Acyls alkylation

Dimethylaminopyridine [1122-58-3] (DMAP) (24) has emerged as the preferred catalyst for a variety of synthetic transformations under mild conditions, particularly acylations, alkylations, silylations, esterifications, polymeri2ations, and rearrangements (100). POLYDMAP resin [1122-58-3], a polymeric version of DMAP, is available, and is as effective as DMAP as a catalyst for acylation reactions. Furthermore, it can be recycled without regeneration more than 20 times with very Htde loss in activity. POLYDMAP is a trademark of Reilly Industries, Inc. 

The initiating step in these reactions is the attachment of a group to the sulfoxide oxygen to produce an activated intermediate (5). Suitable groups are proton, acyl, alkyl, or almost any of the groups that also initiate the oxidations of alcohols with DMSO (40,48). In a reaction, eg, the one between DMSO and acetic anhydride, the second step is removal of a proton from an a-carbon to give an yUde (6). Release of an acetate ion generates the sulfur-stabilized carbonium ion (7), and the addition of acetate ion to the carbonium ion (7) results in the product (eq. 15) ... 

Stannic chloride is also used widely as a catalyst in Eriedel-Crafts acylation, alkylation and cycHzation reactions, esterifications, halogenations, and curing and other polymerization reactions. Minor uses are as a stabilizer for colors in soap (19), as a mordant in the dyeing of silks, in the manufacture of blueprint and other sensitized paper, and as an antistatic agent for synthetic fibers (see Dyes, application and evaluation Antistatic agents). 

When large groups, such as phenyl, bromo, ethoxycarbonyl or nitro are attached at position 3, the principal products are l-alkylcinnolin-4(l/f)-ones. Cyanoethylation and acetylation of cinnolin-4(l/f)-one takes place exclusively at N-1. Phthalazin-l(2/f)-ones give 2-substituted derivatives on alkylation and acylation. Alkylation of 4-hydroxyphthala2in-l(2/f)-one with an equimolar amount of primary halide in the presence of a base leads to 2-alkyl-4-hydroxyphthalazin-l(2/f)-one and further alkylation results in the formation of 4-alkoxy-2-alkylphthalazinone. Methylation of 4-hydroxy-2-methyl-phthalazinone with dimethyl sulfate in aqueous alkali gives a mixture of 4-methoxy-2-methylphthalazin-l(2/f)-one and 2,3-dimethylphthalazine-l,4(2//,3//)-dione, whereas methylation of 4-methoxyphthalazin-l(2/f)-one under similar conditions affords only 4-methoxy-2-methylphthalazinone. 

FRIEDEL - CRAFTS Alkylation-Acylation Alkylation or acylation ol aromatic compounds by means of alryl halides, alcohols.alkenes, acyl halides in the presence of Lewis acids... 

The most efficient intramolecular secondary processes competing with the acyl-alkyl diradical recombination in five-membered and larger cyclic ketones are hydrogen shifts resulting in the disproportionation of the diradical to either ketenes or unsaturated aldehydes [cf. (5) (4) (6)]. 

Although these reactions are thus closely related to the acyl-alkyl diradical disproportionation to ketenes, the stereospecificity of (55) -> (56) and (57) -> (58) shows that these hydroxyketones cannot proceed through free radicals capable of rotating about single bonds prior to the intramolecular hydrogen... 

For further examples of acyl-alkyl diradical disproportionation reactions, see ref. 2 and 91. 

The initially formed ]5-dicarbonyl compounds are subject to further photo-transformations. One example is provided in the case of epoxy ketone (88), where the resulting /5-diketone (89) undergoes partly a-cleavage and acyl-alkyl... 

Acetylenedimagnesium bromide, 66, 84, 137 Acyl-alkyl diradical disproportionations, 299 Acyl-alkyl diradical recombination, 296 Alkaline hydrogen peroxide, 10, 12, 20 Alkylation of formyl ketones, 93 Alkylation via enolate anions, 86 17a-Alkynyl steroids from 17-ketones, 67 2a-Al]yl-17jS-hydroxy-5a-androstan-3 -one, 9 5 Allylic acetoxylation, 242 Allylmagnesium bromide, 64 17 -Aminoandrost-5-en-3 -ol, 145 17 a-Aminomethy 1-5 a-androstane-3, 1718-diol, 387... 

