Propionyl chloride synthesis

A final example is the synthesis of H-shaped copolymer of (PS PEG (PS)2 by ATRP, i.e. [209]. The synthetic strategy involves the synthesis of 2,2-bis(methylene a-bromopropionate) propionyl chloride (1), the preparation of 2,2-bis(methylene a-bromopropionate) propionyl-terminated poly(ethylene glycol) (BMBP-PEG-BMBP) (2), and then ATRP of styrene at 110 °C with BMBP-PEG-BMBP/CuBr/2,2/-bipyridine as the initiating system. The structure (3) was configured by using NMR and SEC measurements (Scheme 116). 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

Friedel-Crafts acylation of benzo[6]thiophene and its derivatives with succinic anhydride132,439,662,663 or the ester chloride of succinic acid614, 618, 650,662 gives a y-keto acid (or ester), which is reduced to the corresponding y-(benzo[6]thienyl)butyric acid by the Huang Minion or Clemmensen method. y-(Benzo[6]thienyl)butyric acids may alternatively be prepared by the diethyl malonate synthesis on the appropriate halide,439,499 by the Arndt-Eistert reaction on the corresponding propionyl chloride,409,618 or by cyclization.347,618 The ketones (317 R = Hor OMe)347 have been prepared by cyclization... 

In total synthesis of the structurally unique natural product calcimycin (15), Grieco and others used Ireland-Claisen rearrangement of the ester 17 to synthesize the key intermediate (18)7 (Scheme 1.3g). Monosilylation of the diol 16 followed by treatment with propionyl chloride in pyridine gave rise to the ester 17 in 90% yield. Treatment of 17 with LDA in THF at —78 C, subsequent addition of ferf-butyldimethylsilyl chloride in HMPA, and brief heating of the resulting silylketene acetal provided the corresponding silyl ester. Subsequent hydrolysis of the silyl ester and esterification with diazomethane gave 18 in 90% yield from 17. 

The Woodward group employed the reaction in the synthesis of cortisone but used free ethyl vinyl ketone rather than the Mahnich base methiodide. Their improvement of an Ccu-ly preparative procedure is as follows." Fricdel-Crafts reaction of propionyl chloride with ethylene in chloroform affords 1 -chloro-3-pentanone. and when a mixture of this with an equivalent amount of diethylamine is heated gradually lu 200° ethyl vinyl ketone dlHlillx. 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

Synthesis from anisole and propionic acid derivatives. Anisole is converted into 4-methoxypropiophenone by Friedel-Crafts acylation with propionyl chloride or propionic anhydride. The ketone is hydrogenated to the corresponding alcohol with a copper chromite catalyst. The alcohol is dehydrated in the presence of acidic catalysts to a cis/trans mixture of anetholes [163b]. 

Improved method for preparation of 173 is reported by Wang and Gu (Scheme 12.29). It comprises of four-step synthesis of 179, conversion of acid into 5-2-(5-fluoropyrimidin-4-yl)propionyl chloride, Friedel-Crafts reaction to obtain ketone 180, and the reaction with 1-methyl-17/-1,2,4-triazole under basic condition. 

SYNTHESIS To a stirred solution of 138 g p-dimethoxybenzene in 400 mL CH2CI2 there was added a suspension of 172 g anhydrous AICI3 in 500 mL CH2CI2 which contained 92.5 g propionyl chloride. After stirring for 1.5 h the reaction mixture was poured into 2 L H20 containing ice. 

Regioselectivity is also critical in the acylation of electron-rich heterocycles other than substituted benzenes. High regioselectivity (94 6 C-4 versus C-2 acylation) observed in the AICI3 promoted intramolecular acylation of 28 a 3-(indol-3-yl)propionyl chloride analogue, to adduct 29, a precursor in the synthesis of Uhle s ketone 30. A donor-acceptor complex between AICI3 and chloroacetyl chloride was proposed to drive the acylation reaction. A sodium methoxide mediated cleavage of the A-BOC moiety of 29 completed the synthesis of 30 in 95% yield. 

