Indoles reaction with acetone

Ring closure reactions can be induced electrochemically in liquid ammonia. For instance, the reaction of o-iodoaniline with acetaldehyde enolate ion gives 95% yield of indole, and with acetone enolate ion 87% of 2-methylindole321. 

Reaction of the cyclopentadienyl rhodium and iridium tris(acetone) complexes with indole leads to the species 118 (M = Rh, Ir) [77JCS(D)1654 79JCS(D)1531]. None of these compounds deprotonates easily in acetone, but the iridium complex loses a proton in reaction with bases (Na2C03 in water, r-BuOK in acetone) to form the ri -indolyl complex 119. This reaction is easily reversed in the presence of small amounts of trifluoroacetic acid. 

The results obtained by the reaction of 39 with p-toluenesulfonic acid (TsOH) in acetone are completely different from those observed in reactions with MsCl and with TsCl as shown in Sections IV.B. 1 and IV.B.2. Although the total yield of products is not high (Scheme 10), 39 produced 2//-l,2-oxazino[2,3-a]indole (68, 9%), 5-tosyloxyindole (69,10%), 53a (7%), and unreacted 39 (14%) (2000H2487). 

This new impurity proved to be derived from the Pd-catalyzed oxidation of DIPA to the enamine via P-hydride elimination. In fact, mixing Pd(OAc)2 with DIPA in DMF-d7 readily formed Pd black along with two species, primary amine and acetone, presumably derived from the enamine through hydrolysis. The resulting enamine or acetone then underwent a coupling reaction with iodoaniline 28. Heterocyclization through the arylpalladium(II) species provided 2-methyl indole 71, as shown in Scheme 4.19. 

Convert indole to indolyl-3-methyl-ketone (I) by treating indolyl-Mg-Br (preparation already described) with acetyl-Cl, by treating indole in POCl3 with dimethylacetamide (Vilsmeier reaction), or by reacting indole with diketene (ACS 22,1064(1968)). 15.9 g (1) in 50 ml methanol cool, stir and add dropwise 16 g Br2. Reflux 1 Vi hours on water bath cool, filter, wash with ether and recrystallize-methanol to get 18 g indolyl-3-Br-methyl-ketone (II). Dissolve 11.9 g (II) in 60 ml warm isopropanol and add 11 g 3 8% aqueous DMA (or equimoiar amount other amine) reflux one hour on water bath. Filter (recrystallize-ethanol) to get 8.5 g indolyl-3-dimethylamino-methyl ketone (III). Add 4.6 g (0.02 M) (III) in 30 ml tetrahydrofuran to 2.3 g lithium aluminum hydride in 50 ml tetrahydrofuran, stir one-half hour at room temperature and reflux two hours. Add a little water dropwise and extract the precipitate with acetone. Dry, evaporate in vacuum the combined organic phases to get an oil which will precipitate with ether-petroleum ether to give DMT. (Ill) should be tested for psychedelic activity. Dialkyltryptamines BCSJ 11,221 (1936), BSC 2291 (1966)... 

Following a newly discovered indole synthesis, it has been shown that photochemical reaction of acetone anion with 3-amino-2-chloropyridine in liquid ammonia gives 2-methylpyrrolo[3,2-6]pyridine in 45% yield (80JOC1546). 

Acetone phenyl-hydrazoue is first prepared by mixing phenyl-hydrazine (30 gms.) with acetone (18 gms.). The mixture becomes warm and water separates it is then heated on the water-bath for half an hour, and at the end of this time heated in a dish on the water-batli, to drive off acetone and steam. The hydrazone is then mixed with five times its weight of anhydrous zinc chloride, and heated under a reflnx condenser in an oil-bath at 180°. A vigorous reaction takes place, and when completed, the dark-coloured mass is distilled with steam. The a-methyl-indole collects in the receiver and soon solidifies to a pale yellow mass. It may be purified by recrystallisiug from ligroin. M.p. 59°. Yield is over 60 per cent, of that calculated. 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

Nitromethane anion gives the corresponding N-allyl-3-(2-nitro-ethyl)- 2,3-dihydro-1-H-indole in 60% yield after photostimulated reaction with the bromide analogue, and in the presence of the enolate ion and acetone as an entrainment reagent (Scheme 10.51) [67]. 

Thermally induced cyclization of the enehydrazine 73, obtained from the sequential treatment of the corresponding arylhydrazine with acetone and TFAA, has been shown to produce the 2,4-disubstituted indole 74 along with the isomeric 2,6-disubstituted system 75. The yields of the products were dependent on the reaction medium however, toluene or chlorobenzene were found to be the solvents of choice, giving 74 as the prevailing product <02H(57)1101>. 

