Propionaldehydes addition reactions

Addition. Addition reactions of ethylene have considerable importance and lead to the production of ethylene dichloride, ethylene dibromide, and ethyl chloride by halogenation—hydrohalogenation ethylbenzene, ethyltoluene, and aluminum alkyls by alkylation a-olefms by oligomerization ethanol by hydration and propionaldehyde by hydroformylation. 

Catalytic aldol dimerizations of aldehydes sometimes lead to unexpected products. An example is shown in equation (12), where the initial aldol has formed an aldoxan derivative by interacting with a third equivalent of propionaldehyde. Although the aldoxan is dissociated to 1 mol each of the aldol and aldehyde upon distillation, the reaction effectively limits the yield of the aldol addition reaction itself to 66.7%. 

Interesting examples for conjugate additions mediated by chiral amines have been described by Alexakis et al. (Scheme 36), who used the nitroalkene 151 as a Michael acceptor in organocatalytic enamine-catalyzed conjugate addition reactions 149, 150, 153). Michael reaction of 151 with propionaldehyde 60 in the presence of the diamine catalyst 152 (15 mol%) gave 153 as a mixture of four diastereomers in good yield. Subsequent aldehyde protection and conversion of the... 

A cmde acetone product is recovered by distillation from the reaction mass. One or two additional distillation columns may be required to obtain the desired purity. If two columns are used, the first tower removes impurities such as acetaldehyde and propionaldehyde. The second tower removes undesired heavies, the major component being water. 

Reactions with Alcohols. The addition of alcohols to acrolein may be catalyzed by acids or bases. By the judicious choice of reaction conditions the regioselectivity of the addition maybe controlled and alkoxy propionaldehydes, acrolein acetals, or alkoxypropionaldehyde acetals produced in high yields (66). 

Garbonylation of Olefins. The carbonylation of olefins is a process of immense industrial importance. The process includes hydroformylation and hydrosdylation of an olefin. The hydroformylation reaction, or oxo process (qv), leads to the formation of aldehydes (qv) from olefins, carbon monoxide, hydrogen, and a transition-metal carbonyl. The hydro sdylation reaction involves addition of a sdane to an olefin (126,127). One of the most important processes in the carbonylation of olefins uses Co2(CO)g or its derivatives with phosphoms ligands as a catalyst. Propionaldehyde (128) and butyraldehyde (qv) (129) are synthesized industrially according to the following equation ... 

A mixture of 2.9 grams of 5-chloro-2,4-disulfamvl-aniline in 20 ml of anhydrous diethylene-glycol dimethylether, 0.44 gram of propionaldehyde and 0.5 ml of a solution of hydrogen chloride in ethyl acetate (109.5 grams hydrogen chloride per 1,000 ml) Is heated to 80° to 90°C and maintained at that temperature for 1 hour. The reaction mixture is concentrated under reduced pressure on addition of water, the product separates and is then recrystal-lized from ethanol or aqueous ethanol to yield the desired 6-chloro-3-ethvl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide, MP 269° to 270°C. 

A closer examination by ex situ analysis using NMR or gas chromatography illustrates that intrazeolite reaction mixtures can get complex. For example photooxygenation of 1-pentene leads to three major carbonyl products plus a mixture of saturated aldehydes (valeraldehyde, propionaldehyde, butyraldehyde, acetaldehyde)38 (Fig. 33). Ethyl vinyl ketone and 2-pentenal arise from addition of the hydroperoxy radical to the two different ends of the allylic radical (Fig. 33). The ketone, /i-3-penten-2-one, is formed by intrazeolite isomerization of 1-pentene followed by CT mediated photooxygenation of the 2-pentene isomer. Dioxetane cleavage, epoxide rearrangement, or presumably even Floch cleavage130,131 of the allylic hydroperoxides can lead to the mixture of saturated aldehydes. 

Nearly quantitative generation of l,3-bis(methylthio)allyllithium was proved, as this solution yielded l,3-bis(methyIthio)propene (88-89%) and l,3-bis(methylthio)-l-butene (89%) by reaction with methanol and methyl iodide, respectively. The checkers found that lithium diisopropylamide can be replaced by w-butyllithium without any trouble for the generation of l,3-bis(methylthio)allyllithium, simplifying the procedure considerably at least in this particular case. Subsequent reaction with propionaldehyde gave l,3-bis(methylthio)-l-hexen-4-ol in 85% yield, and no appreciable amount of by-product, such as the addition product of w-hutyllithium with propionaldehyde or with the intermediate 1.3-bis(methylthio)propene, was formed. 

Butenes were subjected to photosensitized reaction with molecular oxygen in methanol. 1-Butene proved unreactive. A single hydroperoxide, l-butene-3-hydroperoxide, was produced from 2-butene and isolated by preparative gas chromatography, Thermal and catalyzed decomposition of pure hydroperoxide in benzene and other solvents did not result in formation of any acetaldehyde or propionaldehyde. The absence of these aldehydes suggests that they arise by an addition mechanism in the autoxidation of butenes where they are important products. l-Butene-3-hydroperoxide in the absence of catalyst is converted predominantly to methyl vinyl ketone and a smaller quantity of methyl vinyl carbinol —volatile products usually not detected in important quantities in the autoxidation of butene. 

