Propionaldehydes synthesis

Hydroformylation of an olefin usiag synthesis gas, the 0x0 process (qv), was first commercialized ia Germany ia 1938 to produce propionaldehyde from ethylene and butyraldehydes from propylene (12). 

With the exception of acetic, acryUc, and benzoic all other acids in Table 1 are primarily produced using oxo chemistry (see Oxo process). Propionic acid is made by the Hquid-phase oxidation of propionaldehyde, which in turn is made by appHcation of the oxo synthesis to ethylene. Propionic acid can also be made by oxidation of propane or by hydrocarboxylation of ethylene with CO and presence of a rhodium (2) or iridium (3) catalyst. 

Propionaldehyde, 3-(7 -benzo[fe]thiophenyl)-synthesis, 4, 906 Propionaldehyde, 3-hydroxy-... 

BASF led the development of a route based on ethylene and synthesis gas. Its four step process begins with the production of propionaldehyde from ethylene, CO, and H2 using a proprietary catalyst mixture that they aren t telling anything about. Reaction with formaldehyde gives methacrolein. The last two steps are the same as above—oxidation with air yields the MAA subsequent reaction with methanol yields MMA. 

The aldehyde-aldehyde aldol reactions were first nsed in a natural product synthesis setting by Pihko and Erkkila, who prepared prelactone B in only three operations starting from isobutyraldehyde and propionaldehyde (Scheme 40). Crossed aldol reaction under proline catalysis, followed by TBS protection, afforded protected aldehyde 244 in >99% ee. A highly diastereoselective Mukaiyama aldol reaction and ring closure with aqueous HE completed the synthesis [112]. 

In comparable reaction conditions as Pd +Cu +Y, Pd + and Cu2+ exchanged pentasil and ferrierite zeolites show a different type of activity [31]. The main products formed by propylene oxidation on these catalysts are acrolein and propionaldehyde below 120°C and 2-propanol above 120 C. Above 150°C consecutive oxidation of 2-propano1 to acetone is observed. The catalytic role of Pd and Cu in the 2-propanol synthesis is proposed to follow the Wacker concept. It is striking that when Pd + and Cu2+ are exchanged in 10-membered ring zeolites, oxidation of a primary carbon atoms seems possible, as acrolein and propionaldehyde are obtained from propylene. 

Chakrabarti and coworkers at Eli Lilly in the United Kingdom have reported the initial discovery and synthesis of olanzapine (Schemes 5 and,6). The thiophene 22 was synthesized by adding a DMF solution of malononitrile to a mixture of sulfur, propionaldehyde and triethylamine in DMF. The anion of amino thiophene 22 underwent a nucleophilic aromatic substitution with 2-fluoronitrobenzene to provide 23. The nitro group was reduced with stannous chloride and the resulting anihne cyclized with the cyano group to form amidine 24. Finally, a mixture of N-methylpiperazine and 24 were refluxed in DMSO/toluene to afford olanzapine (2). 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

The scope of the synthesis was extended by using a 2-vinyloxazine, which led to the formation of propionaldehyde derivatives.227 Another modification of the aldehyde synthesis started with quaternary salts that were treated with sodium hydride, alkylated, then reduced with sodium borohydride to tetrahydro-l,3-oxazines.229... 

Secondary and tertiary dialkylcuprates, lithium dialkenyl-, and even diphenyl-cuprates, add in very good yields to the reactive propionaldehyde diethyl acetal. The syn addition products may be trapped with a variety of electrophiles such as alkyl, alkenyl, alkynyl and aryl halides. The method has been used for the synthesis of several natural products. Substituted alkynic acetals also react with lithium dialkylcuprates in ether to furnish stable dialkenylcuprates of type (128) which do not eliminate to the corresponding alkoxy allenes (129) if the temperature is maintained below -20 C.164-179... 

The synthesis of a spiroketal fragment 450 of spongistatin 1 has been accomplished utilizing the addition of a metalated pyrone derived from 448 to propionaldehyde to give adduct 449 followed by acid-catalyzed spirocycliza-tion (Scheme 79) <20000L957>. 

Due to the increased reactivity of the aldehyde, alkyl-substituted nitroolefins can also be used as substrates. Nevertheless, these reactions are usually low-yielding and afford moderate selectivity. Alexakis has shown, however, that the bispyrrolidine 5-catalyzed additions may be used in multistep synthesis. The addition of propionaldehyde 34 to nitroolefin 33 resulted an approximate 2 3 mixture of anti/syn isomers in 92% yield and in high ee (93%), allowing the asymmetric synthesis of (—)-botryodiplodin (Scheme 2.46) [23b]. 

Initially, the de novo synthesis of enantiomerically pure carbohydrates [110] and glycolipids [111] using transition metal complexes and chiral auxiliaries afforded only modest success. Ultimately, it was the use of enantiomerically pure aldehydes, such as the R and S enantiomers of 2-(phenylseleno)propionaldehyde, to convey facial selectivity upon the LACDAC reaction that enabled the synthesis of optically pure glycals. Syntheses of several complex monosaccharides such as the main sialic acid-type N-acetylneuraminic acid (Neu5Ac) and rac-3-deoxy-ma o-2-octulosonic acid (KDO) were accomplished with this technology [112, 113], The LACDAC... 

The catalyst used in the process was a Fischer-Tropsch cobalt-thoria catalyst. The temperature was usually between 130-160° and a total pressure of 200 atm. of water gas (1II2 ICO) was usually employed. The reaction was carried out first with ethylene and the products were found to consist of a mixture of diethyl ketone and propionaldehyde. As both products contained a carbonyl or oxo group, the reaction was called the Oxo synthesis. Later it was found that ketone production was relatively unimportant aldehydes were almost always the principal... 

The reduction of a carboxyl group to an aldehyde group can be effected by a reductive desulfurization of the thiol ester with Raney nickel. The thiol esters are prepared by the reaction of the acyl chloride with an excess of ethyl mercaptan in pyridine or by reaction with lead mercaptide in dry ether. The hydrogenolysis is then carried out by refluxing an ethanol ic solution of the thiol ester with Raney nickel for 6 hours. By this new synthesis, propionaldehyde and benzaldehyde have been prepared in 73% and 62% yields, respectively. ... 

In studies directed towaids the synthesis of the fungal isonitrile antibiotic isonitrin B (103), a cy-clopentanoid metabolite related to trichoviridine (104), various trialkylsilyl enol ethers were irradiated with propionaldehyde to produce equimolar amounts of stereoisomeric bicyclic oxetanes (105). The corresponding silyl dienol ethers, however, gave little oxetane product owing to preferential diene photopolymerization. The use of vinyl epoxide derivatives such as (106), however, offers a possible access to the epoxycyclopentanoid system with simultaneous control of the face selectivity of the photoaddition by the epoxide moiety. 

Write equations for all steps in the synthesis of the following from propionaldehyde, using any other needed reagents ... 

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