I. REACTIONS OF ORTHO~SUBSTITUTED AROYL

CHLORIDES WITH TlUALKYL PHOSPHITES

II. SOME SYNTHESES OF OPTICALLY

ACTIVE PHOSPHORUS COMPOUNPS

By

DONALD HOWARD BURPO Ji Bachelor of Science Bethany Nazarene College Bethany, Oklahoma 1963

Master of Science Oklahoma State University Stillwater, Oklahoma 1965

Submitted to the faculty of the Graduate College of the Oklahoma State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May, 1968 OKLAHOMA STATE UNIVERSITY LIBRARY OCT 24 1968

I. REACTIONS OF ORTHO- SUBSTITUT ED ARO¥.J.. .. ,, •· •.. ''"'!-· ··· ... . . ,. ·· ,· .. -. . -. "!.- .. 4 ,,., ... ,: • ...•. , ...... CHLORIDES WITH TRIALKYL PHOSPHITES

II. SOME SYNTHESES OF OPTICALLY

ACTIVE PHOSPHORUS COMPOUNDS

Thesis Approved :

Thesis Adviser

688235 ii .ACKNOWLEDGMENTS

The author would like to express gratitude to his wife, Kay, for

'her understanding and encouragement and to his advisor, Dr. K. Darrell

Berlin, for guidance and encouragement during the course of this in­

vestigation. , Appreciation is also extended to Dr; Rolando U. Pagilagan

for assistance at the outset of this work.

Indebtedness is acknowledged to the Public Health Service and the

Oklahoma State University Department of Chemistry for financial aids in

the form• of research and teaching assistantships, respettively.

iii TABLE OF CONTENTS

Page

INTRODUCTION...... , . . , . . , , . , . . , . . . . , , . ix

Part

I. REACTIONS OF ORTHO-SUBSTITUTED AROYL CHLORIDES WITH TRIALKYL PHOSPHITES, 1

II. SOME SYNTHESES OF OPTICALLY ACTIVE PHOSPHORUS COMPOUNDS ...... 49

iv · PART I

REACTIONS OF ORTHO-SUBSTITUTED AROYL

CHLORIDES WITH TRIALKYL.PHOSPHITES

V' TABLE OF CONTENTS

Chapter Page

.PART I

I. HISTORICAL ••••..• oeoa•••• 1

Michaelis-Arbuzov Rearrangement. 1 Gyclizations InvolvingTrivl;llent Phosphorus Compounds .••.•••.•.• 4 3lp Spectra of Related Compounds • 10

II. DISCUSSION OF RESULTS AND CONCLUSIONS •• 11

III. EXPERIMENTAL. 27

Preparation of o-Phenylbenzoyl Chloride (I). 27 Preparation of Dimethyl Arpylphosphonates (VI...;IX). 28 . Reaction (1: 1) of Trimethyl Phosphite with Phthaloyl Chloride (V) - Run. 1 ••••. 28 Reaction. (2:1) of Trimethyl Phosphite·with Phthaloyl Chloride (V) - Run2 •••••. 29 Thermal Decomposition of Dimethyl 3-Chloro­ phthalidylphosphonate (X) •....•....•• 29 · Reaction. of Triethyl Phosphite with Phthaloyl Chloride (V) •••••• 30 · Reaction of Tri~n-Propyl Phosphite with . Phtha,loyl Chloride (V) • 30

BIBLIOGRAPHY 43

vi LIST OF TA:8LES

·· Table Page -1 . I, IR Absorption Maxima (cm. ), of Dimethyl Aroylphosphonates 22

. II. Proton NMR Data for Dimethyl Aroylphosphonates 23

III. Proton NMR Data for Dimethyl 3-Chlorophthalidyl- phosphonate .•••.•.•.••..•.•• 24

IV. Prepara.tion and Properties of Aroyl Chlorides. 25

V. Preparation and Properties of Dimeth)l Aroylphosphonates, RC(O)P(O)(OCH3) 2 •••..•••.• , • 26

vii LIST .OF ILLUSTRATIONS

.Plate Page

Infrared Spectra

. I. _£-Phenylbenzoyl Chloride (I), Film .on NaCl Plates. . • . • • 32

II. Dimethyl _£-Phenylbenzoylphosphonate (VJ!), Film on NaCl Plates. • • ...... 33

. III. · Dimethyl a-Naphthoylphosphonate (VII), Film.on NaCl Plates.. • . . • • • . • . . • . . . • • • • . 34

IV. Dimethyl Mesitoylphosphonate (V:tII), Film.on NaCl Plates •.•.• , •. 35

Dimethyl.o-Anisoylphosphonate. (IX), v. . · Film on- NaCl Plates •.••.••. 36

VI. Dimethyl 3-Chlorophthalid,ylphosphonate (X), KBr Pellet 37

. Nuclear Magnetic Resonance Spectra

VII. Dimethyl _£-Phenylbenzoylphosphonate (VI) • 38

VIII. Dimethyl a-Naphthoylphosphonate (VII). • 39

IX. Dimethyl Mesitoylphosphonate (VIII). 40

x. Dimethyl o-Anisoylphosphonate (IX) .. 41 - . XI. ,Dimethyl 3-Chlorophthalidylphosphonate (X) 42

viii INTRODUCTION

The thesis is composed of two distinct sections. Each major part

is presented separately with individual subsections and is thus com­

plete within itself.

