I. THE ELECTRIC MOMENTS OF SOME DERIVATIVES OF AZOBENZENE II, THE ELECTRIC MOMENTS OF SOME STEROLS By WILLIAM A, m ALLISTER TRESIS Submitted to the School of Graduate Studies of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOm Department of Chemistry 195U ProQuest Number: 10008377 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10008377 Published by ProQuest LLC (2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 4 8 1 0 6 - 1346 ACKmiSDWffi^rcs * The writer gratefully acknowledges the friendly* discerning advice and guidance of Dr, Max T* Rogers under whose supervision this investigation was undertaken, Sincereet thanks is due Dr* John L* Speira, who constructed the dielectric constant cell used for the sterols. The writer deeply appreciates the generous fellowship grant from the Upjohn Pharmaceutical Company during the academic year 1952*53, and acknowledges the kind cooperation of Dr, E, B, Garrett and his associates who provided pure samples of many of the steroids used here. VITA William A* McAllister Candidate for the Degree of Doctor of Philosophy Major Field* Minor Field* Physical Chemistry Mathematics* Physics Biographical! Bom* October 22* 1923 in Youngstown* Ohio Undergraduate Studies at Bowling Green State University* Ohio* 191*649. Graduate Studies at Michigan State College* 192*942*. Experience* Graduate Assistant in Chemistry at Michigan State College* 192*9*52! United States Army* 192*3*46# Member of the American Chemical Society; Associate Member of Sigma XI. TABUS OF CONTENTS FAST CfKK X. IHTRODUCTIOH ............. 1 xx. tm m $ ........... ............... ............. . XXX. EXPEHXKBHTAL ....... 12 Densities SU I m U I s t a r t n t i .... Preparation of Conpounds ................................. xv. oimtmas V. RESULTS VX. BXSCBSSIOB ....... ifi ........... APPENDIX 12 12 16 21 ..... 36 .... U? .... B B E B m 51 FAST TOO X. HISTORICAL XX. EXPERIMENTAL ...................... 1 ...... 8 Densities ................................................ DielectricConstants ..................................... XXX. CALCULATIONS..... XT. RESULTS V. DISCUSSION...... VI. StJHMAKI ..... 8 8 11 ...... 12 ........ ................... REFERENCES........ ................. .................... 61 91 93 TOST GF TABLES PAST OKS TABUS X. TABUS XX. Ta b u s DIELECTRIC CONSTANTS AMD SPECIFIC VOLUMES OF THE BENZENE SOLUTIONS AT 25*C ................. 22 DIELECTRIC CONSTANTS, SPECIFIC VOLUMES, M3LECULAR REFRACTIONS, AND DIPOLE MOMENTS IN BENZENE AT 25*C.. 35 x x x . observed a n d calculated val ues o f dielectric constant AND SPECIFIC VOLUME QF p-NITRQAZQB£KZENE IN BENZENE AT 25* C....... U8 PAST TOO TABUS I. TABLE XI. DIELECTRIC CONSTANTS AND SPECIFIC VOLUMES OF THE DXOXANB SOLUTIONS AT 25*C ............ 13 DIKLBGTBIC CONSTANTS, SPECIFIC VOLUMES, MOLECULAR REFRACTIONS, AND DIPOLE MOMENTS TO DIOXANE AT 25*C .. 55 TABLE III. LIST OF STEROLS ...... 59 TABLE XV. CROUP MOMENTS FROM THE LITERATURE .................. 67 TABLE V. CROUP MOMENTS FOR CAKBONIL AND HXDROXXL CROUPS TO VARIOUS POSITIONS IN STEROID HOLECUIES 69 OBSERVED AND CALCULATED MOMENTS OF THE STEROLS ..... KITH ONTO FIXED GROUPS 72 TABLE VI. TABUS VII. OBSERVED AND CALCULATED MOMENTS OF THE STEROLS KITH GROUPS CAPABLE OF FREE ROTATION ........... 77 3111083 Mm A ^irTli mf $018 C3*isi$$& ^fMw* 1& ^ ntnilxrtiirlr %*nmapwlff& rWIWilimHim ■ «»••***+**»*•*«•*<»*♦-•**-***•*•*••• 3ftfli ITwikirtwinfiiT $ftocl te ftf«Uritrfrr ftMwtfeiMt lltM88INIWM&$ I W 3. i# *#*>*# ill $p*el&&£ WsAmm Am m 83 ^AmmmmmAmmAAom $mm $** 36 T tm m h * 300888 -Am itSlaw^toB 83 im st pm' %? 333888 0m ^HTSm'iTfcMiilfc ~A.^m JMb jOmmB 8KjAtJMfe. WmwQSmp mB A 38 8 8 3 188 Pm P8llP8BM»li8 « tB I jPMP &£ mmmmmmmmmmmmmmmwrnmrnmm 38 4 Am $ AmmmAAsm *frff Post 29 tm 3* V&temm A m m PmBmAAmm m £ firamanty utlun fmy mmmmAAmA •*# it S^8SB$&8ti of Wmmmmm M t e M m m mi p^WmmaAmmMmmmmmmrnmm ••***« 31 Pm **************»•**•*» 32 20* QunmAmmA Am m m s w i$ m m i mmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmrnm 33 m i* mi ••*•*******•*•**•*■*#♦*****♦*•*»* 3k LXS? OF W i m m s * Continued fas t X* the Experimental Cell Used la the Dielectric OoBiliBl ifeaaarwMtate ft nCHSIE 2* Specific VOlaas As a Function of Concentration for Mexan* Solutions of Progesterone* i*~CMjero~i? «•*•••«*»• 25 ?I0®I 3* %«eillc Valuae As a function of Concentration for M m m m Solutions of 11 *< # XT ©c «^ll^^oagr^o^8tao«s and X? *••••»**•.•*••******»••••• 26 H M I It* specific Velmas As a Function of CkHacentratlon fear i S m e s Solutions of li~J^Gproge*tsrene and Efli* M U $ m %ocific M i a s As a Function of Concentration for M m m sm Solutions of rrogaaa«-3A^#TO-^rio9j® *•••»•«•«•• ^ 26 FiCKflSE 6* Specific As i Function of Conesntrstion for IHmmm Solutions of It-Srost^XT -J^roxy>~2I- ai»to«y|ar^gpai^3*ll«*20**triono sod AllQprfcgnane-3,11,20trione 29 T* Specific VeXum© As « Function of Concentration for BjUma&e Solutions of II ^ ^fdro^^ro^o^«roi$s sod l^efeffidrefscsndroslsi!eifce ********************************* ^ FXOI&E 6* Specific Toluso As a Function of Concentration for Bloxane Solutions of AXIspr0^ON^3«2O«dioas and XloC AcetEo^progestorcme **«•***•*««••+•*»***•••«••**•«««••»• 31 FXGU&E 9* Specific Volume As a Function of Concentration far Moacsn© Solutions of lt^hloro*21-*brafflio»17 ©v ~&$dreagr-» prs^sst^3#ll»20^ricmo and l*-€fcl*»o~17 °< -S^dro ac«tc»TOregiaai^3#ll*20--trio«e ********•**•**•**«*•*••** 32 FXCR&& 30* %«elfk Volume As a function of Coneentration for Diowtne Solutions of 3 *4 fX7 -01l^diow^21*^u?©!ao* ia^ss4l»^*dlQB$ ****•**»*•*•*•*****«•••*****«••**** 33 T i m 11* Specific Velmas As a Function of Concoaatration for Mammrn Solutions of l6»Dehgpdropregn«H»oloii« m & DoiCPdtrolsoandroaterene Acetate ************.♦****♦**♦*,•** 3li LIST OF Harness - Continued fzoaac az* WTiwnn A» fi Function of iSSfififiSlfi w J^ m »eeifis VoXuae A* & Function of Concentration for Dioxane Solutiona of Adrenosterone and * -Estradiol. JG norae U u ■S|N*iifS6 W£I®#B Ao 11 FtBio&iosi of ©eBOtolaNdbSMEi for trtagp^ft S63b$tiSB®8l Of filOi A^^^^fi3b^yiimpn^||jlflOOdOOm jAOfi^foftftfi so*di^ *0'a ss♦ s9^^-9 3$ Florae 33* %aei£l« ftftsaae As t Function of Concentration for IHOJBftli# ^foTbfltf Of ?!*"*ftCirtfyfrj^reffiRWTV^lCTHfr &COttftiO OOf ^FOOOOOSfiXfflfcC •»*'»**.■*♦♦♦#*«»♦•-<*•#**■••■•*•*♦**#♦#*•*•* 3$ fxqubk 16. %«eif^ I o t a As « Function of Concentration for fliftftMttff ^ of 1>FH»grpratM»I-Qyid^3— Sl^ACfttOiXr* y%|yty #.***#** 39 As & 1'tiseilftft of Concentration for Mflini Solutions of 31 o{ *$& 8£&x&&tRm ofitoroao and «•*****•••**••♦a*****♦•••#»••# 1*0 FXOOBB 17. SgMttciflc rasas M . "Tjifirlf1 n WitibBW® A# s. Ihgncifon of nfflnKttfttt tariff ©f gt&l for i^atJitA *********** i}^ FlfflffiS 39* p^ 0Onfi&fif£& A® fi FOOfittPftl of i^r*yjMprfri, irot:1ia,>? for Uioataao Solutions of Frognoaolone, %f l *1? << «* BSA3^yfedHKiKl y*^X*,ifefOiw^ro^ooisow^IX.yfB,,iidtAoiio *«»*«* Iif r x m x 20. Dielectric Genatant As * Function of Concentration for Dionm© Solutions of XX >3 «%d^mipro^^oroiM^ AFi-wara^fftffr^TM*, raid lAeTk^^wa ^ fiiMraslflttw Aefttfttft ••• hi fioohe 21. Dielectric Constant As a Function of Concentration for Dioacimo Solutions of XX * -Acotorypro^steroiso* Pr*gmBu^3,20^one, and Xl^atojn^gesleren© **».«•• feb nairac 22* Dielectric Constant As a Function of Concentration for Dioacan© Solutions of . Bielsctrle Constant As a Function of Concentration for Dioxane Solutions of 21-Aeetoxyallopregnanedlone and Stigjnasteryl Acetate 52 FIGURE JO. Dielectric Constant As a Function of Concentration for Dioxane Solutions of Estrone and Defay&roisoandrosterone 53 FIGURE 31* Dielectric Constant As a Function of Concentration for Dioxane Solutions of Dehydroisoandrosterone Acetate and Pregnenolone Acetate 5k The primary aim of this work has been the correlation of electric dipole moment and structure for two general types of organic molecules, some derivatives of azobenzen© and a group of steroids. In both series the electric moment was calculated from dielectric constant and density data for dilute solutions of the substances in non-pclar solvents. How­ ever, interpretation of the data required the application of quite differ­ ent concepts, which are discussed below. The azobenzene molecule has a number of conjugated double bonds, a situation conducive to the existence of resonance. This phenomenon can be simply illustrated in the ease of benzene for which several structures can be written, the two most important being This method of representation does not imply independent existence of the forms which can possibly be written. These forms are intellectual con­ structions while the molecule behaves like a composite of these foms, rather than like any single one which can be drawn. In the language of quantum mechanics, upon which the theory of resonance is based, the wave function, ~y/f a mathematical function of time and coordin­ ates for all the particles constituting the system, represents a stationary state of the molecule* In theory \f/can he obtained as a solution of the Sehrodinger wave equation but the coa^lications involved make an approximation method more feasible. One can assume, as above, that is a linear combination of known functions closeness with which 'i j / and 4> 2* The approximates the solution of the wave equation for the molecule depends upon the number of functions, ^, and the Judgment exercised in choosing them# When <\> 2,*** <^>n can be correlated with certain structures of the molecule under consideration, the mole* cule can be said to resonate among these structures# In the case of bensene the equivalence of the two major structures means that neither <|>^ nor c^> 2 alone is a good ^proxmation to the eigenfunction desired* rather a function intermediate between them is used. As long as undue physical significance is not attached to these resonating structures, they are quite useful, and were used here, When polar groups are substituted on the benaene nucleus, it is often possible to find evidence for resonance from the properties of the result­ ing molecule. Thus phenol Is a stronger acid than aliphatic alcohols and also tends to direct many second substituents entering the ring to the ortho and para positions. Both effects are understandable in light of the resonance structures, The positive charge m the oxygen repels the proton increasing the acidic character while the accumulation of negative charge in the ortho and para positions seme to