Sodium amide bromide

Of the several syntheses available for the phenothiazine ring system, perhaps the simplest is the sulfuration reaction. This consists of treating the corresponding diphenylamine with a mixture of sulfur and iodine to afford directly the desired heterocycle. Since the proton on the nitrogen of the resultant molecule is but weakly acidic, strong bases are required to form the corresponding anion in order to carry out subsequent alkylation reactions. In practice such diverse bases as ethylmagnesium bromide, sodium amide, and sodium hydride have all been used. Alkylation with (chloroethyl)diethylamine affords diethazine (1), a compound that exhibits both antihista-minic and antiParkinsonian activity. Substitution of w-(2-chloroethyl)pyrrolidine in this sequence leads to pyrathiazine (2), an antihistamine of moderate potency. 

Butylation of ethyl phenylacetate, /-butyl phenylacetate, and ethyl 2-phenylhexanoate has also been accomplished with M-butyl bromide and sodium hydride in refluxing monoglyme in 64%, 66%, and 56% yields, respectively.6 In contrast to the sodium amide reactions above, however, careful fractionation of the crude products was required to obtain pure products. 

Silver fluoborate, reaction with ethyl bromide in ether, 46, 114 Silver nitrate, complexing with phenyl-acetylene, 46, 40 Silver oxide, 46, 83 Silver thiocyanate, 45, 71 Sodium amide, in alkylation of ethyl phenylacetate w ith (2-bromo-ethyl)benzene, 47, 72 in condensation of 2,4-pentanedione and 1 bromobutane to give 2,4-nonanedione, 47, 92 Sodium 2 ammobenzenesulfinate, from reduction of 2 mtrobenzenesul-finic acid, 47, 5... 

The procedure given above is essentially the method of Paul.1 The interaction of tetrahydrofurfuryl bromide and sodium amide... 

A suspension of sodium amide (0.275 mole) (Note 1) in liquid ammonia is prepared in the following manner in a 1-1. threenecked flask equipped with an air condenser (Note 2), a sealed mechanical stirrer, and a dropping funnel. Commercial anhydrous liquid ammonia (600 ml.) is introduced by pouring from an Erlenmeyer flask (Note 3). To the stirred liquid ammonia is added a small piece of sodium. After the appearance of a permanent blue color (Note 4) a few crystals of ferric nitrate hydrate (ica. 0.1 g.) are added, followed by small pieces of freshly cut sodium (Note 5) until 6.32 g. (0.275 g. atom) has been added. After all the sodium is converted to the amide (Note 6), 42.0 g. (0.250 mole) of diphenylmethane (Note 7) in 20 ml. of anhydrous ether is added (Note 8). The deep red suspension is stirred for 15 minutes. n-Butyl bromide (37.6 g., 0.274 mole) (Note 7) in... 

Diphenylmethane, alkylation with rebutyl bromide and sodium amide, 48, 80... 

A 10% excess of sodium amide and -butyl bromide with respect to diphenylmethane was adopted. 

Benzyl-6-methylcyclohexanone has been prepared by the hydrogenation of 2-benzylidene-6-methylcyclohexanone over a platinum or nickel catalyst, and by the alkylation of the sodium enolate of 2-formyl-6-methylcyclohexanone with benzyl iodide followed by cleavage of the formyl group with aqueous base. The 2,6-isomer was also obtained as a minor product (about 10% of the monoalkylated product) along with the major product, 2-benzyl-2-methylcyclohexanone by successive treatment of 2-methylcyclohexanone with sodium amide and then with benzyl chloride or benzyl bromide. Reaction of the sodium enolate of 2-formyl-6-methylcyclohexanone with potassium amide in liquid ammonia formed the corresponding dianion which was first treated with 1 equiv. of benzyl chloride and then deformylated with aqueous base to form 2-benzyl-2-methylcyclohexanone.i ... 

Clemastine Clemastine, 2-[2-[l-(4-chlorophenyl)-l-phenylethoxy]ethyl]-l-methylpyrroli-dine (16.1.4), is synthesized by reacting l-(4-chlorophenyl)-l-phenylethanol (16.1.3) with 2-(2-chlorethyl)-2-methylpyrrolidine using sodium amide as a base. The starting l-(4-chlorophenyl)-l-phenylethanol (16.1.3) is synthesized either by reacting 4-chloroben-zophenone with methylmagnesium chloride, or by reacting 4-chloroacetophenone with phenylmagnesium bromide [6-8]. 

The preferential syn elimination of hydrogen fluoride from r/ am-l -bromo-2-fluorocyclohexane (trans-40) to give 1-bromocyclohexene (42) is achieved only when a strong base such as sodium amide is used.81-82 Potassium lerl-butoxide treatment results in elimination of hydrogen bromide to form 3-fluorocyclohexene (43).82... 

By Wittig and related reactions (3-Dimethylaminopropyl)-triphenylphosphorane, 119 Sodium amide, 278 Vinyl(triphenyl)phosphonium bromide, 343 (E)-Alkenes By elimination reactions Arylselenocarboxamides, 22 Dichlorobis(cyclopentadienyl)-titanium, 102 Hydrogen peroxide, 145 From three-membered heterocycles Tributyltinlithium-Trimethylalu-minum, 320 Trisubstituted alkenes Chloromethyldiphenylsilane, 74 Organocopper reagents, 207 Alkenes (Methods to form alkenes)... 

Sodium amide 3-Methoxybenzyl cyanide Magnesium Ethyl bromide... 

Formaldehyde Sodium amide Hydrogen Hydrogen bromide... 

Hydrochloric acid Phenyl magnesium bromide Sodium amide Hydrogen Thionyl chloride... 

To a suspension of 3.12 g of sodium amide in 50 ml dry toluene was added dropwise 12 g of 2-(dimethylamino)ethylaminopyridine. The mixture was refluxed for 2 hours, cooled to 50°C, and 21 g 3-thenyl bromide was added dropwise. When reaction subsided, the brownish-orange mixture was refluxed for 0.5 hour, cooled, and poured into 150 ml of water. The toluene layer was separated, extracted with 5% hydrochloric acid. This extract was saturated with potassium carbonate. The free base was extracted with ether, dried and fractionated. Yield of N,N-dimethyl-N -2-pyridinyl-N -(3-thienylmethyl)-l,2-ethanediamine 31%, boiling point 169-172°C/1 mm. 

Q cyono- 1. sodium amide 2. cyclohexyl bromide 0 1-cyono- ... 

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