Bromo-aryl ether

Bromo-aryl ether 46 (Scheme 18), on treatment with one equivalent of sodium amide in boiling benzene, underwent rearrangement into 47 in 92% yield. The presence of an N-alkyl substituent on the anihne nitrogen atom was essential for the rearrangement. Flowever, 46 heated with potassium carbonate in dimethylformamide afforded 2-chloro-lO-(3-dimethylaminopropyl)phenoxazine 48 in 90% yield [33]. It was later proved [34] that the cyclization of 46 into 48 involves the rearrangement via 47. Rearrangements of orfho-aminodiphenyl ethers have been reviewed [35]. 

Decafluorobiphenyl [434-90-2] C F C F (mol wt, 334.1 mp, 68°C bp, 206°C), can be prepared by I Jllmann coupling of bromo- [344-04-7] chloro- [344-07-0] or iodopentafluorobenzene [827-15-6] with copper. This product shows good thermal stabiHty decafluorobiphenyl was recovered unchanged after 1 h below 575°C (270). Decafluorobiphenyl-based derivatives exhibit greater oxidative stabiHty than similar hydrocarbon compounds (271). Therm ally stable poly(fluorinated aryl ether) oligomers prepared from decafluorobiphenyl and bisphenols show low dielectric constant and moisture absorption which are attractive for electronic appHcations (272). 

Bromo-9-borabicyclo[3.3.0]nonane (9-Br-BBN), CH2CI2, reflux, 87-100% yield.9-Br-BBN also cleaves dialkyl ethers, allyl aryl ethers, and methylenedioxy groups. 

The extent of C-alkylation as a side reaction in etherification varies about 1% of allyl 2-allylphenyl ether is formed when phenol is used in the acetone and potassium carbonate method with allyl bromide with cinnamyl bromide or 7,7-dimethylallyl bromide the extent of C-alkylar tion is greater.16 A complicated mixture of C- and O-alkylation products results from the treatment of phenol with 4-bromo-2-hexene and 4-chloro-2-hexene. 9 4-Hexenylresordnol has been obtained in about 40% yield from the reaction of l-bromo-2-hexene, resorcinol, and potassium carbonate in boiling acetone.99 An appreciable amount of C-alkylation occurs when 2,6-dimethyIphenol is treated with allyl bromide and sodium ethoxide in ethanol.70 Since, in general, the ampunt of C-alkylation is greatly increased by carrying out the alkylation on the sodium salt of the phenol in benzene,16 this method is unsuitable for the preparar tion of allyl aryl ethers. 

The synthetic utility of ion exchange resins in combinatorial chemistry has been demonstrated by the use of a basic polymeric base PTBD (l,5,7-triazabicydo[4.4.0]dec-5-ene) 26 in a series of O- and N-alkylation experiments (Scheme 7) [15]. For example, deprotonation of the phenol 27 with this polymeric base PTBD 26 gave the ionic polymeric species 28 which contained the more nucleophilic phenolate. Addition of the 2-bromo aryl ketone 29 gave the aryl ether 30 in reasonable yield and in high purity (Scheme 7). The basic polymeric scavenger PTBD 26 removed all the unwanted HBr produced within the reaction mixture (in the form of 31) and advantageously eliminated the need for an aqueous extractive work-up procedure. 

Multiple arylations of polybromobenzenes have been conducted to generate electron-rich arylamines. Tribromotriphenylamine and 1,3,5-tribromobenzene all react cleanly with A-aryl piperazines using either P(o-tolyl)3 or BINAP-ligated catalysts to form hexamine products [107]. Reactions of other polyhalogenated arenes have also been reported [108]. Competition between aryl bromides and iodides or aryl bromides and chlorides has been investigated for the formation of aryl ethers [109], and presumably similar selectivity is observed for the amination. In this case bro-mo, chloroarenes reacted preferentially at the aryl bromide position. This selectivity results from the faster oxidative addition of aryl bromides and is a common selectivity observed in cross-coupling. Sowa showed complete selectivity for amination of the aryl chloro, bromo, or iodo over aryl-fluoro linkages [110]. This chemistry produces fluoroanilines, whereas the uncatalyzed chemistry typically leads to substitution for fluoride. 

There is one very special feature of the benzyne mechanism. The triple bond could be attacked by nucleophiles at either end. This is of no consequence when we are dealing with bromo benzene as the products would be the same, but we can make the ends of the triple bond different and then we see something interesting, ortho-Chloro aryl ethers are easy to prepare by chlorination of the ether (Chapter 22). When these compounds are treated with NaNH2 in liquid ammonia, a single amine is formed in good yield. 

While often considered undesirable pathways in the past, radical hydrogen transfers have also been shown to constitute intriguing possibilities for organic synthesis. Curran has for instance defined the concept of protection and radical translocation (PRT) groups, fii this context, 2-0-(2-bromo-aryl)dimethylsilyl ethers, aryl amides and 2-bromo-4-methoxyphenyl ethers... 

