Patent GB-978680-A (GB)
Title: Organic nitrite esters and processes for the preparation of derivatives therefrom
Inventor: BARTON DEREK HAROLD RICHARD
IPC: C07C203/00
Filed: 1960-04-04
Abstract: The invention comprises an organic nitrite ester of a condensed ring organic compound in which the nitrite radical is linked to one carbon atom and is conformationally adjacent to a hydrogen atom attached to another carbon atom which is spuced from said one carbon atom by a carbon adjacent the nitrite radical and a carbon, oxygen, sulphur or nitrogen atom, and a process for the preparation of an organic nitroso compound having a skeleton of at least 6 carbon atoms and a further atom selected from the group consisting of carbon, oxygen, sulphur and nitrogen, said nitroso compound including the grouping ON-C-X-C-C-OH wherein X represents a methylene, methylidene or methylidyne group or a nitrogen, oxygen or sulphur atom and/or a compound resulting from the stabilization of the said nitroso compound such as an oxime or a nitrone wherein a nitrite ester having a skeleton consisting of at least 6 carbon atoms and of an atom selected from the groups consisting of carbon, oxygen, sulphur and nitrogen and including the grouping <FORM:0978680/C1/1> wherein ONO is a nitrite group, H is a hydrogen atom conformationally adjacent to such nitrite radical and X has the above significance) is irradiated in solution preferably a substantially water free and substantially oxygen free solution, by ultraviolet radiation the wavelength of which is within the range of from 2,000 to 4,500 A, preferably 3,400 to 4,000 A, to effect the exchange of the NO portion of said nitrite group with said hydrogen atom. The organic nitrites for use in the above process may be prepared by reacting the required organic hydroxy compound with a nitrosyl halide.  A large number of suitable organic hydroxy compounds from which the nitrites are obtainable are referred to. Thus the organic nitrite may be an alkyl-, alkene-, alkyne-, aryl-, alicyclic-, heterocyclic- or steroidal-nitrite. The nitrite may also be derived from antibiotics containing a hydroxy group such as penicillin and erythromycin; reserpine; Vitamin A; and terpenes such as nerol, geraniol, citronellol and menthol. The steroidal nitrite may be a 1b ,- 2b -, 4b -, 6b -, 7b -, 11a -, 11b -, 15a -, 18-, 19-, 20a -, 20b - or 24-nitrite steroid compound such as a steroidal nitrite of the estrogen, androgen, methyltestosterone, pregnane, cardiac azlycone, bile acid, chlolesterol, ergosterol or stigmasterol series. In the case of an organic hydroxy compound containing more than one hydroxy group it may be necessary to protect some of the hydroxy groups to avoid reaction with the nitrosyl halide, for example by acylation. The process is useful for the preparation of polyols such as a triol by the following type of process:  1-decanyl-nitrite is formed from 1-decanol, the nitrite is irradiated to form 4-oximino -1- decanol, then acetylated to form the 1-acetate and reduced to the 4-amine -1- acetate, oxidised to decan-diol-1, 4 1-acetate, then to the 4-nitrite 1-acetate which is irradiated to form 7-oximino-1, 4-decandiol 1-acetate and then reduced and oxidised as before, to form decanyl-1, 4, 7-triol 1-acetate and finally decanyl-1, 4, 7-triol.  Substituted resperine of the formula <FORM:0978680/C1/2> is prepared by reducing reserpine with lithium aluminium hydride to form a diol of the formula, <FORM:0978680/C1/3> acetylating this compound to form the corresponding diacetate, and selectively hydrolysing the diacetate. 4-Amino -2- methyl-heptanol-1 are prepared and the corresponding trimethyl ammonium iodide by reducing the corresponding 4-oximino compound with sodium and ethanol to form the free 4-amino compound and, when required, treating the product with methyl iodide. By a similar procedure the following are prepared: 4-amino-heptanol-1 and the trimethylammonium sulphonate thereof, 4-amino -1- lauryl alcohol, 4-amino -1- cetyl alcohol, 4-amino -1- stearyl alcohol, 5-amino -2- heptyl alcohol, 6-amino -3- heptyl alcohol, 5-amino-octanol-2 (the three previously mentioned compounds may be treated with sulphuric acid to form the corresponding amino-sulphates), 4-amino -2- ethyl hexanol, and 4-amino-undecenyl alcohol.  4-Keto-octanol-1 is prepared by treating 4-oximino-octanol-1 with acetic acid and aqueous sodium nitrite. By a similar method the following are prepared. 4-keto-undecenyl alcohol, 4-keto-nerol, 3-b -hydroxyethyl-cyclohexanone, 4-hydroxy-cycloheptanone, 4-hydroxy-cyclo-octanone, tropine ketone of the formula <FORM:0978680/C1/4> (this compound may be converted into the corresponding tropic acid ester), 2-acetyl -3- hydroxymethyl-pyridine, 2-aldehydro- 3-hydroxymethyl-pyridine, dihydrocodeinol ketone of the formula <FORM:0978680/C1/5> keto-reserpine of the formula <FORM:0978680/C1/6> b -(N-ethyl, N-acetyl) amino -a - phenylethyl alcohol, 1-(p-chloro -a - phenylbenzyl)-4-[a (2-acetoxyethyl)] piperazine and propionyl-(b -hydroxy -g - chloro-propyl) sulphide.  