Alcohols 4-dimethylaminopyridine

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

AC2O, AcCl, Pyr, DMAP, 24-80°, 1-40 h, 72-95% yield. The use of DMAP increases the rate of acylation by a factor of 10. These conditions will acylate most alcohols, including tertiary alcohols. The use of DMAP (4-N,N-dimethylaminopyridine) as a catalyst to improve the rate of esterification is quite general and works for other esters as well. 

Giacomelli et al. constructed 3-propylisoxazole-5-yl-methanol via a [3-1-2] cycioaddition (Fig. 15) [158]. Nitrobutane was converted to nitrile oxide in the presence of 4-(4,6-dimethoxy [1,3,5]triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) and catalytic 4-dimethylaminopyridine (DMAP). Trityl chloride resin-bound propargyl alcohol was employed as the dipolarophile to trap the nitrile oxide, forming the cyclo adduct isoxazole ring under unusually mild conditions (i.e., microwave irradiation at 80 °C for five times 1 min). Disappearance of the starting material was monitored by FT-IR. 

Figure 25 Synthesis of naturally occuring phenylpropenoid (3-D-glucopyranosides. (a) allyl alcohol/immobilized (3-glucosidase with ENTP-4000, (b) Ac20/4-dimethylaminopyridine/pyridine, (c) organoboron reagents/Pd(OAcyCu(OAc)2/LiOAc/DMF, (d) K2C03/Me0H.

The second step, nucleophilic attack of an alcohol or phenol on the activated carboxylic acid RCOIm (carboxylic acid imidazolide), is usually slow (several hours), but it can be accelerated by heating[7] or by adding a base[8] [9] such as NaH, NaNH2, imidazole sodium (ImNa), NaOR, triethylamine, diazabicyclononene (DBN), diazabicycloimdecene (DBU), or /7-dimethylaminopyridine to the reaction mixture (see Tables 3—1 and 3—2). This causes the alcohol to become more nucleophilic. Sodium alcoholate applied in catalytic amounts accelerates the ester synthesis to such an extent that even at room temperature esterification is complete after a short time, usually within a few minutes.[7H9] This catalysis is a result of the fact that alcoholate reacts with the imidazolide very rapidly, forming the ester and imidazole sodium. 

Tetrahydrobenzyl alcohol (( )3-cyclohexenene-l-methanol) and 30% aqueous hydrogen peroxide were purchased from Fluka, AG. 3-Cyclohexene-1-carboxylic acid and cis-4-cyclohexene-l,2-dicarboxylic acid were used as purchased from Lancaster Chemical Co. Methyl iodide, acetic anhydride, Oxone (potassium peroxymonosulfate), Aliquot 336 (methyl tri-n-octylammonium chloride), sodium tungstate dihydrate and N,N-dimethylaminopyridine (DMAP) were purchased from Aldrich Chemical Co. and used as received. 3,4-Epoxycyclohexylmethyl 3, 4 -epoxycyclohexane carboxylate (ERL 4221) and 4-vinylcyclohexene dioxide were used as purchased from the Union Carbide Corp. (4-n-Octyloxyphenyl)phenyliodonium hexafluoroantimonate used as a photoinitiator was prepared by a procedure described previously (4). 

In a NMR tube, to a solution of the epoxy alcohol (2.5 mg) in CDCI3 (0.5 mL) was added 4-dimethylaminopyridine (5 mg) and (R)-(+)-a-methoxy-a-(trifluor-omethyl)phenylacetyl chloride (5 mg). The mixture was allowed to stand overnight at room temperature. The reaction was monitored by TLC to ensure complete consumption of the starting material. H and 19F NMR spectra were carried out on the crude reaction mixture. In the 19F NMR spectrum, each enantiomer gave a signal an additional signal at —71.8 ppm was ascribed to residual MTPA. (19F NMR (250 MHz, CDCI3) 8 - 70.7 (s, (2R,3R)-enantio-mer) —72.0 (s, (25 ,3.S)-enantiomer)). 

Protection of an alcohol function by esterification sometimes offers advantages over use of acetal or ether groups. Generally, ester groups are stable under acidic conditions. Esters are especially useful in protection during oxidations. Acetates and benzoates are the most commonly used ester derivatives. They can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amines. 4-Dimethylaminopyridine (DMAP) is often used as a catalyst. The use of A-acylimidazolides (see Section 3.4.1) allows the... 

In 1998, Evans published an improved synthesis of bu-box 3 starting from the same amino acid. The updated synthesis began with sodium borohydride-iodine reduction to afford amino alcohol 23 followed again by treatment with dimethyl-malonyl dichloride 24 to afford 25 in 88% yield (from 23). Cyclization was achieved by treatment of 25 with toluenesulfonyl chloride and triethylamine in the presence of a catalytic amount of dimethylaminopyridine to afford bu-box 3 in 82% yield (Fig. 9.6). 

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

Acyl triflamides are excellent acylating agents for alcohols and amines [52], Classical methods for carboxyl activation include formation of anhydrides, either homo- or mixed (e.g. phosphoryl, sulfonyl, etc.). Further activation is possible by adding 4-dimethylaminopyridine as catalyst [53], The active acylating agents are throught to be... 

