Ullmann condensation

Cl Reactive Blue 19 (9) is prepared by the reaction of bromamine acid (8) with y -aminophenyl-P-hydroxyethylsulfone [5246-57-1] (76) ia water ia the presence of an acid-hinding agent such as sodium bicarbonate and a copper catalyst (Ullmann condensation reaction) and subsequent esterification to form the sulfuric ester. 

Ullmann condensation of the sodium salt of p-chlorothiophe-nol (31) with 2-iodobenzoic (32) acid gives 33. Cyclization by means of sulfuric acid affords the thioxanthone, 34. Reaction with the Grignard reagent from 3-dimethylaminopropyl chloride affords the tertiary carbinol (35). Dehydration by means of acetic anhydride affords chlorprothixene as a mixture of geometric isomers, 36. (Subsequent work showed the Z isomer-chlorine and amine on the same side—to be the more potent compound.) Chlorprothixene is said to cause less sedation than the phenothiazines. ... 

Secocularine (228) and secocularidine (229) were synthesized by Hofmann degradation of the corresponding cularine and cularidine methiodides, respectively (181). Both secocularidine (229) and norsecocularine (230) were transformed to secocularine (228) by O- and N-methylation, respectively (181,182). Total synthesis of noyaine (231) was achieved by Ullmann condensation of 8-hydroxy-7-methoxy-2-methyltetrahydroisoquinoIine (232) with 6-bromoveratric acid methyl ester followed by oxidation of the intermediate 233 (183) (Scheme 35). 

The same group of authors has recently reported a combination of various palladium- and copper-catalyzed Suzuki, cyanation, and Ullmann condensation reactions for the synthesis of thiophene-based selective angiotensin II AT2 receptor antagonists (Scheme 6.24) [55],... 

Ukraine, titanium production in, 24 847 UL 94 flame testing, 19 588 UL94 flammability test, 10 175-176 Ulexite (boronatrocalcite cottonball), 4 133t, 241, 243t, 245, 5 785t Ullmann condensation reaction, 9 309, 310, 444... 

Finally, replacement of the methylene bridge by a sulfur bridge leads to compoxmds such as 117 and 123 which are major tranquilizers. Thus, Ullmann condensation of thiosalicylic acid 112 with ortho-chloronitrobenzene affords thioether 113 the nitro group is then reduced to the aniline (114). Cycliza-tion as above leads to the lactam 115, which is then converted to the iminochloride derivative (116). Condensation with N-methylpiperazine affords clothiapine... 

The novel indolo[3,2-/ ]carbazole compound 58 has been prepared in good yield by an Ullmann condensation reaction of 5,ll-dihydroindolo[3,2-/ ]carbazole with 1-iodonaphthalene. The product was found to exist in two isomeric forms, cis and trans, attributable to the hindered rotation of the bonds binding the naphthyl groups <1999JA5097>. 

Additional studies showed that iodoferrocene was approximately as reactive as l-iodo-2-nitrobenzene under Ullmann conditions. A mixed Ullmann reaction involving these two reactive aryl halides produced 2-nitrophenylferrocene. Ullmann condensations of iodoferrocene with various sodium phenoxides and sodium arenethiolates likewise led to ferrocenyl aryl ethers and sulfides, respectively (84, 85). 

Ullmann Condensation in Synthesis of N-Arylazoles M. A. Khan, Rec. Chem. Prog., 1970, 31, 43-50. 

Low molecular weight aromatic ethers have been prepared principally by the condensation of phenolate salts with aromatic halides 82). The Ullmann condensation (81), which employs copper or its salts as catalysts has been used in most cases in the laboratory. Recently a modification of the Ullmann condensation which consists of heating copper (1) oxide, the free phenol, and the aromatic halide in s-collidine has been reported (3). This method is recommended for alkali-sensitive aromatic compounds. In addition, reaction of phenolate salts with copper (1) oxide and the aromatic halide in boiling N,N-dimethyl formamide is described. When the halogen is activated by electronegative groups as in -chloroni-... 

In the past, various copper salts or copper metals have been commonly used as catalysts in the Ullmann condensation. No other metals or salts... 

Hanaoka et al, (39, 71) condensed pelletierine (126) with 6-bromoisovanillin and obtained in quantitative yield the /raw-quinolizidone (149). The methyl ether (150) was selectively reduced with Henbest catalyst, and the axial (151) and equatorial (153) alcohols were separated in 9 1 ratio. The Ullmann condensation of the acetyl derivative (152) with methyl 4-hydroxy hydro-... 

In another similar approach (40, 72) Wrobel and Gol biewski obtained the methyl ether (150) in the same way. The Ullmann condensation with methyl 4-hydroxycinnamate afforded a mixture of stereoisomers 160 and 161. Catalytic reduction of the trans-fused quinolizidone (160) gave a mixture of axial and equatorial epimers (162 and 163) in 4 1 ratio. Hydrolysis of the axial hydroxyester (162) followed by lactonization with thionyl chloride in chloroform yielded racemic decaline. 

