Anhydrides acetals, intramolecular

Heating dicarboxylic acids, HOOC(CH,) COOH n = 2 or 3), forms cyclic anhydrides by intramolecular dehydration [Problem 16.22(a), (6)]. Anhydrides resemble acid halides in their reactions. Because acetic anhydride reacts less violently, it is often used in place of acetyl chloride. Acid anhydrides can also be used to acylate aromatic rings in electrophilic substitutions. 

The generally accepted mechanism for the Perkin reaction is shown in Scheme 2. Much of the early woik leading to this view, which was the result of numerous investigations spanning a period of greater than SO years, has been reviewed in some detail. Formation of the anhydride enolate (1) and aldol-type condensation generates the alkoxide anhydride (2). Intramolecular acylation provides an acetoxycaibox-ylate (3), which forms a mixed anhydride elimination of acetic acid and hydrolysis affords the unsatu-... 

Potassium acetate has been used in combination with acetic anhydride to form mixed anhydrides (eq 41). This is a convenient method to prepare ketene intermediates, presumably by the elimination of the mixed anhydride, for intramolecular [2+2] ketene cycloaddition reactions (eq 42). ... 

The thiazolyl-2-thioglycollic acid (119) undergoes intramolecular ring closure to give mesoionic compound 120 under treatment with acetic anhydride and triethylamine (Scheme 60) (192). The parent acid (119) can be recovered from 120 by hydration with hot 50% aqueous sulfuric add. Compound 120 affords monohydrate of bis(-cyclopentenothiazolyi-2-thio)acetone (121) (192). 

A useful approach to the substitution of ring C—H positions lies in the activation of the heteroaromatic system by an A-oxide group, initiating a formal intramolecular redox reaction. 1-Methyllumazine 5-oxide reacts with acetic anhydride in a Katada rearrangement... 

Formation of 5-oxazolones (or azlactones ) (2) by intramolecular condensation of acylglycines (1) in the presence of acetic anhydride is known as the Erlenmeyer-Plochl azlactone synthesis. ... 

Coumarin formation proceeds via an intramolecular attack by enol ester 9 on the ketone to give 10. Dehydration of 10 then affords coumarin 11. It has been observed that coumarins are favored when higher order homologs of acetic anhydride and their corresponding salts such as propionic anhydride/sodium propionate and butyric anhydride/ sodium butyrate are used. 

Sulfates 2-Carb-25. N-Substitution 2-Carb-26. Intramolecular anhydrides 2-Carb-27. Intermolecular anhydrides 2-Carb-28. Cyclic acetals... 

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

The reaction starts with the formation of a mixed anhydride and an acetate on treatment with an excess of acetic anhydride at 80 °C. There follows a Dieckmann condensation to give 2-590 and an intramolecular rearrangement/Michael addi-hon/retro Michael addition to afford the desired tetracyclic compound 2-592 via 2-591 in an overall yield of remarkable 92%. 

In another variant of these intramolecular 1,3-dipolar cycloadditions, the alkyne-containing amino acid amide 183, when reacted with acetic anhydride, produces a zwitterionic thiazolo-oxazolium intermediate, which may then react intramolecularly with the dipolarophile and give the triheterocycle 184 < 1999J(P 1) 1219, 2002JOC4045> (Equation 18). The benzo-fused analogue 185 is obtained similarly (Equation 19). 

Monosulfoxide 13 undergoes the Pummerer rearrangement when treated with acetic anhydride in the presence of sodium acetate.85 The experiments with tetradeuterated and 180-labeled sulfoxide confirm intermediate formation of a dication.86 The ratio of 2,8,8-trideuteriated to 4,4,6,6-tetradeuteriated product 37 is equal to the intramolecular isotope effect ku k0 =1.7 (Scheme 21).85... 

In 1974 the first example of asymmetric induction in an intramolecular Pummerer reaction was observed and reported. Stridsberg and AUenmark (300) treated optically pure o-benzylsulfinylbenzoic acid 271 with acetic anhydride in the presence of dicyclohexyl-carbodiimide (DCC) and found that the Pummerer reaction product, 3,l-benzoxathian-4-one 272, was optically active. The sign and optical rotation values ([alp varied from +42° to -11°) of 272... 

Formation of 5-oxazolones (or azlactones ) by intramolecular condensation of acylglycines in the presence of acetic anhydride. 

By Dehydration of a-Diketone Hydrazone Oximes Another general method of synthesis of 2i/-triazoles involves intramolecular elimination of water from adjacent hydrazone and oxime functions (Scheme 32). The usual reagent is acetic anhydride, but others, including phosphorus pentachloride and urea, have been used. 

The delocalised carbonium ion formed by the anodic oxidation of 3,4-dimeth-oxyphenol will take part in intramolecular [5 + 2] cycloaddition with an attached alkene [146, 147], This step has been used in the synthesis of a number of complex diterpenes. Acetic anhydride, containing acetic acid, is the best solvent for these... 

Treatment of the alcohol ( ) with trifluoromethylsulfonic anhydride (triflic anhydride) at -78 C afforded the ester (1 ) which could be isolated and characterized. We knew from previous experience (2J that sulfonyl esters vicinal to an isopropylidene acetal are relatively stable. The triflate T,) reacted cleanly with potassium azide and 18-crown-6 in dichloromethane at room temperature. The crystalline product [68% overall from (1 )] was not the azide ( ) but the isomeric A -triazoline ( )- Clearly the initially formed azide (18) had undergone intramolecular 1,3-cyclo-addition to the double bond of the unsaturated ester (21- ). The stereochemistry of the triazoline (1 ), determined by proton nmr spectroscopy, showed that the reaction was stereospecific. There are several known examples of this reaction ( ), including one in the carbohydrate series ( ). When the triazoline was treated with sodium ethoxide ( ) the diazoester ( ) was rapidly formed by ring-opening and was isolated in 85% yield, Hydrogenolysis of the diazo group of (M) gave the required pyrrolidine ester ( ) (90%). 

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