Propionic anhydride reactions

Iridium complexes containing triphenylphosphine, e.g., HIr(CO)2(PPh3)2, in propionic acid catalyze ethylene carbonylation to propionic anhydride . Reaction occurs at a reasonable rate at 195°C and 5 Pa of CO/ethylene pressure. The corresponding Rh complexes are ineffective. The reaction is inoperative with higher olefins, even propylene. 

Yields of the order of 85% were secured in the dry reaction (48). (Propionic anhydride and butyric anhydride can be obtained similarly from their sodium salts.) Inasmuch as dinitrogen tetroxide can be regenerated, the economic prospects of this novel way of making anhydride are feasible. 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

The ring-contracted analog of alphaprodine is prepared by a variation of the scheme above. Alkylation of 109 with ethyl bromoacetate affords the lower homolog diester (115). Dieckmann cyclization followed by saponification-decarboxylation yields the pyrrolidine (116). Reaction with phenylmagnesium bromide leads to the condensation product (117) acylation with propionic anhydride gives the analgesic agent prolidine (118)... 

Somewhat milder oxidative conditions lead to loss of but one carbon. Periodic acid cleavage of the side chain in 65, leads to the so-called etio acid (66). Reaction with propionic anhydride leads to acylation of the 17-hydroxyl group (67). Possibilities for neighboring group participation severely limit the methods available for activating the acid for esterification. Best results seemed to have been obtained by use of a mixed anhydride from treatment with diphenyl chloro-... 

The excess of N-chlorosuccinimide is destroyed by the addition of about 15 drops of allyl alcohol and 180 ml of water is then added with stirring. This mixture is held at 0°C for about one hour. The precipitated 16/3-methyl-1,4-pregnadiene-9o-chloro-11/3,17o,21-triol-3,20-dione-21-acetate is recovered by filtration. A solution of 250 mg of the chlorohydrin in 5 ml of 0.25N perchloric acid in methanol is stirred for about 18 hours at room temperature to produce 16/3-methyl-9o-chloro-11/3,17o,21-trihydroxy-1,4-pregnadiene-3,20-dione which is recovered by adding water to the reaction mixture and allowing the product to crystallize. Propionic anhydride is then used to convert this material to the dipropionate. 

Clobetasol is usually converted to the propionate as the useful form by reaction with propionic anhydride. 

A mixture of 50 grams of a-dl-1,2-diphenyl-2-hydroxy-3-methyl-4-dimethylaminobutane hydrochloride, 50 grams of propionic anhydride and 50 cc of pyridine was refluxed for about 5 hours. The reaction mixture was cooled to 50°C and ethyl ether was added to the point of incipient precipitation. The hydrochloride salt of 0 -dl-l,2-diphenyl-2-propion-oxy-3-methyl-4-dimethylamlnobutane formed in the reaction precipitated upon cooling and was removed by filtration and washed with anhydrous ether. On recrystallization from a mixture of methanol and ethyl acetate, a-dl-l, 2-diphenyl-2-propionoxy-3-methyl-4-dimethyl amlnobutane hydrochloride melted at 170°-171°C. 

The feasibility of operating highly exothermic reactions in a HEX reactor has been demonstrated, some considerations can also be given concerning the inherently safer characteristics of an intensified continuous HEX reactor. This type of evaluation has been conducted on the OPR, using the esterification of propionic anhydride by 2-butanol as test reaction [36, 37]. 

The first examples of a homogeneous reduction of this type were reported in 1971. Cobalt carbonyl was found to reduce anhydrides such as acetic anhydride, succinic anhydride and propionic anhydride to mixtures of aldehydes and acids. However, scant experimental details were recorded [94]. In 1975, Lyons reported that [Ru(PPh3)3Cl2] catalyzes the reduction of succinic and phthalic anhydrides to the lactones y-bulyrolaclone and phthalide, respectively [95], The proposed reaction sequence for phthalic anhydride is shown in Scheme 15.15. Conversion of phthalic anhydride was complete in 21 h at 90 °C, but yielded an equal mixture of the lactone, phthalide (TON = 100 TOF 5) and o-phthalic acid, which is presumably formed by hydrolysis of the anhydride by water during lactoniza-tion. Neither acid or lactone were further hydrogenated to any extent using this catalyst system, under these conditions. 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Ring closure of 167 to thiazolo[3,2-b][l,2,4]triazoles can also be effected by acid anhydride, but the course of the reaction depends on the starting materials. Refluxing 167 with acetic or propionic anhydride (3-4 h) leads directly to 176. With pentafluoropropionic, heptafluorobutanic, and benzoic anhydride only diacetylated products 177 were produced (further details [76JHC(13)1225]). 

To a cooled suspension (0 C) of 3.07 g (20 mmol) of ( + )-(l.S,2fl)-norephedrinc in 30 mL of diethyl ether are added 3.17 g (24 mmol) of propionic anhydride and 3.4 g of solid NaHCOj in portions at a rate such that the pH of the two-phase system is between 7 and 8. The reaction mixture is stirred at 25 C for 45 min and then extracted with three 50-mL portions of ethyl acetate. The combined extract is washed successively with dilute hydrochloric acid and sat. brine, dried over MgSQ4. and concentrated leaving 3.81 g (90.5%) of crystalline material. Recrystallization (benzene/petroleum ether) uives pure A-(l-oxopropyl)norcphednne mp 107.5 -108.5°C [x] J9 +26.72 (c = 2.62, ethanol). 