Sulfar fibers are extruded from polyphenylene sulfide) or PPS by the melt-spinning process. The first PPS polymer was made in 1897 by the Friedel-Crafts reaction of sulfur and benzene. Researchers at Dow Chemical, in the early 1950s, succeeded in producing high-molecular weight linear PPS by means of the Ullmann condensation of alkali metal salts of p-bromothiophenol. 

A synthesis of 0-methyldauricine (XXVII) has been described in Volume VII, p. 446 (2). A similar approach, applied recently, resulted in the formation of a mixture of the racemates XXIX 17). The Ullmann condensation of (+ )-3 -bromo-4 -0-acetylarmepavine (XXXI) and ( )-armepavine (III) yielded a noncrystalline phenolic product which was found to have several physical properties identical with those of dauricine. A difference in the pattern of the XMR-spectra indicated that the synthetic product was a mixture of diastereoisomers. 

Compound ii S -LVIII was synthesized by the Ullmann condensation of (— )-6 -bromolaudanosine (XL) with isocorydine (LVI) and was reported to be identical with thalicarpine. However, scrutiny of the spectral properties of thalicarpine showed that they are incompatible with structure i S-LVIII (32). For example, there is no AB quartet in the aromatic proton region of the NMR-spectrum of the alkaloid as would be expected of the neighboring aromatic protons in structure i (S-LVIII. Accordingly the condensation of compounds XL and LVI was reexamined and, as expected, the earlier result was not reproduced. 

The alkaloid was synthesized by the Ullmann condensation of l-(3 -bromo - 4 - benzyloxybenzyl) - 2 - methyl - 6,7 - dimethoxy -1,2,3,4 - tetra-hydroisoquinoline (XXXIV) and l-(4 -benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydroisoquinoline (IX) followed by removal of the benzyl groups (40). 

A synthesis of tetrandrine, annoimced by Tomita and his co-workers (69), started from the coclaurine derivative /S-II (a product obtained by cleavage of 0-methylberbamine). Ullmann condensation of the phenol (S-II with the bromo compound XCV, obtained from the former compound through the steps of bromination and methylation, furnished tetrandrine. 

A synthetic route to ( )-0,f>-dimethyltubocurarine iodide (CXXV), via the racemate of 0,0-dimethylbebeerine (CXXIII), was announced in 1959 by Tolkachev and his collaborators (94). It started by the condensation of 3-methoxy-4-hydroxyphenethylamine with 4-benzyloxy-phenylacetic acid to give the amide CXXVI. Reaction of the potassium salt of the latter with the methyl ester of 3-bromo-4-methoxyphenyl-acetic acid in the presence of copper powder gave compound CXXVII. This on condensation with 3-methoxy-4-hydroxy-5-bromophenethyl-amine afforded compound CXXVIII, which was methylated to CXXIX. The latter compound was cyclized with phosphorous oxychloride to the dihydroisoquinoline derivative CXXX. Debenzylation of CXXX followed by intramolecular Ullmann condensation yielded compound CXXXI. The latter was converted to racemic dimethylbebeerine (CXXIII) by reduction with zinc dust in acetic acid followed by methyla-tion. Finally, treatment of ( + )-CXXIII with methyl iodide furnished the dimethyl ether of ( + )-tubocurarine iodide, identified by comparison of its UV-spectrum with that of the dimethyl ether of natural tubo-curarine iodide and by melting-point determination of a mixture of the two specimens. 

The intramolecular Ullmann condensation was used by D.L. Boqer and co-workers to form the 15-membered macrocyclic ring of the cytotoxic natural product, combretastatin D-2. This compound possesses unusual meta- and paracyciophane subunits, which are also found in a range of antitumor antibiotics. The first approach where the final step was a macrolactonization was unsuccessful, so the researchers chose to form the biaryl ether moiety as the key macrocyciization step. Methyicopper was found to mediate the cyclization and gave moderate yield of the corresponding biaryi ether. Finaiiy boron triiodide mediated demethylation afforded the natural product. 

The highiy oxygenated antifungai/anticancer naturai product ( )-diepoxin o was prepared in the laboratory of P. Wipf. The coupling of the two substituted naphthalene rings was achieved via the Ullmann condensation of a phenolic compound with 1-iodo-8-methoxynaphthalene. The aryl iodide coupling partner was used in excess and the condensation was conducted in refluxing pyridine in the presence of a full equivalent of copper(l)-oxide. 

In the laboratory of K.C. Nicolaou, a novel mild method for the preparation of biaryl ethers was developed. The di-ort/70-halogenated aromatic triazenes underwent efficient coupling with phenols in the presence of CuBr. This mild modified Ullmann condensation was utilized in the synthesis of the DOE and COD model ring systems of vancomycin. 

Tomita, M., Fumitani, K., Aoyagi, Y. Cupric oxide as an efficient catalyst in Ullmann condensation reaction. Chem. Pharm. Bull. 1965, 13, 1341-1345. 

---