Pyridines anhydride

Without pyridine, anhydride formation would be incomplete, as a result of an equilibrium reaction of the anhydride with hydrogen chloride which regenerates the acyl chloride and the carboxylic acid. 

Gribble and Saulnier (79) have extended their ellipticine synthesis 43) to the synthesis of 9-methoxyellipticine (2) (Scheme 24). One of the key features of this approach is the regioselective nucleophilic addition to the C-4 carbonyl group of pyridine anhydride 28. The other noteworthy transformation is the conversion of keto lactam 142 to the diol 143 with methyllithium, a process that presumably involves cleavage of the initial adduct to a methyl ketone which undergoes cyclization at the C-3 position of the indolyl anion. Reduction of 143 with sodium borohydride completes the synthesis of 2, in 47% overall yield from 5-methoxyindole (139). Gribble and students 80) have also used this method to synthesize 8-methoxyellipticine (134), 9-fluoroellipticine (144), and the previously unknown 7,8,9,10-tetrafluorellipticine (145), each from the appropriate indole. 

Strong pyridine anhydrides sulfoxides tertiary amines aliphatic or aromatic hydroxyl carboxylic acid urea urethane sulfonic acids primary and secondary amines amide phosphonic acids... 

Pungent odour. Formic acid, acetic acid, acetyl chloride, acetic anhydride, benzoyl chloride, benzyl chloride, pyridine. Benzoquinone (when warmed with water). 

Method. A known weight of the alcohol is heated w ith a definite volume of a mixture of acetic anhydride and pyridine until acetylation is complete ... 

The absolute concentration of a reagent e.g., the exact amount of acetic anhydride in the above pyridine. solution) need not be determined, since if the same amount of the reagent is used in the actual and in the control experiments, the difference gives at once the actual amount used. 

Prepare the acetylating mixture by adding i volume of acetic anhydride to 4 volumes of pure anhydrous pyridine, and shaking thoroughly. Immediately before use, transfer the mixture to a clean dry burette having a welUfitting glass tap, and then close the top of the burette by means of a soda-lime tube. 

Bromination of fatty acids in the a-position can be effected quite readily in the presence of phosphorus trichloride, red phosphorus or pyridine as catalysts or halogen carriers with acetic acid, the addition of acetic anhydride (to ensure the absence of water) improves the yield and facilitates the bromination. Examples are —... 

Thus benzoic anhydride and o chlorobenzoic anhydride (m.p. 79°) can bo readily prepared by this method (compare n-Heptoic anhydride, Section 111,91). It is sometimes convenient to use pyridine as the reaction medium. 

In a modification the acid chloride is treated with excess of dry pyridine whereby the addition complex ArCOCl. CgHjN is formed decomposition of the latter with water aflFords the acid anhydride ... 

Place a mixture of 17 -5 g. p-chlorobenzoyl chloride (1) and 50 ml. of dry pyridine (Section 11,47,22) in a loosely-stoppered 250 ml. flask and warm on a steam hath for 5 minutes. Pour the reaction mixture upon 100 g. of crushed ice and 50 ml. of concentrated hydrochloric acid. The anhydride separates out at once. When the ice has melted sufficiently, filter the mixture by suction. Wash the sohd with 15 ml. of methanol and then with 15 ml. of dry benzene. The yield of crude p-chlorobenzoic anhydride is 14 5 g. Recrystalhse from 250 ml. of dry benzene 13 g. of the pure anhydride, m.p. 192-193°, are obtained. 

When pyridine is treated with zinc dust and acetic anhydride, a type of reductive coupling occurs and the product is diacetyltetrahydrodipyridyl (I) this undergoes a curious change on heating yielding pyridine and a new diacetyl compound, 1 4 diacetyl 1 4-dihydropyridine (II). The latter is reduced by zinc and acetic acid to 4-ethylpyridine (III). 

Other 4 alkylated pyridines may be prepared by the use of the appropriate anhydride. 

Formation - acetic anhydride, pyridine - acetyl chloride, pyridine... 

The desired pyridylamine was obtained in 69 % overall yield by monomethylation of 2-(aminomethyl)pyridine following a literature procedure (Scheme 4.14). First amine 4.48 was converted into formamide 4.49, through reaction with the in situ prepared mixed anhydride of acetic acid and formic acid. Reduction of 4.49 with borane dimethyl sulfide complex produced diamine 4.50. This compound could be used successfully in the Mannich reaction with 4.39, affording crude 4.51 in 92 % yield (Scheme 4.15). Analogous to 4.44, 4.51 also coordinates to copper(II) in water, as indicated by a shift of the UV-absorption maximum from 296 nm to 308 nm. 

