Bromo derivatives

Certain phenols give white bromo derivatives with bromine water. 

An alternative procedure, more suitable for the preparation of somewhat larger quantities of the bromo derivative, is the following. Dissolve 10 g, of the compovmd in 10-15 ml. of glacial acetic acid, cautiously add 3-4 ml. of hquid bromine, and allow the mixture to stand for 15-20 minutes. Pour into 50-100 ml. of water, filter off the bromo compound at the pump, and wash with a httle cold water. Recrystallise from dilute alcohol. 

Fluorescein is obtained by condensing phthahc anhydride (1 mol) with resorcinol (2 mols) in the presence of anhydrous zinc chloride. The tetra-bromo derivative, readily prepared by the addition of the calculated quantity of bromine, is eosin. 

The 2-anilinoselenazoles follow an analogous reaction path. The entry of bromine into the 5-position is in agreement as seen in Scheme 35. The 2-anilino-4-phenylselenazole gives a 5-bromo derivative by bromination. It is not identical with either of the bromo derivatives prepared by direct synthesis (Scheme 35) (99). 

Bromo derivatives have been synthetized in this way (229, 233, 234). 

Tertiary alkyl chlorides have been converted to the tertiary nittiles with trimethylsilyl nittile ia dichioromethane ia the presence of SnCl (131). The reaction was appHed to the synthesis of several bridgehead nittiles, such as 1-adamantyl and 1-diamantyl nittiles from the corresponding chloro or bromo derivatives usiag SnCl or AIBr. catalysts (132). 

Similarly, the reaction with bromine yields the corresponding 5-bromo derivatives, which are suitable substrates for nucleophilic displacement or dehydrohalogenation reactions. Typical nucleophiles (Nu) are H2O, NH, RNH2, and sodium barbiturates ... 

The organic iodine compounds have lower heats of formation and greater reactivities than their chloro and bromo analogues. As ia the case of the inorganic iodides, their iadexes of refraction and specific gravities are higher than the corresponding chloro and bromo derivatives (121). 

This mixture is known as Quinoline Yellow A [8003-22-3] (Cl 47000) and is most widely used with polyester fibers (109). Upon sulfonation, the water-soluble Quinoline Yellow S or Acid Yellow 3 [8004-92-0] (Cl 47005) is obtained. This dye is used with wool and its aluminum salt as a pigment. Foron Yellow SE-3GL (Cl Disperse Yellow 64) is the 3-hydroxy-4-bromo derivative. Several other quinoline dyes are commercially available and find apphcations as biological stains and analytical reagents (110). 

True electrophilic substitution is very difficult in pyridopyridazines. For example, the [3,4-d] parent (286) is inert to hot 65% oleum (68AJC1291), and although formation of a 3-bromo derivative (308) was reported in the [2,3-d] series, it seems to have arisen by an addition-elimination reaction via the dibromide (309) (69AJC1745). Attempted chlorination led to ring opening. A similar effect was observed in the [3,4-d] system, where an 8-bromo derivative was obtained (77BSF665), and in iV-oxides of the pyrido[2,3-c]pyridazine and fused pyridazino[3,4-c]isoquinoline series (72JHC351). The formation of (311) from (310)... 

Bromination of 1,2-benzisoxazoles gave primarily the 5-bromo derivative, although other isomers have also been reported (67AHC(8)277). Bromination of 5-methoxy-3-methyl-l,2-benzisoxazole at room temperature gave a mixture of the 4- and 6-bromo compounds, while at elevated temperatures a 4,6-dibromo compound was produced (Scheme 27) <79IJC(B)371). 

The o-bromo derivative is quantitatively cleaved with hydrogen fluoride (0°, 10 min). ... 

