Isobutyric anhydride, acylation

A new class of chiral 4-A,A-dialkylaminopyridine acyl-transfer catalysts has been developed that are capable of exploiting both van der Waals (jt) and H-bonding interactions to allow remote chiral information to control stereochemically the kinetic resolutions of secondary alcohols with moderate to excellent selectivity (S = 6-30). Catalysts derived from (.S )- , -diarylprolinol (89 Ar = Ph, 2-naphthyl) in combination with isobutyric anhydride were found to possess high activity and selectivity across a broad range of substrates 89... 

The same effect is found for toluene acylation over BEA zeolite with derivatives of isobutyric acid isobutyric anhydride presents a higher initial activity compared with isobutyric chloride.[6]... 

A further example of the use of phenyl sulphones in prenylation reactions is provided in the recent synthesis of deoxytrisporone (37) (Scheme 5)7 An interesting feature of this synthesis is the regiospecific acylation of the diol (35) with isobutyric anhydride. 

The PBO catalyst lc was recently applied to the kinetic resolution of allylic alcohols 2e-l by acylation with isobutyric anhydride [18]. The enantioselec-tivity depends strongly on the structure of allylic alcohols and increases with the conformational flexibility of the substrate. The dienyl alcohols 2i-l are good substrates for this kinetic resolution as shown by the high selectivity factors (30-80) obtained (Table 1). 

The acylation of 2-MN with different anhydrides at low temperature (100°C) in the presence of the moderately protic acid MCM-41 mesoporous zeolite was studied. The selectivity toward 1-isomer 28 is practically 100% with the less bulky AAN (Scheme 4.20), whereas with the more bulky isobutyric anhydride, a small amount of 6-isomer is produced. At a higher temperature (-130°C), the reversibility of the acylation at the 1-position plays a fundamental role in the distribution of products, and a decrease in the selectivity for 1-position is observed. The catalyst can be recycled three times after each cycle, the catalyst is filtered, washed, dried, and reactivated by calcination for 2 d at 450°C, showing quite similar conversion (-40%) and selectivity (-97%) with respect to compound 28. 

DMAP-catalyzed acylation of various l, -liner diols (n = 2-5, and 5 ) with 1.03 equiv. of isobutyric anhydride gave 3 1 1 1 mixtures of the monoacylates and the diacylates as shown in Fig. 5b. On other hand, almost pure monoacylates were obtained by the acylation of diols in the presence of 10 mol% of catalyst 8 (Fig. 5a). However, a significant amount of the diacylate formed when further longer linear diols (n 6) were used as the substrates (data not shown). These results suggest that catalyst 8 is able to distinguish the diol structure from the monoacylated monool in the case where the chain length is shorter or equal to 5. 

Both catalysts are especially suitable for the KR of benzylic alcohols (eq 1). Cl-PIQ is generally more catal)dically active and achieves good to excellent enantioselectivity (selectivity factors s in the 30-100 range), while BTM is much more enantioselective (s in the 100-350 range). Both propionic and isobutyric anhydrides have proved to be useful as achiral acyl donors in BTM-catalyzed acylations, the latter usually leading to higher enantios-electivities, but somewhat lower reaction rates. Cl-PIQ has been used primarily in combination with propionic anhydride. Chloroform is the solvent of choice in most cases. BTM-catalyzed reactions are sensitive to moisture (rapid catalyst deactivation) and, therefore, should be carried out in the presence of anhydrous Na2S04. 

System (6) has been described for the simultaneous determination of submicrogram amounts of 17a-deoxy and 17a-hydroxy corticosteroids [145]. Prior to analysis, the corticosteroids were treated with periodic acid in 50% aqueous dioxane, and extracted with dichloromethane. Acylation of the 3- and 17a-hydroxyl groups was carried out using 1 1 butyric anhydride and pyridine. 4- C -cholesterol was added as the tracer, and cholesterol isobutyrate as the internal standard. The column used was glass (8 ft X 5 mm) packed with 1% SE 30 or QF-1 on GasChrom Q (100-120 mesh), and was operated at 250-260°C. Argon (at a flow rate of 30 mL/min) was used as the carrier gas, and detection was by a Sr detector. It was reported that the corticoids could be determined with a precision of approximately 15% down to levels as low as 0.1-0.2 pg. 

Steric effects were evaluated by a study of the DMAP-catalysed acylation of 1 y, 2y and 3y alcohols by acetic, propionic, isobutyric, isovaleric, and pivalic anhydrides in CH2C12 at 20 °C. In all cases the reaction kinetics could be described by rate laws containing a DMAP-catalysed term and an uncatalysed (background) term. Steric effects were evident in both reactions, but were generally greater for the DMAP-catalysed reaction. For example, the uncatalysed reactions between cyclohexanol and acetic and pivalic anhydrides differed about 500-fold, but for the corresponding DMAP-catalysed reactions the factor was 8000-fold. The implications of these findings for the kinetic resolution of alcohols were discussed.32... 

The acylal (4) can also be used to carry out reactions with nascent dimethylketene formed in situ. It is stable to t-butanol at the reflux temperature but with potassium carbonate present to ciitaly/,c cleavage it reacts smoothly to form /-butyl isobutyrate It reacts with an amine without other catalyst at room temperature to give an isohutyramide. In the presence of an alkali carbonate or the salt of a carboxylic acid, it converti an acid Into Its anhydride, probably via a mixed anhydride. With... 

Preparation by acylation of 2,6-di-tert-butylphenol with isobutyric acid in trif-luoroacetic anhydride at r.t. [8231], first at 0°, then at r.t. for 3 h (92%) [7727]. 

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