Di-C-alkylation

A mixture of C-alkyl-ethylene diamine and di-(C-alkyl)-diethylenetriamine, with an alkyl side chain of 8 to 26 carbon atoms is suitable [ 1876] as a corrosion inhibitor. This product can be further reacted with an alkylating agent or an alkylene oxide [836,837]. 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

Alkylation of 2-ethoxycarbonylcyclohexanone, followed by hydrolysis and decarboxylation, has been used as a convenient route to 2-alkylcyclohexanones [74, 92]. Polymer-supported catalysts have also been used [e.g. 93] 2-acylcyclohexanones are C-alkylated at the 2-position almost exclusively, whereas cyclohexane-1,3-dione produces a mixture of mono- and di-C-alkylated products, together with the O-alkylated derivative. In all cases, less polar solvents promote the O-alkylation. 

Rust (Ref la) patented the use of this other di-c-alkyl peroxides as polymerization catalysts diesel oil additives Refs 1) Beil-not found la) W.E. Vaughan F.F. Rust, USP 2403771(1946) CA 40, 5757(1946) 2) N.A. Milas D.M. Surgenor,... 

Y. Ali and W. A. Szarek, Synthetic approaches to gem-di-C-alkyl derivatives of carbohydrates Nucleophilic addition reactions of 3-C-methylene compounds derived from l,2 5,6-di-0-isopropylidene-ot-D-rifto-hexofuranos-3-ulose using phase transfer catalysis, Carbohydr. Res. 67 Cll (1978). 

Depending on the temperature and the reaction time, the solvent-free iodination of 1 with I2 in a sealed tube allowed the regioselective synthesis of 9-iodo-o-carborane (17, 97% yield), 9,12-diiodo-o-carborane (18, 62% yield), and 8,9,10,12-tetraiodo-o-carborane (26, 93% yield. Scheme 6.4) (Barbera et al., 2008 Vaca et al., 2006). Shorter reaction times were reqnired when mono/di-C-alkyl- and mono/di-C-aryl-substituted o-carboranes were iodinated nsing the same method (Barbera et al., 2008). Tetraiodination of 1,2-diphenyl-o-carborane (27) and 1,2-dimethyl-o-carborane (28) required only 3.5 h and 2.5 h, respectively, to give 29 and 30. These results were in agreement with previous studies showing that the presence of methyl substituents at the carbon atoms increased the electron density at the boron atoms of 1 (Boer et al., 1966 Pbtenza and Lipscomb, 1966). 

V-Alkylaniline and /V,/V-di alkyl aniline hydrochlorides can be rearranged to C-alkyl anilines by heating the salts to 200—300°C. In this reaction, known as the Hofmann-Martius rearrangement, the alkyl group preferentially migrates to the para position. If this position is occupied, the ortho position is alkylated. 

Solvent dependence of k, for di-r-alkyl peroxides is small when compared to most other peroxide initiators.128 212 For di-/-butyl peroxide,128 d is slightly greater (up to two-fold at 125 °C) in protic (/-butanol, acetic acid) or dipolar aprotic solvents than in other media (cyclohexane, triethylamine, tetrahydrofuran). 

The effect of C ,C -disubstituted amino acids (aaAAs) on peptide secondary structure has been studied in recent years.2a d While longer side-chain C ,C -di-n-alkyl amino acids promote extended peptide conformation,23 alicyclic aaAAs, in which the Ca carbon forms a cyclic bridge with itself, such a 1-aminocyclopentane-l-carboxylic acid (Ac5c) and 1-aminocyclohexane-l-carboxylic acid (Ac6c), have helix-forming characteristics similar to those of 1 -aminoisobutyric acid (Aib).2ax... 

Lindblom and Blander (1980) have given a number of examples of relevance in the pharmaceutical industry. These include C-alkylations, 0-alkylations, and A-alkylations. The C-alkylation of phenylacetonitrile, (mono- and di-) alkylation of benzylpenicillin with a-chlorodiethyl carbonate (where the acid part and the halide part in the esterification would have degraded quickly under normal conditions adopted for the reaction), A-alkylation of purines and adenine, etc. are discussed at some length and the supremacy of PTC is clearly shown. 

