Alkylation of acetals

Examples are given of common operations such as absorption of ammonia to make fertihzers and of carbon dioxide to make soda ash. Also of recoveiy of phosphine from offgases of phosphorous plants recoveiy of HE oxidation, halogenation, and hydrogenation of various organics hydration of olefins to alcohols oxo reaction for higher aldehydes and alcohols ozonolysis of oleic acid absorption of carbon monoxide to make sodium formate alkylation of acetic acid with isobutylene to make teti-h ty acetate, absorption of olefins to make various products HCl and HBr plus higher alcohols to make alkyl hahdes and so on. 

Because of its generality, acetylide alkylation is an excellent method for preparing substituted alkynes from simpler precursors. A terminal alkyne can be prepared by alkylation of acet dene itself, and an internal alkyne can be prepared by further alkylation of a terminal alkyne. 

The synthesis of racemic Tic (rac-33) can be accomplished by alkylation of acet-amidomalonates in a reasonable yield (Scheme 15). Racemic Tic can then be subjected to resolution using menthol.1[7 ] This route is a good alternative for synthesizing both enantiomers of Tic. 

A similar alkylation of acetals has been reported,198,199 while 2-pyrrolidone200 (218 X = NH) and y-butyrolactone201 (218 X = 0) are also alkylated under identical conditions to give a major (219) and a minor (220) photoproduct. The addition of 2-methyltetrahydrofuran to acetylene [Eq. (56)] is also initiated by photolysis in acetone.202... 

Preparation of Homologues by Homolytic Alkylation of Acetic Acid and Related Compounds. J. chem. Soc. 1965, 1918. 

The enantiopure phosphinooxazolinidines (POZ)s were a type of N—P chiral ligand developed by Nakano and used for asymmetric Pd-catalyzed allylic alkylations [133] and Diels-Alder reactions [59]. A PS-supported version of this type of chiral hgand 210 was prepared and apphed to the asymmetric aUylic alkylation of acetate 201 with dialkyhnalonates [134], affording the product in exceUent yield (99%) with 99% ee, as shown in Scheme 3.69. 

Zerth, H.M., Leonard, N.M., Mohan, R.S. (2003) Synthesis of homoallyl ethers via alkylation of acetals in ionic liquids catalyzed by trimethylsilyl trifluoromethanesulfonate. Org. Lett., 5,55-57. 

Alkylation of acetals. When applied to mixed acetals bearing an a-stannylalkyl branch, the catalyzed reaction with alkynylstannanes gives propargyl ethers, which are precursors of allenyl carbinols. ... 

Alkylation of acetic acid with isobutylene to make (-butyl acetate... 

Alkylation of the sodio derivative affords the C-substituted cyanoacetic ester, which when heated with dilute acid gives the mono-substitut acetic acid. 

Another category Ic indole synthesis involves cyclization of a-anilino aldehydes or ketones under the influence of protonic or Lewis acids. This corresponds to retro.synthetic path d in Scheme 4.1. Considerable work on such reactions was done in the early 1960s by Julia and co-workers. The most successful examples involved alkylation of anilines with y-haloacetoacetic esters or amides. For example, heating IV-substituted anilines with ethyl 4-bromoacetoacetate followed by cyclization w ith ZnClj gave indole-3-acetate esterfi]. Additional examples are given in Table 4.3. 

The general pattern of alkylation of 2-acylaininothiazoles parallels that of 2-aminothia2ole itself (see Section III.l). In neutral medium attack occurs on the ring nitrogen, and in alkaline medium a mixture of N-ring and N-amino alkylation takes place (40, 43, 161. 163). In acidic medium unusual behavior has been reported (477) 2-acetamido-4-substituted thiazoles react with acetic anhydride in the presence of sulfuric acid to yield 2-acetylimino-3-acetyl-4-phenyl-4-thiazolines (255) when R = Ph. but when R4 = Me or H no acetylation occurs (Scheme 151). The explanation rests perhaps in an acid-catalyzed heterocyclization with an acetylation on the open-chain compound (253), this compound being stabilized... 

By performing two successive alkylation steps the malonic ester synthesis can be applied to the synthesis of a a disubstituted derivatives of acetic acid... 

Sulfonated styrene—divinylbensene cross-linked polymers have been appHed in many of the previously mentioned reactions and also in the acylation of thiophene with acetic anhydride and acetyl chloride (209). Resins of this type (Dowex 50, Amherljte IR-112, and Permutit Q) are particularly effective catalysts in the alkylation of phenols with olefins (such as propylene, isobutylene, diisobutylene), alkyl haUdes, and alcohols (210) (see Ion exchange). Superacids. 

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

In the piepaiation of ioveisol (12) (41), the key intermediate (23) is prepared from the diacid (20) by the action of thionyl chloride followed by 3-amino-l,2-propanediol. The alcohol groups of (23) are protected as the acetates (25), which is then N-acylated with acetoxyacetyl chloride and deprotected in aqueous methanol with sodium hydroxide to yield (26). N-alkylation of (26) produces ioversol (12). 

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) ... 

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

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