Diazomethane reaction with benzene

Bis(trifluoromethyl)diazomethane is a reactive, electrophilic compound. It forms adducts with nucleophiles such as amines and phosphines5 and adds to olefins, acetylenes,5 and thiocar-bonyl compounds6 to form heterocycles. It has been used as a source of bis(trifluoromethyl) carbene in reactions with benzene,5 saturated hydrocarbons,7 carbon disulfide,8 and transition metal compounds,8 and it undergoes a unique radical chain reaction with saturated hydrocarbons to form adducts that are hydrazoncs and azines.7... 

On oxidation with Cr03, the 2-carboxy-derivative is readily obtained, which can be converted with diazomethane into the methoxycarbonyl analogue. The carboxy-compound gives an acid chloride with PC15 and a benzoyl derivative on Friedel-Crafts reaction with benzene.92... 

Monoesterification of a symmetrical dihydroxy aromatic compound can be effected by reaction with polymer-bound benzoyl chloride (Pyr, benzene, reflux, 15 h) to give a polymer-bound benzoate, which can be alkylated with diazomethane to form, after basic hydrolysis (0.5 M NaOH, dioxane, H2O, 25°, 20 h, or 60°, 3 h), a monomethyl ether. ... 

Hydroxypyridine (86, R = H) and its derivatives also belong to the class of heterocyclic enols. In benzene and dioxane, 3-hydroxy-pyridine occurs as the neutral molecule (and not as a betaine).Its reaction with diazomethane, in heterogeneous media, gives a mixture of 3-methoxypyridine (86, R = Me) (10%) and l-methyl-3-hydroxy-pyridinium betaine (87) (30%If tert-butanol is used as a... 

Reactions of 4,7-phenanthroline-5,6-dione have been the subject of considerable study. It is reduced to 5,6-dihydroxy-4,7-phenanthroline by Raney nickel hydrogenation226,249 or by aromatic thiols in benzene,262 and oxidized by permanganate to 3,3 -bipyridyl-2,2 -dicarboxylic acid.263 It forms bishemiketals with alcohols226 and diepoxides with diazomethane.226 The diepoxides by reaction with hydrochloric acid form diols of type 57, R = Cl, which on oxidation with lead tetraacetate give 3,3 -bipyridyl diketones of type 58, R = Cl. Methyl ketones of type 58, R = H, are also obtained by lead(IV) acetate oxidation of the diol 57, R = H, obtained by lithium aluminum hydride reduction of 57, R = Cl. With phenyldiazomethane and diphenyldiazomethane the dione forms 1,3-dioxole derivatives,264,265 which readily hydrolyze back to the dione with concomitant formation of benzaldehyde and benzophenone, respectively. 

Perhaps the most significant of the numerous applications of radiotracers in chemistry has been the study of chemical reaction mechanisms. In fact, most of the proposed reaction mechanisms have been verified by means of a radiotracer study. One of the simplest mechanistic experiments using radiotracers is to test the equivalence of various atoms in molecules in chemical reactions. An example of this type of study is the work of Volpin et al. (1959) on the equivalence of the seven carbon atoms in the tropylium ring. Volpin et al. reacted labeled diazomethane with benzene and brominated the cyclohepatriene product to form a labeled tropylium bromide, as shown below ... 

Ring expansion of aromatic compounds by carbene, carbethoxycarbene, chlorocarbene, and carbenoid is well known 256, 336, 351-356). Muller and co-workers reported the reaction of aromatic compounds with carbene generated from a catalytic decomposition of diazomethane with copper salts, and proposed a bimolecular two-step mechanism involving an inverse ylid for the reaction. Miller (336) proposed another bimolecular two-step mechanism for the reaction of benzene with alkylcarbenoids of aluminum. Baldwin and Smith (25) proposed a concerted mechanism for the reaction of aromatic compounds with carbethoxycarbene. Reaction of alkylbenzene with diethylzinc and ethylidene iodide gives 7-methylcyclohepta-l,3,5-triene derivatives in yield 369). The... 

Buchner ring enlargement. A recent application is the reaction of benzene with diazomethane catalyzed by cuprous bromide to give tropilidene (see Cuproui bromide). 

Thioamides of two cyclopropanecarboxylic acids undergo coupling reactions with diazomethane derivatives in refluxing benzene containing rhodium(II) acetate. The reaction conceivably takes place via a thiirane intermediate which undergoes reductive elimination by reaction with excess diazo compound. An example of an intramolecular reaction is the formation of indolizine 2. If the diazo compound is not in excess a thiol is formed, this can be removed by Raney nickel desulfurization. ... 