Subsequently, this version of Claisen rearrangement was extended to tertiary allyl amines and acyl chlorides [87], Using Lewis acid catalyst, excellent stereoselectivity of the product was found. For example, 3,3-disubstituted aUyl morpholine 125 with propionyl chloride in the presence of TiCLt gives highly stereoselective syn product 126 [87]. This method is useful for the synthesis of... 

Diethylamino Group Transfer. Trimethylsilyldiethylamine can be used for the convenient synthesis of amides that retain the A,lV-diethyl moiety in their structures. Propionyl chloride is converted into the amide with 2 equiv of trimethylsilyldiethylamine in hexanes at ambient temperature in 5 h. Oxalyl chloride gives monoamide when treated with 1 equiv of trimethylsilyldiethylamine at — 23 °C, and gives bisamide with excess of the reagent at room temperature. Trimethylsilyldiethylamine has been successfully used for the conversion of phenylselenyl chloride into the phenylselenenamide. ... 

Synthesis of polyamides containing disulfide linkages were achieved by condensing 2,2 -dithiobis(acetyl chloride) and 33 -dithiobis(propionyl chloride) with diamines like hexamethylene diamine [143]. The polymers are crystalline and can be drawn into fibers. The disulfide bonds in the main chain are dissociated by mercaptan exchange reactions [144] ... 

The acid chloride precursor for the multicomponent reaction was accessed (Scheme 11) through the method that was developed in the theopederin D synthesis. The sequence largely followed the excellent route that was reported by Nakata." Our variation on this route was the incorporation of a catalytic asymmetric (3-lactone formation" " from acetaldehyde and propionyl chloride in the presence of 44 to yield, after opening with the lithium enolate of t-butyl... 

During the last two decades the synthesis of levofloxacin and its S-(-)-pre-cursors has been improved considerably, and new approaches have been advanced [243-255], In particular, kinetic resolution of 7,8-difluoro-2,3-dihydro-3-methyl-4H-[l,4]-benzoxazine racemate using naproxen, N-[sulphonylsubstituted]-(/ )-proline and (2S)-(6-methoxynapht-2-yl)propionyl chloride, has been advanced [256-261], The optically active (5)-isomer obtained by this method has been used for the synthesis of levofloxacin (5)-(-)-80 [256]. Also a new synthetic approach to (5)-isomer through catalytic reduction of 7,8-difluoro-3-methyl-2 (-l,4-benzoxazine with use of chiral Bronsted acids as catalyst and substituted dihydropyridine as a source of hydrogen has been described [262],... 

Gray s group also prepared the propanoate of (2-hydroxypropyl)cellulose (PPC or C3PC) from the esterification reaction of HPC (Mw = 100,000 g/mol) and propionyl chloride or propionic anhydride in acetone (Tseng et al. 1982). The appearance and behavior of the polymer is similar to APC, however this ester displayed iridescent colors at room temperature. In the same year (Bhadani and Gray 1982), the synthesis of the benzoic acid ester of HPC (BzPC) from the reaction of the aromatic benzoyl chloride with HPC in pyridine was described. The polymer showed a thermotropic liquid crystalline phase below 160 °C. Benzoic acid ester of HPC was fractionated from acetone solution by precipitation with methanol-water and polymers with different molecular weights were obtained (Bhadani et al. 1983). 

At least two derivatives of pyran have been used for the primary synthesis of quinoxalines. Thus o-phenylenediamine (390) and 6-(p-methoxyphenyl)-6-methyl-5,6-dihydro-2//-pyran-2,5-dione (391) in methylene chloride at 20°C open to the air for 48 h gave 3-[2-hydroxy-2-(p-methoxyphenyl)propionyl]methyl-3,4-dihydro-... 

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