Reduction of Methyl Butyrate

In this reaction, the initial reactant methyl butyrate is reduced by diisobutyla-luminum hydride (Dibal-H) toluene to an unstable organometallic intermediate [38]. In a second step, the intermediate is further reduced to butyraldehyde, which is the desired product. A further reduction leads to the unwanted formation of 

This consecutive reaction shows high sensitivity to mixing as well as to temperature variations. Whereas in a lab-scale batch reactor 63% of the target product C is obtained only at temperatures lower than 218 K, similar selectivity 

Reactions with Grignard Reagent in Muiti-injection Reactor 

In order to work safely with multi-injection reactor, an accumulation of the limiting reactant and of heat in the main channel has to be thoroughly prevented. As the considered reactions are mostly Umited by mixing, the time required to mix can be estimated by using the correlation between specific energy dissipation and mixing time. Sufficient residence time should be provided between two injection points to minimize the hot spot. 

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Figure 5.33 Reaction scheme of the reduction of methyl butyrate [38].

Dibal-H reduction of methyl butyrate into butyraldehyde using microreactors. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

Reduction of the quaternary immonium salt 161, obtained by treatment of l-methyl-2-ethylidenepyrrolidine with ethyl bromoacetate, by means of either sodium borohydride or formic acid, leads to (—)-erythro-2-(2-N-methylpyrrolidyl)butyric acid (162), in agreement with Cram s rule (196). 

Reductions of keto esters to esters are not very frequent. Both Clemmensen and Wolff-Kizhner reductions can hardly be used. The best way is desulfurization of thioketals with Raney nickel (p. 130). Thus ethyl acetoacetate was reduced to ethyl butyrate in 70% yield, methyl benzoylformate (phenylglyoxy-late) to methyl phenylacetate in 79% yield, and other keto esters gave equally high yields (74-77%) [82J]. 

A very interesting modification of method B was applied to the stereospecific synthesis of ( )-pseudoheliotridane.27 Condensation of ethyl bromoacetate with l-methyl-2-ethyl-4,5-dihydropyrrole (42) afforded the quaternary salt 43, which was reduced, without isolation, with formic acid to give ethyl /3-(Ar-methyl-2-pyrrolidyl)butyrate (44). The amino alcohol (45), obtained by reduction of 44 with lithium... 

The latter complex undergoes CO loss to generate coordinatively unsaturated 4.28. Conversion of 4.28 to 4.30 is the crucial step that is responsible for the formation of the branched isomer. Obviously this reaction is possible only when propylene is present as one of the reactants, or under reaction conditions where propylene from //-propanol is generated in situ. Conversion of 4.28 to 4.30 is an example of alkene insertion into an M-H bond in a Markovnikov manner (see Section 5.2.2 for a discussion on Markovnikov and anti-Markovnikov insertion). The anti-Markovnikov path leads to the formation of 4.29, which is in equilibrium with 4.24. Complexes 4.25 and 4.26 are analogues of 4.4 with //-butyl and /-butyl groups in the place of methyl. They reductively eliminate the linear and branched acid iodides. In the presence of water the acid iodides are hydrolyzed to give //-butyric and / -butyric acids. 

The D-enantiomer of 393 was obtained in an identical sequence of reactions starting frc m 2,3-0-isopropylidene-4-deoxy-D-threitol (395). This compound was prepared from L-threonine (394) in the following way the amino acid was deaminated to 25 3/ -dihydroxy-butyric acid. Esterification of the carboxyl group and protection of both hydroxyl groups with an isopropylidene grouping gave methyl 4-deoxy-2,3-0-isopropylidene-D-threonate. Reduction of the ester group afforded 395 smoothly. 

The asymmetric reduction of keto-esters via hydrosilylation has also been achieved in the presence of chiral rhodium catalysts. a-Keto-esters give the corresponding lactates after hydrolysis, and by varying the hydrosilane the optical yield can be increased to 85%. Acetoacetates give the corresponding 3-hydroxy-butyrate, but in much lower optical yield (ca. 20%), whereby levulinates give chiral 4-methyl-y-butyrolactones with optical yields of up to 84% [equation (4)]. 

