Alcohols chloride-dimethylaminopyridine

Studies on reactions of various types of alcohols with the related tosyl chloride/dimethylaminopyridine (TsCl/DMAP) system have led to the following conclusions allylic, propargylic, and glycosidic hydroxyls quickly react to form the corresponding chlorides, 2,3-epoxy and selected primary alcohols )deld chlorides... 

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. 

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. 

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). 

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. 

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. 

In general reaction of an alcohol with the appropriate anhydride or acid chloride in pyridine at 0-20 JC is sufficient. In the case of tertiary alcohols, acylation is very slow in which case a catalytic amount of 4-dimethylaminopyridine (DMAP) can be added to speed up the reaction by a factor of 10,000. Reaction of polyols with acyl chlorides (1.2 equiv) in the presence of hindered bases (2.0equiv) such as 2,4,6-collidine, diisopropylethylamine or 1,2,2,6,6-penta-methylpiperidine in dichloromethane at -78 °C leads to selective acylation of a primary alcohol. Primary alcohols can also be acylated selectively with isopro-penyl acetate or acetic anhydride in the presence of a catalytic amount of 1,3-dichlorotetrabutyldistannoxane 325.1 [Scheme 4.325].602 The catalyst 325.1 is available commercially or can be easily prepared by simply mixing dibutyltin oxide and dibutyldichlorostannane. No aqueous workup is necessary since the catalyst can be removed by simple chromatography. 

Butyrylaminopropionic acid (45mmol) and pyridine (10.67 g) were dissolved in 45 ml THF, a spatula tip of 4-dimethylaminopyridine added, and the mixture refluxed. Thereafter ethyl oxalyl chloride (90 mmol) was added dropwise and the mixture refluxed 3 hours. It was poured into ice water, extracted with EtOAc, and concentrated. The residue was dissolved in 15 ml ethyl alcohol, NaHCOj (2.15 g) added, refluxed 2.5 hours, filtered, and the intermediate isolated. 

Acyl halides such as acetyl chloride react with water to regenerate the starting acid and they react with alcohols to yield esters. The reaction is often facilitated by the presence of a tertiary amine catalyst. Although this may function purely as a base to neutralize the hydrochloric acid which is formed in the reaction, bases such as dimethylaminopyridine can also activate the carboxyl group via the formation of the intermediate shown in Scheme 3.66. 

Preparation of Derivatives. Enoate derivatives are prepared from the corresponding chiral alcohol by treatment with acry-loyl chloride in the presence of Triethylamine and catalytic 4-Dimethylaminopyridine or the appropriate carboxylic acid chloride and Silveril) Cyanide. Alkynyl ethers are readily available from the potassium alkoxide by treating with Trichloroethylene, in situ dechlorination with n-Butyllithium, and electrophilic trapping. Trapping the intermediate anion with a proton source or lodomethane followed by Lindlar reduction of the alkynyl ether affords the corresponding vinyl and l-(Z)-propenyl ether, respectively, while reduction of the alkynyl ether with Lithium Aluminum Hydride affords the l-( )-propenyl ether. 

For a variety of reasons, we chose to design our sensitizers around the alkyl sulfonates. We found that both 5-alkyl and aryl sulfonates of 1 can conveniently be prepared in excellent yields from the corresponding sulfonyl chloride through the use of catalytic amounts of sulfonyl transfer reagents such as 4-dimethylaminopyridine (DMAP) in the presence of triethylamine. This procedure is more convenient then the more traditional Schotten-Baumann conditions or those employing pyridine and allowed the preparation of sulfonate derivatives from both 1° and 2° aliphatic alcohols in high yield. 

With pyridine, acid chlorides and acid anhydrides yield A-acyl pyridinium salts 6 which are very reactive and sensitive to hydrolysis, unlike the quaternary salts 2-5 they are involved in the acylation of alcohols and amines in pyridine as solvent (Einhorn variant of the Schotten-Baumann reaction). However, 4-dimethylaminopyridine 12 (Steglich reagent) and 4-(pyrrolidin-l-yl)pyridine 13 are better acylation catalysts by a factor of 10 [46a]. Reactions with sulfonyl chlorides in pyridine proceed via A-sulfonylpyridinium salts 14. 

There are several examples where I-LLPTC has been used to synthesize acid anhydrides, by means of a substitution reaction, and ketones from oxidation of alcohols [37-40]. The reaction of an acid chloride (RX) with the carboylate ions (M R catalyzed by PNO is to proceed through an intermediate l-(acyloxy)pyridinium chloride formed in the organic phase. PNO and Af,A -dimethylaminopyridine (DMAP) are widely used as inverse PT catalysts. The formation of hippuric acid was conducted in the presence of 4-dimethy-laminopyridine as inverse PT catalyst [41]. 

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