A-Bromo adds

Azido-2-methylpropanoic Add a-Azido Acids from a-Bromo Adds and NaN3 i i 2-Bromo-2-methylpropanoic acid (4.96 g, 29.7 mmol) and NaNj (2.88 g, 44.3 mmol) were mixed in dry DMF (50mL) and stirred under argon for 2d. The mixture was concentrated, redissolved in HjO (30 mL) and acidified to pH 2 with 3 M HCl. The aqueous phase was extracted with CHCI3 (3 x 30 mL) and the organic phase was dried, concentrated, and purified by vacuum liquid chromatography (VLCI " ) (AcOH/EtOAc/heptane 5 20 75) yield 2.68 g (70%). 

If a catalytic amount of PBr3 is used, and not the full equivalent as shown in the reaction in Figure 19.41, the product of the reaction is the a-bromo acid, not the a-bromo acid bromide (Fig. 19.43a). The a-bromo acid bromide is still an intermediate, but only a small amount of it can be made at any one time, because its formation depends on PBr3. The small amount of a-bromo acid bromide produced is attacked by a molecule of the acid in an anhydride-forming reaction (Fig. 19.43b). The anhydride undergoes addition-elimination by bromide to give the carboxylate anion and a new molecule of a-bromo add bromide that recydes. A final hydrolysis gives the a-bromo acid itself This reaction surely involves a complicated mechanism. 

Reactions of a-Bromo Adds vnth Ammonia and Amines... 

Equip a 1 litre bolt-head flask with dropi)ing fuuncl and a double surface reflux condenser to the top of the latter attach a device (e.g.. Fig. II, 8, 1. c) for the absorption of the hydrogen bromide evolved. Place 100 g. (108 ml.) of dry iso-valeric acid (Section 111,80) and 12 g. of pmified red phosphorus (Section 11,50,5) in the flask. Add 255 g. (82 ml.) of dry bromine (Section 11,49,5) slowly through the dropping funnel at such a rate that little or no bromine is lost with the hydrogen bromide evolved the addition occupies 2-3 hours. Warm the reaction mixture on a water bath until the evolution of hydrogen bromide is complete and the colour of the bromine has disappeared. Pour off the liquid reaction product into a Claisen flask and distil mider the reduced pressure of a water pump. Collect the a-bromo-wo-valeryl bromide at 117-122°/25-30 mm. The yield is 150 g. 

In a 500 ml. bolt-head flask provided with a thermometer (reaching almost to the bottom) and a calcium chloride (or cotton wool) guard tube, place 100 g. of a-bromo-wo-valerj l bromide and 50 g. of dry, finely-divided urea. Start the reaction by warming the flask on a water bath the temperature soon rises to about 80°. Maintain this temperature for about 3 horns the mass will liquefy and then resolidify. Transfer the sticky reaction product to a large beaker containing saturated sodium bicarbonate solution, stir mechanically and add more saturated sodium bicarbonate solution in small quantities until effervescence ceases. Filter at the pump, suck as dry as possible and dry the crude bromural upon filter paper in the air. RecrystaUise the dry product from toluene. Alternatively, recrystaUise the moist product from hot water (ca. 700 ml.). The yield of pure brommal, m.p. 154-155°, is 28 g. 

A -Halogenated compounds such as iV-chlorotnfluoroacetamide, A -chloro-imidosulfuryl fluonde and N N dichlorotnfluoromethylamine add across C=C bonds to form saturated amides [14] tmidosulfury I fluorides [15] and amines [16], respectively Allylic halogenation also occurs with the use of A-bromo- or A-chIo roperfluoroamides The primary amine A,A-dichlorotrifluororaethylamine selectively affords 11 or 2 1 adducts with either tetrafluoroethylene or chlorotrifluoroethylene [16] (equation 7) The reaction mechanism is believed to involve thermal free radicals, with control achieved principally by reaction temperature The 1 1 adduct is formed even in the presence of a large excess of olefin... 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

The crude bromo add on standing two or three days may deposit an amorphous solid which is probably a polymerization... 

Table 3. Relative Rates of Dehydrofluorination of ot-Bromo-a -fluorosuccinic Adds Compared with Fluorinated Succinic Adds by Using 0.05 M Disodium Salts of the Adds in 0 JO M Solutions of NaOD in D20 at 6 °C [35,36, 37]...

A closely related synthesis of /8-hydroxy esters is provided by the Refor-matsky reaction. This synthesis starts with an aldehyde or ketone, RCOR, and an a-bromo ester, such as ethyl bromoethanoate. Zinc in a nonhydroxylic solvent (usually benzene) transforms the bromo ester into an organozinc compound, which then adds to the aldehyde or ketone carbonyl. Hydrolysis produces the /3-hydroxy ester ... 

Bromobenzaldehyde, 17, 20 18, 62 />-Bromobf.nzaldiacetate, 18, 63 -Bromobenzoic acid, 17, 21 -Bromobiphenyl, 16, 85 a-Bromo-iio-caproic acid, 11, 22 a-Bromo-M-caproic add, 11, 22 Bromocyanogen, 11, 30 /3-B ROMOETHYLAMINE HYDROBROMIDE,... 

Cognate preparation. a-Bromo-p-phenylacetophenone (p-phenylphenacyl bromide). Suspend 36 g (0.183 mol) of p-phenylacetophenone in 200 ml of glacial acetic acid in a 500-ml flask, warm gently on a water bath until a clear solution results, then cool as far as possible without the formation of crystals. To this solution add 29.5 g (9.5 ml, 0.184 mol) of bromine do not allow the temperature to rise above 45 °C during the addition. The brominated product... 

Rodriguez, N. Cuenca, A. Ramirez de Arellano, C. Medio-Simon, M. Asensio, G. Unprecedented Pd-catalyzed cross-coupling reaction of a-bromo sulfoxides with boronic adds. Org. Lett. 2003, 5,1705-1708. 

Oxazolidinones are the products of the acid-catalyzed condensation of a-hydroxyamides with aldehydes and ketones (equation 178). Tertiary amides derived from pyruvic acid undergo intramolecular cyclization when irradiated (equation 179) (78JOC419). Treatment of the a-bromo amide (308) with sodium hydride yields inter alia the dimeric oxazolidinone (309), presumably by way of an a-lactam, which adds to the carbonyl group of a second molecule of the amide (equation 180) (80JCS(P1)2249). 

Queiroz and coworkers [130] have devised a sequential Pd-catalyzed borylation-Suzuki coupling as the key step to thienocarbazole precursors. This one-pot processes begins with a Pd-catalyzed borylation using pinacolb-orane and a bromo benzothiophene derivative and concludes with the add-... 

Once the sodium has dissolved completely in the ethanol, add the contents of the addition funnel. Stir the mixture for 20 min. Meanwhile prepare a solution of a-bromo-p-tolunitrilea (12 g, 61 mmol) in dry DMF (60 mL) and add this solution from the addition funnel over a period of 20 min. Replace the glass stopper with a water-cooled condenser, and boil the mixture under reflux for 24 h under nitrogen. 

Another Lewis add-catalyzed atom-transfer domino radical cydization, to produce various bicydic and tricyclic ring skeletons, has been developed by Yang and coworkers [54], Reactions of the a-bromo- 3-keto ester 3-125 with Yb(OTf) 3 and Et3B/02 led to the bicyde 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a 6-ertdo-trig and 5-exo-trig cyclization after initial abstraction of the bromine... 

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