Aliphatic aldehydes, isobutyraldehyde

At present, most enamine-catalyzed aldol reactions are reliable only with electron-poor aromatic aldehyde acceptors, hi addition, a handful of aliphatic aldehydes (e.g. isobutyraldehyde or pivalaldehyde) are often used as acceptors. The use of unbranched aldehyde acceptors is difficult, and generally only modest yields have been obtained. In addition, unsaturated aldehydes are curiously absent from the list of commonly used acceptors. On a positive side, it should be noted that even potentially racemizing a-chiral aldehydes have been employed as acceptors. As an example, in the recent synthesis of caUipeltoside C, MacMillan and coworkers were able to employ protected Roche aldehyde 113 as a starting material (Scheme 22) [204]. 

The oxidation of 2-ethylhexan-l-ol to 2-ethyl-hexanal by the Oppenauer oxidation with aliphatic aldehydes such as acetaldehyde, propionaldehyde, and isobutyr-aldehyde has been investigated with gas-phase reactants and MgO as the catalyst (196). Reaction with propionaldehyde was found to be an effective synthetic route for 2-ethylhexanal preparation, whereas with acetaldehyde and isobutyraldehyde a gradual catalyst deactivation in a flow reactor was observed. 

C), various (hetero)aromatic aldehydes were transformed into nitroalcohols 1-6 in consistently high yields (90-99%) and ee values (86-92%) as shown in Scheme 6.146. The protocol failed for aliphatic aldehydes such as cyclohexanecar-boxaldehyde and isobutyraldehyde that displayed incomplete conversion to the respective nitroalcohols even after 1 week reaction time and gave low ee values (<20%) of the adducts. Catalyst 132, the pseudoenantiomer of 131, gave access to nitroalcohols with the opposite configuration and comparable enantiomeric excess, as exemplified for three aldehydes (e.g., (R)-adduct 3 87% yield 93% ee). 

Primary aliphatic aldehydes such as RCH2CH=0 react with ammonia to give addition compounds called aldehyde ammonias. These compounds can be converted into the starting materials again, or they may lose water to give imines which then polymerize. Secondary aliphatic aldehydes such as R2CHCH=0 react with ammonia by a different course. For example [10a, b], isobutyraldehyde reacts with ammonia to give the products shown in Eq. (5). 

Other aliphatic aldehydes have been identified and quantitatively measured in various brandies (31, 32). These include small amounts of formaldehyde, propionaldehyde, isobutyraldehyde, isovaleraldehyde, furfural, etc. Furfural is a normal component of pot-still distillates, but its presence in continuous still brandies is negligible before aging in wood. 

Fig. 5.3. Gas chromatogram of 2,4-dinitrophenylhydrazones of ten aliphatic aldehydes. Peaks 1 = formaldehyde 2 = acetaldehyde 3 = propionaldehyde 4 = acrolein 5 = isobutyraldehyde 6 = n-butyraldehyde 7 = isovaleraldehyde 8 = n-valeraldehyde 9 = crotonaldehyde 10 = n-capronaldehyde. For conditions see text. (Reproduced from / Chromatogr., 120 (1976) 379, by courtesy of Y. Hoshika.)...

Data for aliphatic aldehyde enolisation are very scarce, probably because the enolisation process is often complicated by oxidation and hydration. Nevertheless, the rate constants for base- and acid-catalysed iodination of R R2CHCHO were determined in aqueous chloroacetic acid-chloroacetate ion buffers (Talvik and Hiidmaa, 1968). The results in Table 4 show that alkyl groups R1 and R2 increase the acid-catalysed reactivity in agreement with hyperconjugative and/or inductive effects. This contrasts with aliphatic ketones for which steric interactions are important and even sometimes dominant. Data for base-catalysis are more difficult to interpret since a second a methyl group, from propionaldehyde to isobutyraldehyde, increases the chloroacetate-catalysed rate constant. This might result from a decrease of the a(C—H) bond-promoted hyperconjugative stabilisation of the carbonyl compound... 

Oxidative coupling of aUelfydesJ Aliphatic aldehydes bearing an ci-hydrogcn atom on treatment with activated manganese dioxide undergo x-hydrogen abstraction and C-C and C-O dimerization. For example, isobutyraldehyde (I) is converted in about... 