Acid chlorides and trialkyl phosphites react in a Michaelis-

. Arbuzov reaction with the formation of compounds containing C-P bonds.

Evidence is provided in Part I that phthaloyl chloride and trimethyl

phosphite g;ive·a new phosphorylated heterocycle in an unusual cycliza­

tion process. The mechanism of the reaction and structure determination

of the products are discussed.

Several new optically active organophosphorus compounds were

synthesized as described in Part II. Synthetic methods outlined include

formation of P-0 and. P-N bonds via nucleophilic displacement reactions

on phosphorus by the oxygen and nitrogen atoms of alcohols and amines.

In all cases optical activity, in the products resulted from an asym­

metric center in the alcoholic or amine portion of the molecule rather

than an asymmetric phosphorus atom.

ix CHAPTER I

HISTORICAL

·The Michae1is-Arbuzov Rearrangement

Since 1898, when the reaction of trialkyl phosphites with alkyl 67 halides to yield phosphonates was discovered by Michaelis and Kaehne, the Michaelis-Arbuzov rearrangement has been one of the most versatile methods for the formation of carbon-phosphorus bonds. This reaction

+ + RX has been extended to other trivalent-phosphorus esters for the synth~sis of phosphinic esters and phosphine oxides. The order of reactivity of trivalent-phosphorus esters in this reaction has been demonstrated to be phosphite < phosphonfte < phosphinite. 88 The usual reactivity sequence of the halide is: secondary alkyl< primary alkyl< aGyl, and chloride< bromide< iodide, 42 Several reviews on the scope and limita- tions of this rearrangement and related reactions may be found in the

11.tera. t ure. 8,42,47,54,55 2 A two-step mechanism was first proposed by Arbuzov. Crystalline

R' .. I -P-OR + R'X - P--.0 + RX I I

1 2

1:1 adducts, which decompose to phosphine oxides upon warming, were isolated from low-temperature reactions of alkyl dialkylphosphinites with alkyl halides. 89 The degree of ionic character in the quasiphos- . . . d. . . 42 ph onium interme iate is uncertain.

In the first step of the rearrangement, an assumed SN2 mechanism with primary halides has not been established by the existing kinetic 42 and stereochemical data. When some optically active secondary halides were heated with triethyl phosphite, the halides underwent extensive racemization in preference to furnishing the expected phosphonates.as

shown below, 35 Ari SNl mechanism for the first step has been suggested

+ +

e I

for the fast-;te,act;ing benzhydryl arid 9-fluorenyl bromides93 and triaryl- . 42 methy], halides.

· Stereochemical evidence for inversion of configuration in the

attack of the halide ion on the alkyl carbon of the ester has been . 15-17 35 57 35 reported by various workers. ' ' Gerrard and Green, using

tri-2-octyl phosphite prepared from (+)~2-octanol, found that reaction 3 with ethyl iodide proceeded_with inversion to yield (-)-2-iodooctane.

· From treatment of benzyltriphenoxyphosphonium chloride with optically 57 . active 2-octanol, Landauer and Rydon obtained 2-chlorooctane of the

inverted.configuration .. Presumably interchangeof an octyloxy for a

phenoxy group was followed by an inversion step in the decomposition

of the quasiphosphonium salt.

A series of bicyclic phosphonates were synthesizedby reacting

_l-phospha-2,8,9-trioxaadamantane with sever,1:11 alkyl halides. 16 , 17

Cl + RCl

An equatori_a_l chl_orine · in the bic.yclic phosphonates,. indicated by IR,

mm.,. and clipole moment studies, suggested an 8N2 displacement by chlor-

ide ion at a bridgehead atom in the quasiphosphonium intermediate.

Recently, Berlin and coworkers15 reacted trans=4-,!-butylcyclohexyl

diphenylphosphinite v1ith benzyl chloride and with carbon tetrachloride.

In both reactions, ~-4-,!-but,ylcyclohexyl chloride and none of the

trans-isomer was produced. This: is indicative of a· stereo specific

-inversion at the C-1 position as expected if a Michaelis-Arbuzov

H Cl 4 reaction followed an SN2 mechanism in the last step.