4-Amino-undecylenic alcohol is prepared by reducing the corresponding 4-oximino compound with lithium aluminium hydride. By a similar method the following are prepared: 4-amino- -9- octadecen -1- ol (may be converted into the corresponding trimethyl ammonium quaternary salt by reaction with methyl iodide), dihydrocodeinol amine of the formula <FORM:0978680/C1/7> and an amino-reserpine of the formula <FORM:0978680/C1/8> 1, 2-Hemiacetal of 2-hydroxymethylbenzaldehyde of the formula <FORM:0978680/C1/9> is prepared by treating 2-(oximinomethyl)-benzyl alcohol with nitrous acid. (The product may be converted to a mixed acetal of the formula <FORM:0978680/C1/100> By a similar method hemiacetals of the formulae <FORM:0978680/C1/111> and <FORM:0978680/C1/122> and the corresponding mixed acetal of the formulae <FORM:0978680/C1/133> and <FORM:0978680/C1/144> are prepared.  An acetal of the formula <FORM:0978680/C1/155> is prepared by treating an oxime of the formula <FORM:0978680/C1/166> with acetic acid and sodium nitrite.  The hydrazone of 3-hydroxymethyl-pyridine-2-aldehyde is prepared by treating 2-oximinomethyl-3-hydroxymethyl-pyridine with nitrous acid to form 3-hydroxymethyl-pyridine-2-aldehyde and then the hemiacetal thereof of the formula <FORM:0978680/C1/177> and treating the hemiacetal with hydrazine sulphate. The hydrozone of 2-acetyl -3- hydroxy-methyl-pyridine is prepared by a similar method.  D 7,22-Ergostadiene-3b , 5a , 6b -triol 3-acetate is prepared by acetylating ergosterol to form the corresponding 3-acetate and treating the acetate with perphthalic acid.  6b -Hydroxystigmast -22- enyl acetate is prepared by acetylating stigmasterol to form the corresponding acetate, nitrating the acetate to form 6-nitro-stigmasterol acetate, reducing this compound with zinc dust and water to form 6-ketostigmast -22- enyl acetate and reducing this compound with sodium borohydride.  Isorubijervine 3-acetate is prepared by treating isorubijervine with acetic anhydride.  Estrone -3- acetate 11-18 hemiacetal of the formula <FORM:0978680/C1/188> is prepared by treating the corresponding 18-oxine of the formula <FORM:0978680/C1/199> with glacial acetic acid and sodium nitrite. By a similar method the following are prepared: aldosterone 21-acetatewhich may be converted to aldosterone, and the 11-18 hemiacetals of estradiol 3, 17-diacetate, D 4-androstene-3, 17-dione, androsterone, 17a -methyl-testosterone acetate, cortisol 21-acetate, 16a -acetoxycorticosterone 21-acetate, (16a - (and 16b )-methylcorticosterone 21-acetate, 16a -acetoxy -1- dehydrocorticosterone acetate, 16a  (and 16b )-methyl -1- dehydrocorticosterone 21-acetate, pregnane -3a , 17a , 20b -triol-3, 30-diacetate, prednisolone acetate, 17a , acetoxyprogesterone, 16a  - acetoxy - prednisolone 21-acetate, 16b -methyl-prednisolone acetate, 16a  (and 16b )-methyl-D 1,4-pregnadiene-3, 20-dione-9a - fluoro-11b , 17a -dihydroxy -21- acetate, pregnane-3a , 11b , 20b -triol 3, 20-diacetate, and cholestanol -3- acetate.  18-Amino-testosterone acetate is prepared by reducing 11b -hydroxy -18- oximinotestosterone 17-acetate with lithium aluminium hydride and oxidising the reaction product with manganese dioxide and, if desired, reacting the 18-amino compound with methyl iodide to form a quaternary ammonium compound. 3b , 6b , 21-Trihydroxy -20- keto -5a - pregn-19-al-3, 21-diacetate 6, 19-hemi-acetal is prepared by treating the 19-oximino-3b , 21-diacetoxy -20-keto -5a - pregnane 6b -nitrite with glacial acetic acid and sodium nitrite, and the 6, 19-hemiacetals of the formulae <FORM:0978680/C1/200> <FORM:0978680/C1/211> are prepared by a similar method from the corresponding 19-oximino -6- hydroxy compound. The 6, 19-hemiacetal of the formula <FORM:0978680/C1/222> is prepared by reducing the corresponding 6-hydroxy -19- oximino compound with hydrazine and alkali.  Steroid lactone of the formula <FORM:0978680/C1/233> is prepared by oxidising the corresponding 18-oxime of the formula <FORM:0978680/C1/244> with chromic acid in acetone. Similar lactones are prepared from 18-oximes of 11-hydroxy-progesterone.  11-Keto-strophanthridol 3-acetate is prepared by treating the corresponding 11-oxime with nitrous acid. Steroid aldehyde of the formula <FORM:0978680/C1/255> is prepared by treating the corresponding 19-oxime with chromous chloride and nitrous acid. By a similar method the following are prepared: 11b -hydroxy-4b , 5b -oxido-androstane-3, 17- dione 19-aldehyde (further treatment with chromous chloride forms an equilibrium mixture of D 4-androstene-3, 17-dione-11, 19-hemiacetal and 11b -hydroxy -D 4- androstene-3, 17-dione 19-aldehyde), and 4b , 5b -oxidohydrocorticosterone 21-acetate 19-aldehyde in equilibrium with the corresponding 11, 19-hemiacetal (further treatment with chromous chloride forms corticosterone 21-acetate 11, 19-hemiacetal).  2, 19-Hemiacetals of cholestanyl acetate is prepared by treating 2-hydroxy -19- oximinocholestanyl acetate with nitrous acid. The 4, 19-hemiacetal of cholesteryl acetate is prepared by a similar m