Baek et al. [110] prepared pyrrolidium-based ILs carrying different substituents including butyl, butyronittile, pentenyl, and methyl butyrate (Scheme 8.7). The nitrile- and ester-functionalized ILs show higher viscosities and lower conductivities than the other two. Their potential windows (vs. Li/LP) fall in the range of 4.19. 97 V and are primarily dependent on the oxidation power of the functional group on cations. It was also found that the peak currents at the reduction on the graphite electrode were 100 times stronger in butyl- and pentenyl-substituted ILs than in nitrile- and butyrate-functionalized ILs. 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

Challenger and Harrison found both thienothiophene 1 and its isomer 2 in the products of the reaction between acetylene and sulfur. To identify these compounds, Challenger et developed syntheses of unsubstituted and 2-alkyl-substituted thieno[3,2-f>]thiophene (2) from thiophene derivatives. Cyclization of (3-thienylthio)acetic acid in the presence of sulfuric acid gave 2,3-dihydrothieno[3,2-6]thiophen-3-one (22) (R = H) in 14% yield reducing the latter with lithium aluminum hydride resulted in thienothiophene (2) formation in 80% yield [Eq. (9)]. Similarly 2-methyl- and 2-ethyl-2,3-dihydrothieno[3,2-/>]thiophen-3-one were obtained from a-(3-thienylthio)propionic and a-(3-tWenylthio)-butyric acids in 30% and 27% yields, respectively their reduction yielded 2-methyl (32%) and 2-ethylthieno[3,2-6]thiophenes (52%). The parent acids were prepared from 3-mercaptothiophene. ... 

Ring closure of substituted 3-(2-furyl)butyric acids and 3-(3-furyl)-butyric acids (or their chlorides) should lead to 4,5,6,7-tetrahydro-benzofuran-4(or 7)-ones. The former should give the corresponding 4-hydroxybenzofurans or benzofurans (by reduction and dehydrogenation). While the ring closure of 3-(5-methyl-2-furyl)butyryl chloride (330, R = Me) actually affords 331 (R = Me 77% yield),740 the... 

We have studied the electrolysis of y-butyrolactone (BL) and methyl formate (MF) in TBAP solutions. A typical voltammogram of y-BL/TBAP with a gold electrode is also shown in Figure 1. Butyrate (CH3CH2CH2COO ) and a cyclic (3-keto ester were identified as the major electrolysis products. The latter is a product of a nucleophilic attack of y-BL anion (in the a position) on the carbonyl center of another molecule [3], The FTIR spectra of this product, as well as its lithiated derivative, are shown in Figure 2. The basic reduction mechanisms of y-BL, based on the above product analysis, as well as on other arguments [3], are presented in Scheme 2. 

The most important esters in connection with Li batteries are y-butyrolactone (BL) and methyl formate (MF). Li is apparently stable in both solvents due to passivation. Electrolysis of BL on noble metal electrodes produces a cyclic 0-keto ester anion which is a product of a nucleophilic reaction between a y-butyrolactone anion (produced by deprotonation in position a to the carbonyl) and another y-BL molecule. FTIR spectra measured from Li electrodes stored in y-BL indicate the formation of two major surface species the Li butyrate and the dilithium cyclic P-keto ester dianion. The identification of these products and related experimental work is described in detail in Refs. 150 and 189. Scheme 3 shows the reduction patterns of y-BL on lithium surfaces (also see product distribution in Table 3). In the presence of water, the LiOH formed on the Li surfaces due to H20 reduction attacks the y-BL nucleophilically to form derivatives of y-hydroxy butyrate as the major surface species [18] [e.g., LiO(CH2COOLi)]. We have evidence that y-BL may be nucleophilically attacked by surface Li20, thus forming LiO(CH2)3COOLi, which substitutes for part of the surface Li oxide [18]. MF is reduced on Li surfaces to form Li formate as the major surface species [4], LiOCH3, which is also an expected reduction product of MF on Li, was not detected as a major component in the surface films formed on Li surfaces in MF solutions [4], The reduction paths of MF on Li and their product analysis are presented in Scheme 3 and Table 3. 

Oxidation of coniine with chromic acid produces butyric acid (115, 124), while dehydrogenation of the alkaloid with silver acetate converts it to abase, conyrine (125), which is also obtained from coniine hydrochloride by distillation with zinc dust (126). Conyrine, CgHnN, is a colorless, fluorescent oil, b.p. 166-168°, which forms a chloroplatinate and an aurichloride it can be converted back to coniine by reduction with hydriodic acid, it behaves on methylation like a pyridine base, and further, it gives rise on oxidation to a-pyridinecarboxylic acid. Therefore, conyrine is a 2-propylpyridine (XCIV) while coniine is a 2-propylpiperidine (XCV) (126), in which the side chain is normal since conyrine is not identical with 2-isopropylpyridine (127). 

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