account for the directive effects* Much dipole moment evidence for resonance is based In general on changes In moments for compounds containing a given polar group as one gees from aliphatic to benzenoid character* In this work comparison was made between analogous benzene and azbbenzen© compounds. Incidental to this work, the group moment and angle of the diinethylamino group was determined in both series of compounds studied. By way of contrast to the as© compounds, there is no opportunity for resonance in the saturated steroids, having the common ring system they often have two or more polar groups in various positions on the carbon skeleton or side chains* Their similarity causes difficulty in Isolation of naturally occurring steroids or synthesis from less complex starting materials. On the other hand, relatively slight changes in the molecule often have large effects on the properties thereof* Thus the reactivity of epimers may differ greatly, epimers being chemically Identical but differing in the position of one group with respect to the methyl group at C^Q. This group is assigned the position above the plan® of the ring* Therefore, g ro u p s on the same side are f t •oriented, those on the opposite side, ©( •oriented. The reason for differences in re- actions of epimers has been ascribed to eteric hindrance, especially at Si* ^^urement of angles between polar groups in a molecular model, 3 ^ — 'I £ 1 jfcwsk' tl# *f1f‘ j(^ y$tf**lfft $jf|pqfj|^^ ’ j p||^||j~||' ||In jj$|ffif:f» ^s8(^^jpsbbjbj^ ^&8ti^8K£9j8yi8i)^4N8^ ftfl|f|fff#jfy 4888^3f^fe^ i8^ft*fcS!8flN^ilj^*58888(8^13S^§N8^ 3S38fe ^fcSfeli8^ ^l^t8fi£fe|8 i^^V8 ^fei®883fc ^feSWl^i ^88^®8R8PWB8^iil0^jN^ ^(fejSlBijdi 8ft ^te8lP6N8^6l88^ ,8?i3^jfipt ^6B3f^ l^i^l^(fe 8W SW 3ti 8iy8t8^H8 88^lS^ h ^WOsfWrtSSB^^t ^S^88l^88t^ THEORY When a chemical bond is formed between two atoms differing in electron©gativity, the more electronegative atom tends to accumulate negative charge, leaving the other atom more positive. Such a bond constitutes an electric dipole* two equal charges of opposite sign separated by some distance* r, Labeling the charges +q and ~q, the electric dipole moment is qr by definition,1 this electric moment (^0 is a vector having both magnitude and direction* Since the electronic charge is of the order It,8 x lO*1® esu and internuelear distances are usually listed in Xngstrom units (1& * 1 x 10^ cm,) most dipole moments have a magnitude of about ICf^® esu or one Debye unit. For polyatomic molecules with several such dipoles* the resultant moment may be considered the vector sum of the individual bond moments. This sum is what one observes experimentally and is useful in discussing the geometry of molecules and character of valence bonds. The theoretical basis for the evaluation of electric moments is the concept of polarisation of dielectrics. From classical electrostatics the electric field in a parallel-plate capacitor, with plates of area large compared with the distance between them, is e » kJTcr (i) where ) and (6) that PB. «■*<* + (6) T Use of (||) and the relation, D *»£ E gives the equation ItTfPj) - E (£ -1) which, whensolvedfor (9) F|jand inserted in (8), leadsto §■*»§ « IfcES* or multiplying both sides by M/d, (is) ratio ofmolecularHeight to density, £ -1 H . ItTTHot , . where the right hand side is the molar polarization. Any thermal collision which disturbs the position of a non-polar molecule has no lasting effect, since the field immediately induces the dipole again. However, for permanent dipoles, random thermal collisions oppose the tendency for them to align with the field. Thus the average component of the permanent dipole in the field direction as a function 7 of temperature must be computed.^ If there I® no field, all orien­ tations are equally probable and the number of dipoles directed within the confines of a given solid angle, dft, is AdJZ, where A is a constant depending on the number of molecules considered* If a dipole with a moment, / a, , is oriented at an angle © with a field of strength F, its potential energy is If *-/iF cos © and according to Boltzmann* s (12) Law the number of dipoles oriented in the solid angle is A exp (»V/k?)4a* A cap (yUF oos ©/kT)dJL (13) where k is the Boltzmann constant and f is absolute temperature. The average moment for one molecule in the field direction is 5 - I f W . i/jj| J k Letting exp (yUF cos ©/kT)d s l (ii,) F/kT - x , cos © * y, and noting that dil » 2 TT sin ©d© • 2TTdy, (1U) becomes - s/-l **** Jd»/dat (IS) ^ J*ti «*p (*y> dy J ® Evaluating the denominator 2 * --- (16) and numerator, dz/dx, and combining 1 « i(*) 2 - (coth * - §) (17) where L(x) Is the Langevin function* Expansion of the terms of this function in power series gives, for small x values, 8 (IB) and (ISO This Is the contribution of the permanent dipoles to the total polarizability and when added to the distortion polarizability# # leads to a total polarization J?U - w ♦ X Z/3kT). Bat by (11)# we can obtain a value of experimentally by measuring dielectric constants over a range of temperatures* then a plot of against l/T permits simultaneous evaluation of j a and o ( from slope and intercept* In the absence of permanent dipoles there are two contributions to the total polarization to consider* These are the atomic (PA) and electronic (%) polarizations caused by displacement of nuclei and electrons by the impressed field. To use (20) in calculating the dipole moment# we must either eliminate or evaluate these quantities. This is done in practice by measuring the dielectric constant in an alternating field of frequenoy sufficiently high to cause the atomic polarization to disappear* For polar molecules the orientation polarization will also disappear at such frequencies* These facts are the basis for one common experimental method for measuring dipole moments# the refractivity method# described below,^ At long wave lengths in the infrared the Maxwell relation (21) 9 bolds and the total polarization can be expressed by *%> (22) which is seen to be equal to the molar refraction as defined by the Lorenz-* Lorentz equation. Now the molar refraction Is essentially constant since there is no orientation term involved, thus# by determination of the total polarization from dielectric constant and density values, and of molar refraction from the refractive index in a portion of the infrared region where no absorption occurs, one can get the orientation polarization by difference. Experimental difficulties make it more expedient to use the sodium 0 line for refractive index measurements and to take the resultant molar refraction to be ?A ♦ Pg. The term is usually small and either neglected or estimated to be about ten percent of PB* Since the orientation polarization term is btT lI M ^ 9kT wo s.. that PT*®b“ * u (23) 9kT or in terms of ju t and known constants /• - 0.0128 V (Pj-MBjj)!. The preceding discussion applies to gases or vapors* (2l») Since many compounds are not obtainable as such, dilute solutions of polar solutes in non-polar solvents are used and give much useful information. This entails some modi­ fication of the aXasuius*JNSosottl relation. for the solution is 12 P12 “ 12 10 Thus, the molar polarization K f 0+w r .arSrTrl ~ " T ---- <25) wbw» subscripts 1, 2, and 12 refer to solvent, solute, and solution respectively* and f Is mole fraction* Now F12 * PXfl * p2*2 (26) sc solving for Pg and using the fact that f^ * 1-fg, one finds that p2 * - H — i - P1# 2 (27) is the molar polarisation of the solute in terms of molar polarizations of solvent and solution and mole fraction of solute. By using a series of solutions containing low concentrations of solute, the corresponding Pg values are obtained, plotted graphically as a function of concentration and the best line through the points extrapolated to zero concentration tp give tbe true polarization F°g of the solute in the absence of solvent affects* Substitution of t? for £ in (2$) gives the molar refraction of the solu­ tion* Then nfc * *% # * ®B * 12 l1! 2*2 (28) (29) and the best line through the points on the — concentration graph is 2 extrapolated to infinite dilution giving the molar refraction of the solute$ U SXJPEK2KE3STAL Densities The density values were determined at 25*0* using a modified Ostwald pyenometer.^ All weights were corrected for the buoyant effect arising when weighing in air with brass weights* Dielectric Constants Dielectric constants were measured using the heterodyne beat method* In which the frequencies of two oscillating circuits are made identical* One circuit contains known elements of resistance* capacitance and in­ ductance* while the other contains the experimental cell with the solu­ tion* The oscillations from the two circuits are fed into a miser ^tube (6S&7)# the emerging frequency being the difference between the two im­ pressed frequencies* This signal* when amplified* can be heard through a speaker* the pitch decreasing to a null point idien the frequencies are matched. For sharper* more sensitive detection of this condition* a visual method employing a “Hagio Eye* indicator tube (6s5) was used* The circuit used was essentially that described by Chien^. It had a two-hundred kilocycle quarts crystal as a control element in the fixed frequency oscillator* The experimental cell* a calibrated variable pre­ cision condenser (General Radio* Type 722D}* and an inductance are con­ nected in parallel in one of the tuned circuits of the variable frequency oscillator* The frequency of this second circuit is 32 ec bJ CO z UJ g ° oc LU o LaJ X , O — IO ZD — I GJ q ljj a: y o » i* n it O' o —j cc D *“*“ S —j O CC C O U- o 1. X So o 13 Figure > - o o O Z tr LJ UJ ^ A block diagram of the circuit used in measuring the dielectric constants of the solutions. o TO OSCILLATOR CIRCUIT TO AIR AND ASPIRATOR ZT /G LA SS ENVELOPE zz F i gu re The e x p er im en ta l cell used cons tan t me as ure men ts. 11+ in die lec tr ic V » a/2 Vlci where % Is inductance and C Is capacitance* so changes in the ce22 capacitance must be matched by a compensating change in the precision condenser setting for the null condition to be retained* Figure 1 is a block diagram of the circuit used in the dielectric constant measurements* The experimental dielectric constant cell consists of three concentric* rhodiaa-plated* brass cylinders which are separated by glass spacers* The middle cylinder is at high potential and shorter than