Homogeneous catalysis by lin compounds is also of great indusirial importance. The use of SnCU as a Friedel-Crafts catalyst for homogeneous acylation, alkylation and cyclizaiion reactions has been known for many decades. The most commonly used industrial homogeneous tin catalysis, however, are the Sn(ll) salts of organic acids (e.g. acetate, oxalate, oleale, stearate and ocToate) for the curing of silicone elasloniers and, more importantly, for the production of polyurethane foams. World consumption of tin catalysts for the.se Iasi applications alone is over 1000 tonnes pa. 

Phenyl-l-benzothiepin-3,5(2//,4//)-dione (8) (see Section 2.1.3.1.) is the precursor of 3,5-di-oxy-substituted 1-benzothiepins. The enolizable diketone can be transformed by acylation, alkylation, substitution or reduction reactions. 

Acetylated 1-thioaldoses react with alkenes in the presence of azobis(isobuty-ronitrile) (AIBN) to give acylated alkyl 1-thioglycosides.55... 

Two examples from ketone photochemistry that has been recently analyzed within the context of solid-to-solid transformations are the Norrish type and Nor-rish-Yang type Ip44,i45 tactions. In general terms, the type I reaction consists of a homolytic cleavage of bond a-to the carbonyl to generate an acyl-alkyl radical pair (RP-A) or an acyl-alkyl biradical (BR-A) when the ketone is cyclic (Scheme 7.15). 

R = H, oxy, hydroxy, acyl, alkyl, alkoxy A = O or NH X = H, sulpho, carboxyl Y = alkylene, arylene, substituted arylene (identical or different)... 

Intramolecular acyl alkylation affords cyclic carbene ligands, e.g., (t 5-C5H5)Ru(CO)2 + C1CH2CH2CH2CC1 -> (t 5-C5H5)(CO)2RuCCH2CH2CH2C1... 

Large changes in nitrogen hyperfine interaction are brought about by attachment either of alkoxyl groups or of acyl groups to the nitroxide nitrogen. In an alkoxy alkyl nitroxide, aN rises to nearly 30 G, whilst a typical acyl alkyl nitroxide has an aN-value of ca. 8 G, and in diacyl nitroxides this may fall below 5 G (Lemaire and Rassat, 1964). 

In most reported cases, the covalently bound chiral auxiliary has been attached to the dienophile via an acyl linkage, but there are also many examples known in which the auxiliary has been attached to the diene via an acyl, alkyl or heteroatom linkage, the first example of the latter being Trost s diene147. Lewis acids are often added to the reaction mixtures when the chiral auxiliary attached to the dienophile contains an additional Lewis basic site. This is not only to enhance the reaction rate, but especially to enhance the diastereofacial selectivity by complexing to the dienophile in a bidentate fashion. This makes the dienophile more conformationally rigid. 

This has been applied to the cyclization of dihalides [45, 46], nonconjugated, unsaturated ketones [47] and esters [48], oxoalkylpyridinium salts [49], aldehydes and unsaturated nitriles [50], halides, and unsaturated esters [51], The umpoled acceptors, mostly radical anions or carban-ions (see Scheme 1), can also be used in intermolecular reactions such as acylation, alkylation, or carboxylation (Eq. 5). 

Schwendener RA, et al. New lipophilic acyl/alkyl dinucleoside phosphates as derivatives of 3 -azido-3 -deoxythymidine Inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens. Antivir Res 1994 24 79. 

The fifth method involves the simultaneous formation of the N1-C2 and Nj-Cg bonds, thus enabling the facile introduction of Ni-substituents by the use of primary amines as reactants. An example of this approach is the tandem acylation-alkylation of an amine with a suitable halo-ester (see Figure 1 for numbering sequence). 

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