Oxidative Acetoxylation Step

4- diacetoxy-2-butene obtained in the diacetoxylation step. Usually, a Pd-based 

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In the BASF process the 1,2-diacetate is the substrate for the hydroformylation step. It can be prepared either directly via oxidative acetoxylation of butadiene using a selenium catalyst or via PtCl4-catalyzed isomerization of the 1,4-diacetate (see above). The latter reaction affords the 1,2-diacetate in 95% yield. The hydroformylation step is carried out with a rhodium catalyst without phosphine ligands since the branched aldehyde is the desired product (phosphine ligands promote the formation of linear aldehydes). Relatively high pressures and temperatures are used and the desired branched aldehyde predominates. The product mixture is then treated with sodium acetate in acetic acid to effect selective elimination of acetic acid from the branched aldehyde, giving the desired C5 aldehyde. 

A neat way of preparing96 the system (215) (useful in bufadienolide synthesis) from (214) is illustrated for compound (216). Bromination to (217) followed by dehydrobromination with lithium bromide in DMF gave the dienone (218), which on triethylsilane reduction produced (219) and thence, by condensation with diethyl oxalate, (220). Methylthiotoluene-p-sulphonate in ethanol-potassium acetate now produced (221) whose oxidation with N-chlorosuccinimide in 2% methanolic sulphuric acid gave (223). A previous route to such compounds was by way of the a-acetoxy-ketones (219) but suffers from a low yield at the acetoxylation step, (219) —> (222). 

In the BASF process the 1,2-diacetate is the substrate for the hydroformylation step. It can be prepared either directly via oxidative acetoxylation of butadiene... 

Examples for necessary process improvements through catalyst research are the development of one-step processes for a number of bulk products like acetaldehyde and acetic acid (from ethane), phenol (from benzene), acrolein (from propane), or allyl alcohol (from acrolein). For example, allyl alcohol, a chemical which is used in the production of plasticizers, flame resistors and fungicides, can be manufactured via gas-phase acetoxylation of propene in the Hoechst [1] or Bayer process [2], isomerization of propene oxide (BASF-Wyandotte), or by technologies involving the alkaline hydrolysis of allyl chloride (Dow and Shell) thereby producing stoichiometric amounts of unavoidable by-products. However, if there is a catalyst... 

Since more than 60% of the EO production is converted directly to EG, the obvious question some macho chemist might ask is why don t we do an end run and just convert ethylene directly to EG Skip the oxidation step. Research starting 50 years ago led to several promising commercial processes, oxychlorination and acetoxylation. Exotic catalysts were used, and both avoided the EO step. But neither process was quite effective enough to replace the ethylene-to-EO-to-MEG route, which predominates today. 

The acetoxylation reaction is carried out at 70°C under 70 atm pressure by reacting 1,3-butadiene and acetic acid in the presence of air and a small amount of polymerization inhibitor. A special three-step activation (reduction-oxidation-reduction), also used in regeneration of the used catalyst, ensures high activity and selectivity. Regeneration of the catalyst is necessary after about one year of operation. 

Allylic acetoxylation.1 The combination of r-butyl hydroperoxide and Se02 has been used for allylic hydroxylation of alkenes (8, 64-65), but this system is not useful for oxidation of cycloalkenes. Allylic acetoxylation of cycloalkcnes is possible, but in modest yield, with PdCl2 and AgOAc, which probably form a reactive species such as [PdCl(OAc)] . This system can be used in catalytic amounts in the presence of t-butyl hydroperoxide for a reoxidation step. The yield is improved by addition of TcO, which seems to accelerate the oxidation. The most satisfactory ratios of... 

Thiazoline-azetidinone 36 is a versatile intermediate for the synthesis of varieties of beta-lactam antibiotics 24>. The most straightforward route to 36 must be the removal of the feta-lactam A-substituents of thiazoline-azetidinone 35, which is readily obtained from penicillins by Copper s method 4>. This has usually been done by the two-step operation, involving ozonolysis and subsequent methanolysis 25). Direct transformation of 35 to 36 also has been achieved by oxidation with potassium permanganate or osminum tetraoxide, but yields are unsatisfactory (—37%)25). An efficient method for the removal of A-substituents of 35 is the electrochemical acetoxylation procedure which may lead to the compound 36 along with 37 (Scheme 2-12)3). For example, the... 

