Acetophenone derivative reactions

Turnkey Process for Celiprolol Celiprolol has a unique Af,Af-diethylurea in its structural framework we wished to integrate HKR into a process. The existing route starts with 4-ethoxyaniline which was treated with diethylcarbamoyl chloride in the presence of potassium bicarbonate to give A -p-ethoxyphenylacetamide (Scheme 30.7). Friedel-Crafts acylation with acetyl chloride and anhydrous aluminum chloride followed by acid hydrolysis furnished the acetophenone derivative. Reaction of the urea derivative with epichlorohydrin followed by treatment with hydrobromic acid yielded a bromohydrin. Celiprolol was obtained as a free base by reaction of this bromohydrin with feri-butylamine in the presence of triethylamine, and was later converted to its hydrochloride salt. 

Synthesis and Properties. Polyquinolines are formed by the step-growth polymerization of o-aminophenyl (aryl) ketone monomers and ketone monomers with alpha hydrogens (mosdy acetophenone derivatives). Both AA—BB and AB-type polyquinolines are known as well as a number of copolymers. Polyquinolines have often been prepared by the Friedlander reaction (88), which involves either an acid- or a base-catalyzed condensation of an (9-amino aromatic aldehyde or ketone with a ketomethylene compound, producing quinoline. Surveys of monomers and their syntheses and properties have beenpubhshed (89—91). 

The comparison of a bis(imino)pyridine iron complex and a pyridine bis (oxazoline) iron complex in hydrosilylation reactions is shown in Scheme 24 [73]. Both iron complexes showed efficient activity at 23°C and low to modest enantioselectivites. However, the steric hindered acetophenone derivatives such as 2, 4, 6 -trimethylacetophenone and 4 -ferf-butyl-2, 6 -dimethylacetophenone reacted sluggishly. The yields and enantioselectivities increased slightly when a combination of iron catalyst and B(CeF5)3 as an additive was used. 

In a similar vein, the keto bridge in 5 can be replaced by oxygen with retention of activity. Reduction of acetophenone derivative 19 by means of sodium borohydride leads to the corresponding alcohol (20). Reaction with phosphorus tribromide with cyanide gives... 

Phenylacetamides were prepared in the MBR from the corresponding styrene or acetophenone derivatives by Willgerodt reactions (Scheme 2.8) [44]. Yields were comparable with those obtained by others with conventional heating. At similar temperatures, the microwave-heated reactions were completed within minutes rather than hours. Optimization was readily accomplished through the capabilities of the MBR for rapid heating and cooling. The substantially shorter reaction times probably re-... 

This reaction was used as the basis for the development of a procedure for the synthesis of carbonyl compounds (182) from acetophenone derivatives (180) (386) (Scheme 3.138). 

Iridium complexes are known to be generally less active in hydrosilylation reactions when compared to rhodium derivatives, although iridium-based catalysts with bonded chiral carbene ligands have been used successfully in the synthesis of chiral alcohols and amines via hydrosilylation/protodesilylation of ketones [46-52] and imines [53-55], The iridium-catalyzed reaction of acetophenone derivatives with organosubstituted silanes often gives two products (Equation 14.3) ... 

This protocol complements Akiyama s method which provides P-amino carbonyl compounds as i yn-diastereomers [14], It tolerated aromatic, heteroaromatic, and aliphatic aldehydes. Cyclic ketones, acetone, as well as acetophenone derivatives could be employed. The use of aromatic ketones as Mannich donors was up to that time unprecedented in asymmetric organocatalysis. Rueping et al. independently expanded the scope of the asymmetric Brpnsted acid-catalyzed Mannich reaction of acetophenone [45]. 

In 2003, Banerjee et al. designed an efficient photoremovable protecting group for the release of carboxylic acids based on similar p-elimination from photoenols (Scheme 14). They showed that o-alkyl acetophenone derivatives with various ester groups in the p-position release their ester moiety in high chemical yields. The authors proposed that the photorelease took place as shown in Scheme 14 but did not support the mechanism with transient spectroscopy. Formation of 21, which is expected to be the major product in the reaction, was not confirmed, and thus, the authors speculated that 21 undergoes polymerization to yield oligomers. 

Dixon reported that saturated BINOL 45 sufficiently activates various N-Boc aryl imines toward Mannich reaction with acetophenone-derived enamines to yield P-amrno aryl ketones in good yields and enantioselectivities (Scheme 5.62) [116]. The same group applied a BINOL-derived tetraol catalyst to the addition of meth-yleneaminopyrroHdine to N-Boc aryl imines. Interestingly, appendage of two extra diarymethanol groups to the BINOL scaffold resulted in a marked increase in enantiomeric excess [117]. 

The reaction of o-nitrobenzaldehydes with some benzene derivatives in the presence of strong acid (H2S04, PPA) is a classical synthesis of acridinol N-oxides (373) (37BSF240) The synthesis works for benzyl alcohol, benzene, toluene and halobenzenes, but not for benzoic acid, benzonitrile, dimethylaniline, or nitrobenzene. Isoquinoline N-oxides (374) have been obtained from o-bromobenzaldoxime or the acetophenone derivative, and active methylene compounds with copper bromide and sodium hydride (77S760). The azobenzene cobalt tricarbonyl (375) reacts with hexafluorobut-2-yne to give a quinol-2-one (72CC1228), and the 3,4,5-tricyanopyridine (376) is formed when tetracyanoethylene reacts with an enaminonitrile (80S471). 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Substitution of hydrogen with phenyl, as in trifluoro-substituted acetophenone derivative 14h, enhances the rate of Lhe isomerization reaction. In fact, small amounts of 15h have been formed in the preparation of 14h, presumably catalyzed by benzylamine.14 Use of the stronger base l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) accelerates the isomerization and is a very effective catalyst for the tautomerization reaction in the ketimine series.13... 

