Pyrrole 4 - acetyl - 5 - methyl

Pyrrole, 5-methyl-N-acetyl Sd Hu Pyrrole, N-(2 -furfuryl), 2-carboxaldehyde Sd... 

The anion formed from the acetyl methyl group under reaction conditions then attacks one of the carbethoxy groups to form a cylohexanone to give (74-4) as the isolated product. The free acid obtained on hydrolysis of the ester decarboxylates to give the (3-diketone (74-5). In a classic apphcation of the Knorr pyrrole synthesis, the diketone is then allowed to react with 2-aminopentan-3-one. Since the latter is unstable, it is generated in situ by reduction of the nitrosation product from diethyl ketone. There is thus obtained piquindone (74-6) [76], a compound that displays antipsychotic activity. 

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... 

Oxidation of the 3-(hydroxyalkyl)pyrrole derivative gives a pure 3-acylpyrrole derivative which is difficult to obtain by direct substitution in the pyrrole ring. Acylation of pyrrole yields 1- and/or 2-acetyl pyrrole, whereas acylation of 1-methyl pyrrole forms both 2- and 3-acetyl-1-methyl-... 

In certain cases where the heteroaromatic amine is insufficiently soluble in aqueous acid, it can be dissolved in the minimum volume of an organic solvent miscible with water. Dilute mineral acid and a solution of sodium nitrite are then added. An example is the diazotization of 2-phenyl-3-amino-4-acetyl-5-methyl-pyrrole (Dattolo et al., 1983). 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl- and 2 4-dimethyl-dicarbethoxy-pyrrole (V,12-V,13) 2-amino- and 2 4-dimethyl-thiazole (V,1 V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylpyridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanopyridine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi ox3depidine (V,29). 

Figure 7.1 The overall pathway of haem biosynthesis. 5-AminolaevuIinate (ALA) is synthesized in the mitochondrion, and is transferred to the cytosol where it is converted to porphobilinogen, four molecules of which condense to form a porphyrin ring. The next three steps involve oxidation of the pyrrole ring substituents to give protoporphyrinogen fX, whose formation is accompanied by its transport back into the mitochondrion. After oxidation to protoporphyrin IX, ferrochelatase inserts Fe2+ to yield haem. A, P, M and V represent, respectively acetyl, propionyl, methyl and vinyl (—CH2=CH2) groups. From Voet and Voet, 1995. Reproduced by permission of John Wiley Sons, Inc.

Similarly, 4-acetyl-2-(l,4-anhydro-D-ara fno-tetrahydroxybutyl)-5-methyl-pyrrole has been oxidized to 2-(4-acetyl-5-methylpyrrole-2)diglyoolaldehyde.S0... 

Itahara has also found that the phenylation of A-aroylpyrroles can be achieved using Pd(OAc>2 [30, 31]. Although A-benzoylpyrrole (22) yields a mixture of diphenylpyrrole 23, cyclized pyrrole 24, and bipyrrolyl 25 as shown, l-(2,6-dichlorobenzoyl)pyrrole 26 gives the diphenylated pyrrole 27 in excellent yield. The IV-aroyl groups are readily cleaved with aqueous alkali and the arylation reaction also proceeds with p-xylene and p-dichlorobenzene. Unfortunately, N-methyl-, iV-acetyl-, and A-(phenoxycarbonyl)pyrroles give complex mixtures of products. 

The protonation of acetyl- and formyl-pyrroles occurs on the carbonyl group (Skylar et al., 1966). So, for example, in the nmr spectrum of 2,4-dimethyl-3-acetyl-pyrrole in concentrated acid the vinyl (C-5) proton resonance is retained, although there is exchange in deuteriated acid (Melent eva et al., 1971). The behaviour of carbethoxy-substituted pyrroles is more complicated, however. While 3-carbethoxy derivatives [168] and the 2-carbethoxy derivatives unsubstituted at the 5-position [169] protonate at the a-position of the ring and are not exceptional, the 2-carbethoxy derivatives with a methyl group at the 5-position [170] give evidence in the nmr... 