This is a way to do this procedure without having to use one of those crazy tube furnaces stuffed with thorium oxide or manganous oxide catalyst [21]. The key here is to use an excess of acetic anhydride. Using even more than the amount specified will insure that the reaction proceeds in the right direction and the bad side reaction formation of dibenzylketone will be minimalized (don t ask). 18g piperonylic acid or 13.6g phenylacetic acid, 50mL acetic anhydride and 50mU pyridine are refluxed for 6 hours and the solvent removed by vacuum distillation. The remaining residue is taken up in benzene or ether, washed with 10% NaOH solution (discard the water layer), and vacuum distilled to get 8g P2P (56%). 

As a catalyst for ester and amide formation from acyl chlorides or anhydrides, 4-(di-methylamino)pyridine has been recommended (DMAP G. Hdfle, 1978). In the presence of this agent highly hindered hydroxyl groups, e.g. of steroids and carbohydrates, are acylated under mild conditions, which is difficult to achieve with other catalysts. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Later, fireflv oxyluciferin was successfully synthesi2ed (403. 408) and has been isolated and identified in firefly lanterns (luciola cruaciata) after the lanterns were treated with pyridine and acetic anhydride to prevent decomposition (409). In 1972, Suzuki and Goto firmly established that oxyluciferin is involved in the bioluminescence of firefly lanterns and in the chemiluminescence of firefly luciferin (403. 410).. A. mechanism involving a four-membered ring cyclic peroxide has been proposed for the reaction (406. 411). However, it was not confirmed by 0 -labelinE experiments (412). 

Alkoxythiazoles are prepared by heterocyclization (274, 462). The Williamson method using catalytic amounts of KI and cupric oxide is also possible (278. 288, 306). 5-Acetoxy-4-alkenylthiazoles are obtained by treatment of 242 with acetyl chloride and triethylamine or with acetic anhydride and pyridine (450). Similarly, the reaction of diphenylketene with 242 affords 5-acyloxy-4-alkenylthiazoles (243) (Scheme 120) (450). The readiness of these o-acetylations suggests that 4-alkylidene thiazoline-5-one might be in equilibrium with 4-alkenyl-5-hydroxythiazoles (450). 

The stereo aspect of the condensation has been studied for pyridine derivatives, and according to the nature of solvent, either ethanol or acetic anhydride, a cis or a tmns dye could be obtained (59). 

Thiazolomonomethine cyanines result from the condensation of 2 moles of 2-alkylmercaptothiazolium on 1 mole of malonic acid in pyridine (method C) but could not be obtained from this intermediate in acetic anhydride as is the case for other rings (26). 

Two different access routes are used, whether the leaving group is carried on thiazolium derivatives such as anilinovinyl (method A), acetanilidovinyl (method B), formyl methylene, or thioformylmethylene or on the ketomethylene compound (method C). The use of acid anhydride together with pyridine has been patented (method E). 

Acyl chlorides react with carboxylic acids to yield acid anhydrides When this reaction is used for preparative purposes a weak organic base such as pyridine is normally added Pyridine is a catalyst for the reaction and also acts as a base to neutralize the hydrogen chloride that is formed... 

Acid anhydrides react with alcohols to form esters The reaction may be carried out in the presence of pyridine or it may be catalyzed by acids In the example shown only one acyl group of acetic anhydride becomes incorporated into the ester the other becomes the ac yl group of an acetic acid molecule... 

Chromic(VI) acid Acetic acid, acetic anhydride, acetone, alcohols, alkali metals, ammonia, dimethylformamide, camphor, glycerol, hydrogen sulflde, phosphorus, pyridine, selenium, sulfur, turpentine, flammable liquids in general... 

Maleic anhydride Alkali metals, amines, KOH, NaOH, pyridine... 

Perchloric acid Acetic acid, acetic anhydride, alcohols, antimony compounds, azo pigments, bismuth and its alloys, methanol, carbonaceous materials, carbon tetrachloride, cellulose, dehydrating agents, diethyl ether, glycols and glycolethers, HCl, HI, hypophosphites, ketones, nitric acid, pyridine, steel, sulfoxides, sulfuric acid... 