·The acid chlorides of a series of long-chain aliphatic dibasic acids and trimethyl phosphite react to give tetramethyl diphosphonates

in. near 1y quantitative. . yie· ld s. 68 When trimethyl phosphite was added to terephthaloyl chloride, the reaction apparently proceeded as expected

to form tetramethyl terephthaloyldiphosphonate. 95 However, the product

76 was not isolated. Only tar was reported for the vigorous reaction of

triethyl phosphite with maleoyl chloride. Addition of a trialkyl phos-

phite to either oxalyl chloride or phosgene yielded not the expected

diphosphonate, but instead the phosphorochloridate, carbon monoxide,

and alkyl halide. 42

0 II C-Cl (R0) 3P + I [or coc1 2J--=+ (Ro) 2P(O)Cl + zco + RCl C-Cl II 0

Cyclization.s Involving Trivalent Phosphorus Compounds

.. 13 30 31 63 73 77 80 In recent years several reviews ' ' ' ' ' ' of the chemis-

try of cyclic phosphorus compounds have appeared. These reviews

describe the synthesis and reactivity of phosphorus heterocycles con-

taining· · ot h er h etero atoms, 30 eye 1·ic systems f orme d f rom car b ony 1 5

73 77 80 compounds • ' and systems based on phosphorus and carbon as the . 13 63 77 only ring atoms. ' '

A variety of carbonyl-containing compounds (which possess electron- withdrawing groups adjacent to the carbonyl group) react with trivalent- 69,86 phosphorus esters. Monocarbonyl compounds of this type, such as 86 perfluroacetone, are reported to produce 2:1 adducts (1 1 3,2-dioxaphos- pholanes) with phosphines or trivalent-phosphorus esters. A 2:1

85 adduct formed from reaction of acenaphthenequinone with trimethyl . 81 82 phosphite. Addition of phosphorus esters to ortho-quinones, '

0

. 56 81 82 84 84 a-diketones, • ' a-ketoaldehydes, and triketones led to 1,3,2- 80 dioxa-4-phospholenes. An example of this ring system is that pro- duced by reaction of triisopropyl phosphite with phenanthrenequinone.

The structure of this compound was confirmed by IR and Raman spectra, proton and 31P NMR spectra, and X-ray analysis. Not only phosphites but also triphenylphosphine, alkyl diphenylphosphinites, and dialkyl 6

0 + P(OR) 3 0

phenylphosphonites86 add~d to phenanthrenequinone to give 1,3,2-diox~-

4-phospholenes.

Ramirez · 80 note d tat h a 3 : 1 mo 1 e ratio. o f propiona. ld eyeh d an d

trimethyl phosphite, when stirre,q for 14 days at 20°, yielded a 2: 1

adduct (a 1,4,2-dioxaphospholane). An a,S-unsaturated ketone, 3-

benzylidene-2,4-pentanedione, and tri'methyl phosphite condensed to form 83 the_phosphbrus heterocycle shown below.

o"-. /p'-- H CH3o I ucH3 OCH 3

Cye 1izations. · 31 o f a,wmIII d"fi unctiona. 1 organic. compoun d s wit. h

trivalent-phosphorus halides or esters give rings containing two hetero-

atoms. Included in the studies were aliphatic diols, dithiols, dia~

mines, and their aromatic counterparts. 7

XH x ( -2HZ ( \ + Z PR" ~.',t~~~r-;~.; P-R II (eR' )n 2 (e:R' )n I XH x

Aliphatic and alicyclic diols react with phosphorus trichloride to produce cyclic phosphorochloridites. 3- 6 Most attention30 has been devoted to 1,2- and 1,3-diols, which give rise to the 1,3,2-dioxaphos- pholane and 1,3,2-dioxaphosphorinane ring systems, respectively. These

same ring systems result from reaction of diols with phosphorodichlori­ dites,4'7 catechol with phosphorus trichloride, 30 and diols with tertiary. p h osp h"ites 10,36,71 or d"ia lky 1 p h osp h"ites. 71 Transesterifica- . 19 25 tion has also been applied to the preparation of bicyclic systems ' ' 27 32 . ' from triols and tertiary phosphites.

Some unusual ring systems containing phosphorus and nitrogen have been synthesized recently.· A cyclic product was formed from dichloro­ phosphines and esters of oxalodiimidic acid. 28 Cyclization of a ROYN.\ ,,l. P-R' ROI N./ triaminewith phosphorus trichloride afforded 2,6,7-trimethyl-4-methyl-

2,6,7-triaza-l-phosphabicyclo[2.2.2]octane.58 An even more unusual .,, CH 3 \ R3R.~... Ni Ip ,__ __ N 'CH3 8

heterocycle results from reaction of an aromatic ortho-diamine with

trip. h eny 1 p h osp h..ite. 74

Trivalent-phosphorus halides generally add to dienes producing 13 77 phospholenes. ' Phosphorodichloridites, phosphorodibromidites, and

cyclic phosphorochloridites condense with dienes to give initially what 77 91 is thought to be an aryloxy- or an alkoxyphosphonium salt. The

latter adducts decompose giving an alkyl halide and a 3-phospholene

l-oxide. 1' 90 Likewise phosphonous dihalides64- 66 and phosphorus

0

+ RX C\x

trihalides9 , 44 add to dienes yielding phosphonium salts. Both 2- and

3-phospholene structures are reported from this reaction when the

h a 1 ogen is. c h l orine.. · 44, 7 8, 7 9

Carboh.,..,phosphorus heterocycles13 have also been synthesized by

treating a,.W-difunctional compounds, such as dihaloalkanes, di-Grignard

. reagents, di-lithium reagents, and dialdehydes with an appropriate

trivalent-phosphorus compound. Both 1,4- and 1,5-dihaloalkanes react

with dilithium salts of phosphonous diha1ides to produce phospholanes . 49 50 39 40 and phosphorinanes, respectively. ' Di-Grlgnard reagents ' or 9 0-R 0-R