the outer and inner cylinders* which are grounded* (see Figure 2)* This geometry helps to eliminate the edge effect which causes inhomogeneity in the electric field 10 between the plates* The cell and glass envelope require fifty milli­ liters of solution for measurement* The temperature was maintained at 25*00 £ 0*01*C. by using a thyratroncontrolled thermoregulator device in conjunction with a knife heater, and a motor-driven stirrer to minimise temperature gradients within the bath* The General Radio condenser was calibrated by the National Bureau of Standards and the corrections indicated by their calibration chart were applied to each capacitance reading* In a typical experiment* six dilute solutions ranging in concentration from 0*0001 to 0*001 mole fraction were prepared* The measurements on any set of six were completed, in a single day to assure reasonably constant conditions. Most of the compounds used were prepared by hr* T*W* Caupbell, the exceptions being noted under the section entitled ^Preparation of Compounds*'• They were recrystallized from acetone* ethyl alcohol* or isopropyl alcohol, or any two of these which proved satisfactory* until the melting points after two consecutive recrystaHiaationa were identical* are corrected* 15 fell,melting points The non-polar solvent used was benzene, purified by freezing a major portion of some G.P, thiophene-free material, filtering, remelting the solid residue, and repeating the process* The solvent obtained in this manner was then distilled and stored over sodium* It was found to have a refractive index of 1. W 0 and density of 0.873U3, both measured at 25*C* Preparation of Compounds p-Aminoazobenzene, This compound was an Eastman Kodak Company product which was purified to give a melting point of X2li**C* The liter** ature value for the melting point is 126*C* p~N±troazobenzene+ This was prepared by condensation of p-nitraniline with nitrosobenzene*^* ^ in concentrated alcohol solution containing a drop of acetic acid* The compound melted at 13U0C* The literature value for the melting point is 13 k* G. p~p *-Dinitroazobenzene^ This was prepared by reducing p-dinitrobenzene with glucose in an alcohol solution made alkaline by two grams of sodium hydroxide* The product was allowed to stand twenty*four hours in the reaction medium, then isolated,^ the melting point being 223-2U°C* Tetramethyl-p-phenylenediamine* This compound was also Eastman Kodak Company whit© Label material which had a melting point, on purifica­ tion, of k9*C $ the meltihg point in the literature being 5>0*C. p~p <-Tetrametbyldlaminoazobenzene* This could not be isolated by methods suggested in the literature,^ so it was prepared by the action of lithium aluminum hydride on an ether solution of p-nitrodimetbyianiline l6 and extracted with hydrochloric acid from which the free amine was re­ covered by neutralization with ammonia. The erode product was extracted with dioxane and reprecipitated by water, A melting point of 260*61*C was observed, p-Benzalaminoagobenzene, This was the product resulting from the condensation of benzaldehyde with p-aminoazobenzene.^ 128*C$ It melted at the value reported in the literature was 129*0, p-Tolualaminoazobenzene, This compound was obtained from the reaction between p-arainoazobenzene and p-tolualdehyde in boiling alcohol containing a drop of acetic acid, The melting point was 117*0* and in the literature was 120*C, p-(p-Dimethylaininobenzalamino)-azobenzene, This cca^ound was pre­ pared by mixing concentrated alcoholic solutions of p-aminoazobenzene aid p-diiaethylasdnobenzaldehyde• The melting point was 176*G| the liter­ ature value is 1?6*C, 17 CAICUXiATIOMS Following a suggestion by Halverstadt and Kumler,£ the method of calculating the total polarization discussed above was revised in an effort to eliminate accumulation of error* these workers have shown that both dielectric constant and specific volume (l/d) are linear functions of weight fraction of solute in a majority of cases* the re­ lation being of the form v12 - rl+P W2 where the subscripts have the same meaning as before while txr and ft are the slopes of the lines obtained when £ ^2 are plotted against weight fraction, W^j also v12 respectively and v^ are the cor­ responding intercepts at infinite dilution. Substitution of these values of 6^2 the specific solute polarization, v12 ^ *"he expression for where gives, in terms of mole fraction* instead of weight fraction, (30) This equation was used in all calculations reported here* the extrapolated values of £ m15> and v,? * la should agree fairly well with those found for the pure solvent. Often, however, deviations not attributable to experimental error are noted, ft has been asserted that 18 discrepancies indicate absorption of water by the solutions in the handling process and that these mines should be used in lieu of the experimental data for the pure solvent. This viewpoint has been contested and some workers^ advocate inclusion of accepted values oi the pur© solvent as points on the and graphs. He have chosen to use the extrapolated values# with the accepted values used as a guide in plotting. In the calculation of molar refraction using refractive index data the relation £ » i ? is assumed to be valid. However* this is subject to several restrictions* one of which is that the molecule must not absorb near the wave length used for the measurement. H e compounds used here were all colored* and since the Abbe refraetoiaeter available is useful only for sodium D line* refractive index data seemed to be of doubtful value. Instead* the additivity of bond redactions was assumed and literature values? of these used to arrive at a figure for the molar refraction. Before measuring the dielectric constant* it is necessary to get the cell constant for the experimental cell. This is done by measuring the capacitance of the cell at 2$*G. with air* then bens&ene* as dielectrics, Hen Cell Constant * .Jfe.ILnfSS £ mi foss Where £. m 2.272$. bs With this cell constant and capacitance readings for air and a solution of given concentration* the dielectric constant is £ -(cair * gSolfn) + Cell Const. ^2 Cell Const. The density of each solution was determined at 2$*C. Then plots a$ of £ 22 O Figure 8. o o o o to O CO CM CM go uO o ICM * CM C \i 31 CM Dielectric constant as a function of concentration for benzene solutions of p-benzalaminoazobenzene. o in 2.3500 Figure 9. - 8 ) o o aan U aily *<*«*! to th a t o f a n ilin e CUSJ B }* OtOOOtOfOO OttOt* 00 XV# XVI* Mid XVII 0 C ontributions f r a XVI XVII where the charge separation is not .usably different from that in aniline s itself* could explain this agreement*2^ Evidence indicating that the above compounds have the trans configura­ tion about the -ON bond is found in the moment of p-chlorobenzylidene pwhich is the same as benzalaniline* the phenylaao derivatives of these compounds* which were studied here* have been assumed to have the trans configuration. Benzalamlnoazobenzene has a moment of 2.03 B* as found in this work* this being larger than that of benzalaniline by 0.1*8 0. this increment is only half as large as the increment observed for aminoazobenzene over aniline and may be traced to the replacement of amino hydrogen atoms by the benzal group. This group may participate in resonance through such structures as XVIII and XXX. XVXII XIX a contribution from a structure placing a negative charge on the benzal carbon atom (XX) also being possible* 1*0 XX The last structure would not be as significant as the others since the electronegativity of nitrogen is greater than that of carbon. However, it could contribute enough to account for the observed difference in increment since it produces a moment in opposition to those noted in other polar structures. Other structures can be written which tend to place a negative charge on this carbon, e.g., H TTT ‘ flies# would imply an «dal symmetry*1 through the adjacent double bonds and this is not found by an X*ray investigation of a z o b e n z e n e .^2 Such structures evidently make no contribution to the ground state of the molecule* In p-(p-tolualamino)-azobenzene the observed moment, 2.lt7 D# is larger than that calculated for p-tolualaniline (about 1*9$ 0), indicating that structures such as H , C - O t N - 0 - N = 0 - H mcTT H j C ' O c -n O n - ^ O * H xxin i which are analogous to those postulated for benzalaminoazobenzene itself, contribute appreciably to the ground state of the molecule. hi Since the Moment observed is higher than that for benzalamino aaobenaene by 0,b D, the moment assumed for the methyl group, the structure in which the carbon assumes positive character must make a more significant contribution. The substance p-(p-diraethylaminqbenzalamino)-azobenzene has a moment (iw5l B) which Is larger than that of p-dimethylaminobenzalaniline (3*60 X>).26 reflects the increased ability of bensalaniline to accept electrons as a result of its conjugation with the phenylaso group* Structures with large charge separations would account for the increment of 0.9 D over the benzalaniline coai^ound* The compound p,p*«^initroasobenzene was studied to obtain evidence that these substances were really Hi the trans form* Since the nitro groups are coplanar with the ring, the resultant moment should be zero* There are probably several reasons that the value observed, Q*?8 B, should be considered not fundamentally different from zero* As noted in the theoretical section, the molar refraction should be measured in the infra­ red region of the spectrum* When sodium D line is used, one assumes the molar refraction to equal the sum of electronic and atomic polarizations* This causes no serious difficulty until the moment is below 1*0 D, in which case the latter quantity can be significant* Many workers, especially hz in England, assume that the atomic polarization is ten percent of the value found t o r the molar refraction* Since we used molar refractions ealeclated from bond refractions instead of refractive index values* and the Moment is less than 1*0 B, this latter correction should be implied* the result is a value of 7*3 cc, for the atomic polarization* This is quite close to the value for the difference between molar polarization and molar refrac­ tion, 6*9 cc*, used to get the final dipole moment* On this basis the electric moment of p,p1-dinitroazobenzene is indistinguishable from aero* The fact that the nitrobenzene