DEP0056042DA - Process for the preparation of new phenanthrene carboxonitriles - Google Patents

Description

CIBA AKTIENGESELLSCHAFT, BASEL (SWITZERLAND) Patent attorney

Hamburg 36 Harnburq OG ο ι o _{Qn r}

New WoIl 10, 4th floor New WdI 10, 4th floor * * ^{ου! Λ} ^

Call 347900

Germany ^^

Process for the production of pbenanthrencarboxylic acid nitriles »

The subject of the present invention is the hex position -of l-keto-2, IS'-ainistrnrl ^ perhydroph ^ nanthrene ^ a-

f / it -y ;. _T ; .l, -ν- "

The new Csroonsäurorsitrilü :. can also have alternate substituents, especially in the / position, an oxy group or a substitute that can be converted into one of these, a prior or reinforced oxy group, possibly also halogen atoms hB in the position; = The method relates particularly to the Production o.ea l-lvato · "'/" - ■ »oxy == · ?, _s I3 ™ clin>athyl-"i4-p6rhyclroph; ixi £ rrthr3: a'"2 ~ car'bor; .3 acids: Ltrilii and dos 1-keto »7-oxy ·»

their magpie ond Asth &r,; ^ ie ^^. ibrar Acetate. Fi'opionate or 3onaοatβ,

The new compounds are obtained when m _s-l Ieto-2 _f 13 '= ³ ö.isiethyl £ @ perhydrophenanthrers treated with halogenating agents and the Halogenid® obtained with metal cyanides * = · did order se,

The starting materials used are in particular l = K @ to = 2 _s 13 »aiinethy ^ £ perhydrophenanthrene5 which in 7 = position © in © Cteygruppe oäsr iron in © ine have such convertible substituents a'.j as j ^^ O an etherified © or Esterified oxy group = Very valuable are also starting materials which, in addition to the stated substituents and a hydrogen atom in the delivery, have halogen atoms, as a precaution in the li. position. The starting materials are: l-keto-7-oxy ° 2.13 ° di = methyl perhydrophenanthrene and l-keto ⁱ = 7 ^c O3cy ° 14 = chlorine = · '2.13 ° diraethyl perhydrophenanthrene their esters and ethers, such as f% ^ "their acetates, propionates or Bensoat ©. These starting materials can be 2J. in the oxidation of sterols or through other known transformations, the compounds obtained thereby gain 0

For halogenation used are in particular halo such as bromo ₅ wherein one vorsugsweis® in an inert solvent such as ether _s, works "

According to the invention, the halides obtained are treated, j ^ * S.B. the bromides with a metal cyanide in first and foremost with an alkali ^^^^ eyaRid, such as potassium cyanide «, This process step is also advantageous in the presence a solvent carried out. Thus it becomes' on a halide in the presence of a diluent such as acetone or methanol, an aqueous solution of a metal cyanide / s 2u = given »

The nitriles obtained by the process are valuable intermediates for therapeutic production more effective 'compounds. "

The invention is described in more detail in the following examples, without restricting its scope, whereby unless otherwise noted "parts by weight mean"

it'! QTV'iJ ^ l 1

CH,

O
• C-0-

To a solution of 10 parts of 1-keto ° 7-ac © toxy-2,13 = dlmethyl »14 ° ^> tran ^^, erydroph @ naiithren of melting point 144 ° in 250 parts of absolute ether are added within 30 minutes 5j5 parts of bromine , and swar first at room temperature and then under ice-cooling. After the bromination is charged with 200 parts of ice water, wash the ether solution with ice-cooled sodium bicarbonate solution, dried and evaporated and the residue crystallized from methanol or acetone recrystallized "We recovered the l = keto ~ 2» brQm ~ 7 »acetO3ey = 2 _t 13 ~ dimethyl ~ 14 = trans ^ psrhydrophenanthren with the decomposition point 134 ° In Böfoler yield »

5 parts of 1 - K © to-2-broni '= 7 ~ ac®toxy = 2 "13- = dimethyl ~ 14-trans ^ gerhydrophenanthren are dissolved in 50 parts of acetone and mixed with a solution of 4-5 parts of potassium cyanide in 12 parts of water are added _o iach 20 minutes, 250 parts V / ater

admittedly, Vi / obei that

perhydropheEis! at.li: ren-2-carboxylic acidsi-cr ^> ii precipitates out α It is removed and sifted after dissolving from aqueous alcohol

/ Γ «

the Qsmr » 110-111 *.

Example 2:
I ^ Qg ^^ 4r ^ E§Q§j = i £ h 3: jir "JL _A 1 j> r .4 j ^ ethjrl = · -

CH

H-C

HoO-G-G =

JU

10, 5 part © l

diraethy ^ £ p @ rhydrophenanthr © n are suspended in 150 parts of ether and _{halogenated as in Example 1 with 5 S} 2 parts of bromine, water is then added, the solution is sucked out with ether, the ethereal solution is washed neutral, dried and evaporated βΌ obtained l = keto = 2 = broffi-7 ™ acetoxy = l4 = trans ™ chlorine = 2.13 = dimethy ^ # p _j Qrhydrophenanthr © n Schmilst after dissolving from a mixture j®i \ acetone and methanol at 135 ° with decomposition Yield 0.5 part =

8,, 5 part® 'l-keto ^ -brom ^ -acetoxy-H-trans-chloro-

2jl3 = "// diaiethyl TCrfiydrophenanthren are suspended in 60 parts of methanol and versetat with a Lösimg of 12 parts Kaliuracyanid in 20 parts of water After 20 minutes d® \ is precipitated with water, -.. Kied@rscb.lag suction and from a mixture ^ # a Acetone and methanol recrystallized, sr = f 7 part l ~ keto = 7-acetoxy = 14-trans-chloro-2 _P 13 ~ diroothyl °

ff f Λ ^ ₁

perhydrophenanthrsn = "2 °» carboxylic acid nitrile from S ^ = S "2Ql ⁰ ,, The one used as the starting material in the above example

pfaenanthren can be derived from the <£ $. ^s ~ l ~ keto "= 7-acetoxy ~ 2 ₉ 13-dimethyl ^ ^ ODA hydrophenanthrsa gain by Absnttigung of the double bond with hydrogen chloride in a mixture of glacial acetic acid and chloroform ψψτ at low temperature ,,,

Claims (1)

förfe © at ummmmk s ftrfates ⁵ © !! είχε? E. in © iii © that ms mfeütitissslea i3 © @ its®s, _t di® j ^ entonwcit