Figure 4B. Plots of log kc, for the photoinduced electron transfer reactions from [Ru(bpy)3]2+ to organic electron acceptors (Nos. 1-16) in the absence of HC104 and acetophenone derivatives (Nos. 17-21) in the presence of HC104 (0.10 mol dm-3) in MeCN vs. the difference between the one-electron redox potentials of [Ru(bpy)3]2 + and the electron acceptors in the absence of HC104 in MeCN, [42].

The ke[ values of photoinduced electron transfer reactions from [Ru(bpy)3]2 + to various nitrobenzene derivatives in the presence of 2.0 mol dm-3 HC104 are listed in Table 1, where the substituent effect is rather small irrespective of electron-withdrawing or donating substituents. A similar insensitivity to the substituent effect is also observed in the acid-catalyzed photoinduced electron transfer from [Ru(bpy)3]2+ to acetophenone derivatives [46,47]. The stronger the electron acceptor ability is, the weaker is the protonation ability, and vice versa. Thus, the reactivity of substrates in the acid-catalyzed electron transfer may be determined by two reverse effects, i.e., the proton and electron acceptor abilities, and they are largely canceled out. Such an insensitive substituent effect shows a sharp contrast with the substituent effect on the acid-catalyzed hydride transfer reactions from Et3SiH to carbonyl compounds, in which the reactivity of substrates is determined mainly by the protonation ability rather than the electron acceptor ability. 

N-Unsubstituted tetrahydro-l,3-oxazines (3 R3 = H) take part in Mannich-type reactions, e.g., 3-(2-nitrobutyl)-tetrahydro-1,3-oxa-zine1,37,47-53 and the corresponding bicyclic compound1,37 were thus obtained. A reaction with paraformaldehyde and acetophenone derivatives yields 3 (R1 = H, alkyl, or Ph, R2 = CHaCHaCOPh).71,72... 

When reactions (40b) and (40d) proceed slowly, the product of reaction (40 a) is not further reduced. This species is further reduced only when it is transformed by the acid- (40 b) or base- (40 d) catalysed reactions to an acetophenone derivative. The range of pH in which the... 

First, it was observed that substrates of lower basicity were hydrosilated by Ph3SiH much more rapidly than substrates of higher basicity. Thus, for the substrates benzaldehyde, acetophenone and ethylbenzoate, observed turnover numbers were 19, 45 and 637 h 1, respectively, while the measured equilibrium constants for adduct formation of these substrates with B(C6F5)3 were 2.1 X 104, 1.1 X 103 and 1.9 X 102. A similar inverse correlation between turnover number and equilibrium constant was observed for a series of para-substituted acetophenone derivatives, where much faster hydrosilation rates were observed for substrates with strongly electron withdrawing groups in the para position. Clearly, if activation of the substrate via adduct formation is important in the hydrosilation reaction, the opposite correlation between TON and Keq should be observed. 

A multinuclear Zn-binaphthoxide complex prepared from Et2Zn and the linked-BINOL 28 has recently been developed as an effective catalyst for the Michael reaction (Scheme 13) [15], The a-hydroxy acetophenone derivative 29 was a suitable substrate, reacting with the Zn complex to afford the configurationally stable Zn enolate. Reaction with a variety of enones proceeded smoothly and... 

Addition of THF is necessary with benzophenone derivatives and enhances the efficiency of phenyl acetophenone derivatives as shown by the following reactions (the photochemistry of these compounds are very well known in homogeneous solutions) ... 

Many examples of the intramolecular [2 + 2] photocydoaddition of alkenes to benzene derivatives have been reported. The acetophenone derivative 41 undergoes an efficient [2 + 2] photocydoaddition, leading to the cyclobutane derivative 42 (Scheme 5.9, reaction 18) [46, 47]. It was shown that, in this case, a nn triplet state is involved. The presence of a nitrile group in compound 43 induces a [2 + 2] cycloaddition at position 1,2 of the aromatic moiety, leading to intermediate VIII (reaction 19) [48]. Following tautomerization, the final product 44 is formed. 

Nickel boride prepared from Nil2 and two equivalents of LiBH4 [42] was utilized as an oxazaborolidine catalyst support (Scheme 4) [43]. Reaction of nickel boride with 0.1 equivalents of chiral amino alcohol in THF at room temperature gave the anchored catalyst 6, which produced chiral alcohols in optical yields of up to 95%, and which furthermore showed higher activity as regards the reduction of acetophenone derivatives than that of the corresponding homogene-... 

Cyclic dehydration of o-methylselenobenzaldehyde oxime with PPA affords 1,2-benzoselenazole (2). Interestingly, the corresponding acetophenone derivative gives 2-methyl-l,3-benzoselenazole (28a). 1,2-Benzotellurazole (3), the only known compound in the isotellurazole series, is synthesized by cyclic dehydration of o-butyltellurobenzaldehyde oxime (29) as well as by the reaction of ammonia with o-bromotellurobenzaldehyde (30 Scheme 9) (78JHC865). 

If chelation to a neigbouring group is possible, the use of HMPA is often not required for reduction of the carbonyl and reactions can be carried out under mild conditions. To examine the impact of chelation, Flowers studied the rate of reduction of 2-butanone, methyl acetoacetate and /V,/V-dimethylacetoace-tamide by Sml2.20 Reduction of the (1-keto ester or amide was several orders of magnitude faster than that of the unsubstituted ketone, which is consistent with chelation playing a major role. Further rate and mechanistic studies on the reduction of acetophenone and a series of 2 - and 4 -substituted acetophenone derivatives showed that both chelation and coordination provide highly... 

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