediates. There is some independent evidence that dichlorocarbene is formed in the vapor phase decomposition of chloroform. ... 

Reaction of ketocarbenoids with pyrrole and N-alkylpyrroles yields the product of formal insertion into the a-C—H bond (256) in many cases the -insertion product 257 is formed concomitantly, but generally in lower yield 238-241 >. The regioselectivity varies according to the catalyst, the diazo compound and the N-alkyl substituent. Some examples concerning the former two variables are given in Table 18 239 240). 

The trifluoroacetyl and acetyl groups show the same qualitative conformational preference, at least when bonded to N-alkylpyrrole (80JCR(S)42) and benzo[h]furan (840MR197). 

Furans can be converted into N- alkylpyrroles by heating with primary amines and alumina. Similar thermal conversions of furans and benzo[6]furans to their sulfur analogues in the presence of alumina or other metal oxide catalysts and hydrogen sulfide are also known. l,3-Diphenylbenzo[c]furan is converted into the thiophene by heating with phosphorus pentasulfide. The mechanism of these reactions is obscure. 

A further chracterization of these pyrrole type nitrogen compounds in the very weak base concentrate can be made by using the colorometric pyrrolic nitrogen value of 6.8% (Table III) as the value for a, -unsub-stituted pyrrole type compounds. This leaves 22.2% of the nitrogen in pyrroles and indoles which have both a- and -substitution. The affi-unsubstituted pyrroles and indoles also have no N-substitution because these N-substituted compounds would titrate as weak bases and not as very weak bases. The lack of N-substitution on the pyrroles and indoles is consistent with the research of Jacobson (18, 19) who reported that N-alkylpyrroles and N-alkylindoles thermally and irreversibly isomerize to give the a and alkyl isomers and therefore would not likely be present in crude shale oil. 

Hundreds of compounds have been identified in the volatile flavor components of processed foods. Hydrocarbons, alcohols, ethers, aldehydes, ketones, acids, acid anhydrides, esters, aromatic, lactones, pyrones, furans, pyridines, pyrroles, n-alkylpyrrole-2-aldehydes, pyrazines, sulfides, disulfides, thiols, thiophenes, thiazoles, trithiolanes, thialdine. ..etc. 

Alkyl substituents. The steric effect of 1-alkyl substituents in the pyrrole series has been demonstrated in, for example, Vilsmeier formylation reactions. Thus as the bulk of the alkyl substituent on nitrogen is increased (e.g. from Me to Bu ) so does the proportion of /3 substitution (70JCS(C)2573). A similar trend has been observed in a series of experiments on the trifluoroacetylation of N-alkylpyrroles with trifluoroacetic anhydride (80JCR(S)42). 

The behavior of 1-alkylpyrroles to autoxidation was studied by Smith and Jensen12 with 1-methyl-, 1-isopropyl-, and 1 -w-butylpyrrole. It was found that N-alkylpyrroles reacted much more slowly with oxygen than C-alkylpyrroles. The reactions were characterized by an induction period, during which the colorless liquid turned yellow and no oxygen uptake was detected successively an autocatalytic reaction took place. The simple oxidation products formed in the case of 1-methylpyrrole were isolated and the structures 10-13 assigned. 

The fact that the percentage of jS-aldehydes from Vilsmeier formylation of N-alkylpyrroles increases from M-methyl- to N-(f-butyl)pyrrole can be explained by the increasing steric shielding of the a-positions by an N-alkyl group in the same sequence (70JCS(C)2563) (Scheme 23). 

Thus, the calculated values of total energies of cationic cr-complexes formed by a- and /1-protonation of model molecules of N-phenylsulfonyl-and N-(4-nitrophenyl)pyrroles are consistent with experimental data concerning preferable reactivity of their a-positions, while the role of steric factors and charges on atoms should be considered for interpretation of the increase in percentage of jS-substituted derivatives on formylation of N-alkylpyrroles in the sequence Me[Pg.169]

Alkylation of N-heteroeycKc compoumb. Pyrrole can be N-alkylated sali ractorily by conversion to pyrrylthallium(I) by reaction with thallous ethoxide. This is a relatively stable solid the structure is uncertain. Reaction of this salt with an excess of an alkyl halide (or an alkyl tosylate) for 1-32 hr. at 20-60° gives N-alkylpyrroles in good yield. Alkylation of pyrrylmagnesium bromide gives isomeric 2- and 3-alkylpyrroles as the major products. 

With bulky N-alkylpyrroles, 2,4-dilithiated products can be obtained also . N-Aryl pyrroles provide both o- and a-lithiations " . 

N-alkylpyrroles are metallated much less easily than furan and thiophene. This is reflected in the higher temperature, longer reaction time and excess of the pyrrole derivative necessary to obtain a satisfactory yield in the subsequent alkylation (compare the metallation conditions with those in the preceding experiments). If no excess of A-methylpyrrole were used, THF would seriously compete with this substrate for butyllithium in the end stage of the metallation. In other experiments in this chapter (14, 39, 40) TV-methylpyrrole is metallated under different conditions, which permit a more economic use of this compound. 

Patterson and co-workers113 observed that the thermal rearrangement of N-alkylpyrroles led to a mixture of 2- and 3-alkyl derivatives and suggested that a 2JF/-pyrrole was an intermediate. Photolysis of the same class of compounds, using a low-pressure Hg lamp, led to isolable 2/f-pyrroles as well as 3-alkylpyrroles (Scheme 42).19,20 A chiral group migrates with some retention of optical activity,19 and an /V-(a-methallyl) derivative gave a mixture of a-methallyl and cis- and trans-crotyl products.20 The 3-isomer appears to arise from a direct [l,3]-shift rather than via the 2f/-pyrrole.20... 

Kou, C.T., and T.R. Lion. 1996. Characterization of metal-oxide-semiconductor field-effect transistor (MOSFET) for polypyrrole and poly(N-alkylpyrrole)s prepared by electrochemical synthesis. Synth Met 82 167. 

Diaz, A.F., J. Castillo, K.K. Kanazawa, and J.A. Logan. 1982. Conducting poly-N-alkylpyrrole polymer films. / Electroanal Chem 133 233-239. 

Zotti G, Zecchin S, Schiavon G, Vercelh B, Berlin A, Dalcanale E. Potential-driven conductivity of polypyrroles, poly-n-alkylpyrroles, and polythiophenes role of the pyrrole nh moiety in the doping-charge dependence of conductivity. Chem Mater 2003 15 4642-4650. 

Hydroxylamine hydrochloride and sodium carbonate in ethanol with pyrroles lead to dioximes of 1,4-dicarbonyl compounds [109], for example, 2,5-dimethyl-N-alkylpyrroles give the dioxime of hexane-2,5-dione (32) and primary amines R-NH2 ... 

We observed in Chapter 4 that unlike furan and thiophene derivatives, N-alkylpyrroles fail to form a DA adduct. Thus, from iV-methylpyrrole, an alkylation product 105 is isolated.Thus electrophilic substitution is the primary course of the reaction. (Also see Chapter 4.)... 

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