itself has a reported atomic polarization of 3*6 ee*»33 ggg trinitrobenzene a value of 12*0 cc#,^* makes figur© of 7*3 oc* for the dinitroazobenzene compound appear not m unreasonable one* In addition to such considerations, the low solubility of the substance in benzene made the experimental error greater than normal* The solutions were all saturated solutions and the concentration may have bean altered by slight precipitation of solute during the measurements, although this could not be detected* In such solutions the benzene solvent may associate with dinitroazobenzene to form a molecular compound* Then interaction of the nitre groups with the TT electrons of the benzene ring could disturb the symmetry of the azo com­ pound and give the moment noted* Unfortunately, the magnitude of such m effect Is hard to determine quantitatively, while the atomic polarization contribution estimated from the molar refraction has some foundation in experi­ mental work and is to be preferred in explaining the discrepancy* One a*” of electric moment studies is the computation of the moments due to individual groups or bonds in different environments. Such data, 2£ when available* assist la the calculation of moments to be ejected for molecules* containing the group or groups in question* The moment cf P*P1^tetramethyldiaainoazobenaene (1*95) was used In conjunction with th»t found for dln«thyXaaiiio*zob«naono23 (3,22) to e*lcul*U the nen*at of the dimetbylaraino group In azobenzene compounds* The procedure involves application of the law of Cosines for vectors to the grotq> moments and resultant total moments in each confound* Asaum~ ing free rotation the equation /* 2 * ®°® a eo® ^ 1 ®°® ^ 2 Where /4 * total moment, and are bond or grotq> moments* ^ and the angles which the rotating vectors make with the axes of rotation* for p*pf^tetramethyldiaminoasobengene* this equation becomes {X .95)2 * 3 .8 0 * 2a2*2»2 cos2 <$> while for p~p *^imethylan&noazobensene the equation becomes (3,22i2 m 10.hO m C0.ii)2 ♦ a2*0.Sn cos ^ since the moment of the O H bond is estimated jbo be O.fc with , * 0° {the negative end of the dipole being toward the ring). By eliminating <§> between these equations and solving the resulting expression h^-21.12b 2 ♦ 301.71 - 0 for a* it was found that the roots were m • e 3,70 and a * ♦ 2,73, Negative values of the group moments were disregarded as lacking physical meaning and the positive values were used to calculate the angle £ • hh this was 22®21 for m * 3.70 and 30°7* for m * 2*73* In a similar manner, the moments of tetraraetbyl-p-phenyleiiediasdne (1*29) and dimethylanHine (1.58)2^ wore used to get a value for the dimethylamino group moment In benzenoid compounds* the values obtained were m * 1*92, • 28°?*, and m * 1*28, (f> * li5°10** The fact that the original set of simultaneous equations Is satis­ fied by two different group moments and their corresponding angles poses a problem in that there is no apparent basis for choosing either aoaant-«rigle pair as the desired one* However, in neither azo nor benzenoid type compounds is the group moment along the direction of the nitrogen to aromatic carbon bond, regardless of the z&oment and angle used* The fail­ ure to obtain a unique solution of the equations may lie in the assumption of complete freedom of rotation which determines the equations to be solved for group moment and angle* Although molecular models give no indi­ cation of steric hindrance in these substances, there may be relative spatial positions of the dimethylamino groups which minimize the potential energy of the system* In such a case the equation for the dipole moment assuming free rotation would be altered in some unknown manner, which could give two results instead of the single unambiguous solution desired, i*e«, one angle and moment for the dimethylamino group. The estimation of an electric moment for p-tolualaniline, for subse­ quent cosgmrlson with p-(p~tolualamlno)-&zob«nzene, presented a problem since benzalaniline can participate in resonance* A calculation of a group moment for Ph-C * N- from two derivatives (p-chloro and p-nitrobenzalH aniline, for example) is not feasible* Therefore, the p-tolual compound US M S ftMMNNt to hoto ft ftflftMHfc 0*fe D gTOfttftT th *a th ftt o f ta H O o O U o i {/* ♦ ItSSj* fl**» the r r a ltling o&o* o f 3U3S H m s oonparod with p j% 4 ^ < a lo r tM N i* W M O i^{ /4 * 2Jb?}« A ft foo* Til "litIPHiaolHIII liftI Hi MOliP O f li to ^ aliaaiwW ifclftiMil ftMSMBB' Oft j wr tw *8» af Mat OiSmtliMMi muI WOO^^V^^O ftteiwi ■fttOft’ Sftft^Sftffap tlOftOi awrtjkM ^Kftt««J jj^OoSBW^^Wft^O*OO^P^WftWftOO wM* o tetite iiOMml» $&• oerfclmtod orroro *ro * $«|6 ee* for tho malar polos** SftsldfcOB ftNP ft Q«96.0 for Sbo oloolBRi© osnosii (gtt i ^fynind^T) t OftZgf o j^pESflPPPPfciS^P9^fcP9fejpPM(flK^fc43PKKE PMptPp^ ^B^fiP3PP90P93^l3P^^ j8EtfeP*993p^9M6|jy^^9^^ ^0l£P9Pi^^EPBWREWflB^JP^'' ftftfttft ftB O W ft tliO Offftftt Of thft O&SftOftt Oft tllft fiftftt ftOftSfti ift IB dO SO H tt# P tX E IP d P 9 9^ p P 9 P s ^ P P ^ PP P S P P P M P B K P" P S C 9P p pP H S 9 P feJ S ^ tS fe fiP P^ ^ 3 fiM PP P B l^ ^ B 4 P P ^ 3 ^ B 9 P OSft Oft fOr 0000%O Otft ff|^*' O Q b O ft gffff apyi 863bHSS8ft ^^4Wfc^Mk m ^UaMd SiKnftdib jawr < tftft*.^a- onmo oos$KftiiiO£ -dooo fcSWjto, .d &aNEf OuUMdft fti^k xroft ftawMa o ftft oft&ft ftro mtaS"^tmm i&& oftsrosroaeft ftwooo *s to 0*3 ^ 1ft ft g**0ftlTWGtiS&tit ftf OlfcMMS* ^|f yp**** 3&KSO QHWa^f l tSftOt W¥lliiivtMiit*tT Jii^scl4jui **» satiMteft *ft ift *mmm »^-iiri»Mi^|J l yimft. b« APPENDIX Using the data for p-nitroazobenzen© the deviations o f the experi­ mental values o f dielectric constant versus concentration (Figure 9 ) and specific volume versus concentration (Figure h ) from those on the best straight line through these points was noted* From these figures the average deviation for a single reading was calculated* A summary of these results is presented in fable III with the absolute values of the individ­ ual deviations used to get the average. The effect of such errors in the final value for molar polarization %a estimated by using the total differential form for expressing F as a function of £ and v , F d£ * P dv a V By combining equations (28) and (27) one sees that „ P W " A ?x % <*12f2 *2 2 which* on partial differentiation* leads to ^C-12 ” *2F 12 £ 2 loosing from Table 1 values of a dielectric constant (2*3151) end Specific volume (1*1^375) for a given intermediate solute concentration (0.001572)* it was found that k7 TABUS XXX OBSERVED ABO CALCULATED VALUES OF DIELECTRIC CONSTANT AND SPECIFIC VOLUME OF P-NITROAZOEENZBHE XN BENZENE AT 25*C Dielectric Constant Observed least Deviation Squares Specials VoltaM Observed Le&et Deviation Squares 2.331*8 2.331*6 .0002 1.11*292 1.11*297 .00005 .3236 .321*0 .0001* .11*333 .11*331* .00001 .3151 .3X52 .0001 .11*375 .11*365 .00010 .301*7 .301*7 .0000 .11*1*02 •11*1*02 .00000 .2225 .231*1* .001? .31*1*1*3 .11*1*2*0 .00003 .2802 .2615 .00X3 .11*1*82 .11*1*82 .00000 2.3306 2.3305 .0001 1.12*282 1.11*278 .00005 .3232 .3221 .0011 .11*296 .U*307 .00011 .3171* .3260 .0011* .11*325 .11*328 .00003 .308? .3087 .0002 .11*352 .11*31*7 .00005 .3077 .307? .0002 .11*360 .11*357 .00003 .2357 .2968 .000? .11*397 .11*398 .00001 .2891* .2891* .0000 .11*1*23 .11*1(25 .00002 Average Average 0.0005 1*8 0.00005 The dependence of molar polarization on specific volume Is found to be c?Po e»* 5 t 12 Then, sine© d£ * ^Vo-l i * IjkOQOe TZ ^ 3 * ,0005 and dw • *0000$, (*0000$) • 5*30 c.c. dP2 * 9100 (*000$) ♦ ai900 the effect of such an error in molar polarization on the final moment is determined by considering the moment to be a function of the polarization only, i*e*, Z Since / * - 0.0126 1/ (Pg-HR^Jt , JM 7TZ m 0.0128 \l t - V which, on substitution, gives • M r * 0*0056* 2 this in turn leads to an estimated error in dipole moment due to un­ certainty of the polarization value, & j4* ♦ 0*03 Debyes* The molar refraction is also a polarization tern which does not indlude the orientation effect and the equations for molar polarization and refraction are of the same form as shown in the theory section* Thuo, in the absence of refractive index data, it was necessary to assume the molar refractions calculated by adding bond refractions to be subject to the same error as the molar polarization, ;* 5«30 c.c. This results in another 0.03 D error in electric moment if it is con­ sidered as a function of molar refraction alone* The over-all result is a value of the electric moment with a probable deviation of ^ 0*06 D, for compounds with moments of about lu50 d . references X. ti* Page and R. I. Adams, Electricity and Magnetism, B. Van Nostrand Co.* New York* H.Y.* 1949* 2# W. J. Mwroi Physical Chemistry* Prentiee-Hall Co.* New York, N.Y.* 1950* 3. P. Debye* Polar Molecules* Dover Publications* New York* N.Y.,1950. 4. E* J. W. leFevre* Dipole Molecules* Dover Publications* New York, N.Y.* 1950. 3, I* F* Halverstadt and W* D* Kuraler, 4. Am* Chan* See,* 6U, 2988 (191*2). 6. J. W* Smith and B. Clever&on, trans. Faraday Soe.* 4 S 109 (1949). 7. F. Daniels* Outlines of Physical Chemistry, Wiley and Sons* New York* N.Y.* 191*8. 8. 0.R. Robertson* Ind. Eng. Chom.* Anal. Ed.* 11* 464 (1936). 9. Jen-Tu&n Chien* J. Cham* Kdu©«* 2^, 1*91* (1947)* 10. Reference X* pp. 57*58. 11. E . Baafeerger and R. Buhner* Ber., J6* 3811 (1903). 12. A. Pongratz, 0. Markgraf, and E. Mayer^Pitsch* ibid.* 71B* 1287 (1938). 13. E. Idppman and R. Lange* Bar.. 13* 2137 (1880)i D. Fischerand L. Waefcar* Ibid.* 21* 2612 (1808)j s. lilting, ibid.* 18, 1144(1885b E. Rolting and l7 Foumeaux* ibid.* JO* 2946 (3S74)| A. Quilico and M. Freri* Gazz* chiia. ital.* 59. 2/3 \1929). 14. 0. Berju, Ber.* 1£* ll|G3 (1884). 15. X. Antener* Helv. Chim. Acta.* 21* 812 (1938). 16. G. W. Wheland* The Theory of Resonance* Wiley and Sons* Inc.* New York* N.Y.* 19li4. 17# H.gyring* Phye. Rev.* J2* 746 (1932). 51 18. 0* P. Smyth in A* Weisaberger, Physical Methods of Organic Chemistry* Vol. I* Part H * Second edition, Chapter 2k, Interscience Publishers, New fork* H.X.* (191*9). 19. G. S. Hartley and W. loFevre* 4 m Chem. Soe.* 531 (1939). 20* E. Bergmaim* I*. Engel, and 8. Sander* Ber«, 6%, 2572 (1930)* 21* E. Bergmaim and A* Welamann, Trans* Faraday See** J£* 1318 (1936)* 22* A. Weizmem, ibid** |6* 978 (19k0). 23* T. W. Caambell* D. A* Xouag* and H* T* Rogers* J* Am. Chem* See** n * 5789(1951). 