5-Hydroxy-4,5-dimethyl-3-hexane

Fig. 1. New types of plant growth retardants. / Tetcyclacis (BAS 106. . W. LAB 102 883). 5-(4-chlorophenyl)-3,4,5,9,10-pentaazatetracyclo-5,4,10- 0 "-dodeca-3.9-diene. II Flurprimidol (EL 500). a(l-methylethyl)-a-[4-(trifluoromethyloxy)-phenyl]-5-pyrimidine-methanol. Ill Inabenfide (CGR-811). [4-chloro-2-(a-hydroxybenzyl)]-isonicotinanilide. IV Paclobutrazol (PP 333). l-(4-chlorophenyl)-4.4-dimethyl-2-(lH-1.2.4-triazol-l-yl)-pentan-3-ol. V Uniconazole (S-3307. XE-1019). (E)-l-(4-chlorophenyl)-4.4-dimethyl-2-(lH-1.2.4-triazol-l-yl)-l-penten-3-ol. L7 Triapenthenol (RSW 0411). (E)-l-cyclohexyl-4.4-dimethyl-2-(lH-1.2.4-triazol-l-yl)-l-penten-3-ol. VII BAS 111. . W. 1 -phenoxy-3-( 1H-1.2.4-triazol-1 -yl)-4-hydroxy-5.5-dimethyl-hexane...

Isobutyroin (Z-Hydroxy-d-keto-2 5-dimethyl-hexane, 2 5-dimelhyl-3-hexanoloneA, isoprojtyl-i,sobutyrylcarbi not)... 

An ethereal solution approximately 2.5 molar in methyllithium is prepared from 17 ml of methyl iodide and 4 g of lithium metal in 200 ml of anhydrous ether. A mixture consisting of 150 ml anhydrous ether, 3 g (10 mmoles) of 3jS-hydroxy-5a-androstane-ll,17-dione and 60 ml (0.15 moles) of the above methyllithium solution are stirred at room temperature for 40 hr. The reaction mixture is diluted with 100 ml of water and the ether is removed by distillation. Filtration of the chilled aqueous phase yields 2.6 g (77%) of 1 la,17a-dimethyl-5a-androstane-3a,l l/ ,17j5-triol mp 149-154°. Recrystallization from acetone-hexane yields pure material mp 164-166° [a] —5° (CHCI3). 

A mixture of 3.18 g (10 mmoles) of 17 -hydroxy-2-hydroxymethylene-5a-androstan-3-one, 20 ml dry dimethyl formamide and 0.3 g (13 mmoles) of sodium hydride is stirred for 0.5 hr at room temperature under nitrogen. A total of 1.51 g (12.5 mmoles) of redistilled allyl bromide is added and the mixture is stirred for 1 hr on the steam bath. Aqueous potassium hydroxide (2 g in 5 ml of water) is added and stirring is continued for 1 hr on the steam bath. The reaction mixture is diluted with 50 ml of methylene dichloride followed by careful addition of 300 ml of water. The organic phase is separated and the aqueous phase is again extracted with 50 ml of methylene dichloride. The combined extracts are washed with water, dried over sodium sulfate, filtered and chromatographed on 200 g of silica gel. Elution with pentane-ether (4 1) provides 2a-allyl-17j -hydroxy-5a-androstan-3-one 0.85 g (26%) mp 118-119° [aj 14° (CHCI3), after crystallization from ether-hexane. 

Benzhydryl 3Sodium hydride, 24 mg (4B mg of a 50% suspension of NaH in mineral oil, which has been washed with hexane to remove the oil), is added. When hydrogen evolution has ceased, 126 mg dimethyl sulfate is added. The solution is stirred for one hour at room temperature,diluted with 100 ml benzene and washed six times with water the last wash is made to pH B, if necessary, by adding sodium bicarbonate. The solution is dried over MgS04, filtered and evaporated, leaving benzhydryl 3eluting with 25 1 chloroform-ethyl acetate. 