Very recently, the first examples of aryl ethers derived from 2a were reported. While Siv Ar-type reactions with various fluorobenzenes only led to partial etherification, the tetra-p-nitrophenyl ether was obtained with K2CO3/CUO in refluxing pyridine (46% partial cone, 16% 1,2-alternate, see below) . Reaction of 2a or 2na with 2-bromopyridine or 2-bromo-4-methylquinoline in refluxing diphenyl ether in the presence of CSCO3 gave the tetraaryl ether in the 1,3-alternate conformation . 

OAr From PTBD-resin (cf. Table 1.6.7, polymeric bases) by treatment with ArOH in MeCN.198 Alkyl aryl ethers from primary, allylic and benzylic bromides as well as from a-bromo ketones, esters and amides. Bis-aryl ethers from aryl fluorides. ... 

Bromine adds to the alkene but substitutes on the aryl ether, evolving gaseous HBr. 17.11. Strong add is used for nitration, and the amino group of aniline is protonated to a deactivating —NH3" group. 17.13. l-Bromo-l-chlorocydohexane the intermediate cation is stabilized by a bromonium ion resonance form. 17.14. (a) 2,4- and 2,6-dinitrotoluene (b) 3-chloro-4-nitrotoluene and 5-chloro-2-nitrotoluene ... 

In contrast to the well-known alkylation paths, namely, S l and Sn2, the fluoroalkylation reaction was rationalized by an unusual ionic chain mechanism [26]. As shown in Scheme 14.3, the reaction was initiated with the direct attack of electron-positive bromine (5+) on the BrCF2CF2Br by phenoxide. Tetrafluoroethy-lene (CF2=CF2) was generated in situ after loss of bromide anions. The phenoxides added to the CF2=CF2 to give the reactive fluorocarbanions, which were quickly terminated by bromide to form 2-bromo-tetrafluoroethyl aryl ethers. In the elimination step, zinc inserted into the C—Br bond of 2-bromo-tetrafluorethyl aryl ethers in a similar way to the preparation of Grignard reagents. Finally, the aryl trifluorovinyl ethers were obtained by the elimination of ZnBrF salt at elevated temperature. 

More recent studies have been concerned with the utilization of acetylene functionality and designing a system which would have all the processing criteria of an epoxide system. Materials which process analogously to the state-of-the-art epoxides require a very flexible backbone which will exhibit a low Tg before cure. The study provided a flexible aryl-ether system which Incorporates a phenylsul-fone backbone and has been referred to as ATS. The initial synthesis of ATS Involved the nucleophilic displacement reaction of various leaving groups in the 4,4 positions of diphenylsulfone with the metallic salt of m-hydroxyphenylacetylene. Research in our laboratory for lower cost precursors to ATS has led to the synthesis of bromo end-capped phenylsulfone oligomers via the Ullmann ether synthesis. 

The synthesis of the oligomers was carried out by the reaction of various aromatic bis-diols with m-dibromobenzene leading to a series of bromo end-capped, aryl-ether systems. Pyridine was used as the solvent for the reactions, and anhydrous potassium carbonate was utilized to generate the metallic salts of the bis-diols.. In an effort to promote low molecular weight oligomers, the molar ratio of m- dibromobenzene to aromatic bls-diol used in the S3mthesls... 

A series of acetylene-terminated, aryl-ether thermoset systems were prepared by an Ullmann ether synthesis involving the condensation of various salts of aromatic bis—diols with m—dibromobenzene. The bromo end-capped oligomers were converted to the acetylene-terminated systems by the catalytically-induced, bromo-displacement reaction with 2-methyl-3-but3m-2-ol, followed by base hydrolysis. 

Bromo-l,3,2-benzodioxaborole, CH2CI2 (cat. BF3 Et20), 25°, 0.5-36 h, 95-98% yield. Aryl benzyl ethers, methyl esters, and aromatic benzoates are also cleaved. ... 

For example, all three isomeric aryl acetates (1) undergo bromo- and iododesilylation, providing a route (6) to radio-halogen-labelled phenols the free phenols and methyl ethers corresponding to (1) proved too reactive, giving products of both substitution and desilylation. 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

Handy and coworkers [38] have also offered a very useful approach (Scheme 14) to lamellarin G trimethyl ether (36) and they have referred to this strategy as being modular in nature . The route starts with an N-protected 4-bromo-2-carboethoxypyrrole (72) and involves introduction of three different aryl groups via three sequential, regiospecific halogenations, which are... 

That the second option can also be successfully used has recently been revealed by our synthesis of 2-methoxyphenazine (117) [90]. The reduction of o-bromo-o -nitrodiphenylamine 132 accessible via intermolecular Pd-catalyzed JV-arylation provides the o-amino-o -bromodiphenylamine 133, which can then be cyclized to give 117 in a Pd-catalyzed intramolecular AT-arylation by employing Pd2(dba)3 as the Pd complex and 134 as the phosphine ligand. It should be noted that the outcome of both the intermolecular and the intramolecular AT-arylations heavily depends on the appropriate choice of the Pd complex as well as the phosphine. Ether cleavage leads to 2-hydroxyphenazine (9). 

---