On the other hand, with propionic anhydride as substrate, in which case there is no solubility problem, the course of the reaction was very much the same as in the experiments with acetic anhydride. The rate constants for decomposition of propionylimidazole are strikingly similar to those for acetylimidazole. 

A. (1 S,2S)-N-(2-Hydroxy-1 -methyl-2-phenylethyl)-N-methylpropionamide, ((1S,2S)-pseudoephedrinepropionamide). A flame-dried, 1-L, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar is charged with 21.3 g (129 mmol) of (1S,2S)-(+)-pseudoephedrine (Note 1) and 250 mL of tetrahydrofuran (Note 2). The flask is placed in a water bath at 23°C, and to the well-stirred solution, 18.0 g (138 mmol) of propionic anhydride (Note 3) is added by a Pasteur pipette in 1-mL portions over approximately 5 min. The flask is sealed with a rubber septum containing a needle adapter to an argon-filled balloon, and the clear, colorless solution is allowed to stir at 23°C for an additional 10 min. The rubber septum is removed, and the reaction solution is neutralized by the addition of 400 mL of saturated aqueous sodium bicarbonate solution. After thorough mixing (Note 4), the biphasic mixture is poured... 

Isatin, acetic anhydride, and pyridine gave a purple condensation product 195.547 Replacement of the acetic anhydride by propionic anhydride caused the reaction to make a different path, and three... 

Cellulose esters of the 2-.. 3-. and 4-carbon acids are readily prepared by the cellulose-anhydride reaction the acetate ester and the mixed acetate butyrate and acetate propionate esters arc manufactured and used in large amounts. Esters of higher acids require different synthesis techniques and tend to be prohibitively expensive except as specialty products. Some arc in commercial production, however. Cellulose acclalc phlhalatc, for example, is manufactured for use as an enteric coating on pills. 

For the reaction of MOH(n 1)+ with propionic anhydride,200 the Bronsted plot of log kMOH versus the pKa of MOH2n+ follows a smooth curve if the values for HzO and OH- are included (Figure 4). However, if the line is drawn to exclude the fcHj0 value, a Bronsted /3 of ca, 0.25 is obtained. Although kMOH for [Co(NH3)5OH]2+ (3 M s 1) is some 103-fold less than k0H, this reaction will compete favourably at neutral pH with base hydrolysis. At pH 7 where the cobalt(III) complex exists almost completely as the MOH2+ species the observed first order rate constant for nucleophilic attack by OH would be ca. 10-4 s 1. AIM solution of [Co(NH3)5OH]2+ would give a value of kobs 2.5 s 1, a rate acceleration of > 104-fold. Since the effective concentration of a nucleophile in the intramolecular reaction could be ca. 102 M, rate accelerations of 10° are possible. The role of the metal ion in such reactions is to provide an effective concentration of an efficient nucleophile at low pH. 

Figure 4 Plot of log kMOH uersus pKa (of MOH +) for the reaction of various metal hydroxide complexes with propionic anhydride at 25 °C and / = 1.0 M (NaC104) (reproduced with permission from biological Aspects of Inorganic Chemistry , Wiley, New York, 1966)...

Buckingham and Engelhardt200 have studied the hydrolysis of propionic anhydride in the presence of kinetically inert complexes of the type [M(NH3)5OH]n+. These reactions occur by nucleophilic attack of coordinated hydroxide on the anhydride (Scheme 32). For reactions of M-OHl" l,+ with propionic anhydride, the Bronsted plot of log kMOH versus the p.Ka of M—OH2k+ is a smooth curve if values for reaction with HzO and OH- are included. Although Icmoh for [(NH3)5CoOH]2+ (3 M-1 s-1) is about 103-fold less than fcoH. its reaction will compete favourably at neutral pH with base hydrolysis. Such effects are considered in more detail in Section 61.4.2.2.3. 

The solution of phenyl-lithium is cooled to -20°C and to this a solution of 12.7 grams of l,3-dimethyl-4-piperidone, prepared according to the method of Howton, J. Org. Chem. 10, 277 (1945), in ether is added dropwise with stirring. After the addition, the stirring is continued for a further 2 hours at -20°C. The lithium complex, l,3-dimethyl-4-phenyl-4-oxylithium piperidine, which forms is soluble in the ether and can be recovered there from. To prepare the piperidinol, the lithium complex, while in the reaction mixture is decomposed by the addition of an ice and hydrochloric acid mixture. The acidified layer is separated, basified and extracted with ether. After drying the ether solution and removing the solvent, the residue on distillation in vacuum distills chiefly at 155°C/10 mm, yielding the product, l,3-dimethyl-4-phenyl-4-hydroxypiperidine, which, on crystallization from n-hexane melts at 102°C. On treatment with propionic anhydride catalyzed with a trace of sulfuric acid,... 

---