The residue is triturated with methanol to afford a crystalline solid. This material contains no detectable amount of starting material by paperstrip chromatography but shows two UV absorbing spots near the solvent front (methanol-formamide 2 1 vs benzene-n-hexane 1 1). An aliquot is recrystallized three times from a mixture of benzene and n-hexane to give 17a,20,20,21-bis(methylenedioxy)-11(3-hydroxy-6,16a-dimethyl-4,6-pregnadiene-3-one which is used in the subsequent step of the synthesis without further purification. 

To 6a-fluoro-16a-hydroxy-hydrocortisone 21-acetate, described by Mills et al, J. Am. Chem. Soc., volume 81, pages 1264 to 1265, March 5, 1959, there was added acetic anhydride in dry pyridine. The reaction mixture was left at room temperature overnight and was then poured with stirring into ice water. The resulting precipitate was filtered, washed with water and crystallized from acetone-hexane to give 6a-fluoro-16a-hydroxy-hydrocortisone-16a,21-diacetate. This was reacted with methane-sulfonyl chloride in dimethyl formamide in the presence of pyridine at 80°C for 1 hour. The mixture was cooled, diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and the ethyl acetate was evaporated. By recrystallization of the residue from acetone-hexane there was obtained 6a-fluoro-A <" -pregnadiene-16o ,17a,21-triol-3,20-dione 16a,21 diacetate. 

Neben den Reaktionen mit Formaldehyd sind auch analoge thermische 1-Hydroxy-alkylierun-gen von 1-Methyl-, 1-Benzyl- und 1-Methoxymethyl-imidazol durch Umsetzung mit Benzal-dehyd, Hexanal, 2-Methyl-propanal oder 2,2-Dimethyl-propanal bei 145 160° beschrieben (12-46% Ausbeute)764. 

Pantolactone, dihydro-3-hydroxy-4//-dimethyl-2(3//)-furanone (103) which is an important starting material of the synthesis of pantothenic acid, was also easily resolved by complexation with 10a. When a solution of 10a (5.5 g, 9.93 mmol) and rac-103 (2.6 g, 20 mmol) in 1 1 benzene-hexane (20 ml) was kept at room temperature for 1 h, a 1 1 complex of 10a and (.S)-(-)- 03 was obtained, after two recrystallizations from 1 1 benzene-hexane, as colorless needles (2.05 g), which upon heating in vacuo gave (S)-(-)-103 of 99% ee (0.39 g, 30%).40 In order to clarify the mechanism of the precise chiral recognition between 10a and (S)-(-)-103, their inclusion complex crystal was studied by X-ray analysis40 and by AFM technique.41... 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Also, the primary amine moities of polar lipids catalyze the aldol condensation of Cm-Cig aldehydes resulting from plasmalogen hydrolysis, thus forming a,3-unsaturated aldehydes (l2t). Phosphatidyl ethanolamine reacted with propanal and n-hexanal forming phosphatidyl l-(2-hydroxyethyl)-2-ethyl-3,5-dimethyl pyridinium, and phosphatidyl-1-(2-hydroxy ethyl)-2-hexyl-3,5-dipentyl pyridinium, respectively (125). The peridinium ring is formed by the reaction between one mole of amino-N of phosphatidyl ethanolamine and three moles of n-alkanals. The same reaction took place in the synthesis of substituted pyridines by condensation of carbonyl compounds with ammonia (126, 127). 

The typical caramel flavor is the result of a number of sugar fragmentation and dehydration products, including diacetyl, acetic acid, formic acid, and two degradation products reported to have typical caramel flavor by Jurch and Tatum (1970), namely, acetylfor-moin (4-hydroxy-2,3,5-hexane-trione) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone. 

