Methyl 4-methylpyrrole-2-carboxylate

The Barton-Zard pyrrole synthesis has now been extensively applied to synthesis of natural and unnatural products containing pyrrole units. Methyl 4-methylpyrrole-2-carboxylate is the trail-maker pheromone of the Texas leaf-cutting ant Atta texana.24 It is readily prepared by the Barton Zard method in 60% yield (Eq. 10.22).22... 

Acromyrmex ubterraneus subterraneus W-VG Trail following Methyl 4-methylpyrrole-2-carboxylate 64 [158]... 

Within Hymenoptera, pheromones produced by workers in social colonies are the best studied across many genera, principally in ants [6], with those eliciting trail following most extensively studied. The distinct behavior and the relative ease of the bioassay have resulted in chemical identifications in many species [ 113,114]. Those that have been recently identified are listed in Table 5. In addition, several alarm and recruitment signals have recently been identified. Many of the compounds recently identified in ants have previously been reported as trail or alarm pheromones in other ant species. For example, methyl 4-methylpyrrole-2-carboxylate 64, 3-ethyl-2,5-dimethylpyrazine 65, (9Z)-hexadec-9-enal 66,4-methylheptan-3-ol 67, and methyl 6-methylsalicy-late 68 have been identified as trail pheromone components, and heptan-2-one 69,4-methylheptan-3-one 70, formic acid 71, undecane 61,4-methylheptan-3-ol 67, methyl 6-methylsalicylate 68, and citronellal 72 have been identified as alarm pheromone components [6]. The use of the same chemicals across genera, with some used for very different functions, is an interesting phenomenon. 

Methyl 4-methylpyrrole-2-carboxylate, trail pheromone of the leaf-cutting ant... 

Methyl 4-methylpyrrole-2-carboxylate (Ar7) was the first trail pheromone identified in ants. It is used by Atta texana,231 Atta cephalotes232 and Acromyrmex octospinosus233 Two Metapone ant species use the unsubstituted derivative Ar40 as the trail pheromone.234 Methyl nicotinate (Ar41) is the minor component of the trail pheromone of an Aenictus sp.196... 

A trace constituent in the venoms of the myrmicines Atta texana, A. cephalotes, A. sexdens, and Acromyrmex octospinosus is methyl 4-methylpyrrole-2-carboxylate (X) ( 13, L4, lj[). This simple pyrrole... 

Insect pheromones, which serve to convey messages between insects, have been isolated from many species and found to be both highly specific, and effective in mere traces. They are often aliphatic compounds, such as the termites trailfollowing substance, dodecatrien-l-ol, but that secreted by the town ant is methyl 4-methylpyrrole-2-carboxylate, and several ant and beetle pheromones are derivatives of pyrazine (Barlin, 1982). 

Methyl 4-methylpyrrole-2-carboxylate (Figure 9.16) is non-basic. It is the trail pheromone of some leaf-cutting ants. It is probably made from leucine by oxidation and cyclization. 

Methyl-3-heptanone (386a, Scheme 68), the alarm pheromone of the Texas leaf-cutting ant (Atta texana) was synthesized by Riley et al 173, 174) and required resolution of the intermediate, racemic 2-methyl-4-pentenoic acid (384). A convenient synthesis of methyl 4-methylpyrrole-2-carboxylate (392), the trail pheromone of A. texana, has been reported by Sonnet (775) (Scheme 69). Formylation of ester (390) with CUCHOMe and AICI3 gave predominantly the desired 4-formyl derivative (391). 

Methyl pyrrole-l-carboxylate (14) and hot dimethyl acetylenedi-carboxylate give trimethyl pyrrole-1,3,4-tricarboxyIate (15) and acetylene, presumably through the addition-elimination sequence shown. Dimethyl acetylenedicarboxylate and 1-methylpyrrole com-... 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyi-l-methylpyrrole and with 3-formylindole produces (443 Hetero= l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

Methyl 4-Amino-l-methylpyrrole-2-carboxylate Hydrochloride Salt (5) 1 01... 

Methyl 4-amino-l-methylpyrrole-2-carboxylate hydrochloride (5 340 g, 1.78 mol) was dissolved in 10% aq Na2C03 (1L) in a 3-L flask equipped with a mechanical stirrer Boc20 (400 g, 1.83 mol) slurried in dioxane (500 mL) was added over a period of 30 min while a temperature of 20 °C was maintained. The reaction was allowed to proceed for 3 h and was determined complete by TLC the mixture was cooled to 5 °C for 2 h and the resulting white precipitate collected by filtration. The product, which was contaminated with Boc20, was used without further purification for the next step. 

Crude methyl 4-(ferf-butoxycarbonylamino)-l-methylpyrrole-2-carboxylate (6) from the previous step was dissolved in MeOH (700 mL) 2M NaOH (700 mL) was added and the soln was heated at 60 °C for 6h. The mixture was cooled to rt and washed with Et20 (4x1 L), the pH of the aqueous layer lowered to ca. 3 with 10% H2S04, and the mixture was extracted with EtOAc (4 x 2000 mL). The combined EtOAc extracts were dried (Na2S04) and concentrated under reduced pressure to provide a tan foam. The foam was dissolved in CH2C12 (500 mL) and petroleum ether (2 L) added, and the resulting slurry was concentrated. The residue was redissolved and concentrated three additional times to provide 7 as a fine white powder yield 320 g (75% from 5). 

A solution of 0.8 g of diethyl N-[l-methyl-3-(2-nitro-3-chlorophenyl)-3-oxopropylidene]aminomalonate in 4 ml of absolute tetrahydrofuran was added dropwise with stirring to a solution prepared with 8 ml of absolute ethanol and 100 mg of metallic sodium. After the reaction mixture was refluxed for 4.5 hours, the solvents were distilled off under reduced pressure. The residue was added with an ice-water and the solution was extracted with ether. The extract was washed with water, dried over anhydrous magnesium sulfate, after which ether was distilled off. The residue was recrystallized from benzene to obtain ethyl 3-(2-nitro-3-chlorophenyl)-5-methylpyrrole-2-carboxylate as colorless needles having MP 220°-223°C. 

Examples of selective side-chain oxidation were reported for two reagents Ceric ammonium nitrate was found to convert 5-methylpyrrole-2-carboxylates to 5-formylpyrrole-2-carboxylates. <95TL4345> Several examples of oxidation of C2 and C3 methyl groups to formyl in 1-(phenylsulfonyl)indoles with Mn02 were reported. <95SC2407>... 

Formylation of methyl l-methylpyrrole-2-carboxylate with dichloromethyl methyl ether and aluminum chloride occurs in the 4-position, while under Vilsmeier conditions the main product is the 5-formyl derivative. 

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