Butyric 4-bromo

B-Butyraldehyde, condensation with N-phenylhydroxylamine, 46, 96 -Butyric acid, reaction with iron powder to yield 4-heptanone, 47, 75 Butyric acid, 7-bromo-, ethyl ester, 46, 42... 

Hydrolysis, of 2 benzyl 2 carbometh oxycyclopentanone with lithium iodide m 2,4 6-colhdme, 46, 7 of 7 butyrolactone to ethyl y-bromo-butyrate with hydrogen bromide and ethanol, 46, 42 of 2,5 dicarbethoxy 1 4-cyclohexane-dione to 1,4 cyclohexanedione, 46, 25... 

ETHYL y-BROMOBUTYRATE (Butyric acid, Y-bromo-, ethyl ester)... 

To bracket the N1 site of thymine, we will use dichloroacetic acid (Hjcid = 328.4 kcal/mol), difluoroacetic acid (331.0), hydrochloric acid (333.3), pyruvic acid (333.5), 2-bromo-butyric acid (336.8), 2-chloropropionic acid (337.0), and trifluoro-m-cresol (339.3). These acids have acidities in the range that should allow us to bracket the acidity... 

Automated parallel experiments were carried out to rapidly screen and optimize the reaction conditions for ATRP of methyl methacrylate (MMA) [34]. A set of 108 different reactions was designed for this purpose. Different initiators and different metal salts have been used, namely ethyl-2-bromo-tTo-butyrate (EBIB), methyl bromo propionate (MBP), (1-bromo ethyl) benzene (BEB), and p-toluene sulfonyl chloride (TsCl), and CuBr, CuCl, CuSCN, FeBr2, and FeCl2, respectively. 2,2 -Bipyridine and its derivatives were used as ligands. The overall reaction scheme and the structure of the used reagents are shown in Scheme 2. 

In a SOO-ml. round-bottomed flask fitted with a calcium chloride drying tube are placed 226 g. (1.35 moles) of a-bromo- -butyric acid (Note 1) and 284 g. (175 ml., 2.39 moles) of thionyl chloride (Note 2). A small piece of porous plate is added, and the reaction mixture is allowed to stand at room temperature for 48 hours (Note 3). The excess thionyl chloride is removed by distillation, and the acid chloride is collected at 147-153° (Note 4). The yield of colorless product is 168-197 g. (67-78%). 

The a-bromo-w-butyric acid obtained from the Eastman Kodak Company, which had a boiling range of 2°, proved to be satisfactory. 

Bromobenzaldehyde, 100 Bromobenzene, 97 a-Bromo- -butyric acid, 62 a-Bromo- -butyryl chloride, 62 Butadiene, 93... 

Cyclization of 2-bromo-4-(2-pyridylthio)butyric acid hydrobromide... 

Tetrahydrobenzo[6]thiophen-4-one (103) may be prepared from y-(2-thienyl)butyric acid by cyclization with phosphoric acid854 or by Friedel-Crafts cyclization of the corresponding acid chloride.194, 355.358 j s 5-methyl,357 2-ethyl,194 2-isopropyl,358 2- and 3-tert-butyl,359 2,3-dimethyl,360 2-ethyl-3-methyl,360 and 2-bromo 354 derivatives and diethyl 4,5,6,7-tetrahydrobenzo[6]thiophene-4,5-di-carboxylate861 may be prepared similarly. 4,5,6,7-Tetrahydrobenzo-[6]thiophen-7-one (104)357 362,863 and its 5- and 6-methyl 357 and 2-chloro 362 derivatives are obtained from the appropriately substituted y-(3-thienyl)butyric acid, A recent patent 364 describes the vapor phase cyclization of y-(2-thienyl)butyric acid to 103. Ketones (103 and 104) are useful intermediates for the synthesis of 4- and 7-substituted benzo[6]thiophenes, respectively their reactions are discussed in Section VI, B, 4. 

A solution of 34 ml of n-butyl lithium in 30 ml of anhydrous ether was cooled to -65°C under nitrogen and 5.3 ml of 3-methyl-2-bromothiophene in 10 ml anhydrous ether was added dropwise over a period of 10 min. The reaction mixture was stirred at -65°C for 1 h and 2.7 ml of ethyl 4-bromo-butyrate in 10 ml of anhydrous ether was added slowly. The reaction was stirred for 4 h while the temperature raised to -20°C, 20 ml water was added, and the mixture was stirred for 5 min after which the aqueous layer was removed. The ether layer was washed with 20 ml of water, and the combined aqueous phases were extracted with 50 ml of ether. The combined organic phases were dried over anhydrous sodium sulfate, which after evaporation yielded 9 g of 1-bromo-4,4-bis(3-methylthien-2-yl)but-3-ene as an oil. 

Secondary and tertiary alkyl bromides react with active zinc at ambient temperature. However, the reaction time for the oxidative addition can be shortened by heating the reaction mixture at reflux in THF. Methyl 3-bromo-butyrate gives the organozinc bromide intermediate upon reaction with active zinc and reacts with 2-cyclohexen-l-one to afford the 1,4-addition product (Protocol 6, Scheme 2.3).14... 

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