Allen Hexyloxy- Vl/ld, 169 Bicyclo 2.2.1]heptan 1,7-Dimethyl-2-hydroxy- Vl/la, 1, 481 Bicyclo 4.1.0]heptan 7-Ethoxy- E19b, 1633 (Carben + En) 7-Ethyl-7-hydroxy- E17b, 1397 (7,7-Br2 - 7-OH/7-C2H5) Bicyclo[2.1.1]hexan 2-a-Hydroxy-... 

Hexan 2-tert.-Butylazo-2-hydroxy-E14a/2, 22 (aus Hydrazon) 1,3,4-Oxadiazolidin 3,4-Dimethyl-2,5-dipropyl- X/2, 68 Pentan 2-tert,-Butylazo-2-hydroxy-3(bzw. 4)-methyl- E14a/2, 22 (aus Hydrazon)... 

Hexanal 2-Ethyl- -(1-hydroxy-methyl-propylimin) E14a/2, 598 (R —CHO + Amin) Hydroxylamin N.N-Dicyclohexyl-EI6a. 184 (O — P-Spalt.) Isoborneol (1 / ,4.5)-3-c j- Dimethyl-amino- E21f, 5864 (NH2 - NR2)... 

The first lithiopyrazine derivative was prepared by Hirschberg et al. (1015) from 3-iodo-2,5-dimethylpyrazine and butyllithium in ether subsequent reaction with (a) carbon dioxide gave 3-carboxy-2,5-dimethylpyrazine, and (b) several aromatic aldehydes gave the carbinols (62, R = H, p-methoxy, m-nitro) (1015). Similar reactions were observed when 2-formylpyridine and 2-acetylpyridine (1016) were used as the carbonyl compounds, but with acetaldehyde attempted reactions were unsuccessful (1015). A patent also describes the preparation of many carbinols from 2,5-disubstituted 3-iodopyrazines (164). The lithio reagent derived from 3-iodo-2,5-dimethylpyrazine (with butyllithium in hexane) with 2-nitrobenzaldehyde gave 2,5-dimethyl-3[ 1 -hydroxy-1 (2"-nitrophenyl)methyl] pyrazine (1017). 

CIC The powerful odour is dominated by 2-isobutyl thiazole and 3-pentanethiol. The green notes are lipid degradation products like (E)-2-hexenal, hexanal and higher unsaturated aldehydes, the pineapple-pear like fruity notes are derived from methyl hexanoate, ethyl-2-hexenoate and hexyl acetate. The spicy cinnamon notes are represented by 3-phenyl propyl acetate, cinnamyl acetate, methyl cinnamate, ethyl cinna-mate and ciimamaldehyde. Gamma-decalactone and 2,5-dimethyl-4-hydroxy-furan-3(2H)-one and 3-hydroxy-2-butanone add the sweet, creamy body. Beta-famesene, citronellol, 2-phenylethanol, beta-ionone add the sweet, floral, quincelike part and methyl benzoate and ethyl benzoate impart a characteristic medicinal, exotic topnote. 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

The cyanide anion is a powerful nucleophile. When methyl 2-oxobicyclo[3.1.0]hexane-l-carboxylate (1) was treated with sodium cyanide in dimethylsulfoxide, the 3-cyanomethylpen-tanone derivative 2 was obtained in 69% yield.With 2-hydroxy-2-methylpropanenitrile in methanol, dimethyl 3-cyanomethylhexane-l,4-dioate (3) was isolated as the sole product. Its formation involved nucleophilic opening of both rings by a homo-Michael addition and the reversal of an ester condensation. 

Dimethoxy-benzaldehyd 2,4-Dimethyl-5-hydroxy-benzaldehyd 60-65% 77% Hexanal 40-50°/o... 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-l(1S)-1,2-DIHYDROXYETHYL]-1,5-D HYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceraldehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an ally diazoacetate is illustrated in the preparation of (1R,5S)-( )-6,6-DIMETHYL-3-OXABICYCLO[3.1.0]HEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (lR,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R)-(+)- and (4SM-Hert-BUTYLDIMETHYl SILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

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