Naphthoic acid has been prepared principally by the hydrolj sis of d-naphthonitriled the overall yields from (3-naph-thylamine, from sodinm-/3-naphthalene sulfonate, and from calcium d-naphthalene sulfonate being given as (approximately) 20 per cent, 21 per cent, and 50 per cent, respectively. The acid has been prepared also by the carbonation of the Grignard reagent from the less accessible /3-bromo derivative and. more recendy, from the readily available methyl ketone. ... 

Cracking of the ester at about 500°C leads to the formation of the undecylenic acid ester together with such products as heptyl alcohol, heptanoic acid and heptaldehyde. Undecylenic acid may then be obtained by hydrolysis of the ester. Treatment of the acid by HBr in the presence of a peroxide leads to w-bromoundecanoic acid together with the 10-isomer, which is removed. Treatment of the w-bromo derivative with ammonia leads to w-aminoundecanoic acid, which has a melting point of 50°C (Figure 18.8). 

Replacement of halides with deuterium gas in the presence of a surface catalyst is a less useful reaction, due mainly to the poor isotopic purity of the products. This reaction has been used, however, for the insertion of a deuterium atom at C-7 in various esters of 3j -hydroxy-A -steroids, since it gives less side products resulting from double bond migration. Thus, treatment of the 7a- or 7j5-bromo derivatives (206) with deuterium gas in the presence of 5% palladium-on-calcium carbonate, or Raney nickel catalyst, followed by alkaline hydrolysis, gives the corresponding 3j3-hydroxy-7( -di derivatives (207), the isotope content of which varies from 0.64 to 1.18 atoms of deuterium per mole. The isotope composition and the stereochemistry of the deuterium have not been rigorously established. 

A" -3-ketones from 4-bromo compounds in the 5j5-series. Frequently it is necessary to prepare A -B-ketones from starting materials with the 5a stereochemistry, and this has to be done indirectly. (See sections Ill-C and VI-B for conversion of 5jS-3-ketones into A -3-ketones.) The Syntex group has devised a method of doing this via the thermodynamically stable 2a,4a-di-bromo derivatives. 

Direct halogenation of a 20-ketopregnane (lacking an hydroxyl at C-17) generally does not give satisfactory yields of the 21-bromo derivative, unless the presence of a C-16 substituent e.g., methoxyl or methyl) inhibits formation of the usual 17-bromo primary product. However, an indirect method has been devised. If the 20-ketaI is first prepared, it can be brominated satisfactorily at C-21 using trimethylphenylammonium tribromide as halo-... 

This ionic mechanism is supported by kinetic data. A free radical mechanism has been proposed for the unique bromination (with bromine) of 3a, 12a-diacetoxypregnan-20-one ethylene ketal, which gives the 21-bromo derivative in excellent yield. ... 

Halo-2-methylbutanes (X = F, Cl, Br) all produce the same carbocation upon dissociation, yet one of these halides is unreactive. Calculate the dissociation energies for 2-metbyl-2-butyl fluoride and 2-metbyl-2-butyl-cbloride. (Energies of fluoride and chloride are given at right.) Compare these to the dissociation energy of the corresponding bromo derivative. Which hahde is most likely to be unreactive ... 

Although bromo derivatives have been used, the two most common ot-halocarbonyl compounds for this reaction are chloroacetaldehyde and chloroacetone. The dicarbonyl component is typically ethyl acetoacetate or one of its derivatives. A variety of bases including triethylamine and potassium hydroxide can promote the reaction however, the most popular base is pyridine. Conversion to the furan takes place either at room temperature or upon heating to 50°C with reaction times varying from four hours to five days and yields ranging from 30-86%. 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

The photochemical conversion of the 2-bromo derivative 144, derived from l-o-methylphenyl-l,2,3,4-tetrahydro-j8-carboline by treatment with hypobromite, into a dihydro-j8-carboline, regarded as 145, has been reported. ... 

Isothiazole-3-carboxylic acid and its 4-bromo derivative have been obtained by oxidation of the corresponding aldehydes with silver oxide. They form acid chlorides, esters, and amides. The amides may be dehydrated to give the corresponding nitriles. ... 

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