alkyl-substituted 1-(alkyloxyphenyl)ethylamines , Hive Chemistry Discourse
 
    foxy2 (Distinctive Doe) 12-03-01 10:52 No 243532
      alkyl-substituted 1-(alkyloxyphenyl)ethylamines </td> <td class="text_bg" align="right" valign="top">    </td> <td> </td> </tr> <tr class="text_bg"> <td colspan="2" valign="top" align="left"> <br> Here is a reference that might interest somebee's?<br><br>Synthesis of alkyl-substituted 1-(alkyloxyphenyl)ethylamines.<br>McCoubrey, A.    <br>J. Pharm. and Pharmacol.  (1956),  8  648-52.  <br>Abstract<br>cf. C.A. 46, 9068f.  Me, Et, and Pr derivs. of 1-(p-cyclohexyloxyphenyl)ethylamine (I) were readily prepd., but amyl and hexyl derivs. could not be synthesized.  The allyl ether of dihydromorphine (prisms from petr. ether, m. 77-8) was rearranged by boiling in diethylaniline, the alkali-sol. product was hydrogenated to 2-propyldihydromorphine (95%), prisms from petr. ether, m. 99.  4-Hydroxy-3-methylacetophenone gave the cyclohexyl ether (16%), b0.4 145-50; 2,4-dinitrophenylhydrazone, red needles from EtAcO-EtOH, m. 181.  Huang-Minlon reduction of 5-bromo-2-hydroxyacetophenone gave 4-bromo-2-ethylphenol (II) (75%), b22 160-70; a-naphthylurethan deriv., red needles from C6H6, m. 140.  The cyclohexyl ether (16%), b16 210-12, of II was converted to the Grignard reagent and added to Ac2O at -70 to give 4-cyclohexyloxy-3-ethylacetophenone, b3 190-2 (2,4-dinitrophenylhydrazone, red needles from EtAcO, m. 152).  The same ketone was prepd. by acetylation of o-ethylphenol.  The product yielded on fractional distn. 3-ethyl-4-hydroxyacetophenone, b1 170-80, m. 95.  3-Allyl-4-hydroxyacetophenone reduced over Pd-C gave 4-hydroxy-3-propylacetophenone, prisms from C6H6EtOH, m. 89-90; the cyclohexyl ether (14%), b0.3 145-50 (2.4-dinitrophenylhydrazone, red needles from EtOAcEtOH, m. 141).  3-Cyclohexyloxy-4-hydroxyacetophenone formed an allyl ether which rearranged to 3-allyl-5-cyclohexyloxy-4-hydroxyacetoph<wbr>enone (69%), b0.6 170-80, needles from petr. ether, m. 58.  4-Benzyloxy-3-hydroxyacetophenone gave the n-hexyl ether (77%), plates from petr. ether, m. 74, which was debenzylated (Pd-C) to 3-n-hexyloxy-4-hydroxyacetophenone (III) (89%), needles from petr. ether, m. 48.  The crude allyl ether of III heated 35 min. at 200 gave 3-allyl-5-n-hexyloxy-4-hydroxyacetopheno<wbr>ne (47%) b0.9 175-80, needles from petr. ether then EtOH, m. 83.  p-Bromophenyl caproate (5 g.), b2 125-30 mixed with AlCl3 (5 g.) in tetrachloroethane, then heated 30 min. at 120 gave 4-bromo-2-caproylphenol (80%), b1 145-50, plates from petr. ether, m. 58-9 (2,4-dinitrophenylhydrazone, orange needles from EtOAc, m. 206), was reduced with hydrazine to 4-bromo-2-n-hexylphenol (86%), b1 125-45, needles from petr. ether, m. 52%.  2-Bromo-4-n-hexylphenylcyclohexyl ether (16%), b0.5 195-200 slowly treated with Mg in boiling Et2O, then treated with Ac2O at -70 gave a trace of ketone isolated as the 2,4-dinitrophenylhydrazone (not purified).  p-Bromophenylvalerate gave 4-bromo-2-valeroylphenol (45%), b1 120-1 (2,4-dinitrophenylhydrazone, red plates from EtOAc, m. 231).  2-n-Amyl-4-bromophenol, needles from petr. ether, m. 30.  Amines were prepd. by reduction of the corresponding acetophenone oximes.  The following 3,4,5-RR'R''C6H2C(:NOH)Me (IV) and 3,4,5-RR'R''C6H2CHMeNH2 (V) were prepd. (R, R', R'', m.p. of IV, and m.p. of V.HCl given): cyclohexyloxy, HO, allyl, 107, 175; n-hexyloxy, OH, allyl, 85, 148; H, cyclohexyloxy, Me, 100, 202 (free base, b1 140-5); H, cyclohexyloxy, Et, 121, 226 (free base, b2 150-60); H, cyclohexyloxy, Pr, 114, 169.  Introduction of alkyl groups into the C6H6 ring of 1-(p-cyclohexyloxyphenyl)ethylamine or of dihydromorphine abolished their analgesic activity.  