Aliphatic aldehydes are among the most important components used in perfumery. Although the lower fatty aldehydes C2-C7 occur widely in nature, they are - with the exception of hexanal - seldom used in fragrance compositions. The lower aldehydes (e.g., acetaldehyde, isobutyraldehyde, isovaleraldehyde, and 2-methyl-butyral-dehyde) impart fruity and roast characters to flavor compositions. Fatty aldehydes C8-C13, however, are used, singly or in combination, in nearly all perfume types and also in aromas. Their odor becomes weaker with increasing molecular mass, so that aldehydes >Ci3 are not important as perfume ingredients. 

Extension to aliphatic aldehydes leads to the 2,4,6-trialkyl-5-phenyl derivatives (342). When H3PO2 is refluxed in toluene with benzaldehyde or isobutyraldehyde the phosphinic acids (343 R = Ph, Pr ) are formed <68IZV397, 92EUP463994>. Di(hydroxymethyl)phosphines (344) react with aldehydes, ketones and acetals to form the 2-mono- or 2,2-disubstituted 1,3,5-dioxaphosphinanes (345) <86IZV2506,86ZOB2256>. With triethyl orthoformate the 2-ethoxy derivatives (346) are obtained (Scheme 70) <86IZV418, 86IZV640>. 

Condensation of 273 with urea/thiourea and an aliphatic aldehyde provided bicyclic and tricyclic derivatives 277 and 278. Thus, 273 (n = 2 and 3) with thiourea (X = S) and isobutyraldehyde gave 277 (Scheme 108). Similarly, 277 was derived from 273 (n = 4 and 8) and series of aliphatic aldehydes. 278 was obtained from 273 (n = 1) with thiourea (X = S) and isobutyraldehyde and -heptaldehyde. Urea, 273 (n = 8) and isobutyraldehyde or -heptaldehyde furnished 277 (X = O) (Scheme 108) (05EJO2354). 

Some of the highest ees are obtained with ligand (6.61) 8 and (6.62). The former also shows good scope and catalyses the cyanation of aliphatic aldehydes such as isobutyraldehyde with up to 95% ee. Ligand (6.60) is notable for its high catalytic efficiency in this procedure, since only 0.1 mol% is required. 

The one- and two-carbon aldehydes, formaldehyde and acetaldehyde, are gaseous products at ambient temperatures. Formaldehyde boils at -2PC while acetaldehyde boils at 20 C. Formaldehyde is most often used as a 37-55 wt% aqueous solution or as an alcoholic solution containing some 55 wt% formaldehyde. Methanol and n-butanol are the two alcohols often used for the formaldehyde solutions. Other aliphatic aldehydes useful as chemical intermediates include propionaldehyde (b.p. 48 C) and two butyl aldehydes, rt-butyraldehyde (b.p. 75"C) and isobutyraldehyde (b.p. 64"C). The one commercially important heterocyclic aldehyde, furfural, is a high boiling-point (161.7 0 liquid. 

The aliphatic aldehydes, except isobutyraldehyde, generally provide poor yields. 

Higher Aliphatic Aldehydes Propionaldehyde and isobutyraldehyde reiict with aqueous formaldeliyde in a manner analogous to that observed in the case of acetaldehyde. 

The effect of cryptands on the reduction of ketones and aldehydes by metal hydrides has also been studied by Loupy et al. (1976). Their results showed that, whereas cryptating the lithium cation in LiAlH4 completely inhibited the reduction of isobutyraldehyde, it merely reduced the rate of reduction of aromatic aldehydes and ketones. The authors rationalized the difference between the results obtained with aliphatic and aromatic compounds in terms of frontier orbital theory, which gave the following reactivity sequence Li+-co-ordinated aliphatic C=0 x Li+-co-ordinated aromatic C=0 > non-co-ordinated aromatic C=0 > non-co-ordinated aliphatic C=0. By increasing the reaction time, Loupy and Seyden-Penne (1978) showed that cyclohexenone [197] was reduced by LiAlH4 and LiBH4, even in the presence of [2.1.1]-cryptand, albeit much more slowly. In diethyl ether in the absence of... 

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. 

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