The reaction proceeds smoothly, and the application to 13 examples was demonstrated, including those that are sterically demanding and electron-rich, albeit observing generally lower yields with these substrates. Palladium-catalyzed cross-coupling with selectivity for the more electron-rich C-5 position, gave monoarylated product 403. %PDF-1.3 For the synthesis of aryl chlorides, chloroform is the solvent of choice. Macroporous polystyrene ion-exchange resin Amberlyst A-15 was employed as support, allowing the use of aqueous based chemistry. Iodobenzene can also serve as a substrate for the Sonogashira coupling, Heck reaction, and other metal-catalyzed couplings. Halogen exchange also can be achieved; thus, treatment of 2,6-dichloropyridine with a high concentration of iodide ion gives 2,6-diiodopyridine 〈80JOM(186)147〉. These possibilities are shown below. However, when only CuI was used in a stoichiometric amount to mediate the reaction, the cross-coupling reaction went specifically at the 2-position to give 405, although the yield was poor. By continuing you agree to the use of cookies. In our initial synthesis of SN30000, we typically isolated ∼ 10% recovered starting 1-oxide and ∼ 50% of SN30000. Fig. {+h�n�4�uԨؼ5MJ&�tDŽ2=0P��Ǹ��^h�k�Tz���Nɤ�S�sZ�bFk0=g�E��6jVL�B)53$J�UK%j�V�)cznl�|=zZS�[m�˸����$�v�*M�c������q���$3����$�GO FOٜ�'3�F�J�4�cK���L���4�BǸ�c_�O[꒡�G��s�c2�S'x/�����h�h]�H%���1cX-y=��g.gƓ��|f@���̀2�g��I�o����&`����7��NfX3����ýZjޤn��Y��m�O�͂բ5\��'��o���9�f�;/ZXg�����h�0��DXr$����'���j]��Z Extensive crystallization trials were conducted on SN30000 to establish a purification process. Some examples of the synthetic applications of the Sandmeyer reaction are provided below. Multisubstituted 4-iodoimidazoles <2003TL7115, 2004TL1869> and 4-bromoimidazole <2004SPH15> were cross-coupled with methyl acrylate in high yields catalyzed by Pd(OAc)2 with PPh3 in the presence of TEA in DMF. OEt2 in dichloromethane at low temperature (see Section 2.15.8.4, Scheme 60) <1996JOC8160, 1999TL2105, 2000AG(E)3681, 2002BMCL1845, 2002TL9717>. 1-Methylimidazole was arylated only once with solid phase bound (chloromethyl polystyrene as solid phase precursor) aryl iodide 409. Similarly, sodium iodide in refluxing acetonitrile converted 2-chloroquinoline-3-carbaldehyde (63) into 2-iodoquinoline-3-carbaldehyde (64) in 90% yield (Equation (39)) 〈81JCS(P1)2509〉. A series of 2-substituted thieno[2,3-d]thiazoles 30 were subsequently prepared from 2-chloro-4-carbomethoxythieno[2,3-d]thiazole 27 by nucleophilic substitution reactions using a range of nitrogen, oxygen, and sulfur electrophiles (Equation 5) <2001ARK34>; sulfur electrophiles, in particular, gave excellent conversions to the products, whereas nitrogen and oxygen nucleophiles required elevated reaction temperatures. It is an example of a radical-nucleophilic aromatic substitution. Recent Literatur. When 2-iodoimidazole 381 was treated with 382 bearing both a terminal alkene and a terminal alkyne, in the presence of copper and palladium as catalysts, only the Sonogashira product was obtained in high yield (Scheme 91) <2006T3798>. For conversion of a diazonium intermediate to the corresponding chloride, bromide, or cyanide, the copper(I) salt is used. 8 0 obj Diazonium salts and diazo compounds are important intermediates in organic chemistry given their versatility and wide availability of the required starting materials. Bromination of 2-amino- and 2-acetylamino-4-(2-furyl)thiazoles 66 occurs on C-5 when 1 equiv of reagent is used at 10 °C in a kinetically controlled reaction (Scheme 11). regioselectivity of this reaction. This process of trifluoromethylation provides unique chemical properties with a wide variety of practical applications. The radical mechanism of the Sandmeyer reaction is supported by the detection of biaryl byproducts. The use of cHNO3 in acetic acid with careful temperature control gave an excellent yield of 70 with only ∼ 9% of 71 after an aqueous workup. Particularly, pharmaceuticals with CF3 groups have enhanced metabolic stability, lipophilicity, and bioavailability. A reaction that resembles the Sandmeyer reaction occurs when iodine is introduced into an aromatic compound through treatment of the arenediazonium salt with potassium iodide (KI). Thiazole undergoes selective iodination at C-2 with iodine in tetrahydrofuran (THF) after metallation with diisopropylmagnesium chloride <2001J(P1)442>. 