Oxidation of steroidal alketies. Mercuric acetate (2 eq.) reacts with A -steroids (I) to give as the major product A -15-ones (2) rather than the expected allylic acetates, 16(J-acetoxy-14-enes. The tetrasubstituted bond of A -cholestene is unreactive under the same conditions. A -Cholestene (disubstituted) reacts only slowly to give A -cholestene-3-one in 20 % yield with 70% recovery of the starting material. This unexpected reaction of steroidal trisubstiluted double bonds may proceed through an allylic acetoxylation followed by an oxidation step. 

Oxidation of quinoxaline with nitric acid yields 6-nitroquinoxaline-2,3(lW,4//)-dione. Treatment of 6,7-dialkoxyquinoxaline-2,3(l/7,4//)-diones with fuming nitric acid in acetic acid results in acetoxylation, giving 5-acetoxy-6,7-dialkoxyquinoxaline-2,3(l//,47/)-diones in moderate yields (48-52%). A mechanism involving attack of nitronium ion as the first step has been proposed. " ... 

Boar et al. (116,117) established the 2-acetoxylation of enamides 405 by use of LTA oxidation (Scheme 54). Dorn et al. (118) applied the reaction to oxyprotoberberines to achieve the synthesis of ( )-l3)8-hydroxytetra-hydroprotoberberines, the key step being C-13 acetoxylation. LTA oxidation in benzene of CHiCL of 2,3-dimethoxy-, 2,3,10,11-tetramethoxy-, and 2,3-methylenedioxy-9, lO-dimethoxy-oxyprotober-berines (406,407, and 245) led to the corresponding 13-acetoxy-oxyprotober-berines 408, 409, and 410 in 62, 55, and 71% yield, respectively. Successive reduction of 409 and 410 with LAH and sodium borohydride gave ( )-13)3-hydroxyxylopinine (391) and ( )-ophiocarpine (411) in 60 and 52% yield, respectively (Scheme 54). 

Enone (22) with thionyl chloride in pyridine produced bicyclic enone (24) in 41% yield. This on oxidation gave a mixture of diastereoisomeric hydroxyl ketones which on acetoxylation produced acetoxy ketone (25), which on hydrolysis afforded glutinosone (1) in 60% yield. The synthesis only involved nine steps and the overall yield amounted to 3.64% from the bicyclooctanone mixture of (17) and (18). 

As a major step in the evaluation of the above mentioned high-throughput tools and techniques, a scale-down of different types of catalysts for several applications was performed. For that purpose, two well established commercial catalysts, one of the mixed metal oxide type for selective olefin oxidation and one impregnated catalyst for ethylene acetoxylation to vinyl acetate monomer (VAM), respectively, were prepared in the small-scale and their catalytic performance was compared. As shown in Fig. 1 with the selective oxidation catalyst, the scale-down of this catalyst was successful, since both, the commercial and the high-throughput prepared catalyst are showing identical performances. Regarding the calcination procedure one can point out, that only if this step is carried out in the 5-fold rotary kiln, equal catalysts were obtained. 

Nuclear acetoxylation is the slow step (Andrulis and Dewar, 1966). It has been suggested that the slow step in oxidations of toluene by Co(III) acetate (Heiba et al., 1969b Sakata et al.,... 

With Zn Lewis acids, only single a-insertion of alkynes (—> 42) is observed, while with AlMes double alkenylation (— 43) dominates. It is proposed that oxidative Ni(0) insertion to the 2-CH bond, hydronickelation of the triple bond, alkenyl transfer to C-2 of the pyridine, and reductive Ni-elimination are the decisive steps in the catalytic cycle, (d) The pyridyl residue may serve as a directing group in C-H insertion reactions of phenyl substituents at pyridine mediated by transition metals like Cu and Pd. For instance, 2-phenylpyridine can be regioselectively halogenated, acetoxylated, and cyanided (- products 44, 45, and 47) in the presence of Cu(OAc)2 [92] or amidated — 46) in the presence of Pd(OAc)2 [93] ... 

Reaction with Heteroatom Oxides. The key step in a method for a-acetoxylation of aldehydes involves rearrangement... 

Hypervalent iodine-mediated oxidation of the phenol component of 141, and the following sequential implementations of oxidation of the benzylic alcohol functionality and reduction of the quinone moiety in the same pot, gave palmarumycin C3 142. Methoxyacetylation of hydroxy groups of the hydroquinone was carried out, and subsequent acetoxylation using lead tetraacetate afforded 143 as an equimolar mixture of diastereomers. Further two-step operations including the oxidative cyclization completed the synthesis of 137. 

Reaction with Heteroatom Oxides. The key step in a method for a-acetoxylation of aldehydes involves rearrangement of an AcCl-nitrone adduct (eq 14). Analogous methods for a-benzoylation and a-pivaloylation are higher yielding. 

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