Pyridine Chlorosulfonic acid, chromium trioxide, formamide, maleic anhydride, nitric acid, oleum, perchromates, silver perchlorate, sulfuric acid... 

The acetylation reaction, [1], is carried out in pyridine to avoid the hydrolysis of acetic anhydride by water. After the acetylation is complete, water is added to convert the remaining acetic anhydride to acetic acid, [2]. 

Acetaldehyde, first used extensively during World War I as a starting material for making acetone [67-64-1] from acetic acid [64-19-7] is currendy an important intermediate in the production of acetic acid, acetic anhydride [108-24-7] ethyl acetate [141-78-6] peracetic acid [79-21 -0] pentaerythritol [115-77-5] chloral [302-17-0], glyoxal [107-22-2], aLkylamines, and pyridines. Commercial processes for acetaldehyde production include the oxidation or dehydrogenation of ethanol, the addition of water to acetylene, the partial oxidation of hydrocarbons, and the direct oxidation of ethylene [74-85-1]. In 1989, it was estimated that 28 companies having more than 98% of the wodd s 2.5 megaton per year plant capacity used the Wacker-Hoechst processes for the direct oxidation of ethylene. 

Figure 3 shows the production of acetaldehyde in the years 1969 through 1987 as well as an estimate of 1989—1995 production. The year 1969 was a peak year for acetaldehyde with a reported production of 748,000 t. Acetaldehyde production is linked with the demand for acetic acid, acetic anhydride, cellulose acetate, vinyl acetate resins, acetate esters, pentaerythritol, synthetic pyridine derivatives, terephthaHc acid, and peracetic acid. In 1976 acetic acid production represented 60% of the acetaldehyde demand. That demand has diminished as a result of the rising cost of ethylene as feedstock and methanol carbonylation as the preferred route to acetic acid (qv). 

Bromoacetic acid can be prepared by the bromination of acetic acid in the presence of acetic anhydride and a trace of pyridine (55), by the HeU-VoUiard-Zelinsky bromination cataly2ed by phosphoms, and by direct bromination of acetic acid at high temperatures or with hydrogen chloride as catalyst. Other methods of preparation include treatment of chloroacetic acid with hydrobromic acid at elevated temperatures (56), oxidation of ethylene bromide with Aiming nitric acid, hydrolysis of dibromovinyl ether, and air oxidation of bromoacetylene in ethanol. 

Bisa.codyl, 4,4 -(2-PyridyLmethylene)bisphenol diacetate [603-50-9] (Dulcolax) (9) is a white to off-white crystalline powder ia which particles of 50 p.m dia predominate. It is very soluble ia water, freely soluble ia chloroform and alcohol, soluble ia methanol and ben2ene, and slightly soluble ia diethyl ether. Bisacodyl may be prepared from 2-pyridine-carboxaldehyde by condensation with phenol and the aid of a dehydrant such as sulfuric acid. The resulting 4,4 -(pyridyLmethylene)diphenol is esterified by treatment with acetic anhydride and anhydrous sodium acetate. Crystallisation is from ethanol. 

Ethynodiol diacetate (53) is prepared by reduction of the 3-oxo group of norethindrone (28) with lithium tributoxyalurninum hydride, followed by acylation with acetic anhydride-pyridine (78,79). It has been reported that higher yields can be obtained in the reduction step by using triethylanainoalurninum hydride (80). 

Norethindrone may be recrystakhed from ethyl acetate (111). It is soluble in acetone, chloroform, dioxane, ethanol, and pyridine slightly soluble in ether, and insoluble in water (112,113). Its crystal stmcture has been reported (114), and extensive analytical and spectral data have been compiled (115). Norethindrone acetate can be recrystakhed from methylene chloride/hexane (111). It is soluble in acetone, chloroform, dioxane, ethanol, and ether, and insoluble in water (112). Data for identification have been reported (113). The preparation of norethindrone (28) has been described (see Fig. 5). Norethindrone acetate (80) is prepared by the acylation of norethindrone. Norethindrone esters have been described ie, norethindrone, an appropriate acid, and trifiuoroacetic anhydride have been shown to provide a wide variety of norethindrone esters including the acetate (80) and enanthate (81) (116). 

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