F Isobutyraldehyde

Chiral homoallylamines are valuable synthons for the preparation of biologically active components including P-amino carboxylic acids or esters, obtained by oxidation of the ally lie functionality.1-29 Because removal of the chiral auxiliary by hydrogenation leads to the loss of the allylic functionality, we developed alternative routes for the conversion of the adduct into the unprotected homoallylamines. As a typical example, (f ,f )-PGA-homoallylamine derived from isobutyraldehyde Hi was used to develop the so-called mroStrecker and the decarbonylation method for the conversion of (R)-phenylglycine amide protected homoallylamines into /V-benzylidene protected homoallylamines 15 (Scheme 25.7). 

The high-pressure (12 kbar) reaction of isobutyraldehyde pyrrolidine enamine with benzylideneaniline or benzylidenemethylamine in f-butyl methyl ether gives azetidines... 

The first stage of the process is a hydroformylation (oxo) reaction from which the main product is n-butyraldehyde. The feeds to this reactor are synthesis gas (CO/H2 mixture) and propylene in the molar ratio 2/f, and the recycled products of isobutyr-aldehyde cracking. The reactor operates at f30°C and 350 bar, using cobalt carbonyl as catalyst in solution. The main reaction products are n- and isobutyraldehyde in the ratio of 4 f, the former being the required product for subsequent conversion to 2-ethylhexanol. In addition, 3% of the propylene feed is converted to propane while some does not react. 

In the oxidation of an alcohol RCH2OH to an aldehyde by chromic acid, the chief side-reaction is formation, not of the carboxylic acid, but of the ester RCOOCH2R. Experiment has shown that a mixture of isobutyl alcohol and isobutyraldehyde is oxidized much faster than either compound alone. Suggest a possible explanation f or these facts. Hint See Sec. 19.9.)... 

M.A. Tius et al. reported a formal total synthesis of the macrocyclic core of roseophilin. The aliphatic five-membered ring of this core was prepared via a variant of the Nazarov cyclization. The precursor for this cyclopentannelation reaction is an ( )-a, 3-unsaturated aldehyde, which was prepared using the Peterson ole nation on the f-butylimine of 5-hexenal. First the a-TMS derivative of the imine was generated then after a second deprotonation, the additon of isobutyraldehyde gave the ( )-a, 3-unsaturated imine upon aqueous work-up. Acidic hydrolysis of this imine gave the desired ( )-a,(3-unsaturated aldehyde in good yield. 

When an allylsilane containing a C(3) substituent reacts with an aldehyde, two new stereogenic centers are established. The reaction of ( )- and (Z)-2-butenyI-trialkylsilanes with aldehydes was first reported by Hayashi and Kumada in 1983 [28]. In these studies either ( )- and (Z)-2-butenyltrimethylsilane or ( )- and (Z)-cinnamyltrimethylsilane combined with various aldehydes in the presence of TiCl4 (Scheme 10-9). The ( )-2-butenylsilane and ( )-cinnamylsilane both afford >95 f of the syn diastereomer upon reaction with either propanal, isobutyraldehyde, or pivalaldehyde. When the Z-silanes were subjected to the same reaction conditions much lower selectivities were observed (65-72% syn selectivity). An acyclic transition structure with an antiperiplanar arrangement of double bonds was proposed to account for the diastereoselectivity observed in these reactions. A transition stmcture which includes a synclinal arrangement of double bonds may be necessary to explain the lower selectivities observed with the Z-allylsilanes. 

ISOBUTYRALDEHYDE (78-84-2) Forms explosive mixture with air (flash point — 1°F/—18°C). Oxidizes slowly in air, forming isobutyric acid. Violent reaction with strong oxidizers, strong acids, bromines, ketones. Incompatible with caustics, ammonia, amines. 

Acyl radicals can fragment by loss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. For example, rates for decarbonylations giving tertiary benzylic radicals are on the order of 10 s whereas the benzoyl radical decarbonylates to phenyl radical with a rate on the order of 1 s (see also Table 11.3, Entries 45 to 48). When reaction of isobutyraldehyde with carbon tetrachloride is initiated by f-butyl peroxide, both isopropyl chloride and isobutyroyl chloride are formed, indicating that decarbonylation is competitive with the chlorine atom transfer. 

Isobutanol forms isobutylamine (toxic—erythema and blistering) with NH3 isobutyl chlorocarbonate, (CH3 )2CH—CH2—COOCl (eye and mucous membrane irritant) with phosgene and isobutyraldehyde (flammable) on air oxidation at 300°C (572°F) in the presence of Cu. 

N-Phenyl-S-chloroisothiocarbamoyl diloride added drop wise during 2 hrs. at 25-30° with water-cooling to a stirred soln. of isobutyraldehyde in dry ether, stirring continued 2 hrs., the crude dry intermediate (Y 96.5%) warmed to 50° until vigorous HCl-evolution starts, and the resolidified mixture stored in vacuo over solid KOH 4-chloro-2-oxo-5,5-dimethyl-3-phenylthiazolidine (Y 81%). F. e. and reactions of the products s. G. Ottmann, G. H. Hofmann, and H. Hooks, Jr., Synthesis 1969, 136. 

The complex reaction of 2-aminopyridine, isobutyraldehyde, cyclohexyl isocyanide, and hydrazoic acid gives 2-[l-(l-cyclohexyl-l/f-tetrazolyl-5-yl)-2-methylpropyl]aminopyridine (IX-72). ... 

An equivalent amount of aq. mineral acid, e. g. H2SO4 or HGl, added dropwise with stirring at 0° to a soln. of cyclohexyl isocyanide in isobutyraldehyde, and allowed to stand for several hrs. -> a-hydroxy- -methylbutyric cyclohexylamide. Y 88%. F.e. s. I. Hagedorn and U. Eholzer, B. 98, 936 (1965). 

Azeotropic water entrainment. A soln. of ethyl N-(j -hydroxyethyl) carbamate, isobutyraldehyde, and some p-toluenesulfonic acid in benzene refluxed 2.3 hrs. with azeotropic separation of the water formed N-carbethoxy-2-isopropyl-oxazolidine. Y 82%. F. e., also with ketones, s. M. Rona and D. Ben-Ishai, J. Org. Ghem. 26, 1446 (1961). 

An aq. soln. of glycine, ca. 0.05 mole of cupric sulfate, and 4 moles of Na-carbonate treated with ca. 8 moles of isobutyraldehyde, refluxed 30 hrs. with efficient stirring, more aldehyde added, and refluxing continued ca. 0.5 hr. until most of the blue color of the cupric ions is discharged -hydroxy-leucine. Y 67%. F. e. s. T. T. Otani and M. Winitz, Arch. Biochem. Biophys. 102, 464 (1963) with the amino acid Gu-chelate and KOH cf. H. Mix and F.-W.Wilcke, H. 337, 40 (1964). 

Isobutyraldehyde allowed to react with trimethylsilyl azide in the presence of ZnGlg 1-trimethylsiloxyisobutyl azide. Y 77%. F. e. and reactions s. L. Birkofer, F. Muller, and W. Kaiser, Tetrah. Let. 1967, 2781. 

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