Cycloheptenes, preparation

Oxime 26 was prepared from 5,ll-dihydro-dibenzo[a,d]cyclohepten-10-one. The Hoch-Campbell reaction of 26 with 3-dimethylaminopropylmagnesium bromide produced aziridine 27 in 46% yield after acidic workup. Extension of the Hoch-Campbell reaction to steroids has also been reported. Thus, treatment of 3(3-hydroxy-5-pregnen-20-one oxime (28) with methylmagnesium iodide furnished a mixture of diastereomers, 20ot/20P,21-imino-20-methyl-5-pregnen-3P-ol (29) in a 50% combined yield and a 3 1 ratio. On the other hand, homo-adamantan-4-one oxime (30) was transformed to homo-adamantano[4,5-b]-2 -ethylaziridine (31) in 76% yield upon the action of... 

Preparation of 4-aza-S-(N-methyl-4-piperidyll-10,11-dihydro-SH-dibenzo[a,d]cycloheptene-S-ol Add 17.4 g of N-methyl-4-chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35°C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo[a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol,... 

Preparation of 4-aza-S-(N-methyi-4-piperidyiidene)-10,11-dihydro-SH-dibenzo[a,d]cyciohep-tene dimaieate To a solution containing 4.3 g of 4-aza-(N-methyl-4-piperldylidene)-10,11-dihydro-5H-dibenzo[a,d] cycioheptene in 55 ml of ethyl acetate, add a solution of 3.45 g of maleic acid dissolved in ethyl acetate. Filter the resulting precipitate and recrystallize the desired product from an ethyl acetate-methanol mixture to yield 4-aza-5-(N-methyl-4-pi-perldylidene)-10,11 -dihydro-5H-dibenzo[a/d] cycloheptene dimaieate, MP 152°-154°C. 

Preparation of 5-[3-(N-Formyl-N-Methyl)-Aminopropyl]-SH-Dibenzo[a,d] Cycloheptene ... 

Preparation of 5-(3-Methylaminopropyl)-5H-Dibenzo[a,d]Cycloheptene from 5-[3-(N-Formyl-N-Methylj-Aminopropyl]SH-Dibenzo[a/i]Cycloheptene 29.5 grams of 5-[3-(N-formyl-N-methyD-aminoprOpyl] -5H-dibenzo[a,d] cycloheptene is refluxed for 24 hours under nitrogen in a solution of 36.3 grams of potassium hydroxide in 378 ml of n-butanol. After cooling to room temperature, the solvent Is evaporated in vacuo, the residue is stirred with 200 ml of water, 300 ml of n-hexane, the layers separated, the water layer extracted with 100 ml of n-hexane and the combined hexane layers washed with water (2 x 100 ml) and then with... 

As previously mentioned, double bonds in relatively small rings must be cis. A stable trans double bond first appears in an eight-membered ring trans-cyclooctene, p. 134), though the transient existence of tran -cyclohexene and cycloheptene has been demonstrated. Above 11 members, the trans isomer is more stable than the cis. It has proved possible to prepare compounds in which a trans double bond is shared by two cycloalkene rings (e.g., 104). Such compounds have been called [m.n]betweenanenes, and several have been prepared with m and n values from 8 to 26. The double bonds of the smaller betweenanenes, as might be... 

Cyclohepten-l-one has been prepared from cycloheptanone by dehydrohalogenation of the ethylene ketals of 2-chloro- and 2-bromocycloheptanone and subsequent hydrolysis. The a,)3-dehydrogenation of cycloheptanone has also been effected via the... 

Using substituted a-methylene-(3-acetoxy ketones 2-494 with R = Me, Et, iPr, Ph and LiOtBu as base, the yields of the cycloheptene oxide 2-498 could be greatly enhanced to up to 77 %, as in the case of2-498b. In addition, cyclooctene oxides can be prepared (though in lower yield and stereoselectivity) starting from a six-membered oxosulfonium ylide. 

Few examples of total syntheses have been reported that involve an intramolecular nitrile oxide cycloaddition and ensuing reduction to an aminoalcohol. The very first example was reported by Confalone et al. (334) and involved a synthesis of the naturally occurring vitamin biotin (287). The nitro precursor 284 was easily prepared from cycloheptene. When treated with phenyl isocyanate-triethylamine, cycloaddition led to the all-cis-fused tricyclic isoxazoline 285 with high stereoselectivity (Scheme 6.102). Reduction with LiAlFLj afforded aminoalcohol 286 as a... 

Dibenzofuro[4,5-c]tropone (8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-one 368, X = CO) and the corresponding thiepin-5,5-dioxide (8//-dibenzo-[6,/]furo[3,4-retro Diels-Alder route. In refluxing benzene, the intermediate (367, X = CO) can be isolated. Further routes to 368 (X = CO) by retro Diels-Alder reaction exist. The 1-methyl derivative of 368 (X = CO) has been trapped as a maleic anhydride adduct. ... 

