Sodium f-butylate

Substituted l,3-dithiole-2-thiones (322) can be prepared by treatment of propargylic bromides with sodium f-butyl trithiocarbonate in acetone at 0 °C giving the trithioesters... 

An approach to nitro-substituted l,3-benzodithiole-2-thiones (325) is based on the reaction of l-chloro-2,6-dinitrobenzenes (323) with sodium f-butyl trithiocarbonate which yields dinitrophenyl f-butyl trithiocarbonates (324). The latter cyclize on heating in acetic acid with formation of nitro-l,3-benzodithiole-2-thiones (325) (80JOC4041). 

A further efficient and general synthesis of l,3-dithiole-2-thiones (169) with a variety of functional groups is the acid-catalyzed ring closure of / -keto f-butyl trithiocarbonates of type (261) which are readily available from a-halo ketones and sodium f-butyl trithiocarbon-ate. The intermediates (262) fragment into isobutene and l,3-dithiole-2-thiones (169) (80JOC175). 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

The hemispherands, spherands, calixarenes, and related derivatives. A number of hosts for which the pre-organization criterion is half met (the hemispherands) (Cram et al., 1982) or fully met (the spherands) (Cram, Kaneda, Helgeson Lein, 1979) have been synthesized. An example of each of these is given by (251) and (252), respectively. In (251), the three methoxyl groups are conformationally constrained whereas the remaining ether donors are not fixed but can either point in or out of the ring. This system binds well to alkali metal ions such as sodium and potassium as well as to alkylammonium ions. The crystal structure of the 1 1 adduct with the f-butyl ammonium cation indicates that two linear +N-H - 0... 

Modifying the reaction medium to involve liquid ammonia with metallic lithium, f-butyl alcohol, and white phosphorus, to which is added the haloalkane, is reported to provide the primary alkylphos-phine derived from the haloalkane.19 Similar results are reported for the reaction of red phosphorus with sodium acetylides20 and by treatment of red phosphorus with sodium metal in an organic medium followed by the addition of two equivalents of f-butyl alcohol and the haloalkane.21 The latter approach is noteworthy in that moderate yields (45%) are obtained for primary phosphines derived from secondary haloalkanes (Figure 2.6). Mixtures of tertiary phosphines bearing one or two acetylenic linkages are produced in low yield ( 15%) by the reaction of lithium acetylides with white phosphorus in liquid ammonia followed by addition of a haloalkane.22... 

Formation of the conjugate base of phosphine under the conditions of aqueous dioxane and KOH with red phosphorus allows also for the formation of C-P bonds by attack of oxiranes.33 Under these conditions, mixtures of phosphines and phosphine oxides are formed. Using red phosphorus in liquid ammonia with sodium metal and f-butyl alcohol, good yields of primary (2-hydroxyalkyl)phos-phines are obtained.34... 

Chloro compounds, poly, reduction with sodium and f-butyl alcohol, 48, 72... 

Palladium on charcoal, catalyst for reductive methylation of ethyl p-nitrophenylacetate, 47, 69 in reduction of /-butyl azidoacetate to glycine f-butyl ester, 45, 47 Palladium oxide as catalyst for reduction of sodium 2-nitrobcnzcne-sulfinate, 47, S... 

To 50 ml. of a well-cooled 6N sodium hydroxide solution is added, with stirring, 32 g. (0.15 mole) of the phosphite salt. The stirring is continued until all the solid has dissolved. The solution is transferred to a 125-ml. separatory funnel, extracted with three 20-ml. portions of ether, and the combined extracts dried over anhydrous sodium sulfate. The drying agent is removed by filtration, the solvent removed under reduced pressure, and the glycine f-butyl ester distilled, b.p. 65-67° (20 mm.), 1.4237,... 

In some cases acid amide formation was observed on attempted deprotonation at oxaziridine ring carbon. 2-f-Butyl-3-(4 -nitrophenyl)oxaziridine (67) was converted to the anion of acid amide (68) by sodium amide (69TL3887), while 2-(4 -nitrobenzoyl)-3-phenyl-oxaziridine (69) afforded the diacylimide (70) by addition of cyclohexylamine to its benzene solution at room temperature (67CB2593). 

To a solution of 17.95 gm (0.0634 mole) of f-butyl-2-(p-bromophenyl) carbazate and 4.94 gm (0.0626 mole) of dry pyridine in 300 ml of methylene chloride is added, in small portions, over a 20 min period, 11.13 gm (0.0551 mole) of N-bromosuccinimide. The red solution is allowed to stand at room temperature for 3 hr. Then the reaction mixture is washed in turn with two portions of 100 ml of water, 125 ml of 10% aqueous sodium hydroxide, and another two portions of water. The product solution is then dried with anhydrous potassium carbonate. The solvent is removed by distillation under reduced pressure, using a water bath at 50°C as the source of heat. On standing, the red liquid crystallizes to a yellow-orange solid which is dissolved in methanol, treated with charcoal, filtered, and the filtrate treated with just sufficient water to cause product precipitation yield 15.34 gm (86%), yellow-orange crystals, m.p. 66°-67°C. 

A third route developed by this group started with the commercially available alcohol 32," a compound which has also been the subject of considerable process development due to its use as a common intermediate in the synthesis of several HMGR inhibitors.Conversion of 32 to the 4-halo or 4-nitrobenzenesulfonate 33 followed by displacement with sodium cyanide provided 34 in 90% yield, which is the z-butyl-ester analog of 29. It was noted that this procedure was most scaleable employing the 4-chlorobenzenesulfonate 33a due to the instability of the 4-bromo and 4-nitro-analogs to aqueous hydrolysis. Ra-Ni reduction as before provided the fully elaborated side-chain 35 as the f-butyl ester (Scheme 8). 

Although catalytic hydrogenation is the method most often used, double bonds can be reduced by other reagents, as well. Among these are sodium in ethanol, sodium and f-butyl alcohol in HMPA,243 lithium and aliphatic amines244 (see also 5-10), chromous ion,245 zinc and acids, sodium hypophosphate and Pd-C,246 (EtO)3SiH-Pd(OAc)2,247 trifluoroacetic acid... 

Tertiary alkyl primary amines can be oxidized to nitro compounds in excellent yields with KMn04.39S This type of nitro compound is not easily prepared in other ways. All classes of primary amine (including primary, secondary, and tertiary alkyl as well as aryl) are oxidized to nitro compounds in high yields with dimethyldioxirane.399 Other reagents that oxidize various types of primary amines to nitro compounds are dry ozone,4,111 various peracids,401 including peracetic and peroxytrifluoroacetic acids, f-butyl hydroperoxide in the presence of certain molybdenum and vanadium compounds,402 F7-H20-MeCN,41123 and sodium perborate.403... 

The orf/to-formylation of 2-aminopyridines can be effected via the rearrangement of the azasulfonium salt prepared from a 2-aminopyridine, 1,3-dithiane, f-butyl hypochlorite and sodium methoxide (74CC685). The crude sulfilimine (815) was refluxed in f-butanol containing potassium f-butoxide to yield the dithioacetal (816). Hydrolysis of (816) with mercury(II) oxide/boron trifluoride etherate gave the aldehyde (817 Scheme 191). This method should be applicable to the formylation of other heterocyclic amines. 

---