Deoxygenation of alcohols.2 Secondary alcohols react with 1 in the presence of pyridine or 4-dimethylaminopyridine to form thiono esters (2), which are cleaved... 

We have previously reported on the synthesis of a series of mono- and bifunctional poly(DMS) having a variety of reactive end groups, such as silan (Si-H), vinyl, hydroxyalkyl, dimethylamino and carboxyllic acid groups.7 We have also described already on telechelic poly(DMS) having tosylate end group, lb and l b, where the hydrosilation reaction of poly(DMS) having silan end group was performed with allyl alcohol in the presence of Pt/C catalyst, followed by the tosylation reaction with tosyl chloride in the presence of dimethylaminopyridine.9... 

MHz of the MTPA ester that was prepared as follows The sample alcohol (0.1 mmol) was placed in a vial along with a solution of (+)-a-methoxy-a-trifluoromethylphenylacetyl chloride (0.15 mmol) in 1 mL of dichloromethane, triethylamine (0.15 mmol), and a crystal of 4-dimethylaminopyridine, and stirred at room temperature overnight. The excess acid chloride was treated with dimethylaminopropylamine (0.1 mmol). The MTPA ester was isolated in pure form after passing the mixture through a 5-g plug of silica gel and elution with 4 1 hexanes ethyl acetate. 

The reaction of methyl 10, l l -dihydropyrrolo[ l, Z-b [ l, 2,5]bcnzothiadiazcpinc-l l -acetate 5,5-dioxide 73 or the corresponding ethyl ester 74 with potassium hydroxide in EtOH at 25 °C gave the acid 75 (Scheme 14), which upon treatment with trifluoroacetic anhydride in tetrahydrofuran (THF) underwent intramolecular cyclization to afford 76. The 1,2,5-thiadiazepines 73 and 74 were then heated with an excess of concentrated ammonium hydroxide to give the carboxamide 77. The acid 75 upon reaction with 4-chlorophenol, 4-chlorobenzyl alcohol, or 4-chloroaniline in the presence of iV-(3-dimethylaminopropyl)-iV -ethylcarbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) afforded the respective esters and amide 78-80 <1996FES425>. 

To a stirred suspension of 4.6 g (13.8 mmoles) of the (S)-3-(2-hydroxyethyl)-5-(2-oxo-l,3-oxazolidin-4- ylmethyl)-lH-indol-2-carboxylic acid ethyl ester in 42 ml of dichloromethane were added 4.2 ml of pyridine, 3.9 g (20.7 mmoles) oftosyl chloride and 170 mg (1.38 mmoles) of dimethylaminopyridine and the stirring continued at room temperature for 20 hours. The reaction mixture was poured over 20 ml of 3 N, HCI precooled to 0°C and extracted twice with dichlormethane. The organic phases were washed with brine, dried on anhydrous sodium sulphate and the solvent evaporated to dryness. The evaporated solid was crystallised with isopropyl alcohol to give 6.4 g (95%) of the title compound as a white crystalline solid. Melting point 166.4°-168.2°C. 

Having proved the synthetic utility of their system, the authors subsequently evaluated a second supported base, 4-dimethylaminopyridine (AO-DMAP) 118, toward the acylation of 2° alcohols (Scheme 30). Employing a premixed solution of phenyl-l-ethanol 119, Et3N 14 and acetic anhydride 37 (0.33, 0.50, and 0.50 M) in hexane, reactions were conducted at room temperature and the effect of residence time evaluated (10-50 s). Using a 60 cm packed bed, the authors were able to obtain near quantitative conversions to 120 employing residence times <20 s, with flow reactions providing superior results to those obtained in analogous batch reactions. 

Esterification.1 This reagent in combination with a catalytic amount of 4-dimethylaminopyridine (DMAP) is very effective for esterification of carboxylic acids with alcohols or thiols at room temperatures. However, reaction of aromatic and hindered acids requires several days at room temperature. French chemists report that only this method is useful for esterification of the protected baccatin III derivative (2) with (2R,3S)-N-benzoyl-0-(l-ethoxyethyl)-3-phenylisoserine (3) to provide the protected taxol derivative (4). A reaction conducted at 73° for 100 hours with 6 equiv. of 1 and 2 equiv. of DMAP produced 4 in 80% yield. Natural taxol, a cancer chemotherapeutic agent, is obtained by removal of the protective groups at C2 and C7 of 4. 

Acetates of fatty [1] and polyhydric [2] alcohols, phenols [3] and chlorophenols [4] have been studied. Fell and Lee [3] described a GC method for the determination of polyhydric phenols in urine, which, having been extracted, were acetylated with acetic anhydride in the presence of 4-dimethylaminopyridine. According to these authors this substance shows much stronger catalytic effects than does the usually used pyridine. The derivatives are formed rapidly and quantitatively even in very dilute solutions. In the absence of the catalyst, bifunctional phenols provide more than one GC peak. Slightly polar OV-210 is recommended for the separation of phenol acetates, but analysis on nonpolar OV-101 leads to tailing, probably as a consequence of insufficient deactivation of the column. 

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