Alkylation aldehydes with alcohols

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

In the case of the bases derived from quaternary heterocyclic ammonium salts, the carbinolamines (5) can react as cyclic aldehyde-ammonias with many reagents with which the amino-aldehyde (7) could react. However, reactions of the carbinolamines which are not characteristic of amino-aldehydes are also known. Carbinolamines can easily be reconverted into the quaternary salts by the action of dilute acids, and they form alkyl ethers very easily with alcohols. If these last reactions do not occur, then this is convincing evidence for the base possessing the amino-aldehyde structure. However, if these reactions do occur this does not provide unambiguous confirmation of the carbinolamine structure. They are also given by the bi-molecular ethers (8), and, in the case of a tautomeric equilibrium... 

When the additional nitrogen atom is included in one of the aromatic rings, on the other hand, there is obtained a compound with antihistaminic properties. Reaction of the Grignard reagent from 4-chlorobromobenzene with pyridine-2-aldehyde gives the benzhydrol analog (12). The alcohol is then converted to its sodium salt by means of sodium, and this salt is alkylated with W-C2-chloroethyl)dimethylamine. Carbinoxamine (13) is thus obtained. ... 

Reaction of lithiated allylbenzotriazole 452 with chloromethyltrimethylsilane yields silyl derivative 464 which can be further alkylated to give compound 465 (Scheme 76) <1999JOC1888>. Upon heating, product 465 is readily converted to diene 466 via vicinal elimination of benzotriazolyl and silyl substituents. Additions of lithiated silyl derivative 464 to carbonyl groups of aldehydes lead to alcohols 463 which readily eliminate benzotriazole and silane to furnish 2-(l-hydroxyalkyl)butadienes 466 (R1 = 1-hydroxyalkyl). 

Eleven aromatic and aliphatic aldehydes have been alkylated with Et2Zn in the presence of homoannularyl bridged hydroxyamino ferrocene (—>123. The resulting carbinols have ee values varying from 66% to 97%. This new ferro-cenyl catalyst has been used successfully to alkylate aromatic and linear or branched chain aliphatic aldehydes to secondary alcohols with up to 97% ee. This ligand is effective even for -branched aliphatic substrate. 

Treatment of the alcohol 211 with f-butyklimethylsilyl triflate and 2,6-lutidine affords disiloxyester 212 with high yield. Reduction of the ester function of 212 with DIBAL followed by Swern oxidation gives the corresponding aldehyde 213, and subsequent alkylation with MeMgBr and Swern oxidation produce methyl ketone 214 (Scheme 7-70). 

Alkylzinc iodides These reagents are prepared by reaction of alkyl iodides with Zn/Cu in toluene-N,N-dimethylacetamide (DMA). In the presence of 1 equiv. of chlorotrimethylsilane they can add to aldehydes to form alcohols. DMA may be replaced as the cosolvent by N-methylpyrrolidone (NMP), but HMPT retards this reaction. This reaction can be used to obtain y-, 8-, and e-hydroxy esters from P-, y-, and 8-zinc esters (equation I). 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

Some chiral 1,3,2-dioxastannolanes were used as catalysts in asymmetric Diels-Alder reactions of cyclopentadiene with methyl acrylate <90JCR(S)278>. A-Alkenyl- and -cycloalkenyl 1,3,2-oxaza-stannolanes, generated in situ from chiral amino alcohols, gave optically active 2-substituted aldehydes and ketones in modest to high chemical and optical yields after alkylation with methyl acrylate or acrylonitrile (which is usual for enamines) and subsequent hydrolysis <85CC504,85JOC3863>. 

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

For example, with the Co-I-PPh catalyst, methyl acetate reacts with synthesis gas to form ethyl acetate. All of the primary and secondary alcohols tested (C thru C ) decompose during long-term operation. The major decomposition products include aldehydes, alkyl iodides, and ethers. Ketones are readily hydrogenated and the resulting alcohols decompose. Good solvents in terms of stability are diphenyl ether and alkanes. The acetaldehyde rate is somewhat low (1.8 M/hr) in diphenyl ether, and the selectivity is low in alkanes. In addition, these solvents do not have good solubility properties, especially in product refining. 

In addition to alkylation with alkyl halides, electrophilic amination has been achieved with di-(/< /r-butyl) azodi-carboxylate <2004HCA1016>, and reactions with aldehydes have generated alcohol derivatives <1999JOC8668, 2003TL671>. Dialkylation at the 5-position has also been achieved <1998TA3881>. 

The N-alkylation of amines with alcohols [63] can also be carried out with Ir catalysts through a similar domino sequence reaction. In this case, the aldehyde/ketone resulting from oxidation is condensed with an amine to the corresponding imine, which is hydrogenated to the alkylated amine [63]. By way of example, the reaction of benzyl alcohol with aniline in toluene afforded benzylaniline in a 88% isolated yield by using catalytic amounts of [ lr(/z-Cl)Cp Cl 2]/K2C03. 

More recent patents describe the following preparation from a-methylcinnam-aldehyde. a-Methylcinnamaldehyde (from benzaldehyde and propionaldehyde) is hydrogenated to a-methyldihydrocinnamic alcohol. The alcohol is alkylated with tert-butyl chloride or isobutene to 4-tert-butyl-o -methyldihydrocinnamic alcohol, which is subsequently dehydrogenated to the desired aldehyde [152, 153]. 

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