Reaction of N-acetyl-lO-bromodibenzazepine 51 with potassium ferf-butoxide yields the reactive intermediate 52 that reacts with N-methyl pyrrole 53 (X = NMe) used as a solvent to produce a mixture of Diels-Alder/retro Diels-Alder adduct 54 with the Michael by-product 55 (X = NMe, Scheme 10 (1994JHC293)). 

Pyrrole, 2-acetyl-1-ethyl Sd (roasted) Pyrrole, 2-acetyl-N-methyl Sd (roasted) Pyrrole, 2-carboxaldehyde Sd Hu ... 

Padwa et al. (75) found that the unsymmetrical miinchnone 137, which was generated from A-acetyl-7/-benzylglycine (136) and refluxing acetic anhydride, reacts with methyl propiolate to give an 8 1 mixture of pyrroles 138 and 139. The same product ratio is obtained from the reaction of methyl propiolate and the azomethine ylide derived from 7/-benzyl-A(-(a-cyanoethyl)-A(-[(trimethylsilyl)-methyl] amine. 

Phase-transfer catalysis was found <1996CHEC-II(7)1> to be successful for N-substitution of the furo[3,2-/ ]pyrrole system. The reaction of 81a with methyl iodide or benzyl chloride gave 81b and 81c derivatives. Methyl 4-acetyl-2-[3-(trifluoromethyl)phenyl]furo[3,2-3]pyrrole-5-carboxylate 82 was obtained by reacting 81a in boiling acetic anhydride (Scheme 6) <2005CEC311>. 

The synthesis of pyrrolo[2,3- 7 pyridazines can be achieved by starting either with pyridazine, a tetrazine, or a pyrrole. Pyridazinone 80 reacts with bromomethyl derivatives to give poor yields of 81 <1996H(43)1863> (Equation 34), while 5-acetyl-2-methyl-4-nitro-6-phenyl-3(2//)-pyridazinone, after treatment with sarcosine ethyl ester for a brief time at room temperature, followed by acid hydrolysis afforded a good yield of 82 (70%) <1994S669>. 

Much more studied is the reaction of /8-dicarbonyl compounds with 2-amino-2-deoxyaldoses in particular, with 2-amino-2-deoxy-D-glu-cose (55), both in neutral and alkaline medium. In neutral methanol or aqueous acetone, 2-amino-2-deoxy-D-glucose reacts with 2,4-pen-tanedione to give52 54 3-acetyl-2-methyl-5-(D-arabino-tetrahydroxy-butyl)pyrrole (56a), and, with ethyl acetoacetate,55 the pyrrole 56b. Similar (tetrahydroxybutyl)pyrroles have been prepared from other /3-keto esters, such as ethyl 3-oxohexanoate, ethyl thiolacetoacetate, and diethyl 3-oxopentanedioate.53,56,56a... 

Shkurko and Mamaev50,408 have studied the l//-benzothieno[3,2-6]-pyrrole system 391 extensively. Electrophilic substitution (e.g., Mannich reaction, acetylation, diazonium coupling) takes place at C-2, as predicted by MO calculations.4080 If position 2 is occupied, substitution occurs at C-3.44 The Vilsmeier reaction on the 2-aryl derivative gave the expected product, but bromination of the parent system 391 failed. A 3-bromo derivative was successfully obtained from the N-methyl compound 392 with bromine in chloroform.44... 

Anodic oxidation of l,3-diaryl-5-methyl-A2-pyrazoline-5-carboxylic acids in CH3CN-Et4NBF4 proceeded with decarboxylation to the aromatized pyrazoles in high yield.414 Similarly, electrochemical oxidation of N-acetyl-2,3-substituted A4-pyrroline-2-carboxylic acids in water-tetrahydrofuran (3 1) containing KOH forms the corresponding pyrroles (80-98%).415... 

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