1-Substituted-2-iodoimidazole 391 also coupled with an arylboronic acid 392 under conventional Suzuki conditions forming 393 (Scheme 94) <2005H(65)2721>. Ramachandran, ... P.D. Fig. This was confirmed experimentally; thus, upon heating for 1 h on a steam bath with 1 mol of hydrobromic acid in glacial acetic acid medium, the 5-bromothiazole 67 underwent 90% conversion to 5′-bromofurylthiazole 68, while upon treatment with 2 mol of hydrobromic acid, 5,5′-dibromofurylthiazole 69 underwent 70% conversion to the same compound 68 <2002CH873>. An optimized oxidation procedure was defined using preformed pertrifluoroacetic acid added to a solution of 1-oxide 77 in DCM/HOAc, and the mixture was stirred for up to 4 days to effect maximum conversion to the product. Imidazole-2-stannane 354 was cross-coupled with alkenyl bromide 355 (Scheme 84) <2005HCA707>. Scheme 7. This zinc reagent underwent Negishi cross-coupling with pyridinone triflate 377 to give the highly substituted pyridinone 378 in 51% yield (Scheme 89) <1999TL4069>. The product is separated by steam distillation. Reaction of thienoimidazole 43 with triethyl orthoformate in acetic anhydride gave 1-benzyl-2-(methylsulfanyl)imidazo[4′,5′;4,5]-thieno[3,2-d]pyrimidin-5(6H)-one 44, a thieno-extended purine ring system (Equation 7) <1995T12807>. When catalyzed by copper, imidazole itself was arylated at N-1 to give 413, a structure confirmed by X-ray crystallography. Heating 2-(2-pyridyl)-4-methylthiazole or 2-(2-pyridyl)-5-methylthiazole with 2 equiv of bromine in refluxing chloroform/acetonitrile (1:1) for 48 h results in bromination at C-5 or C-4, respectively, in good yields <2005NJC439>. M.P. Scheme 101 shows the reaction and its proposed mechanism. The sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts using copper salts as reagents or catalysts. The procedure reported by Cohen and coworkers calls for cuprous oxide together with an excess of cupric nitrate in neutral water. Diazotization of 73 with tert -butyl nitrite in the presence of CuI and iodine gave the 3-iodide 74 in moderate to good yields (58–79%) after an aqueous workup and filtration of the organic fraction through a short plug of alumina. Thieno[2,3-c]pyrazole 45 underwent Curtius rearrangement followed by intramolecular ring closure on heating in benzene to give pyrazolo[4′,3′:4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazine-4-one 46 (Equation 8) <2005JCR761>. This reaction displays motifs characteristic of the Sandmeyer reaction. The Sandmeyer reaction provides a method through which one can perform unique transformations on benzene, such as halogenation, cyanation, trifluoromethylation, and hydroxylation. The aryliodoination approach to the preparation of aryl iodides retains many of the advantages of the Sandmeyer reaction, but it is operationally simpler. Sometimes, the role of the coupling partner is important for the success of a coupling reaction. Scheme 8. Scheme 6. Rather than isolate the 6-nitro isomer at this stage, we carried the mixture through hydrolysis of the acetamides and crystallized 6-nitro-5-aminoindane 72 in 73% yield for the two steps. The critical step in the synthesis was the final oxidation of 1-oxide 77 to 1,4-dioxide SN30000. Direct halogenation of thiazole usually requires harsh conditions, often resulting in mixtures. Diazonium salts also react with boronates, iodide, thiols, water, hypophosphorous acid and others,[5] and fluorination can be carried out using tetrafluoroborate anions (Balz–Schiemann reaction).