1- Methylnaphthalene synthesis

As practiced by Hoffmann-La Roche, the commercial synthesis of vitamin is outlined ia Figure 1. Oxidation of 2-methylnaphthalene (4) yields menadione (3). Catalytic reduction to the naphthohydroquinone (5) is followed by reaction with a ben2oating reagent to yield the bis-benzoate (6). Selective deprotection yields the less hindered ben2oate (7). Condensation of isophytol (8) (see Vitamins, vitamins) with (7) under acid-cataly2ed conditions yields the coupled product (9). Saponification followed by an air oxidation yields vitamin (1) (29). 

Muscle relaxant activity is found in the aminoxy-methylnaphthalene structure of nafomine (27). The synthesis proceeds from l-chloromethyl-2-methylnaph-thalene (26), which is reacted with N-carbethoxy-hydroxylamine and base. In this way, the basic nitrogen is protected as the carbamate. Loss of the carbethoxy group either during reaction or on workup affords nafomine (27).10... 

MethyUndanes, 20 281 Methylindene, cyclization, 28 298 Methylnaphthalene, cyclization, 28 298, 299 Methyl-N-phenylcarbamate synthesis, 41 226-227... 

Dehydrogenation (the conversion of alicyclic or hydroaromatic compounds into their aromatic counterparts by removal of hydrogen and also, in some cases, of other atoms or groups) finds wide application in the determination of structure of natural products of complex hydroaromatic structure. Dehydrogenation is employed also for the synthesis of polycyclic hydrocarbons and their derivatives from the readily accessible synthetic hydroaromatio compounds. A very simple example is the formation of p-methylnaphthalene from a-tetra-lone (which is itself prepared from benzene—see Section IV, 143) ... 

H3PW12O40 and H4SiWi204o are also active for the condensation of isophytol and l-acetoxy-4-hydroxy-2-methylnaphthalene, which is a key step in the synthesis of vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) [Eq. (43)] heteropolyacids are approximately 50 times more active than ZnCl2 (362). 

The stereoselective synthesis of sy - and anti-diepoxides has also been achieved by using MCPBA. Naphthalene with MCPBA in methylene chloride-aqueous sodium bicarbonate gave 15-20% of anti-1,2 3,4-naphthalene diepoxide 15. However, 2-methylnaphthalene under similar conditions gave mixed syn-(16) and anti-(17) 1,2 3,4-naphthalene diepoxides.13... 

A typical procedure is that described in Expt 6.119 for the synthesis of 1-naphthaldehyde. The synthesis of p-nitrobenzaldehyde provides an example in which the intermediate crystalline hexamine salt is isolated prior to hydrolysis. 2-Naphthaldehyde is prepared from the bromomethyl compound, the preparation of which illustrates the use of Af-bromosuccinimide for effecting benzylic bromination of 2-methylnaphthalene. 

Substituted naphthalenes (acenaphthene, 2-methylnaphthalene) are also formylated by N,N-dialkylforinainides, but in low (20, 26%) yields. Generally speaking, several other methods of formylation and acylation exist in the organic synthesis repertoire. Nevertheless, the procedure described here is useful, for it uses inexpensive starting materials. 

Use of transition metal catalysts opens up previously unavailable mechanistic pathways. With hydrogen peroxide and catalytic amounts of methyl trioxorhe-nium (MTO), 2-methylnaphthalene can be converted to 2-methylnaphtha-l,4-qui-none (vitamin K3 or menadione) in 58 % yield and 86 % selectivity at 81 % conversion (Eq. 10) [43, 44]. Metalloporphyrin-catalyzed oxidation of 2-methylnaphtha-lene with KHSOs can also be used to prepare vitamin K3 [45]. The MTO-catalyzed process can also be applied to the synthesis of quinones from phenols [46, 47]. In particular, several benzoquinones of cardanol derivatives were prepared in this manner [48], The oxidation is thought to proceed through the formation of arene oxide intermediates [47]. 

The MCPTresearchteam investigated the synthesis of2-methyl-l,4-naphthoquinone (vitamin K3) by the oxidation of 2-methylnaphthalene [57]. 

An analogous synthesis is that of the two hexahelicenes 187a) and 187b), using naphthalene-2-acetonitrile 70a) or 7-methylnaphthalene-2-acetonitrile 70 b) in... 

A new preparative synthesis of 2-arylquinazolin-4(3//)-ones, which was reported recently, involved the pyrolysis of Schiff bases derived from 3-amino-l,2,3-benzotriazin-4-one in paraffin oil at 300 C, or in boiling 1-methylnaphthalene. The yields were as high as 86-100% but failed entirely when p-HO-, P-O2N-, and p-Me2N-benzaldehyde, furfural, and pyridine-2-aldehyde were used. The mechanism in Eq. (5) was proposed although the... 

Disubstituted pyridines are an important group of substrates for the bispidine synthesis. Diethylpyridin-3,5-dicarboxylate can be converted to N-tosylpiperidine-3,5-dicarboxamide, which generates 2,4-dioxo-7-tosylbispidine upon heating in methylnaphthalene. Reduction with lithium aluminium hydride (LiAlH4) yields the bispidine 1 under simultaneous elimination of the p-tosyl... 

Ring expansion of I-methylindenes. Gillespie et al have described a convenient synthesis of phenyl(tribromomethyl)mercury by mixing phenylmercuric chloride, sodium hydride, and bromoform in benzene with methanol as initiator. They have converted l-methyUndenes into 3-bromo-l-methylnaphthalenes by reaction with dibromocarbene generated from this precursor. Reaction of 1-methylindenes with dibromocarbene generated from bromoform with base... 

The methylation of naphthalene and methylnaphthalene with zeolitic catalysts was studied. The main purpose was to achieve a selective synthesis of 2,6-dimethylnaphthalene (2,6-dmn). The alkylation of naphthalene with methanol didn t give interesting results. Best performances were obtained with 1,2,4-trimethylbenzene as solvent/reagent, together with methanol. In such chemical system, among several medium and large pore zeolites, MTW stands out for both activity and selectivity to 2,6-dmn. As transalkylation is the main reaction, this behavior can be explained if a restricted transition state shape selectivity takes place. 

Other new methods used in heterogeneous catalytic reactions include the use of ionic liquids as catalysts and simultaneous applications of ultrasound and microwave irradiation. An ionic liquid as an acidic catalyst has been used for synthesis of cou-marins [78], in esterification of acetic acid with benzyl alcohol [79], in catalytic esterification at room temperature [80], in alkylation of a-methylnaphthalene with long-chain alkenes [81], and in hydrogenation of benzene [82]. 

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