Dimethoxyphosphoryl)(phenyl)diazomethane (11.3 g, 50 mmol) in molten naphthalene (550 mL) was irradiated for 24 h at 85CC. Benzene (1800 mL) was added to the reaction mixture. The solution was subjected to column chromatography on silica gel (170 g) with benzene (1200 mL) (to elute the excess of naphthalene), EtOAc (4000 mL) and a mixture of EtOAc/MeOH (90 10, 1000 mL), affording 2 b as a colorless solid which was recrystallized (EtOAc) yield 14.3 g (88%) mp 136°C. The yellow residue, which was in part on silica gel, was heated in EtOAc (50 mL). After concentration (5 mL), crystallization at — 20"C afforded 3b as a white solid yield 50mg (0.4%) mp 214-216LC. 

Perhydro[l,3]oxazino[3,4-a]quinolin-l-one (146) was prepared from per-hydroquinoline (145) by sequential treatment with O3, NaBH4, LiOH, NaH, and finally diazomethane (80JA1454). Treatment of perhydroquinoline (147) with NaBH4, and then with p-toluenesulfonic acid in benzene under reflux, gave a 1 6 mixture of a- and /3-lactones 148. The /3 isomer of 148 was also converted to 146 in 93% yield with LiOH, NaH, and diazomethane (86CPB2380). Propionate 98 was obtained from 149 by reaction with LiOH and diazomethane [84JCS(CC)597 86CPB2380]. 

Cyclopropanation of olefins. Three laboratories2-4 reported independently in 1960-61 that copper-catalyzed decomposition of diazomethane gives a species that reacts with benzene to give tropilidene (1, 16% yield) and with cyclohexene to give norcarane (2, 24% yield). The reaction was then developed into a useful synthetic method by Doering and Roth,5 who found that cuprous chloride is an excellent catalyst. The method has the advantage that no insertion products are formed such as those obtained when diazomethane is decomposed photo-... 

Methylene is produced from diazomethane by the photodissociation reaction. This carbene reacts with benzene to form toluene and cylohepta-triene (Scheme 4). 

The formation of toluene in the reaction of diazomethane with benzene (8-3) brings us to the second characteristic reaction of carbenes, namely insertion into single bonds, in this case into an sp -C —H bond. Here again prehistoric examples (i.e., investigations before 1950) of Buchner and Meerwein are known (Buchner and Schulze, 1910 Buchner and Scholtenhammer, 1920 Meerwein et al., 1942), as well as early systematic work by Doering s group after 1950. 

Dzhemilev et al. (1991) conducted an interesting investigation on the yield of cycloheptatriene formed in the reaction of benzene with diazomethane with various catalysts. The yield decreases in the presence of transition metal complexes in the series Rh-C (100<7o), Rh2(CF3COO)4 (57q/o), CuCl (39< o), CuBr (37<7o), Rh2(CH3COO)4 (17< o), activated charcoal (15 /o). Toluene, biphenyl, and dimethyl-benzenes yield mixtures of the corresponding regioisomeric cycloheptatriene derivatives in 82-98 yield. With naphthalene, cyclopropanation took place in the 1,2-position only (98< o). The benzonorcaradiene formed resisted isomerization to benzocycloheptatriene. 

Addition of carbenes to aromatic systems leads to ring-expanded products. Methylene itself, formed by photolysis of diazomethane, adds to benzene to form cycloheptatriene in 32% yield a small amount of toluene is also formed by an insertion reaction. The cycloheptatriene is formed by a Cope rearrangement of the intermediate cyclopropane (a norcaradiene). More satisfactory is the reaction of benzene with diazomethane in the presence of copper salts, such as copper(I) chloride, which gives cycloheptatriene in 85% yield (4.87). The reaction is general for aromatic systems, substituted benzenes giving mixtures of the corresponding substituted cycloheptatrienes. 

Full details of the reaction of hexahuoro-Dewar-benzene with the 1,3-dipoles, phenyl azide and diazomethane (see Vol. 1, p. 268) are available, and further examples of reactions with 2,2,2-trifluorodiazoethane, 2,4,6-trimethylbenzonitrile oxide, and benzonitrile JV-phenylimide have been described. 2-Methoxypenta-fluorobicyclo[2,2,0]hexa-2,5-diene yields an adduct with phenyl azide by addition to the CF=<1F bond, and cji o-5,6-dibromohexafluorobicyclo[2,2,0]hex-2-ene, but not the corresponding tra/u-dibromo-compound, yields adduct (125). 

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