The reaction of l-methyl-2-(2 -pyridyl)indole (274) with bromoacetone in acetone gave the dimethyl derivative (275) of indoloquinolizinium salt (42%). The cyclization product from 2-(2 -pyridyl)indole (276), however, was not 7-methyl-12//-indolo[2,3-a]quinolizinium salt (277), but 11-meth-ylindolo[2,1 -a]-2-azoniaquinolizinium salt (278) (34%) (64JOC3584). 

Under acetone sensitization, 3-substituted indoles couple with 5-bro-mo-l,3-dimethyluracil at the indole 2-position (Scheme 29). It is proposed that this reaction proceeds via electron transfer from indole to the uracil triplet excited state since better electron donors than indole quench the reaction [14a, 64,65]. A similar reaction occurs when indole or 3-methylin-dole is photolyzed w ith 3,4-dibromo-AT-methylsuccinimide (Scheme 30) [65]. The quantum yield of this reaction is 0.14 in cyclohexane and 0.49 in diethyl ether, and drops to 0.02 in acetonitrile, which suggests that full electron transfer and radical ion-pair separation does not occur in this case. 

The reaction of propargyl alcohols with dicobalt octacarbonyl to give the complex salts 148 (X = BF4 or PF6) and synthetic uses of the latter have been reviewed. The salts react with electron-rich aromatic compounds ArH, such as anisole, phenol or N,N-dimethylaniline, to yield substitution products 149 after oxidative demetallation with an iron(III) or cerium(I V) salt with j5-diketones or j -keto esters the corresponding propargyl-substituted compounds 150 are obtained k Acetone reacts in an analogous fashion to give 151. The action of the cobalt complexes 148 on allylsilanes 152 leads to enynes 153. Indole reacts with the complex 148 (R = H R = R = Me) in the presence of boron trifluoride etherate to give 154, which was converted into 155 by the action of iron(III) nitrate " ... 

Indoles react with aldehydes and ketones under acid catalysis - with simple carbonyl compounds, the initial products, indol-3-ylcarbinols are never isolated, for in the acidic conditions they dehydrate to 3-alkylidene-3//-indolium cations those from aromatic aldehydes have been isolated in some cases reaction of 2-methylindole with acetone under anhydrous conditions gives the simplest isolable salt of this class. Only where dehydration is not possible have hydroxyalkylindoles been isolated, for example from reaction with diethyl mesoxalate. Reaction with 4-dimethylaminobenzaldehyde (the Ehrlich reaction, see section 13.1.7) gives a mesomeric and highly-coloured cation. 

Electrophilic N-prenylation. Synthesis of Af-prenyltndole derivatives is usually facile by deprotonation of Af-unsubstituted indoles with NaH or, more rarely KH, in DMF [4—17], DMSO [17], THF [18] or acetone [19], followed by reaction with prenyl... 

Baeyer and O. R. Jackson prepared indole derivatives by reducing o-nitro-phenylacetaldehyde and o-nitrobenzylketones. Baeyer and V. Drewsen by the action of alkali on o-nitrocinnamylformic acid prepared o-nitrobenzaldehyde, and by the reaction of this with acetone obtained indigo. 

An enzyme-substrate complex has been detected in the oxidative dimerization of L-(-)-tyrosine by HRP(i) to give HRP(ii). The pH dependence of the reaction reveals an enzyme protonation at pATa 5.42 with a less reactive protonated form. The hydroperoxide of indole-3-acetic acid (lAA) is important in the autoxidation of lAA catalysed by HRP. Formation of HRP(i) by reaction with the hydroperoxide is easier for the neutral isoenzyme than for the acidic species at pH 4.4 and this determines the catalytic activity. HRP(ii) is detected as an intermediate in the reaction and it reacts with lAA to form radicals. The involvement of both HRP(i) and HRP(ii) is proposed in the autoxidation of 2-nitro-propane to acetone and HNO2, catalysed by HRP. 

Mechanistic investigations can also provide insight into unexpected side reactions. For example, in Ir(III)-catalyzed indole synthesis, Messerle and coworkers noted an unexpected side product, N-vinyhndole, when 2-(2-phenylethynyl)anihne was used as substrate with acetone as the solvent By probing solvent effects, deuterium-labeling experiments, and isolation of dormant species formed in stoichiometric experiments, two possible reaction pathways were considered. In collaboration with Eisenstein [303], these pathways were compared computationally, yielding a proposed reaction mechanism that proceeds via the initial formation of imine between the aniline and acetone solvent, followed by imine nucleophilic attack of coordinated alkyne for indole formation. 

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