Reaction of various aldehydes with hydrogen sulfide leads to substituted thiophenes, dihydrothiophenes, dithiolanes and trithiolane, as well as to six-membered ring thiopyran derivatives and dithiins. Ledl (33) obtained 2,4-dimethylthiophene (1, R Me) as a product of the reaction of propionaldehyde with hydrogen sulfide in the presence of ammonia. Sultan (29) reported the formation of 2,4-diethylthiophene (1, R - Et), 2,4-dibutyl-thiophene (1, R - Bu), and their dehydro derivatives from the reaction of ammonium sulfide with butyraldehyde and caproaldehyde (hexanal), respectively. The mechanism suggested for their formation is depicted in Scheme 1. Space limitations do not allow us to discuss the mechanism here in detail (for additional information, see ref. 29). 

Addition to formaldehyde [378] and other aldehydes [379,380] proceeds with high absolute stereoselectivity for the (5f )-configurated products (configurational reference changes for any substrate larger than formaldehyde ). In contrast, no or only a low level of relative acceptor diastereoselectivity at the chiral C-6 was determined in the reactions with acetaldehyde (6S/6R 1 1) [379] and propionaldehyde (130/131 = 1 2.4) [380] as the stereochemical probes. 

NMA+) and 2,4,6-triphenyl-pyrylium tetrafluoroborate (TPP+) in the presence of biphenyl as cosensitizer were suitable for this reaction [174], The assumed mechanism of formation of do by this cosensitization is shown in Scheme 7. Reaction of do with H-donors such as te/t-butylmethylether, propionaldehyde and alcohols results in the formation of 1 1 adducts, the 1-substituted 1,2-dihydro-[60]fullerenes. Product structure support a H-abstraction process [212,213] rather than nucleophilic addition. In Scheme 8, the general formation of 1-substituted l,2-dihydro-[60]fullerenes is shown. Selected examples of the products obtained by this method are summarized in Table 10. 

S)-Proline also catalyzed the Mannich-type reactions of unmodified aldehydes and N-PMP-protected imines to afford the corresponding enantiomerically enriched / -aminoaldehydes at 4 °C (Table 2.13) [71b]. The products were isolated after reduction with NaBH4, though oxidation to the / -amino acid is also possible. These reactions also provided the syn-isomer as the major diastereomer with high enantioselectivities, and proceeded well in other solvents (e.g., dioxane, THF, Et20). In the reaction of propionaldehyde and the N-PMP-imine of 4-nitrobenzaldehyde in DMF, the addition of water (up to 20%, v/v) did not affect the enantioselectivity. Similar results were obtained for the (S)-proline-catalyzed Mannich-type reactions with the glyoxylate imine where water did not reduce enantioselectivity [71b]. However, the enantioselectivity of the reaction of propionaldehyde and the N-PMP-imine of benzaldehyde in DMF was decreased by the addition of water or MeOH [71b]. 

Conditions Entries 1-3 To a mixture of ArCHO (0.5 mmol), 4-methoxyaniline (0.5 mmol), and (S)-proline (0.15 mmol) in DMF (3 mL), donor aldehyde (5.0 mmol) in DMF (2 mL) was slowly added (0.2 mL min-1) at —20 °C. The mixture was stirred at the same temperature for 4-10 h. The mixture was diluted with Et20 and reduction performed by addition of NaBH4 [71b]. Entries 4 and 5 After stirring a solution of ArCHO (1.0 mmol), 4-methoxyaniline (1.1 mmol), and (S)-proline (0.1 mmol) in N-methyl-2-pyrrolidinone (1.0 mL) for 2 h at rt, propionaldehyde (3.0 mmol) was added to the mixture at -20 °C, and stirring was continued for 20 h at the same temperature. The reaction was worked-up and reduction with NaBH4 performed without purification [82]. 

S)-proline-catalyzed reaction using propionaldehyde as donor and the results showed that the imine reactivity was approximately sevenfold higher than that of the aldehyde [83]. Under basic conditions, it is generally accepted that nucleophilic addition to an aldehyde is typically faster than addition to an aldimine, but nucleophilic addition to an aldimine is faster than addition to an aldehyde when protonation of the imine nitrogen occurs [83]. In the (S)-proline-catalyzed three-component Mannich reactions in the absence of arylaldehyde, self-Mannich products were obtained with moderate to high diastereo- and enantioselectivities (Scheme 2.19) [71b, 82]. 

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]. 

Additions of various organic iodides to propionaldehyde /V-acylhydrazone 3a were examined in order to evaluate the scope of the reaction with respect to the radical component. In the presence of ZnCL, radical additions proved successful with secondary and tertiary iodides in moderate yields (Table 3, entries 1-4), while primary and allylic radicals were ineffective under these conditions (entries 5 and 6). Ethyl radicals generated from triethylborane can compete for the radical acceptor and, as a result, the separable ethyl radical adduct 12a (Scheme 2) was observed (<10% yield) in all cases. 

Addition of carbon monoxide and hydrogen to an alkene linkage in the presence of cobalt catalysts gives aldehydes in an average yield of 50%. The reactions may be carried out in the usual hydrogenation apparatus. The poisonous properties of carbon monoxide and cobalt carbonyls call for considerable care. Compounds made by hydroformylation include cyclopentanealdehyde from cyclopentene (65%), /3-carbethoxy-propionaldehyde from ethyl acrylate (74%), and ethyl /3-formylbutyrate from ethyl crotonate (71%). 

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