Haloacetophenones

Anilines react with ct-haloacetophenones to give 2-arylindoles. In a typical procedure an W-phenacylaniline is heated with a tw o-fold excess of the aniline hydrobromide to 200-250°C[1]. The mechanism of the reaction was the subject of considerable investigation in the 1940s[2]. A crucial aspect of the reaction seems to be the formation of an imine of the acetophenone which can isomerize to an aldimine intermediate. This intermediate apparently undergoes cyclization more rapidly (path bl -> b2) than its precursor (Scheme 7.3). Only with very reactive rings, e.g, 3,5-dimethoxyaniline, has the alternative cydiz-ation (path al a2) to a 3-arylindole been observed and then only under modified reaction conditions[3],... 

A highly efficient one-pot, two-step microwave procedure has been developed for the synthesis of l-aryl-l/7-indazoles. Microwave heating of 2-halobenzaldehydes or 2-haloacetophenones with phenylhydrazines at 160°C for 10 min quantitatively yielded the arylhydrazones, which were further cyclized to give l-aryl-17/-indazoles via Cul/diamine-catalyzed... 

Halofluonnation of a-diazoacetophenone by N halosuccimmides in hydrogen fluonde-pyndine provides good yields of a-fluoro-a-haloacetophenones [6] (equation 24)... 

The reaction of salicylates with ortfe-fluoro-a-haloacetophenones in the presence of cesium carbonate forms the intermediates 763, which can undergo ring closure via 7r/>0-fluorine substitution to afford 5,ll-dioxabenzo[/)]fluoren-10-ones (X1 = O) and 5-oxa-l l-thiabenzo[ ]fluoren-10-ones (X1 = S) (Scheme 201) <2001TL8429>. 

The reaction of PhS" ion with 4-bromobenzophenone (154a) and 4-haloacetophenones (154b) was studied in MeCN, DMSO and DMF under thermal (A, 60 °C) or photochemical activation to yield 80-97% yield of products 208 (equation 146)271. 

Table 6.6 Coupling between phenylboronic acid and p-haloacetophenone in [C14(C6)3P]C1 al...

The loss of halide ion from the radical anions of aromatic compounds is a facile reaction in solution. This reaction has been studied extensively by electrode techniques (Lawless and Hawley, 1969a,b Bartek et al., 1970, 1972 Nadjo and Saveant, 1971a Houser et al., 1973 Nelson et al., 1973 M Halla et al., 1978, 1980 Saveant and Thiebault, 1978 Gores et al., 1979 Pinson and Saveant, 1974, 1978 Amatore e/a/., 1979 Parker, 1981k,l). The anion radicals of halonitrobenzenes, halobenzonitrilies, haloanthracenes, halo-naphthalenes, halobenzophenones and haloacetophenones have received the most attention. 

In this respect, theoretical studies have shown that in halobenzenes, halobenzo-nitriles, haloacetophenones and halonitrobenzenes, by considering the intramolecular electron transfer as the rate limiting step of the cleavage reaction, the energy difference between the two isomeric radical anions correlates with the ex-... 

Instead of amino alcohols, enantiopure P-hydroxysulfoximines are also efficient chiral auxiliaries for the ketone reduction with borane [110]. Treatment of P-hydroxysulfoximine 72 with borane would form a boron-containing six-mem-bered heterocycle as a catalyst as shown in Scheme 16. The mechanism may be analogous to that for the oxazaborolidine reduction. a-Haloacetophenone and... 

Reaction of 6-amino-5-thioxo-4,5-dihydro-1,2,4-triazin-3(2//)-one (328) with haloacetophenones provides the 7-aryl-2,8-dihydro-3//-[l,4]thiazino[2,3-e]-l,2,4-triazin-3-ones (329) (Equation (40))... 

Oxazaphospholidine 45 reacts with a-haloacetophenone 45 to give a mixture of vinylphosphonamide diastereomers 47. The product ratios depend on the nature of the halides.33... 

Alkylation reactions of carboxylic acids such as aryloxyacetic acids (unsubstituted furoic acids and benzofuroic acids) with (un)substituted co-haloacetophenones in dry media under the action of MW with PTC have been described [17]. 

Other classes of nickel-catalyzed [3+2] cycloadditions include the addition of 2-haloacetophenone derivatives to alkynes to produce indenol derivatives (Scheme 3-36). This process likely involves initial oxidative addition to the haloaromatic, followed by alkyne insertion and carbonyl addition. In this case, zinc powder serves as reducing agent to regenerate the active nickel(0) catalyst. A mechanistically intriguing cycloaddition that proceeds without the action of reducing agents is the direct formation of bicyclic products from the addition of unsaturated ketones with alkynes. This process likely involves initial metallacycle formation followed by unusual rearrangement steps unique to the requisite doubly unsaturated carbonyl component. 

Fluorine-for-halogen exchange has also been described in DMSO/[K/2.2.2] systems using 4-haloacetophenones and 4-halobenzonitriles. In both series, F-for-F exchange was the most efficient (70-75%). This process, however, is only suitable when high specific activities are not needed. 

The haloacetophenone type of polymer reacted with N-protected amino acids and peptides — as already known from esterifications with the monomer reagent in conventional syntheses [74] — under milder conditions but in better loading yield compared to chloromethylated polystyrene, resulting in enhanced reactivity of the peptide phenacyl ester bond on polymer towards nucleophilic cleavage reagents [74—76]. (For further details on peptide cleavage, see Sect. 3.5.)... 

A novel and simple procedure was developed for the construction of fully substituted thiophenes (13S913). A series of a-haloacetophenone derivatives were converted into fully substituted thiophenes by treatment with sodium sulfide in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and sodium iodide in aqueous ethanol under aerobic conditions. 

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