2b* R. H* Birtlea and 0* C* Hempson* J. Chem* Sec** 1937* 10* 25. C* 0. leFevre and 3U J* W. XoFevre* *T# Ch«mu Sec** 1936* 1230. 26* L. 0. Wesson* Tables of Electric Dipole Moments* The Technology Press* Cambridge* Mass** 19U8. 27* R. Davis* H.S* Bridge* and W. J. Svirbely, «J. Am. Chem* See** 6g* 85? <19k3>. 28. E. Hertel and M* Schinzel* 2. physlk. Chem.* BU8* 269 (19kl). 29. 1C* B. Everard and L. B. Sutton* J. Chem* Sec.* 19k9. 2318. 30* F. de Gaoaek and R* J. W. LeFevre, 4* Chem* See** 1938. 7kl. 31* G* 1* Coates and 1. E* Sutton, J. Chem* See.* 19k8. 3187. 32* 4 * M* Robertson* J* Chem* Sec.* 1939. 232. 33. C. g. Cartwright and F. Errera* Proc. Roy. Sec.* (Ion*), Al5k. 318 (1936) . 3k. A. Parte* 2. phys. Chem.* Bi^* 227 (1929)* 35* Reference 18* p. 161k. v 52 mi mmgpma&B ksvAeg in m m m m Use modt mmiHpr awtt&4&&lsg mam w I80M Btfrrilliinilerf i^faMlfcAl cw»m*», T« ^ H U fla .£& JUKE? ' f»*n«* %&£ .aimHi iwsimm m Am ismm p&anarity rnctm. #ma apt .mwpew^pwpjr SMasAffittflBPtS' • sm» tobe 9l£&6ifc «*»«*** jyp mm An IwiPiMiBAd mmmmMmdte* ttsim m hmm & m $ w M M wt&m- ttom the t»tttw* mtititamt kr pmcSeerSn®. symSfawBMi- pBHmwsfilfemd mboem tv tStsa m i mtmfv&ft Isgr 8$t0mhifi* mho m m mjpapSNfMi j&b w lai esmmMwiam tap m u mmmmM wmem mmmmst* mm wwa mwrnmomB (pm tEtaa^SMMsas tsi^ mast twE^ tsafes TSsssbs jjp^a^s&^ss^ m i m m t e m m m w m m used bgr a sa» PmmgpgdAi mad SSsts^ An •vtsim at tte «arft*bM& k The description of steroids used here is that proposed by Fieser^ and extended by Reiehstein and Shoppee.^ This representation includes both the number of the position and the position of groups above (yd ) or below ( cO the general plane of the ring system* low the perlydro-l,2‘ -cyclopentenophenanthrene system has six centers of asyaanetry associated with the carbon atoms of the A/B, B/G, and C/D ring fusions. The number of optical isomers is given by 2s, where n is the number of asymmetric carbon atoms, there being a possibility of sixtyfour stereoisomers in this instance. Despite this potential source of difficulty in separation and identification, marly all naturally occur­ ring steroids are related to one of two Gg isomers, cholestane and eoprestaas* CH H Cholestane Coprostane Solid lines indicate that the atom involved is above ( /S ) 9 dotted lines that it is below ), the plane of the ring system. The two series of compounds exemplified by cholestane and coprostane are the alio and normal aeries, respectiveiy. 2 Isolation and study of products obtained in reactions or degradations insolving sterols led to the conclusion that the A/B$ B/C* and 0/D ring fusions are trans* trans* trans in the alio series and ois* trans* trana in the nonaal series* respectively*^ Optical and X«*ray diffraction data tend to confirm these configurational restrictions which reduce the number of possible isomers from sixfcy-four to eight* these eight forms differing in the individual orientations of the three ring junctions* The stereochemistry of the nucleus requires correlation of the asymmetric centers at Cg and Gp with those at and C^. In other words* the orienta­ tions of the groups attached to these carbon atoms must be determined. The reference point for such a discussion is the C^q methyl group which is assigned the f t configuration* If androstane is talcen as an ex­ ample^ there is a choice of four structures* shown below as I* II* III end 17* each of which has a mirror image* I XI HI IV % 3Nmbt iUtxmtim r * * u M * wA mum ot i m m m m « m * r «4 « m tha ut Vb*p4 &bmwr <* - o t m a i a f t w M i t n t o t t * wWSw^Ww WWwWBWw^^p- #Wr w PU^BWRnKRHV^i iflhm wwp'w £ *ja *6 tl*' a # "inn A* firm al1H npnt 4 Rt^^ A^amlLv i 4vmw> iBpiW^yf dL*a*tuS*»fc ^W*^9j^^PmWK^PBmml « ^SB*Fm** PW* » ^WWI» I^r ^ VTmnNMl FJP^v^PFN ^j^pflnP cfmpi tea&mtf* «t * amafaaMtttmi «f t*» atruatara «c m M w u w im fsg*rKftt* Gyeiatmmm* tmUU let too •tfeatalam* ring f l aw * tt» m a t * A (I.| jMMfaA \®/ * lihl Tl 4 t ittib;4kA flMlilLktm tttAfrjAkfeAtfiNltfLliii A -JfllfaMrtaMft A *K---» ^fkukLAitt^iJIjj^b .Jfc’ ^fc.^.^ »©»« win m i m m m m m m wmmMm Mmm i n sMWMmtsr far m AmfttrlffcAyia* » Kaa^n j-f tWtwm lm* motaw-MF4I afthttHfj l t wajmafcamdk pppp A Wf-mam*m lm fWtIm fPeSmWp tftll APi^l ^wwwwawwBPWi^nii^jj a, wn r . am ^F hm h#p MMa vl pi ca ta Ai mf AF i IW ir lt MW P m{mm $f I3mi $h$ m % *rn* Ifclm ^NiEfr f j| Hn $$$$•$ tM KIfr Isgprffiffltr $*&$ y^y|>yy|^ji ^j^ i||| i^gn -filltt ,/ ^ tffel&l* ffcwuaa*maamtla muummmm 4m fdbm |$ #jMm. '*Ww Mlftk.iMMt. mUAki^KMSr flWflSiMt I #n g^mm pm Pa R.^ rth-.AaAiiMfr.'JfcjfcriAi^ff cAt AL Mb InkQ 4i4 *” Jtita ttifc« 4f® ta$ AfcyMiwB *44mALAttAk.itH-ti t f *4 ln%aLMf lr%m fl4v4hattf JAM ft l%f weM Pii Si4 »A) w4km *m &n IW wm w lfel wBw Bfe Mdi I ■>'»>»*-*jh4«1|mus life 4ilb4.m »1ma- sflf ’ frijhn x^lii^'fK Slifii IhsisSs i l^ii- ring fa all ofa m a m * jgm3y t^iiMi fkiMi MtiMP# IHNH l^awiMil At2^b mi «fllfi&mtflm tht?iy &b Itifeyn Xn W» mat fam« t m i m Imf ^fj»a at* d&atfagnfm* -ss s f f liy s^RKit»wsB «»fd»3.* fmfcfac* M t « m « fMisaiwraWI fa • tjrtUgfalfa atrucmra, in « m n syiNNwiji iffyitffii sps ^UnnNmiS 1^ 4SNQW mfnim* m & Him imalmtT m m mrttoaf. fa t m apjmlta — warn tfca M m * o( • 4-m vNMf u tim In Wm erf*%*XX&gT*vtty or alio* maim of x*nay Snstioofcoii tfe*t carbon asm* % | f $f f # ft* an* 1G X&* In n pl*m aoparatad ^ 0*77&* tvm a m ifcor oottioiaiiag outai 3.* 9m Op * XU* OteOjii^Aw w1^^WfPOiJi iP^wni Wlf^ Hgi WIM ^W mWt ^Ft saiw®itoii ^PWH^r'^PCisSs WPf^'^lF 41m MsdmsfciUMi WOWPP M m tu w tt m n r t aNnw ant lag^Ubm that rlaga i» s» and <3 a ll jpasaass tha Saehsa-ifefar ebair oonfigwafcian*11 a t laast in tha «*y*tam »ia atata. w ith mdm *& 0 j onft ®%&W ro lo liiro noftxogi o f ftg* 0 |* and C^ w ith o u t Xa in * A/B-^siai s e rio ^ t&# onlar uniw&tguGasi rtp n itn r* in om (b) in which th a sdnaa a ta stsaiiPS tr^*^g*r tM >^ 4a« ts ain» fivaansd **y Xh&s saniigapafciaii is fT arH^ ayaip*!^^ i^a tib^ %aiHiff fra o tim i s m a lt** wf ilia is alastsnn d ifi* I t ia i .tt* d i*a d w *6 *« * o f pradi«U ag an iMfeapad aa la o a la ra th a r than th a O a t la th * dsduaad firm a jwaaioua X*m jr a n a ly s ts *^ fiwravaa* Snrdas has firend that- fa s tha a ia jfH tin a * dasaHns th a s ta b ility saqusnes is *>*»>#« CO m* tea rtwre-mentioned < K t t » <«l£fw»tloa mmm»* Ste dUCfKmity «m£tf b* *oaa2**d U am ammaa tmmb tea mm atefela la aotettte te ll* Jateaaalatular lapana mb to auk* lew t « tea laaapa* tam ar in tea aallAt Tfa*&&$? #$$1SShET bayjplarA ™ "" i’ ' iP H F w iffP W 4-4*»** tehte4-awfogaayfr 4»*-toiiiw^ faM^iwta4tote 'f * w p ip c H R p p f iT^ l R i ^ p V f P ^ P 'W 'P lp W ^W P w V ^ P U p m&mm nanflateanan m v m * te r to t te w h Xn v w w tt a* te la , I t «a* torn* teat tea aaloolata* a la a trl* WwPWWv® «te ffy<*4#&40l M m m m u m m itk m f l a m a / H ‘t > t i a a a s s i t e ...*fr tea nai atoaaa a t a» aquiliferiaa stator* of tea !• - ..- .jta ^ Ail J» flUSp. 8 JPiiiWHV 4HNI jWW# Wttw <$fA II j|u * t t — —.. - « /« # M au W A fw pw tlreay* while tea mmthmAmUmla 1,1 4p®tete^wWnn* 3Sbflptoft n^b^isMBNi# Xjs fwtffo a M i — _ .a i- •*% h a tea** la te I* ^pi'^ jF ph 4^te 14*^®*’ # ^ te te n n A j^ ^U f'te S jP ^^ ^ s lilw S s All# A $% & $do&btiA*®! pflBrMsl-psAss in $$ tJanyj&$# #£ life# An# £#*•*# yfete**^ Ay tffflto r &&be6ti&X& $$$%#F##g3A % S5iSWe^ A iis iijr# Atm stsnnlEWs^ As^wmBlAnn sn^nispiGdbBg sAsrodUis 4m Amm4mmdt frnnmmtot*A4m.mm£ AiniiE IfVinelAln^iU *>*^' ^te«yya^tet.4,at|l| ttkftriltte tii jaih.iir,ifc4*MaMi.„ |2teugMMuiKA 44tat a# m tel-»>arlt«ili*i em% K iduksMUHte haw alaA i n ^ W n i in n ^ W n a n r .J f ^tePte’Wpt teWwPP4^ * W ^ F ^ flt® ^ J ip ^ T P !ta 4Ww*PlP!te ayat^ntjfcK^m ,«ntel.tetejgt K Viia ra Wu WW f»»W4I,lB «^itf" |. |ffiWlk v s n * n w p w n » n p ffp t W P w t W # W SBk* ^hnil u. ^R. a M te te aia « '• ■ ,w aartiiwteiifatellIftwaawhj* •^^WHMpwph '4te 4* ^ p r •tetera Xad to « atgoitleim t mnrialm « t ateaetw* te ll* alaetm a I l f * tn a te n i a a a a lli^ te m aantxteHted ffrte te r te tea Im tea Ite M aaaawa* 4n20*dtMM 0.003188 ^12 2.2289 *12 0.9739% •002687 2*2283 •97230 .00205% 2.2203 .97233 •0Q1%67 2.2175 *97269 2.2160 .97256 2.2116 •97227 *2 .OOQi«69 15 12 2a m *12 m tom a w n a m a im 2am a tm toftttfe a m $ tk d 22 6^33^2 12 2.2553 0.97165 2.21*50 .97177 ,QQlbb2 2.2291* .57221 .000995 2.2216 *97235 •OOQblb 2.211*0 .97251 jm m J *< 0 2 * e. *2 22 0.0023bS 2.276b 0.96982 .001968 2.2665 .97032 .001077 2*2382 •9713b .000789 2.2327 .97157 2.2223 .97162 •0£X* tt 16 J/S *27 *< *a 22 0.97053 .9712U jAmBL •97272 22 0, .97222 ,97292 t. 0.002228 2.271*8 0.9691*8 .00181*7 2.253® *96999 .001M 9 2.21*38 .97056 .002(2*8 2.2322 .97222 .000758 2.222*0 ,9732*9 .0001*20 2.2270 .97222* 17 J l k i W A akt H t '1ft *12 Jmm .91099 ,000704 .97222 .972X7 Q*9TQ2k *n m «7fWf 2<$ ,9?li»2 2a *m99 .97235 % '38 ▼12 CMX&833 8,2307 0.97225 .008688 8.2246 •97208 ,008180 > ,» » .97226 ,0025U» 8.8238 .97384 .000983 2.2345 .97249 ,000039 8.8338 .97242 16 fSUXB X eoatlsa*d loae restate fa en *12 0.002888 2.2332 0.97211 .002960 2.2293 .97218 .00X607 2.2255 .97237 .00137b 2.2216 .97269 .000726 2.2177 .97270 .000652 2.2139 .97293 16-Oehydrap«igBenolon« C 12 *12 0.003256 2.2665 0.97206 .002639 2.2539 .97262 .002092 2.2638 .97263 .001669 2.2356 .97276 .001X07 2.2273 .97276 .000600 2.2177 .97282 21 TABLE X 09RtiXKK«d *2 £ 32 *12 0.003039 2.2b06 0.97175 ,002b33 2.2305 .97215 .002005 2.2276 .97186 .OGlbb? 2.225b ,972bb 2.2186 .9726b 2.21b6 .97268 .000ii75 Estrone *2 C 12 712 0.003822 2.2777 0.97160 .003137 2.2£itS .97228 .002550 2.25b2 .97213 .001916 2.21*15 .97253 .001283 2.2336 .97255 .000517 2.2205 .97296 o< -tis tra d io l *2 ^12 *12 0.00373? 2.21*97 0.97172 .002993 2.21*17 •9721b *0021424 2.2331 .97220 *001622 2.2266 .97239 ,QG10£2 2.2188 .97260 *000572 2.2139 .97293 22 t m u I eontimsftd D«hydrolaaandr<)»t«ron« *2 ^12 ’22 0.003529 2.2512 0.97267 .002889 2.21*51 .97268 •002332 2.2369 .97236 .00X665 2.228b .97278 .00101*6 2.2223 .97280 .00052b 2.2159 .97305 «&#£*&• ’22 0.97379 2.< 2.2X97 97362 2.2X92 97375 9735b 2. 2X1*3 97303 97300 *000379 97333 m* ,001658 2*4 9731*1 .00X330 2.2176 97323 .000911* 2.2156 97327 .ooo5b3 2.213b 97266 23 fable t * * 2.3379 0.9712*3 2.3123 .9 1 lk 9 m m ******* 'I# JMS .mu* mwf -mm •97280 .9726? .97293 ,97287 21* Figure 2, o ~ o o o 10 1^ 25 o o g Specific volume as a function of concentration for dioxane solutions of 0 progesterone, f ij.chloro-17 •< -hydroxypregnane-3,11,20-trione and 0 11* -hyd^oxyallopregnane-3,20-dione. _CO o o o Figure O O o o & 26 Specific volume as afunction of concentration for dioxane solutions of O H ® * * 1?