60 61 98 . di-lithium reagents ' ' with phosphonous dihalides likewise have provided the above ring systems and even 7-membered rings. 61 Dialde- hydes react with secondary phosphines and hydrochloric acid to give ph osp h onium. sa 1 ts, 20 wh' i l e p h osp h'ine pro d uces spirans. · 21

OH OH q@ 0 e P~, Cl PRz ,Cl

OH OH OH OH OH OH

Intramolecular cyclization is another method for synthesizing 13 phosphorus-carbon heterocycles. Examples obtained include phosphonium salts by an intramolecular cyclization, 51 phosphinic esters by an intra­ molecular Michaelis-Arbuzov rearrangement, 45 and tertiary phosphines by irradiation of secondary alkenylphosphines. 26 An intramolecular aro- matic substitution resulted in formation of a substituted phosphanthra- 29 cene.

ZnClz • 10

31P Spectra of Related Compounds

A few general review/4 , 33, 53, 7o, 75 , 96 of 31P spectra are availa-

ble. In phosphoryl compounds, each substituent on phosphorus appears

to make a given contribution to the total shift. 96 Shielding by sub-

st1tuents. h as b een sown h exper1menta. 11 y 96 to occur 1n· t h e or d er:

Se< S < aliphatic C < aromatic C.R:1 P < N.R:1 Cl < H < 0 < F. With the

exception of hydrogen and phosphorus, the above order is that of

increasing electronegativity,

The chemical shifts for a series of phosphonic acids96 and phos- 34 94 96 phonates · ' ' have been discussed and recorded. These compounds

offer a direct way to measure the relative electron-donating ability of

organic groups, •ince carbon is attached directly to phosphorus iri these 96 compounds. As with other phosphoryl compounds, the stronger electron-

donating groups cause reduced shielding of the phosphorus nucleus.

The above correlation has been demonstrated for a series of 20 or 34 96 more dialkyl phosphonates. ' The chemical shift (p.p.m.) relative

. to 85% orthophosphoric acid and the organic group linked to phosphorus 96 are given here for a few diethyl phosphonates: benzoyl (+2::1::1),

acetyl (+2±1), 96 dimethylcarbamyl (0±0.5), 96 trichloromethyl 96 34 34 (-6.5±0.5), dichloromethyl (-9.3), chloromethyl (-18), and

methyl (-30±1). 96 CHAPTER II

DISCUSSION OF RESULTS AND CONCLUSIONS

Trialkyl phosphites were allowed to react with ortho-substituted aroyl chlorides with the intention of preparing ortho-substituted dialkyl aroylphosphonates VI-IX. It was thought that rotation around the carbon-phosphorus bond might be hindered sufficiently by the ortho- substituent to create nonequivalent magnetic environments for the two alkyl groups. However, the ortho-substituted aroylphosphonates pre-

R

VI VIII

VII IX o-CH OC H - - 3 6 4

pared did not show a nonequivalency of alkyl groups at room temperature.

The products X, XVII, and XVIII from the reactions of phthaloyl chlor- ide with trialkyl phosphites contained nonequivalent alkyl groups in unexpected phosphorylated heterocycles.

11 12

0

Cl P(OCH 2CH 2CH 3) 2 x XVII XVIII

The aroyl chlorides used were as follows: _£-phenylbenzoyl chloride

(I), a-naphthoyl chloride (II), mesitoyl chloride (III), ,£-anisoyl chlor~de (IV), and phthaloyl chloride (V). Compounds I-IV reacted with trimethyl phosphite to produce dimethyl aroylphosphonates as expected 11 18 42 for the Michaelis-Arbuzov rearrangement~, ' • The dimethyl aroyl- phosphonates prepared were: dimethyl _£-phenylbenzoylphosphonate (VI), dimethyl a-naphthoylphosphonate (VII), dimethyl mesitoylphosphonate

(VIII), and dimethyl _£-anisoylphosphonate (IX).

The IR spectral data for the dimethyl aroylphosphonates VI-IX listed in Table I (Plates II-V) correlate well with data described 18 elsewhere, Berlin and Taylor reported that IR spectra of some di- methyl aroylphosphonates showed absorption for conjugated carbonyl -1 -1 (1639-1672 cm. ), phosphoryl (1258-1269 cm. ), and the P-0-C linkage -1 (1031~1036 cm. ). The IR spectra of compounds VI-IX display similar -1 peaks for conjugated carbonyl (1645-1675 cm. ) , phosphoryl (1260 ,, -1 -1 cm. ), and the P-0-C linkage (1025-1035 cm. ). 13

NMR data for compounds VI-IX, listed in Table II (Plates VII-X), lend additional support to the proposed structures. The dimethyl aroyl- 18 phosphonates prepared by Berlin and Taylor exhibited doublets in the region of 03.80-3.90 with a JP-O-C-H coupling constant of 11 c.p.s. for the methyl ester protons. Corresponding doublets in the spectra of compounds VI-IX are in the region of 63.68-3.88 with an identical

JP-O-C-H coupling constant of 11 c.p.s.