Isopropylbenzene (A) is alkylated with propylene (P) using HF catalyst. The mono (B), di (C), tri (D) and tetra (E) derivatives are formed. Relative specific rates are given by Rodiguin Rodiguina (Consecutive Chemical Reactions, 1964) for the case of a large excess of propylene which makes the reactions pseudo first order. The relative specific rates used here are kx = 1.0, k2 = 0.5, k3 = 0.3 and k4 0.2. The system of linear differential... 

Tetralone is readily mono- or di-alkylated at the 1-position to the exclusion of O-alky lation with a range of alkylating agents under liquiddiquid two-phase conditions without an added solvent [24], Similarly, it has been reported that anthrone undergoes mono- and di-C-alky lation at the 10-position with propargyl and allyl halides to the almost complete exclusion of O-alkylation [25]. It has been claimed that methyl-ation yields 9-methoxyanthracene [26],... 

C-Alkylation of 2-oxazolin-5-ones under catalysed mildly basic conditions provides a convenient route to a-branched a-amino acids (50-80%) [126]. Similarly, A-alkyloxindoles are mono- and di-alkylated at the 3-position [127], For other examples of the alkylation of heteroaryl systems, see Chapter 5. 

O-alkylation reduces the yield of the more usually desired C-alkylation product. Other drawbacks to the synthetic utility of this reaction are (1) di- and tri-alkylation produces mixtures if more than a single H is present on the a C (2) ketones with H s on more than one a C will give a mixture of alkylation products. 

Isopropylbenzene (A) is alkylated with propylene (P) using HF catalyst. The mono (B), di (C), tri (D) and tetra (E) derivatives are formed. Relative... 

Simple alkylation can be accomplished by use of trialkylaluminums which, with Lewis acids, afford 1-C-alkyl products such as 90, available in 72% yield by reaction between di-O-acetyl-6-deoxy-D-galactal and trimethylaluminum in the presence of titanium tetrachloride in dichloro-methane at —78 °C.109 Importantly, the reaction can also be applied to 1-alkylglycals, also with high stereoselectivity, so that the doubly substituted compound 91 can, for example, be made by allylation of tri-O-acetyl-l-C-methyl-D-glucal. Its C-l epimer is available by C-methylation of the 1-C-allylglucal.110... 

Scheme 3. Intramolecular C-H activation toward mono- and di-o-alkylation of palladacycles and norbornene deinsertion...

Biaryls were obtained by C-alkylation using 2,6-di-tert-butyl phenolate as nucleophile with/rara-chlorobenzonitrile and 2-chloro-5-cyanopyridine676. Bromobenzonitriles and bro-mocyanopyridines have been employed in a study in which it was demonstrated that these compounds can be successfully used to arylate monoanions of / -dicarbonyl compounds677. 

A number of 2-substituted imidazoles are also C-alkylated by soft electrophiles at C(4)/C(5). Thus, 2-phenylimida-zole reacts with 3-thienylmethyl bromide to give mainly 4- and 4,5-di-substituted products N-alkylation occurs only to a minor extent (Scheme 21). Similarly, 2-methoxybenzyl chloride gives rise mainly to C-substituted products benzyl bromide, a harder electrophile, gives largely iV-benzyl derivatives. 

More-detailed examination of the reaction between alkylidene(and arylmethylene)triphenylphosphonium ylides and aldehydo sugars was conducted9 8 -30 in our laboratory with 2,3 4,5-di-0-cycIohexylidene-aldehydo-D-xylose (and -L-arabinose), resulting in the preparation of l-C-alkyl-3,4 5,6-di-0-cycIohexylidene-1,2-dideoxy-D-xylo(and L-ara-hino)-hex-l-enitol (27a-27d and 28a-28d, respectivelyB([Pg.236]

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