«C-dihydroxyprogesterone a n d 0 17oC -hydroxyprogesterone. o 3* __ CM 97300 Figure [(.. o CNJ o o o o o CO r^s o 27 Specific volume as a function of concentration for dioxane solutions of O 11-ketoprogesterone and# 110k -hydro xynregnane -3,20-dione. t -8 o 28 .97300b Figure $, Specific volume as a function of concentration for dioxane solutions of pregnane-3>11»20t rione. .973001- Figure 6. LO o o o 8 29 Specific volume as a function of concentration for dioxane solutions of O i4--bromo-17o(-hydroxy-21-acetoxypregnane-3,11, 20-trione and # allopregnane-3,ll,20-trione. _CNJ O .973001- Figure % o o o o "O o o CM o r\ 30 o CO Specific volume as a function of concentration for dioxane solutions of O 11(5“ hydroxyprogesterone and dehydroisoandrosterone. __ CO 7. o o Figure 8. _ .C M o O O o o o o F2 O o CM o> 31 o CO Specific volume as a function of concentration for dioxane solutions of O allopregnane-3,20dione and# 11* -acetoxyprogesterone. o _ oo / "O /o .97250 Figure 9» O _.20-trione and # !pchloro-17^-hydroxy-21-acetoxypregnane-3,11, 20-trione. __ C O o o Figure 10. _.CM o o o o o CO o o R 33 Specific volume as a function of concentration for dioxane oolutions of O 3of>l?o( -dihydroxy21-bromopregnane-ll,20-dione and® 3/0,17*dihydroxv-2i-bromonregnane-ll,20-dione. — CO o O O Figure o o o o o CM CO o o rx CN O'. fX o . 3k Specific volume as a function of concentration for dioxane solutions of O l6-dehydropregnenolone and f dehydroisoandrosterone acetate. _.CN 11. o o 973401- Figure 12* " O CO _.CM o O o GO o CN CM CN fN fe o . Ch 35 vO Specific volume as a function of concentration for dioxane solutions of O estrone and £ preg­ nenolone acetate. o o o o o CO CM Os 36 Figure 13. Specific volume as a function of concentration for dioxane solutions of O adrenosterone and • o<-estradiol. o o o Figure llj.. __CN) O o o o CO o CN CM 1^O' o 37 o CN O Ch Specific volume as a function of concentration for dioxane solutions of O21-acetoxyallopregnanedione and #l6-dehydropregilenolone acetate. _.co o O O o CO P o o C\J o o . -P CO I P W -P © PP © o £ > P o o o o p •h cd -p P © i—I-P o cd 03+D H P cd cd o o P o O o 0 po p© Ph CO Pi P © p P bO •H o o ID CVJ fv. <> 8 a? 38 Figure 16 , o “ O CM o S 39 o Specific volume as a function of concentration for dioxane solutions of 0 desoxycorticosterone, # 21-acetoxypregnenolone, and Q preg­ nenolone- 3-methyl ether. A O a.co O Figure 17. o CM o o O O CO o o CM r- U-0 Specific volume as a function of concentration for dioxane solutions o f O H ^ -hydroxyprogesterone and 0 nregnane-3>20-dione • o o o & o o co CVJ 00 Figure 18. Specific volume as a function of concentration for dioxane solutions of stigmasteryl acetate* Figure 19. _.C M o O o o CO CM CM , lO k-2 O o 3- CN CM o O o CN CM Dielectric constant as a function of concentration for dioxane solutions of O pregnenolone,# 3/ 3, 17K -dihydroxy-21-bromopregnane-11,20-dione and Q progesterone. o CO o Figure 20. o ro o o CM o O o o o CM CM o o o CM Dielectric constant as a function of concentration for dioxane solutions of O -hydroxyprogesterone, 0 adrenosterone, and©16-dehydropregnenolone acetate. o "3o o Figure 21. O __CM o o o o CO CM o o o CM CM CM Dielectric constant as a function of concentration for dioxane solutions of0 11°(-acetoxyprogesterone,Q pregnane-3,20-dione, and Q 1 1 - k e t o p r o gesterone. o CD o Figure > > __ CM O O o o o o CM CO tO cvi ^5 o o a CM O O O CM CM Dielectric constant as a function of concentration for dioxane solutions of O ©C -estradiol, # pregnane-3 11 20-tr ione, and Qllo( ,17©^-dihydroxyprogesterone. o 22. __ CO O O Figure 23. o o CO CM uj o o ^6 o o o CM Dielectric constant as a function of concentration for dioxane solutions of O 21-acetoxypregnenolone and 0 allopregnane-3,11,20-trione. o o uO o o CM cm h i O O O CM CM Figure 2'j.. Dielectric constant as a function of concentration for dioxane solutions of O Ho< -hydroxypregnane3,20-dione, © 17®^-hydroxyprogesterone, and© )pchloro-17o<-hydroxy-21-acetoxynregnane-3, 11,20trione. Figure 2^. »110C O __CN O o O O O 0 CN 00 01 O O 0. __ 2.2078 33.38 0.97263 -0.b355 rPBJpw^^ 2.2082 6.75 0,97296 -0.3082 Pr*gBana-3»ll»20-trio«» 2.2082 16.81, 0,9726b -0,b59b 55 325.39 £i ** *k fi' **« < /* XI V -HjrircxypreKnanc-l.ZO-dlon. 2*2075 25*00 0.97267 -0**05 302.03 91.* 3*» 3 °( *17 a-ll<20-aiwB* 2.20* 31.* 0.97*6 -102(7 582.1*2 301.23 b.85 lHJMtoro-27 << -fcardpaKypyesMa»-3 »ll>20 -tgl<>a» 2*2087 *.70 0.97268 -0.*80 *3.* 96.80 M 2 lt-Cbloro-21»brono-27 of -ijytiroxypragpan«-3,ll,20-trlon« 2.20* 23.90 0.97256 -1,3* U»0.51 3i*.5? M S tt-Braao-lT of -l^roj?yl-21-aDetox^re®ri«m-3,lI,20-trlon* 2*2096 30*2 0.97260 -l«ltlt6 539.77 211*26 ii.sa 0,97256 -1** *3.* 108.26 Ml 90^(0 2.09 U-Chlow-XM 2,2078 30.77 Alloni^gnane-3*2Q-di>egnanc-3,ll,20-tt*l«BS 2*2068 91*5 90*1 3.85 2.2080 11 <* -Sty«lr<»qrallopr»Kn*&»*3.:U.,20-trlone 2.97268 -0.085U 300.62 95U* **6 3.28 0.97278 -0.3806 56 39U.25 TABBB II continued "ss. i *1 21-Ac#tQxyallopregaan0dlono 2.2100 10.22 0*^7288 «*Q.27I0 26Jwl2 103.50 2.6b 30l**O3 91.45 3.22 Pregnenolone 2.2087 15.08 0.97297 -0.X320 Pregnenolone-3-inethyl ether 2.2120 2.2095 13.b0 0*97302 -0.0883 280.18 96.18 3.00 10.00 Pregnenolone acetate 0.97305 -0,2301 239*50 100.61 2.60 102.37 3.U0 113.26 2.7b 91.01 3.b3 100.35 2.93 229.22 89.73 2.61 3U8.2U 76.66 3.6b 223.60 78.17 2.66 21-Acetoxypregnenolone 2.2065 16.87 0.97293 *0.1006 339*30 22^Acetoxypregnenolone acetate 2.2088 10.57 0.97299 266.96 16-Dehydropregnenolone 2.2075 17.58 0.973H -0.3185 331.15 X6-Dehydropregnenolone acetate 2.2100 12.53 0.97291 -0*2338 275*55 Desoaycorticoaterone 2.2100 10*15 0.97302 -O.U133 Estrone 2.2120 17.07 0.97320 -0.1088 o ( -Estradiol 2.2080 10.80 0.97307 -0.3628 57 TABLE H £i <<* continued t Q »1 ? 2 0 «D2 Adrenosterone 2.2100 37.1b 0*97320 *0*5686 608*62 80.71 5.09 82.21 2.86 91.56 3.26 133.81 1.9b Dehytfroieoandrosterone 2.2100 11.7b 0.97288 *0.0635 22*9.36 0ehydroleoandroeterone acetate 2.2095 lb.56 0*97322 *04282*8 309.62 Stigma&texyl acetate 2.212? k .7 9 8 0.97286 *0*5550 58 220*98 HSf OF STOtOLS 7 K 2* 11 o< 3* 11 ^H5^rox^jrog®»t«r0iite ^ • *»3#20-aien» 323 A3l0pr0gnane*3*2O»diane 200*5 30. P«^jMa^3#12*20-fcrton* 159-160 358*60 31* Al3^«gOTwKJ*12»20**w*®»» 213-211* 211*5 3 2 . 31 33. i«»~ll»2O>(Hon* 36. b^atoP#-«To< **&&m«j*23**wrtio-3»ll*20-trlon« 238*1(0 TABLB III continued Halting Point C O Observed literature IS* b~Chloro-*17 c< ^J^ndroxypregnane*' 3,11,20-trione 19* b-^hloro«»21*broiao**17 o ( -hydros^** pregnane-3#11*20~trione 20* Mrenosterone 2U 21-Aceto3£yallopregnanedione 22* o( -Estradiol 217-20 *$ $ *6 17b 176-7 23* Pregnenolone 189-90 190 2b* l6^Dehydropregn©nolone 213-lb 213-lb 25. 21^Aeetosypregnenolon© 135-7 183-85 26* X6^Dehydropregnenolone acetate 173-b 176 2?* Pregnenolone acetate lbb-5 lb6-7 23* Pregnenolon®-3-*meth2rl ether 123-b 12h*6 29* BeaoKycorticosterone 137*3 lbl-2 30. Estrone 25b*5 256 31* DehyiroisQandx^ateroiie lbS-7 aba 32. Bebydroisoandrosterone acetate 166*5-167.5 33* 138-9 Stigmasteryl acetate 3b* 21^Ac«toaypregnenolone acetate fbe confounds numbered 1-20 were obtained from the Upjohn Pharmaceutical Co^pauyi the remaining sterols were procured from General Biochemical* Company* 60 mmmmm 9am ga&ftraX M M t a am bm 4 m m v o M a k g t&* atructax* at «t*rol* tram m axmXissfe&ai of tho obrorved *l*ctric a m n t * * An attaaapt to a n dl£$ftr«no«a In oloetrle mm m l «a * crttorto® far identify­ ing apl w r m « w elngtiiarly tmoaocoosfia far m m l g M te n * Ba% tte ^lanvad wm wtemat «reh pair* and E /^ progafltnpona m i aneant&a&$$r ideattin^!* CU, o €* "*taQ £F&Qp4l * T O toflfll 1® Ifrtigtlft to M s Blto* iNBl' $6' M ^ l toftMW A IMWPft- to to# tofttturw to wtosto tta fltoWNe j —ftJfc« ~WftS6-<3,20-dione S * m 3*2® *> XX ^ »Hy&roxyproge8terone JA * 3.9k 2> A cfflsparison of the pregnane*»3»20-diones ©1th progesterone Indicate© an Increase el 0*68 D* Ire® 2*0? 0 to 2*?? D* resulting fro m the formation of the /& double bond* CM, cHj -? v O l *4 Allopregnane-3*20-dione M Progesterone ju t • 2*77 0 * 2.09 D Thus, a sterol with a double bond in the k *$ position appears to have an electric moment Q.7-0.& D greater than the corresponding saturated molecule, Although a slight change in the angular relationships of the polar groups occurs upon introduction o f the double bond# the increase in the total moment is probably due principally to resonance in the A ring* Using Progesterone (I) as an example* the result is a structure in which a charge 63 separation occurs (IX), contributes to the ground state of the molecule* I n Previous evidence for such a resonance effect is to be found in the electric aments of cyclohexanone^ and ioophorone^ c M * 2«90 0 c h s /* * 3«PT 0 where a similar, though slighter larger, increase was noted for the im~ saturated aoieeule« Two pairs of sterols differ only In the presence of a double bond in the 0 ring* Cl4, CH^Cro ? £M3 ctt5 C=o ! ctt. Pregnenolone + 16-Dehydropragnenolone M * 3.22 0 * 3J*3 0 6U Pregnenolone acetate /* * 2*60 D l6^ehydropregnenolone acetate /x * 2*93 B The moments increase by 0*21 B and 0.33 B respectively# upon insertion of angular relationship between the polar groups since the distortion of the flve-SKo&bered ring when the double bond is present changes the position of the keto group with respect to the 3-acetoxy group. The affect of introducing an acetoasy group in the side chain of either alia or normal pregnanes at for the four compounds* may be estimated from the moments observed c ria oA c o W CM* CfiO ’D 014 ‘ i >i * M & * £KS$ w e asia# f m eobattp&tom gwi M «n* m » M M l «*£ stLgmasteryl ac*t*fc«* U9i % Stigmasteryi acetate aSase ***— ►of ***** {*£*** B t o T ftf* Tail me i a iit tt gfrawrad w l w e olT eeofKRiM* la ebSeb i w — .a-.— I, ^ >iim M m - J lB h t t A w g -M fc ^ k J K '^ H M fe ^A L -J '- mj^. iilianrun] a jaatfifs -iweati&a* - w ^ a ^ ie mfkrtwi) tar ftk* innpBMdt m $m m torelrad a&ouM n a tu ra l te tte i t—'BO*. /&lL ***-*£*- s ^ c * te *n gee&agr psm? aagpaEiaaaa a t g«e^awspe *» a ^ a R a * ^ s iia j| Y w was carried out P U M E jM L jIfc a* tfe* J I W A t f lU b X a ^ d t a iC eaaapg ceww wnaiMisdt t&a aaaMc^ i«e rausuaL W R W w t i L thft 0f«Mjfc isms M M 9 «pv «r imitiMM to fabto If* tin** *ito wgl»» litiawd «n aoleenlar of to* ftratf* nu*A JJourd typ*. % ■ « * lotto? ***#urea*nt* ware sad* wlto i t o i M i i l« ft M to to i p t o i I t o f t l» H i » t o « A k « « |M t o t f to * w t o o * 0 M | aoswat* to t o l i I ? os to * ooototoato * « * • m with to* M l * of to*** aagto*. aatlaatod I t o t o of to* r**p*ctiv* x » y and s t o t * n w t < tor d l fixed polo? ****** to * sotoed* ******** * t oil gaunt waft a* * to*to tor eampxtUon with to* ob**rv*d figure* Thi* j******** to** not apply to*** group* capable of rotation are pr***at «* the** ***» pound** sosaito containing l*to*ayl group*, will b* considered eeparataly, to* *toto*to* sy t** *** ^ 4*«*p unitor tor to* g * * « noantoroi t o % m m listed to ttoto f* to* n g U s «•***?