The magnetic equivalence of the methyl ester groups at room tern- perature indicates free rotation around the carbon-phosphorus bond.

Examination of molecular models suggests a possible slow rotation around the aryl-to-carbonyl bond and a resulting free rotation of the carbon-phosphorus bond, The relatively large upfield chemical shift

(63.68) for the methyl protons in VI compared to that (63.82) 18 in dimethyl benzoylphosphonate suggests a probable shielding component on the methyl protons arising from the magnetically anisotropic ortho- . 52 p h eny 1 su b stituent.

Addition of trimethyl phosphite to V (1:1 mole ratio) and inverse addition of V to trimethyl phosphite (1:2 mole ratio) gave 64% and 40% yields, respectively, of dimethyl 3-chlorophthalidylphosphonate (X).

An ortho-substituted dimethyl aroylphosphonate structure XI was originally expected for the former reaction (1:1 mole ratio) and a tetramethyl phthaloyldiphosphonate structure XII was considered possible for the latter reaction (1:2 mole ratio). It seems reasonable that production of X in both reactions followed a similar pathway. A 14

Cl

XI XII possible mechanism for the formation of Xis depicted, It is presumed that the close proximity of the second aroyl chloride group results in a ring closure step prior to loss of chloromethane.

0

A very similar compound, diethyl phthalidylphosphonate (XIII), also h as b een prepare d b y ring. c l osure. 87 Reaction of ortho-phthalaldehydic acid with diethyl phosphite (or diethyl hydrogenphosphonate) is thought to produce a phosphorylated intermediate which then condenses to give

XIII. 15

r8YCOOH

~CHO +

XIII

31 1 The IR (Plate VI), P NMR, and H NMR (Plate,XI and Table V) spectral data for X support the proposed heterocyclic structure. Rather strong IR absorption was found for C=O (1~03 cm~ -.1) ;: P--0 (12~7 and. -1 -1 1273 cm. ), and P-0-C (1047 cm. ). This absorption is reminiscent for that observed for dimethyl phthalidylphosphonate (XIV): C=O -1 -1 (1787 cm. ), p-+Q (a doublet peak at 1281 cm, ), and P-0-C (1041 -1 87 cm. ). Carbonyl group absorptions for the dimethyl aroylphosphonates

XIV -1 VI-IX occurs in a markedly different range (1645-1675 cm. ); see

Table I. 16

The 31 P NMR spectrum (benzene; 20% w./w.) of X displayed a septet at -9.7 p.p.m. relative to 80% phosphoric acid, which approximates that for diethyl dichloromethylphosphonate (neat; -9.3·,p.p.m.). 34 It should be noted that both alkylphosphonates contain two electron-withdrawing substituents on the carbon linked to phosphorus, Compound XIII, which contains one electron-withdrawing oxygen atom on the carbon linked to phosphorus, gives a multiplet in the 31P NMR spectrum at -13.2 p.p.m. relative to 85% phosphoric acid. 12 The 31 P NMR signal for diethyl benzoylphosphonate (XV) (neat; +2 p,p,m.) 96 is significantly upfield from that for X.

xv

Proton NMR spectra of X revealed a JP-O-C-H coupling constant of

11 c.p.s. in several solvents at 60 or 100 M.c.p.s. (Table III).

Siddall and Prohaska92 observed a similar temperature effect upon the separation,~' of the chemical shifts for the methyl group protons in both XIII and diisopropyl phthalidylphosphonate (XVI) when the compounds

XVI 17 were examined neat or in deuterochloroform. Inherent asymmetry arising from the asymmetric carbon atom creates nonequivalent environments for the two methyl groups. Presumably a wagging process of the 5-membered ring as well as rotations around the C-P~O-C linkages could be opera- tive at room temperature. However, the magnitudes of 6 (Table III) for carbon tetrachloride and perchloroethylene solutions (near room tempera- ture) were large, 39 and 41 c.p.s., respectively. This suggests a significant population of a molecular conformer having methyl groups with different spatial relationships to the magnetically anisotropic . 52 97 b enzene ring. In another report, a similar argument has been made with respect to the nonequivalence of the methylene protons of 1- phenylethyl benzyl ether; fairly large changes in 6 were observed with variation in solvent. From examination of a molecular model of X it is possible to hypothesize the existence of a given preferred conformer.

(see below). This conformer conceivably may be stabilized by an

CH3

1\-.;.....p~~o

:o ' CHJ

0 Cl

electrostatic attraction between the phosphoryl oxygen and the carbonyl carbon. The nucleophilic nature of phosphoryl oxygen with respect to car b on centers is.. in d' icate db y severa 1 reactions.0 22,23,37,43,48,59,62 37 An example is that of benzyl methylphenylphosphinate with phosgene 18 to give carbon dioxide, methylphenylphosphinyl chloride, and benzyl chloride. The following mechanism was considered most probable by 37 Green and Hudson.