1-(3-Cyclohexyloxy-4-hydroxy-5-propylphe<wbr>nyl)ethy<wbr>lamine had analgesic activity in rats, but was very toxic.  <br><hr>Do Your Part To Win The War </td> <td> </td> </tr> <tr class="text_bg"> <td align="left" valign="bottom"><img src="../forum/images/left_bottom.gif" border="0" height="12" width="9"></td> <td valign="middle" align="center" colspan="7"> </td> <td align="right" valign="bottom"><img src="../forum/images/right_bottom.gif" border="0" height="12" width="9"></td> </tr> <tr class="page_bg"> <td colspan="9"> </td> </tr> <td align="left" valign="top" class="text_bg"> <img src="../forum/images/left_top.gif" border="0" height="12" width="9"></td> <td colspan="7"><a name="Post529122"></a></a> </td> <td align="right" valign="top"><img src="../forum/images/right_top.gif" border="0" height="12" width="9"></td> </tr> <tr class="text_bg"> <td rowspan="2"> </td> <td rowspan="2"> </td> <td valign="top" align="center" rowspan="2"> <font color="#FF0033">Rhodium</font><br> <i>(<span title="The user's title at the time of posting">Chief Bee</span>)</i><br> <span title="Posting date">09-02-04 14:02</span><br> <span title="Link to this post by using the markup [529122]">No 529122</span><br> </td> <td rowspan="2">  </td> <td rowspan="2" width="1" class="vert_ruler"> <img src="../forum/images/hr.gif" border="0" width="1" height="1"> </td> <td rowspan="2">  </td> <td class="text_bg" align="left" valign="top"> <title>What is this article about? </td> <td class="text_bg" align="right" valign="top">    </td> <td> </td> </tr> <tr class="text_bg"> <td colspan="2" valign="top" align="left"> <br> What is this article about? <br> <span title="The signature"><hr><sup>The Hive - Clandestine Chemists Without Borders</sup></span> </td> <td> </td> </tr> <tr class="text_bg"> <td align="left" valign="bottom"><img src="../forum/images/left_bottom.gif" border="0" height="12" width="9"></td> <td valign="middle" align="center" colspan="7"> </td> <td align="right" valign="bottom"><img src="../forum/images/right_bottom.gif" border="0" height="12" width="9"></td> </tr> <tr class="page_bg"> <td colspan="9"> </td> </tr> <td align="left" valign="top" class="text_bg"> <img src="../forum/images/left_top.gif" border="0" height="12" width="9"></td> <td colspan="7"><a name="Post529535"></a><a name="last"></a></a> </td> <td align="right" valign="top"><img src="../forum/images/right_top.gif" border="0" height="12" width="9"></td> </tr> <tr class="text_bg"> <td rowspan="2"> </td> <td rowspan="2"> </td> <td valign="top" align="center" rowspan="2"> cattleprodder<br> <i>(<span title="The user's title at the time of posting">Hive Bee</span>)</i><br> <span title="Posting date">09-04-04 13:29</span><br> <span title="Link to this post by using the markup [529535]">No 529535</span><br> </td> <td rowspan="2">  </td> <td rowspan="2" width="1" class="vert_ruler"> <img src="../forum/images/hr.gif" border="0" width="1" height="1"> </td> <td rowspan="2">  </td> <td class="text_bg" align="left" valign="top"> <b title="The subject of this post">Good question, Rhodium.</b> </td> <td class="text_bg" align="right" valign="top">    </td> <td> </td> </tr> <tr class="text_bg"> <td colspan="2" valign="top" align="left"> <br> I was wondering the same thing myself. </td> <td> </td> </tr> <tr class="text_bg"> <td align="left" valign="bottom"><img src="../forum/images/left_bottom.gif" border="0" height="12" width="9"></td> <td valign="middle" align="center" colspan="7"> </td> <td align="right" valign="bottom"><img src="../forum/images/right_bottom.gif" border="0" height="12" width="9"></td> </tr> <tr class="page_bg"> <td colspan="9"> </td> </tr> </body> </html>