*& tor to* JHtoto $F*ap B*t* n*«ft with to* nonast of cyetotoxftnon* (2.9 B) to gat to* *«*<* ******* tor to* JMtot® g w » Balng to* wmmfo of iaophoro»a (337 B) to*** **■» *toto* €»▼* to* **a$«se»is of to* to* ttotoal 17 /f-ae*tyl group there m m k ^k^HHewto grouping. tor 1mm ®o*d po*ittoB*% otoraetortowl IT ******* Xeto boat (Alio) -2.k7 0.00 ♦1.5k 3—Eeto boat (Normal) +2.1*7 0.60 -1.5k ^ k-3-Keto -3.38 0.00 -2.12 17/3 -Acetyl ♦1.18 -1.0? ♦2*k7 llcK-^y^roay 0.00 0.00 ♦2.00 11 -^jrdrosy 0.00 -2.00 0.00 1 7 ^ -grdroxy -0.90 -x.k8 -0.28 3 ^ -%&raay 0.00 -2.00 0.00 -0 .8$ -0 0 5 1 7 * Hydroxy 3 * -Aecbwy -X.3k ♦1.3k 0.00 3 /? -Ac©toay ♦1.3k ♦1.3k 0.00 0.00 ♦0.33 ♦1.80 11 *< -Acetoxy (9 man» *» % » a, and y * tfMtlWMi wtan liatwt ate HMNI 'tlMI •WWrtat* irav mm«b»« <*) fro* ftbte XV and «b*aagfct»A n M fcjr «MM* vwatom *lth «h» «obm of * M t of mordlnatM fix te la to# IHflftjMttBtitAJI* $tkOfc * ************** *m mg, IkSdtiB^t 4pKP • m m m © E iMPfeiPMHft ISteaj JpwpB&B 4MM& tSbtt *WlB ®WW3? UltQip. wwnpF^w^ipw wj|*li ^Kft ntfwt***** tt **—>**» te*wl*aa> tAb/SHfim jU9£ WfllTtt*>aB^, **twl»^***» 4n 1&Ufe alaaa m£ th« »«&**>* Br *■<»*«»» # 0 JBnp taxsr atfbfttltttM it a t S . mw* dtwmiKHiaii ^ ***** wm*twr *T *w *** Tl ^ ■umittlttt ami ISRPBWVBIIV^I^^PWMRr f lBPWw aoattawttl*»_<*>to Bf^jdtojMUi WlMMMnttir wfwppwp?ip» t&bB IQPfllMI I* invalmda TIm kcto wwairtto U iM #*» for to# «h«lr for* uaUoa otter#!## otctod. TO electric moments were calculated for sterols, for which dipole momenta 21 have been reported in the literature hut no interpretation of the values offered. These were considered in addition to the compounds listed in Table H I and provided a test of the method of calculation, as wall as being useful for interpretative purposes. The observed and Rai^nin^a momenta, along with conclusions, are compiled in Tables 71 and 7H» Thus* the moments have been recorded for a pair of 3,17-diones recently,^ Androstan@~3*l?~*dione Etiocholane-3,17-dione m 3*3S B J* m 3*50 B Addition of the components determined above resulted in values of 2.95 B for both of these. Since the boat conformation should be possible for both molecules, calculations were made to ascertain the percent boat form which might explain the observed differences* This was calculated from the equation / * 2 - * A 2 ♦ (1-x)/'t>2 whereat ** the observed m o m e n t , a n d JU ^ the values calculated for chair and boat forms respectively, and 1 the fraction of molecules in the chair configuration. The results indicate that the alio compound exists with the A ring essentially all in the chair form while the A ring has sixteen percent boat form in the normal conpound. 71 mmmm mt o m i h mamm o r tm mmms w w (m i$ vissb o m s 3*30 iUcgg»«WMW'<3MfiMn P* KR9iHI JHWRJi t.W M i •51 mm Mm sm Mfc 303 3nmi0 n itrtt a b la la td tfw fflifm c th« ta(&*gia3# t 0 fe* la ilM «X1 «M tt> M m * H * «MKUKl* «F feM * M M X lsU d i l l « te l* * t W hW I w n raqultw d to m p la ia tlw d in i^ p u c a r botm oa —XnaUtod m i ofemmml I* This figure is in fairly good agreement with the value of fourteen per­ cent computed by Nace and Turner*1^ for these sterols, for A ^-aadrost*ne-3,17-dione A -Androstene-3*17-dlone J* * 3#32 D (calofd - 3.59 B) the value observed by Kumler (3.32 B)21 is lower than calculated (3.59 B) so no contribution from the highly polar boat form (6.23 B) was expected or found* For the pregnanediones cm, o O Pregnane—3#20—dione Allopregnane-3»20-dione yU * 2.08 £ ** 2.09 B the value calculated for the chair structure is 1.93 B in both cases* The discrepancies can be attributed to five and two percent boat isomer in the normal and alio substances* respectively. 73 Sora^L and a31opregnaiMK3fH|20^jri(me both have a calculated valua fc*20 which is higher than observed for either. (alia) both higher than observed so these should not be a factor in explain* ing the lower moments observed* Also* there is no apparent reason for the values* observed to differ as they do. Other sets differing only in Ihe orientation of the A ring were found to have identical electric m m m v m The calculated value of U.20 B is probably not too much in error since the observed moment for 11-ketoprogesteron® CH, i i 3 3 .C«-0 CH. is 1**26 B# in good agreement with the former value. The reason for the low observed values is not apparent so no ready explanation can be given here* Tfc Although molecules with A ^ double bond do not hare alio and normal forme* the unaaturation limits the A ring to a configuration resembling that of therein. an alio steroid* chair and boat forms being possible For these substances the moment of isophorone and the angles determined for the boat >*keio grouping were used to compute the components necessary for estimation of percent boat form present in the e<|uilibrlum mixture* Then for A. k-androstene~3#17-di©ne21 and ll-ketoprogeeterone ^*Andrestene*3#l?*dlone /A il~Ketoprogesterone /Am k.26 D * 3*82 0 calculations* using the calculated values listed in fable VI* predict no boat form present* However, for progesterone and adrenosterone Adrenosterone Progesterone y U * 5 .09 D / A m 2.77 n n • I # * — A mIm— »— Burnt — — — * * lr t mm laAA— mA to to * 4viae— m IL I< K — i« to aitM in n — > YO O feHlO iK fB M M M & lltft O & iO K lO O & iB H fc44 44 O &O ftTO S ao Otho OtiuriUPidi mambA* "*-■ B f-1 v ■!■■ ^ ■ ■ |» | :^ ^ ^ W W W F S ^ p iF P p |to W W —!W of 4lw44l4 oS M S ti 08ilsf riM-i tott4 ’-•• — — ton— v M V P f^ p 1 to — — W W W W P P W W W t o f*ato— to < —* t t y h i— PW W 'W *O T W W W W iW W i W W o f t o * a— P P P W ^^N P W W IW iW r W P V ’W W W W W '^ W 4 W W I B f f intfififl^i **11**^ ^ oboi &o OoftoovroftoO. 4& ^ (P W W H W W J O rl|F O P O P P —W O O toaa. * ——i to — l a to * ^ #44 tliffit y M M M W O POOW fti 0 —0 0 W |W P O P W O i ^ p w —r W O P O O ’ to Mtowto — A—to * ton* » to — 4P W 4 aintwg t o — » to * «— th* Is J U R d ftiO dw wo o ft th oS w la w S s tt O f ttlOP O ttO O * Jto ^to *to to W to^Wtotor — MAP* 8 8 ( ^ 0 ^ ^ ^OBiF OOW (^F— toIW W FF t o to W P 'W W W in iV lll'W W ^WWV a^Wl^^PF PP .|fP iiif|ii offoofe §4 4hs 4 fiiso C ^fryiH tl^iiflEHis yfwifwii- <#$ SoooOoroBio) pooo oo& xm oo 0$4M M 8%& HNl- O lM O IfN M M Bf&O O PO O4ft 0004 & IM H M M M M M I# iO O O K faftlllO4S4tltiNflS***— OgOOoO&ftKl ywatlil |t6 O&tO&OtltOd w ^ A i ^ y | ^ 09fttrt3*0l46VUl toft* 4 t e tMM& ffrywi of H»o 4 p£$i$* Hfts% too offoofeo ooo^ytiftNMl lii 4&o oolotOy^taMi of Hot iMotrlo fflftffif)y o**o ooiwofc in pfto&tg&o *o*y of o$g§ $4£0I 04401* Of O O iplO M ftO M io for PfcOfOlOiito M B feto tto tto totho fOtO&tf&IOkmtf03ar& £VtW 8»* tho OffOOtiO OO&OlO fcoOooHi Wm M l wtAm owl Hit o*ot# ogam* 4* oMot to otaoty Mppooo* §o 141# m — TllHi to-—tototodOft *&*— 1*0*0:* H4L* totjafitt#ttoaftttoto MuiatoMi 4 ft tototto& altolktiW to to ^ to O o W O B ^ f toPtoPOto toOO^tolPtoto O P 4 B I' to O IO toP W r •W M W W ^ W O P toaWto^Otofp W f to r'^ to to f^ B P ^ ^ ^ ^ P to to -W to «Mtom tolsaw l i» atoiU—toto* — w* to to* A to lto d o to«— t o t o * BMW it» ! • * • » to * —to — to m to — to — yH * • X* tttok y * 1* * 1^ * * to * • — M— «■ ia to * ««»—l — ***f% MMM^I* bw* to * •*— — I — — to— to*— la fa— X to «**» to—I — T%i* awto— w m «toXi— to to * a— to to — to* — rtoA ly wto— i — to—fc—* to— —A to * a t* * — —1 — Iwtoa— • — — »—*«< ia ito A a m * for — •—*— —A «— —to— I* * m m m a m tm m m & m > m m or m s m t m m m J y3 *Xf<^ «•— ^n— I— SHEWS n» SU0 W tmxoUttim t* 9 wmm — I.T O 8 . p w p IMoititiBlMs s.sa tiyiojkgt&y M n M rtii BngaaMtom»>— tkgA — h w I4b flS y tfb llf Wbsfltwsl fl * tffl — — / * 4&M U / wiPP# — m2*. 1Oiiiinailfjsiliiojsrijiiiiin il ons 3Jb3 3 *» ffH.ftM Ay tiindsrsS |4M w n» F— **«o 3*31» FrcftMBblf o nwdsflstofflflon * .* j 3*4* o f s to ri* « ff# # t» «m# J4 6 3*T4 rSSOOttliBS* fmtiwAmwm »u3* b*US m w ra ta tlo B o4SwfSSlM0MPlSiSPCW1# 51.17 M * X?ft• — IT ^^ # th y l*a # to a t« ro n # b.17 ^1 )4 $ W W jfP / ^®4jp— ibJiW O1 *l- 4 *4 *WFG\ 4Hfa Ps W nffA IlftHfUwWm •U g h tiy tadr##*#?#!)# 3.TO 3.50 **## ro ts tio ii —— fc^a M b /3 ^lauA rwwiwm piW wSPW P— SlFW W W 4*33 3*S» 3 flOlBO^rBOolNyBdtiNPStWPBBIS M * 3.«> J>«rU#l f * * • fo ta tts © 3.T3 iuUU ^ ifiy 4,43 *« » «i>—i» ti—iitr ' fro # ro ttfc le a ito m » — U 4 B y — ir* * —M iens — A ^-O b to — M w l-a / — •«*? / 3* ,XIcx;•Aodtro— a d ia l • — T inted r*fftari#fc#d p w tfiH t o w*fcv^®wwMWPIPaNpwwHW y-* * 5*3? /W * In>$8 B (6aA»*4« - U . U 5 8 ) B (8 a l**4 * • t*J < 8 } tli* ig w m t aotwl la tbo ttn w caapouwd SndSeetta* iM a e iU r tirni w t*» tl«n fo r tte U o< •^vtaaagr group* ftwh 1» not tfao ooao fo r tho IX /S« i m m t M n tt» SB | M | ta s u b *»**«r tlio MtfepX group at tho aA> rtat Jmrtur** Using on# of two boat poaaiblo ££xod ffMMBit*-***1# for thto gjpoup* o toSut of S#3LT ^ URtw tttitrtlj tJld&OOtO tfeot thO t9E00t &<§ fOfftfttfltoot Olft it i f fita O o lo Qftnf'tilvf^ tO O 001*1*00 Qy oOiariUt OOjJO&SiOOti 17 o< d M n l M i t M t i n M / * • h M » M n U M * an aawHlnatlaB o f the nedoXo. Bmmrer, tbo autuaX ropuXolo* of ttoo «M M U qr * * « g r l group* oouX* osoooiwMy dlotort ttao S ring uuougfa » to cause Interference of the hydrogen atoms with the alcohol group. The models uaed lack the flexibility required for observation of such an effect if It Is important* Androeterone and Its {$ -Isomer have equal calculated moments but different experimental values were found ^ Androsteroma yu • 3.?0 D (Calc9!. «* 3*50 0) -Androsterone 2.95 D (Calc'd. - 3.50 d ) For the former molecule, the 3 K -hydroxy group is essentially free to rotate but the larger discrepancy In the ^ restriction of the ^ 3 -hydroxy group* -androsterone values implies A calculation based on this assump­ tion gave a moment of 2*26 D, which is lower than the observed figure and indicates that restriction of rotation exists to some degree* Further evidence for restricted rotation In sterols was deduced