180R" I ,Jr e RR' p->Q + --+ RR'P-OCOCl + Cl

0 f'" Q t ---+ co 2 + RR'P + Cl RR'P + R"Cl I I Cl Cl 59 Another example . is shown below.

When the approximate positions of the two methyl groups in the above 52 conformer of X are placed on the plot by Johnson and Bovey for the magnetic anisotropic effect of the benzene ring versus distance from

the benzene ring, a!::. value of 41 c.p.s. is obtained. This approximate

value agrees well with those found for carbon tetrachloride and per-

chloroethylene solutions near room temperature (Table III). The!::.

value observed when the temperature is raised to 100° suggests a large

population of molecules in which free rotation occurs around the P-0-C

linkages but the phosphoryl oxygen and the carbonyl carbon remain in a

relatively fixed spatial relationship. In dimethylformamide, the

existence of solute-solvent electrostatic interactions may destroy the

rigid conformation. In addition to intramolecular steric interactions

in X, the solute-solvent steric interactions may lead to a new 19 conformation. This is supported by the relatively large 6 value which

indicates a large population of molecules in which the two methyl

groups are in different average positions with respect to the benzene

ring.

Thermal decomposition of X occurred at 190° with the formation of

considerable tar, phthalic anhydride, and dimethyl phosphorochloridite.

The phosphorus compound was converted into dimethyl hydrogenphosphonate

by the action of moist ether. It is interesting to note that only tar

was reported from the vigorous reaction of maleoyl chloride with t.ri- . 42 et h y 1 p h osp h1.te. Decomposition of X to give phthalic anhydride and

dimethyl phosphorochloridite may proceed by a pathway similar to that

0

x --~

0 0

. ~ + : P(OCH3) 2 ·- ... ~ • OCH3)2 ~o I /'f Cl ~O Cl 0

37 proposed by Green and Hudson for the reaction of benzyl methylphenyl-

phosphinate with phosgene as discussed previously.

Reaction of V with triethyl phosphite or tri-~-propyl phosphite

gave oils which could not be induced to crystallize. IR absorption of -1 the first oil occurred for C=O (1805 cm. ), P--0.(1272 and 20

-1 -1 1248 cm. ), and P-0-C (1024 cm. ··), Peaks in the IR spectrum of the second oil were existent for C=O (1800 cm.-\ P"'O (1270 and. 1244 cm. -l), -1 and P-0-C (1001 cm. ) . NMR signals of the former oil indicated two nonequivalent ethyl groups [triplets at 61,13 (J = 7 c.p.s.) and 61.45

(J = 7 c.p.s.) and multiplets at 64.02 and 64.42] while those of the latter oil indicated two nonequivalent n-propyl groups [triplets at

60.77 (J = 7 c,p.s.) and 60,98 (J = 7 c.p.s,) and multiplets at 61.43,

61,Jl, 63,89, and 64.35]. Attempted vacuum distillation of either oil gave phthalic anhydride and the respective dialkyl phosphorochloridite.

The obvious similarities of spectral data and decomposition products of the oils to those for X suggest that alkyl homologs (XVII and XVIII) of

X were produced.

In summary, a series of or tho- substituted dimethyl aroylphospho.,,._, ·: . nates were synthesized and characterized. Magnetic equivalence of the methyl ester groups indicates free rotation around the carbon-phosphorus bond at room temperature in most of the cases examined. In the excep- tion, reaction of phthaloyl chloride. with trimethyl pho sphite produced a novel phosphorylated heterocycle which was characterized by elemental analysis and spectral data. Mechanisms for cyclization and decomposi- tion to phthalic anhydride and dimethyl phosphorochloridite are suggest- ed. In dimethylformamide, the magnitude for 6 indicates a large popula- tion of molecules in which the two methyl groups are in different average positions with respect to the benzene ring. A given molecular conformer is hypothesized to exist in significant quantity in carbon tetrachloride and perchloroethylene at room temperature. A large popu- lation of molecules having a relatively fixed spatial relationship of the phosphoryl oxygen and the carbonyl carbon is suggested to explain 21

the slight change in the NMR spectrum of the perchloroethylene solution when the temperature is raised to 100°. Formation of alkyl homologs of

Xis proposed in view of the obvious similarities of spectral data and

decomposition products to those for X. 22

TABLE I

IR ABSORPTION MAXIMA (cm.-l) OF DIMETHYL AROYLPHOSPHONATES

RC(O)P(O) (OCH) 2

Cpd. R Plate C=O p-+O P-0-C

VI _£-C6H5C6H4- II• 1660 1260 1025

VII l-C10H7- III 1645 1260 1035

VIII 2,4,6-(CH3) 3c6H2- IV 1675 1260 1025

IX _£-CH 3oc6H4- v 1650 1260 1030 23

TABLE II

PROTON NMR DATA FOR DIMETHYL AROYLPHOSPHONATESa

RC(O)P(O)(OCH3) 2

0' 6 6 Ester Aromatic Other' Cpd. R Plate Protons Protons Protons

-_iVI £_-C6H5C6H4- VIr 3.68d 7.13,-8.17 ·vII 1-G H - VIII 3.88d 7.40-9.02 10 7 VIII 2,4,6-(CH3) 3c6H2- IX 3.75d 6.83 2.22, 2.27

