Alkylation or 0-Acylation

It is obvious that simple pyrazine N-oxides cannot undergo 0-alkylation or acylation. However, tautomeric N-oxides, for example, (262), can do so. The following examples will illustrate conditions required and results to be expected  

6-diisopropyl-2(l//)-pyr izinone (264, R = Bz) (BzCl, pyridine, CH2CI2, 5 20°C, 12 h 64%) several analogues like 5-chloro-1 -(p-chlorobcn- 

---

The earlier data on initiators used, and on the mechanism of initiation are comprehensively collected in the Lundberg s review [9]. Unfortunately, the evidence presented till now on the mode of initiation and bond cleavage (0-alkyl or 0-acyl) as a function of initiator and monomer structures ... 

Examples of the selective substitution of phenol units in partially O-alkylated (or 0-acylated) calixarenes (reaction c)) are the bromination , iodination, nitration , formylation , chloromethylation , alkylation and coupling with diazonium salts. ... 

Even more information is given when the bonds that are broken and made are specified (level 3). This already needs some knowledge of the reaction mechanism. In the example given a decision has to be made between an 0-alkyl or 0-acyl cleavage of the ester. 

The presence of the N-oxide group in heterocyclic substrate opens another way for flMto-aromatization of the tr -adducts. This is achieved via preliminary 0-alkylation or 0-acylation of the N-oxide group followed by addition of a nucleophile. Aromatization of the ff -adducts in these cases is based on elimination of the corresponding alcohol or carboxylic acid. The 0-alkyl and 0-acyl derivatives are usually not isolated, but it happens quite often that they are formed in situ during the reaction course. For instance, 2-amino-8-hydroxyquinoline has been obtained in... 

In principle the same asymmetric pattern found in 4 or 5 can also be obtained by G-alkylation (or 0-acylation), adding different residues [15-17] to the phenolic oxygen. This strategy has the additional advantage that (with residues laiger than ethyl) simultaneously the conformation is fixed and racemization becomes impossible. 

Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

The chemical structure on the top in Figure 4-18 represents 1-O-alkyl-2-0-acyl-sn-glycero-3-phosphocholine (saturated ether type). In this formulation, n represents 15 or 17 while x is usually 14 or 16 with one or two double bonds present. The compound on the bottom represents 1-O-alkenyl-2-D-acyl-.vn-glycero-3-phosphocholine (vinyl ether form). In this case, n is equal to 13-15 while x usually is 14 or 16 with one or two double bonds present. Similar-type structures are present in mammalian cells as the eth-... 

As already mentioned, the conformational interconversion of calix[4]arenes requires the oxygen function at the narrow rim to pass the annulus and consequently can be hindered by 0-alkyl or O-acyl groups of sufficient size. Thus, the molecule can be fixed in one of the four basic conformations by exhaustive O-alkylation or O-acylation if the residues... 

Fig. 29 Microwave-promoted multicomponent synthesis of polysubstituted thiophenes on soluble PEG support. Reagents and conditions a NCCH2OOH, DCC, DMAP, CHCI3, MW 130 W, 5 min b RCOCH2R, S8, diisopropylethylamine, MW 130 W, 15 min c R"COCl, di-isopropylethylamine, 0 °C to rt, 3 h d 1% KCN in CH3OH, o.n. R = H or alkyl R = alkyl or acyl R" = CH3, Ph...

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Chloroacylation of terminal aryl, alkyl or alkenyl alkynes [Le. the addition of RC(=0)-C1 across the CC triple bond] with aromatic acyl chlorides was catalysed by [IrCl(cod)(lPr)] (5 mol%) in good conversions (70-94%) in toluene (90°C, 20 h). Z-addition products were observed only, hitemal alkynes were umeactive. Surprisingly, a phosphine/[lr(p-Cl)(l,5-cod)]2 system under the same conditions provides decarbonylation products (Scheme 2.34) [117]. 

New procedures to the formation of l,4-dioxa-7,l 1-dithiacyclotridecan-9-ol and 1,4,7-trioxa-10,14-dithiacyclohexadecaen-12-ol utilized 2,3-dibromopropanol with either (CH2OCH2CH2SH)2 or 0(CH2CH20CH2CH2SH)2 with Li2C03 in aqueous EtOH the procedure was shown to proceed via an oxirane intermediate <06CHC206>. The convenient oxidation of the above tridecan-9-ol to the l,4-dioxa-7,ll-dithiacyclotridecan-9-one was accomplished by a Swem oxidation at low (-70 °C) temperatures the alkylation and acylation of the ring alcohol moieties were also reported therein. 

Other conversions of hydroxyl-substituted compounds (or their lactam tautomers), their thio analogues, as well as amines are listed in Table 8. These reactions involve 0-, N-, or -alkylations or acylations, O-S exchange reactions, or other analoguous processes. 

Ketoximes containing a-methylene group can be transformed into aziridines by the action of LAH or Grignard reagent. The reduction of dibenzyl ketoxime (1) with LAH in boiling THE led to c/i-2-phenyl-3-benzylaziridine (2) (equation 1). Similarly, 0-alkylated or acylated dibenzyl oxime derivatives were reduced . 

These meso-ionic compounds are often referred to as isosydnones (146). They are prepared from )V-acyl-iV-(alkyl or aryl)-hydrazines (147, X = 0) or their hydrochlorides and carbonyl chloride. " The isosyd-... 

---