from the data for defcydroisoandrosterane and ^ ^-choleetanol-3 /^-one-7 D*hydroi»oandrost«ron« -one—7 u - 2.86 D (Calc'd. * 3.60 D) 80 3.7? D (Calc'd. - U.UU D) Wring likely fixed positions for the alcohol groups at C3, values of 2 .2 k B end 3*36 0 respectively, were found* Since the figures obtained assuming free rotation and assuming a fixed position bracket the observed moments, the hydroxyl group is probably restricted to oscillation over a limited range* Several pairs of diols were considered here also, the androstanediols below having moments less or greater than calculated, when the 3«*hydroxy 3 0^,17 o i -indrostanediol I ,17 c*-Androstanediol y W * 2*29 (Calc'd. * 2*69 0) y U m z.99 0 (Calc'd. * 2.69 0) For the 3 c f\ epimer, the best fixed position of the hydroxyl group gave a calculated moment of 1*0$ 0 <* much too low to account for the observed difference of Q*h B noted above - so the groups are probably essen­ tially free to rotate* For the 3 ^ modification a calculated value, assuming fixed hydroxyl groups* is 3*^0 D so there may be slight hindrance at the 3 position* The structurally similar agreement with ^J>-Androstenediols had moments in good those calculated for the free rotation* 61 ) £he calcul&ted and. observed soe^te for the c^olestanediols are also comparable in magnitude* ing free rotation, the unsaturation possibly altering the geometry of the s&lecule enough to permit freedom for the 3/3 -hydroxyl group. The cholestanediols probably have unhindered hydroxyl groups* though the difference acted for the 7 o f -isomer might be interpreted as due to hindrance at the 7 o f -position. From the preceding discussion it is evident that the electric moments of alcohols are often ambiguous. This is especially true in a solvent like 82 dioxane which, though*non~pQlar, can participate in hydrogen bonding vltb the sterols of this type, the extent to which such association might occur Is difficult to assess in most instances. A comparison of the electric moments of these polyhydrle sterols in dioxane and benaene might be of some rains but many sterols are difficultly soluble in the latter solvent, lacking such information, it was necessary to neglect effects due to the solvent. Two other dials which should be included with this group are o< estradiol and 17~»ethyl<* z\^~androstanediol~3 ^,17^ c\ -Estradiol p 17~Methyl*» £j*~androstanediol-3 - 2 *66 D (Calc’d. • 2*62 £0 ,17 * 2*7® 0 (Calc'd* * 2*69 D) Here again it is highly probable that the hydroxyl groups are free to rotate. T o r estrone the data agree well justifying the use of the moment of phenol in the calculation and suggesting resonance involving a charge separation as shown in 11. 1 Estrone • 3.61* H (Calc'd. * 3.1*6 D) 83 In the hydroxypregnane and progesterone molecules* the appropriate hydroxy group moment and the moment calculated for the parent compounds (progesterone and pregnane-3*20-dione) were used to calculate moments assuming free rotation of the hydroxyl group* Application of this method to the 11 G^s -hydroxypregnanediones led to estimated electric moments #ilch were Identical for alio and normal Isomers* although somewhat lower than the observed figures* H H 11 « -Sydraiyprognane-3*20-dione U d ~Hydr3Milt< to r « t*ro l« oontm taing *& £• group* lift* 4*1* for lXc< «wotoaqppfOfootftraiM nmm In go©4 agrowitnt /• * M l B («a*<4. <• 30b ») •odi Ij4tii6rffr* &• r^Mb®tit3r s^Hwirrfi#tfiMnwran |, Am* «*<*■«*<»w*«i*»3M amm, j*«wi A *^#diMHL66feiiPO Ct», rmmiMflnm acetate 14»a^y acetate /* • u n yM * t*«0 B («Oo»d. • 3*<8 B) tfat agrawwrrt i* m % «w*ajr as a**!* tte n»i— iTiHl « 4 w M U M f» » (•«J*»4, • 3*68 0 ) m & * ^ * * m t o * a «mmi « « * * • valaea d U f l n i by about 0*5 0* 88 CH l CM. Behydroiaoandrosterone acetate *26 B (Calc*d. * 3#?2 B) The fact that the calculated moment la greater than experimental for the above sterols suggests that the resonance structure * Is Important and augments the keto group moment* This in turn argues for a planar configuration of the acetoay group* However, the srteric and resonance effects are so interdependent in this group that entirely unambiguous conclusions are hard to formulate* In sterols with only fixed groups, the accuracy with which the angles can be measured determines the degree to which the calculated electric moments are correct for a certain assumed conformation. The molecular models used ware the best which were readily available but re­ quired modification in the highly distorted D ring* Thus, the strain, which is probably absorbed throughout the carbon skeleton in the molecule, is localised in this five-menfcered ring* The actual precision of the angle measurements was found to be ♦ 2* so the effect of such m error on the calculated moment was estimated using the data for androstane*»3,17dione* It was assumed that the angles locating the 3-keto group 89 In the reference system were really 2jy higher than observed, while the 17~keto angles were 2*0“ lees than found by measurement. Use of the angles resulting from these assumptions led to the following components of the two keto groups* 3-Keto 17-Kete ** «y -2 .1*0 ♦2.20 0 *i*iiS ♦2*23 -0*57 The electric moment calculated using these data is 1*01 £>* which is to be compared with the 2.9$ B actually obtained* Thus* one would conclude that an error of ♦ 0*06 D is associated with the measurement of angles on molecular models of sterols with a total moment of about 3*0 D* For sterols with freely rotating hydroayl groupsf the error involved in neglecting the cosine tern is a measure of the accuracy of the calculated electric moment* A value of ?£* is given in the literature for the angle 21 between the C**0 bond and the group moment of the hydroayl group. sow polar groups was 106% ,* 75* and • 106% the equation is used and gives a calculated value of 2*72 D for the electric moment* This compares quite favorably with the 2.6? D found assuming the angle between the O O bond hydroxy group moment to be 90* and apparently Justi­ fies the use of this latter assertion* 90 m m m The electric moments have b a m determined at 25*0 t o r e ig h t deriv­ atives of azobemzene end thlrty*four sterols using the refractivity method* the experimental data mere collected on dilate solutions of the compounds in non^polar solvents! benzene was used for the azobenzene derivatives and dioxane for the sterols* Dielectric constant and density values for six different concentrations were plotted graphically and extrapolated to zero concentration to obtain data for the pure solute* These data in turn were used* along with calculated molar refractions, to compute the molar orientation polarisations and electric moments of the solute molecules* The final values so obtained were interpreted from the standpoint of the theory of resonance, qualitative ideas concerning steric hindrance or some combination of these* The azobenzene compounds were found to have moments greater than their bensene analogues! this effect was attributed to resonance structures involving ?large charge separations* Extension of the aao ring system by conjugation with a bensalamln© group led to further increases in moment presumably for the same reason* Seme of the data were used to calculate the moment and angle for the dimethylamino group in both bensene and azobenzene coapounds* The faet that the eleetrie moment of p,p*-dinltroazobenzene was found to be essen­ tially zero has been construed as evidence that the aso derivatives have the trans configuration* The sterols were investigated with the intention of correlating structural features with dipole moment* The angles between groups, from 91 which tht clwtrio moments could he oaleulatidi wort found for various confonaticBis of 'the stiroX molamlM by direct measurements on molecular models* Comparison of the observed values with those calculated in this wgf provided information concerning the restriction of rotation of groups substituted in the various positions and the existence of chair*boat type geometrical isomerism in the rings* In the pregnane and progesterone type sterols* it was necessary to postulate that from two to sixteen percent of the molecules in solution had the boat form of the A ring to explain the data obtained# For sterols with groups capable of free rotation the calculated values were often within experimental error of the observed values and rarely differed from the latter by more than 0*8 D. Where the electric moments calculated for free rotation differed considerably from the observed values it was concluded that the groups were restricted. Further calculations* based on molecular models* for various fixed positions of the groups indicate the source of the hindrance for the various positions. The 11 11/2 , and 1? ^ positions were presumably greatly hindered since the large methyl substitu­ ents or hydrogens attached directly to the ring in known fixed positions interfered physically with free rotation in these positions. For 11 • hydraxypregesterones and pregnandiones the values calculated for fixed positions of the hydroxyl groups were in best agreement with experimentally determined moments* suggesting that the freedom of these groups to rotate has been seriously impaired. n REFERENCES 4* J*D. Bernal, Nature, 12£» 277 (1932)* 2* 0* Diels and W* Gadke, Bar*, 60, 150 (1927)$ 0* Dials, W* Gadke, and P. Hording, Ann*, 559* 1 Tt-927)* 3* 0. Rosenheim and H. King, Chemistry and Industry, gj, 565 (1932)* 5* I>* Fieser and H* F ie s e r, Natural Produets Related to Phananthrene, Reinhold Publishing Go*, Third Edition, 191*9, PP* 119*359* 5. Reference 5, page 92| T* Reichstein and C* Shoppee, Vitamins and Hormones, Vol. 1, Academic Press, New fork, 1953, pp* 359-513* 6* Reference 5* pp* 620*631* 7* 0* Shoppee, £• Chem* Sec*, 1958* 13j8f Am* Rppts. Chem. See*, 53, 200 (1956)| W* D* Kumler, J. Am* Chem. Soc., 67, 1905 (3955)1 C7 Beckett, K* Pitzer, and R» Spitzer, Ibid* 69* 2588 (1957)* * 8. H. Earing* J. to. Chen. Soc., Sk* >JL?1 (1932){ R. Spitzor and R. M. Huffman, ibid.. 69, 211 (19>|9)| J. D. K**p and K. S. Pitaar, 4 , (1936). 9* G* Beckett* K. Pitzer, and R. Spiizer, J. Am* Chem. Soc., 6g, 977# 2588 (1957)* 10* Re P* Linstead, R,B. Whitstone, J* Ohm* Soc*, 1950* 1528$ A* L. Wilds, Paper presented before the Dir* of Org. O hm * of the American Chemical Society, New Xork, N*X*, Sept* 1951* 11* fl* Sachs©, Ber„ 2J, 1363 (l890)|Z.phyoik. 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