Ethyl alcohol alternative routes

There is also an apparent trend in manufacturing operations toward simplification by direct processing. Examples of this include the oxidation of ethylene for direct manufacture of ethylene oxide the direct hydration of ethylene to produce ethyl alcohol production of chlorinated derivatives by direct halogenation in place of round-about syntheses and the manufacture of acrolein by olefin oxidation. The evolution of alternate sources, varying process routes, and competing end products has given the United States aliphatic chemical industry much of its vitality and ability to adjust to varying market conditions. 

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Acetaldehyde can be produced by the partial oxidation of ethanol and the direct oxidation of ethylene. The predominant commercial process, however, is the direct liquid phase oxidation of ethylene. As with many other ethylene-based petrochemicals, acetaldehyde was first produced commercially from acetylene. The acetylene process was developed in Germany more than 70 years ago and was still practiced until the mid-1970s when the high cost and scarcity of acetylene forced it into obsolescence. Another early route to acetaldehyde was based on ethanol. Ethyl alcohol can be either oxidized or alternatively dehydrogenated to acetaldehyde. Site-... 

S)-Sulcatol cannot be made by this route, because the L-sugar is unavailable (even D-deoxyri-bose is quite expensive), so an alternative synthesis was needed that could be adapted to give either isomer. The solution is to go back to another hydroxy-acid, ethyl lactate, which is more widely available as its (5)-enantiomer, but which can be converted simply to either enantiomer of a key epoxide intermediate. From (S)-ethyl lactate, protection of the alcohol, reduction of the ester, and tosylation allows ring closure to one enantiomer of the epoxide tosylation of the secondary hydroxyl group followed by reduction and ring closure gives the other enantiomer. 

This route is especially convenient because no over-alkylation of the anion of acetonitrile occurs. Over-alkylation can be a problem in attempts to methylate the anion of diethyl cyano-methylphosphonate (4) directly a mixture of unalkylated, monoalkylated and dialkylated products in a ratio of 1 2 1 is formed. The same problem arises with the alkylation of triethyl phosphonoacetate (11). For the preparation of a Ca-ester synthon, an alternative method to the propionitrile route is used (Scheme 7). This method has been used in the synthesis of labelled Cio-central units, described in the next Section. The starting material is acetic acid (9) which is converted into ethyl bromoacetate (10) as described above (Scheme 3). The ethyl bromoacetate (10) is reacted with triphenyl phosphine in a nucleophilic substitution reaction the phosphonium salt is formed (yield 97%). The phosphonium salt is deprotonated in a two-layer system of dichloromethane and an aqueous solution of NaOH. After isolation, the phosphorane 22 is reacted at room temperature with one equivalent of methyl iodide (19) the product consists mainly of the monomethylated phosphonium salt (>90%) which is deprotonated with NaOH, to give the phosphorane 23 in quantitative yield relative to phosphorane 22, and 23 is reacted with the aldehyde in dichloromethane. The ester product 12 can subsequently be reduced to the corresponding alcohol and reoxidized to the aldehyde 8. An alternative two-step sequence for this has also been used. First, the ester 12 is converted into the A -methyl-iV-methoxyamide (16) quantitatively by allowing it to react with the anion of A, 0-dimethylhydroxylamine as described above (Scheme 5). This amide 16 is converted, in one step, into the aldehyde 8 by reacting it with DIB AH in THF at -40°C [46]. 

In an alternate approach, an ABB monomer was used as the building block unit. In this monomer, under a certain condition the fiinctionality B reacts with A selectively, while A can react with B under a different set of conditions. The repeat imit used for this purpose was ethyl 3-hydroxy-5-hydroxymethylbenzoate. Here B is the phenol, B is the primary alcohol, and the masked form of A is the ester group. This approach is schematically shown in Figure 4. Another facile route that is capable of introducing seqnences within dendrimers was developed by Simanek, where three different functionalities can be reacted one at a time with a traizine core (23). 

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