Chalcone, 4,4-dimethyl

With ( )-chalcone dimethyl acetal, in the presence of trityl perchlorate, PhSSiMe3 adds to give the 1,3-disubstituted-l-propene as the major product (equation 6)13. 

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

Treatment of 2-isoxazolines with acid usually leads to ring rupture and formation of chalcone products 62HC(l7)l), although 5-methyl-3-phenyl-2-isoxazoline forms a quaternary salt with dimethyl sulfate in the presence of perchloric acid (Scheme 51) (73BSF1390). 

More serious limitations and precautions apply to compounds in which not all three R, R, and R" groups are aromatic. Autocondensation of benzylideneacetone (111) yields an unstable chloroferrate which may be 113 or 115, according to whether a Michael addition to 112 or a crotonic condensation to 114 is first involved. Since compound 113 could readily be prepared from 2,6-dimethyl-4-phenylpyrylium and benzaldehyde, the structure of the reaction product should be easily soluble. Another equivocal product is formed from two moles of benzylideneacetone, but a definite structure (116) results from chalcone and benzylideneacetone. ... 

The conjugate addition to acyclic enones is summarized in Table 5. The chiral hetero-cuprate derived from (S)-prolinol or cinchonidine produced products of low enantiomeric excess on treatment with chalcone (entries 3 and 4), while the cuprate from (S)-yV-methylpro-linol gave 64% ee (entry 6). Under more dilute conditions, 88% cc was obtained (entry 5). (2[Pg.909]

The conjugate addition of lithium dimethylcuprate to chalcone in the presence of (2S)-1-(2,2-dimethyl-l-oxopropyl)-2-diphenylphosphinomethylpyrrolidine gave the corresponding S-adduct with 84% ec in 79% yield79. 

The final conditions were scaled up with no problems chalcone 8a and guanidine (liberated from its hydrochloride with sodium ethoxide) were heated in dimethyl acetamide while bubbling air through the mixture to form pyrimidine 9a. After complete conversion (16 h), the product was cleaved from the support (20% trifluoroacetic acid in DCM). Pure 4-(2-amino-6-phenyl-pyrimidin-4-yl)bcnzamidc 1 was obtained as its trifluoroacetate salt upon evaporation of the filtrate and recrystallisation of the residue from ethanol/water in 56% overall yield based on the solid phase attached 4-carboxybenzaldehyde 6a. 

The amount of molecular sieves 4 A largely influences the product s ee[11]. Usually 100 mg (for the CMHP oxidation) or 1 g (for the TBHP oxidation) of MS 4A for 1 mmol of substrate is enough however, in the case where chemical yield and/or optical yield are not high, use of excess MS 4A often improves them. The addition of achiral ligands such as tributylphosphine oxide, tri-o-tolyl- and tri-/)-tolylphosphine oxides, hexamethylphosphoric triamide, triphenylpho-sphate, lutidine N-oxide, and l,3-dimethyl-2-imidazolidinone were found to be less effective than that of triphenylphosphine oxide in the epoxidation of chalcone. 

Et2Zn addition to 4,4-dimethyl-2-cyclohexenone and chalcone with 81% ee and 90% ee, respectively. 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

Complex LSB 9 is readily prepared either by the reaction of La(0 Pr)3 with 3 equiv. of B1NOL followed by the addition of NaO Bu (3 equiv.) or by the reaction of LaCl nfLO with sodium binaphthoxide. The complex 9 is stable to oxygen and moisture and has been proven to be effective in the catalytic Michael reaction of various enones with either malonates or p-keto esters. The Michael adducts with up to 92% ee were obtained in almost quantitative yield. Typical results with malonates are summarized in Table 8D.1 (Ln = lanthanide) [18], In general, the use of THF as solvent gave the best results except for the case of the LSB-catalyzed reaction of rmns-chalcone with dimethyl malonate, wherein the use of toluene was essential to give the adduct with good enantiomeric excess. The effects of the central metal (La, Pr, and Gd) on asymmetric induction were also examined in the same reaction, and LSB was found to be the best catalyst. 

For example, treatment of l-(2-hydroxyphenyl)-3-arylpropenones 9 with o-PDA 1 carried out in dimethyl sulfoxide in the presence of sodium acetate under microwave irradiation produces dihydrodiazepines 10 in good yields [10] (Scheme 4.3). Chalcone analogues of dihydroacetic acid 11, as well, containing an 6>r /z0-hydroxyl group, react with 0-PDA in boiling ethanol to produce dihydrobenzodiazepines 12 [11, 12]. 

On the basis of the literature data [53,56,57] of the synthesis of dihydrodiazepine and dihydrotriazepine derivatives by chalcone reaction with diamines such as 1,3-dimethyl-5,6-diaminouracil and diaminotetrazole, the suggested structure of the products of these interactions was later proved to be erroneous [61, 62,63]. Analysis of the reaction paths actually observed under such conditions is presented in Sect. 4.5. 

A mixture of 5,6-diamino-1,3-dimethyl-uracil 1 (0.2 g, 1.2 mmol), chalcone 2 (0.25 g, 1,2 mmol) and 0.4 ml of glacial acetic acid in 20 ml of methanol was refluxed for 3 h (Scheme A.33). After cooling, the colorless crystals of 3 precipitated and were filtered. Yield 82%. Melting point 229-231°C. 

As part of the proof of the identity of three newly isolated chalcones, B.M. Abegaz et al. developed a synthetic route which involves a microwave irradiation promoted Ullmann coupling [29]. A mixture of the dimethylated phenolic chalcone and the bromochalcone in the presence of potassium carbonate and copper(I)chloride was microwave irradiated (domestic oven) at 180 °C, giving 19% yield of the resulting bichalcone (Scheme 6). This bichal-cone was converted into a mixture of the desired Rhuschalcones, upon treatment with BBr3, followed by chromatographic separation. 

Reaction between 2 -hydroxyacetophenone and benzaldehyde (Claisen-Schmidt condensation) in the absence of a solvent at 423 K giving 2 -hydroxy chalcones and flavanones has been successfully performed with MgO as a solid base catalyst/581 A conversion of 40 % after 1 h with 67 % selectivity to chalcone was achieved. The influence of the solvent and the effects of a substituent on the aromatic ring were investigated by Amiridis et a//59,6"1 The reaction was carried out on MgO at 433 K. Dimethyl sulfoxide (DMSO) showed a strong promoting effect on the reaction, which was attributed to the ability of this dipolar aprotic solvent to weakly solvate anions and stabilize cations so that both become available for reaction. In this case, a conversion of 2-hydroxyacetophenone of 47 % with a selectivity to flavanone of 78 % was achieved after 30 min in a batch reactor. Further investigations1611 showed that DMSO significantly increases the rate of the subsequent isomerization of the 2 -hydroxychalcone intermediate to flavanone. 

Rehydrated Mg/Al LDH have also been used successfully for the synthesis of several fine chemicals of industrial or pharmacological interest, i.e. jasminaldehyde (a-M-amylcinnamaldehyde), chalcones such as vesidryl (2, 4,4 -trimethoxychalcone) and pseudoionones (6,7-dimethyl-3,5,9-undecatrien-2-one) by aldol and Claisen-Schmidt condensations/13,1091... 

Crystallization processes comprise two sequential steps crystal nucleation followed by crystal growth. Kondepudi et al. demonstrated in a series of experiments that spontaneous symmetry breaking may be induced by growing crystals of non-chiral molecules such as sodium chlorate, binaphthyl, and p, p -dimethyl-chalcone, which crystallize as enantiomorphous crystals of... 

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