Preparation of 4-aza-5-(N-methyl-4-piperidylidene)-10,ll-dihydro-5H-dibenzo[a,d]cycloheptene Heat 5.4 g of the carbinol and 270 g of polyphosphoric acid for 12 hours at 140-170°C. Pour into ice water and make alkaline with sodium hydroxide. Extract with ether. Dry ether solution and concentrate to a residue. Crystallize from isopropyl ether, MP 124-126°C. 

Preparation of 5-[3-(N-Formyl-N-Methyl)-Aminopropyl]-5H-Dibenzo[a,d]Cycloheptene To a suspension of 3.9 grams of potassium amide is slowly added a solution of 19.2 grams (0.1 mol) of 5H-dibenzo[a,d]cycloheptene in 600 ml of ether with stirking. The suspension is refluxed with stirring for 3 hours, then cooled to room temperature and a solution of 0.1 mol of 3-(N-formyl-N-methyl)-aminopropyl chloride in 100 ml of ether added. The mixture is then refluxed with stirring for 5 hours and then 100 ml of water added. The ether layer is then washed with dilute hydrochloric acid, then water and then dried over magnesium sulfate and evaporated to dryness yielding 5-[3-(N-formyl-N-methyl)-aminopropyl]-5FI-dibenzo[a,d]cycloheptene. 

Lactams with larger rings, e.g. seven-,143,144 eight-,145 nine-,148 eleven-, and thirteen-membered lactams,147 yield acyclic amino-ketones as the sole products, as is to be expected. With the seven- and thirteen-membered rings, the existence of both forms might be expected, and the salts of 1-methyl-2-a-naphthyl-l-aza-2-cycloheptene and l-methyl-2-a-naphthyl-l-aza-2-cyclotridecene have been prepared in both the cyclic enamine and the acyclic amino-ketone forms.148 The structure of the products also depends upon the Grignard reagent used. 

From a preparative point of view, the course of the alkylation can be undesirably influenced by the structural arrangement of the starting enamine. Thus, treatment of 1-pyrrolidino-l-cycloheptene with ethyl iodide, followed by hydrolysis, gives about 40% of 2-ethylcyclo-... 

The chemically and radiochemically pure NCA 5-[18F]fluoromethyl- and 5-/ -[18F]fluo-roethyl-10,ll-dihydro-5/7-dibenzo[tf, d]cyclohepten-5, 10-imines 151 and 152 have been prepared for i.v. injection from [18F]fluoride by nucleophilic substitution at the cyclic sulphamates 153 and 154 (equation 96). The labelled products 151 and 152 have been evaluated for receptor binding in animals and in man189. MK801, 155, readily crosses the BBB in mammals and binds to a high affinity site on the TV-methyl-D-aspartate receptor190. 

Blechert and co-workers have also explored the use of cycloheptenes in RRM in processes where the thermodynamic driving force is the final RCM (Scheme 6). In one example of this novel process, ROM-RCM-RCM of 7 leads to an excellent yield of the substituted tetrahydrooxepin 8 <02T7503>. This strategy also featured significantly in the preparation of (+)-dihydrocuscohygrine 9 <02JOC6456>. The more common sequential reactions of strained cyclic alkenes have been reviewed <03EJO611>. 

The phenyl tellurium tribromide can be prepared in situ from diphenyl ditellurium and bromine. Olefins thus far investigated include isobutene, (E)- and (Z) -butene, 1 -hexene, 2-methyl-l-pentene, 1-octene, (E)- and (Z)-4-octene, 1-decene, phenylethene, 1-phenyl-I-methylethene, cyclopentene, cyclohexene, cycloheptene, and cyclooctene. Most of the reactions were carried out with phenyl tellurium tribromide in methanol. 

Alkylation of benzene by an olefin occurs when the olefin is stirred with a cold mixture of benzene and sulfuric acid. The type of product formed depends upon the concentration of sulfuric acid high concentrations (90—%%) are required for alkylations. Alkylation by olefins is also catalyzed by aluminum chloride, ferric chloride, silicophos-phoric acid, and hydrogen fluoride. The last catalyst is the best of four studied for the preparation of phenylcycloheptane from benzene and cycloheptene. ... 

The 10,ll-dihydro-5//-dibenzo[a,d]cyclohepten-5-yl (5-dibenzosuberyl) group was proposed by PlessP l as a system with broad applications in amino, hydroxy, sulfanyl, and also carboxy protection. The ester is prepared from N-protected amino acids with 5-chloro-10,ll-dihydro-5//-dibenzo[a,d]cycloheptene/TEA in dioxane (reflux, 4h). It is cleaved like tert-butyl esters by acid hydrolysis with aqueous HCl/THF (rt, 30 min) or with neat TFA it is also removed by catalytic hydrogenolysis. 

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