IX _£-CH3oc6H4- x 3. 79d 6.87-7.84 3.85

a o Spectra were obtained in CC14 solutions at 22 ; JP-O-C-H for all compounds was 11 c.p.s.; d = doublet. 24

TABLE III

PROTON NMR DATA FOR DIMETHYL 3-eHLOROPHTHALIDYLPHOSPHONATEa

0 'Temp,, · Solvent 0 CH. !::. ' Aromatic' oe. 3 - c.p.s. ' Protons He(O)N(eH3)/ 22 3.85dc 4.03dc 18d eel b 22 3.68d 4.07d 39d 7.60-7,98 4 e e2e14 27 3.59d 4.00d 41 7.49-7.93 e e2e14 100 3.58d 3.96d 38 7.45-7.98

aJ 11 c~p.s.; !::. = separation of methyl signals; d = doublet,P-O-e-H b Spectrum obtained on a Varian A-60 spectrometer.

cAn apparent triplet resulting from overlapping doublets.

dThis value was calculated by multiplying 1.67 by the!::. value (c,p.s.) obtained on a Varian A-60 spectrometer.

eSpectrum obtained on a Varian HA-100 spectrometer. 25

TABLE IV

PREPARATION AND PROPERTIES OF AROYL CHLORIDES

RCOCl

Moles Moles of of Thionyl Yield, B. p., 0 C. Cpd. R Reference Acid Chloride % (mm.)

I .£"':G6H5C6~4- 0.050 0.202 75.8 108(0.44) 38

II 1-C10H7- o. 058 0.232 86.7 131-2(2.2) 41

III 2,4,6-(CH3) 3c6H2- 0.030 0.120 84.8 57.,.8(Q.40) 41 TABLE V

PREPARATION AND PROPERTIES OF DIMETHYL AROYLPHOSPHONATES, RC(O)P(O)(OCH3) 2

Moles of Moles of 0 Analzsis % B. p., C, Yield,a 2 Acid Trimethyl t p Cpd. R (mm.) n % Chloride Phosphite D Ca led. Found

25 VI _£-C6H5C6H4- 0.020 0.024 174-6(0.70) 1. 5792 64 . 10.68 10.75 25 VII l-ClOH7- 0.025 0,028 158-61(0.25) 1. 5958 49 11. 74 11. 74 25 VIII 2,4,6-(CH3) 3c6H2- 0.026 0,030 123-5(0.21) 1. 5100 24 12.11 12.22 4 IX _£-CH 3oc6H4- 0.088 0.100 135-6(0.08) 1,534/ 56 12. 70 12.55

aYields are based on acid chloride as starting material.

N 0\ CHAPTER III

EXPERIMENTALa-e

Preparation of o-Phenylbenzoyl Chloride (I).--This compound and other acid chlorides which were not commercially available were synthe- 46 sized by the following general procedure, The results are summarized

iQ Table IV. A 100-ml,, 1-necked flask was fitted with a condenser, a

drying tube, and a magnetic stirring bar, A sample (10.0 g., 0.0505 mole) of ~-phenylbenzoic acid and 14.5 ml. (24.05 g., 0.202 mole) of

thionyl chloride were added to the flask. The mixture was stirred for

41 hours. The excess thionyl chloride was removed by simple ·

aAll melting points are corrected; all boiling points are uncor­ rected. The Skelly Solvent Fused boiled at 30-60°.

bThe infrared spectra were determined using a Beckman IR-SA spectrometer as films on sodium chloride plates or as potassium bromide pellets.

cThe microanalyses were performed by Galbraith Laboratories, Knoxville, Tennessee.

dThe proton nuclear magnetic resonance spectra were determined on a Varian A-60 high resolution spectrometer with a field-sensing stabili­ zer ("Super-Stabilizer") unless otherwise specified. Tetramethylsilane was used as an internal standard. Unless otherwise stated, the solvent employed was carbon tetrachloride.

eGas chromatographic analyses were performed using an Aerograph Hy-Fi Model A-550 with a hydrogen flame ionization detector from Wilkens Instrument and Research, Inc., Walnut Creek, California. The column used was a 6'xl/8" stainless steel column with a 6% silicone-30 sub­ strate on a 80/100 mesh, acid washed, DMCS-treated Chromosorb G support.

27 28 distillation followed by azeotropic distillation with benzene to remove

the last traces of the inorganic halide, The remaining material was distilled to yield 8,3 g, (75,8%) of material boiling at 108°/0,44 mm,

[lit. 38 99,5-101°/0.3 mm.], IR absorption (Plate I) supported the

structure,

Preparation of Dimethyl Aroylphosphonates (VI-IX).--This synthesis utilized the classical Michaelis-Arbuzov rearrangement studied by Berlin 11 14 18 and coworkers, ' ' The general procedure is described for prepara-

tion of the esters found in Table II. A 200-ml., 3-necked flask was

fitted with a condenser, a drying tube, an immersion thermometer, a pressure-equalizing addition funnel, a nitrogen inlet, and a magnetic

stirring bar. A slight excess of trimethyl phosphite was added drop- wise to an aroyl chloride under anhydrous nitrogen at such a rate that

the temperature of the reaction mixture did not exceed 40°. Efferves-

cence was noted shortly after the addition started, presumably due to

expulsion of chloromethane, The resulting mixture was stirred for 12

hours at room temperature. The products were purified by vacuum dis-

tillation, Elemental analyses (Table V) and spectral data (Tables I

and II) were used to confirm the structures of the unknown dimethyl

aroylphosphonates,

Deviation from the above general procedure was employed in the

reaction of mesitoyl chloride III, An exothermic process with efferves-

cence was not observed in the system during the addition of trimethyl

phosphite to III. Therefore the reaction mixture was immediately

heated to reflux (78)0 and held there for 2 hours.

Reaction (1: 1) of Trimethyl Phosphite with Phthaloyl Chloride

(V) - Run 1. 12 , 72--All solvents were dried, and all manipulations were 29

carried out under a nitrogen atmosphere. To 10,0 g. (0.05 mole) of

phthaloyl chloride dissolved in 125 ml. of benzene held at O0 was added

dropwise 6.2 g. (0.05 mole) of trimethyl phosphite dissolved in 75 ml.

of benzene over a period of 1. 75 hours. After the mixture was stirred

(4 hours) and boiled (1 hour), benzene was removed by distillation. An

oil resulted in which a solid formed after standing overnight. Two

recrystallizations from benzene~Skelly Solvent F yielded 8.8 g. (64%)

of X, m.p. 77.5-78.5 0 .

Anal. Calcd. for c10H10o5c1P: C, 43.75; H, 3.90; Cl, 12.82; P, 11.40.

Found: C, 43.17; H, 3.73; Cl, 12.75;

P, 11.03. 31 1 The IR spectrum, P NMR spectrum, and H NMR spectra (Table III)

confirmed the structure of X. Absorption in the IR (Plate VI) occurred -1 -1 -1 for C=O (1803 cm. ), p-+Q (1287 and 1273 cm. ), and P-0-C (1047 cm. ). 31 A signal in the P NMR spectrum (benzene; 20% w./w.) occurred as a

septet at -9.7 p.p.m. relative to 80% phosphoric acid.

Reaction (2:1) of Trimethyl Phosphite with Phthaloyl Chloride (V) - 12 72 Run 2. ' -oa.Anhydrous solvents and a nitrogen atmosphere were used as

0 in Run 1. To 12.4 g. (0.10 mole) of trimethyl phosphite dissolved in

70 ml. of benzene was added dropwise 10.0 g. (0.05 mole) of phthaloyl

chloride dissolved in 50 ml. of benzene. After heating (3 hours) the

mixture at 60°, benzene was removed by distillation. Upon standing

overnight the resulting oil partially solidified, Recrystallization

of the solid from benzene-Skelly Solvent F produced 5.5 g. (40%) of X.

Thermal Decomposition of Dimethyl 3-Chlorophthalidylphosphonate

(X). 12 •72--When dimethyl 3-chlorophthalidylphosphonate was heated to 30

190°, decomposition occurred with formation of considerable tar, a low- boiling fraction, and a high-boiling component. The latter was charac- terized by mixture melting point determination and IR and NMR analyses as phthalic anhydride. The low-boiling fraction gave a positive test for chloride ion (silver nitrate). When this fraction was added to moist ether and subsequently analyzed by GLC, the major component was identified as dimethyl hydrogenphosphonate.

Reaction of Triethyl Phosphite with Phthaloyl Chloride (V). 12 •72--

The procedure was essentially the same as that for the reaction (1:1) of trimethyl phosphite with V. Deviations are now described. The addition was carried out at room temperature and boiling was continued for 2 hours. The product was an oil which could not be induced to crystallize With benzene~Skelly Solvent F. -1 The IR spectrum of the oil exhibited peaks for C=O (1805 cm. ), -1 -1 p-+Q (1272 and 1248 cm. ), and P-0-C (1024 cm. ). NMR analysis indi- cated 2 nonequivalent ethyl groups [triplets at 61.13 (J = 7 c.p.s.) and 61.45 (J = 7 c.p.s.) and multiplets at 04.02 and 64.42].

Attempted vacuum distillation of the oil at 145° resulted in ther- mal decomposition. Product analysis was analogous to that used for the

pyrolysate from thermal decomposition of X. In this case diethyl hydro-

genphosphonate was identified by GLC analysis of the moist ether

solution. Again the high-boiling component was characterized as phtha-

lie anhydride.

Reaction of Tri-n-propyl Phosphite with Phthaloyl Chloride

(v)._ 12 •72--The. proce d ure was essentia. 11 y t h e same as tath f or t h e

reaction (1:1) of trimethyl phosphite with V. Deviations are now

described, The addition was carried out at 55° and heating at 55° was 31 continued for 7 hours: The product was an oil which could not be induced to crystallize with benzene~Skelly Solvent F.

Peaks in the IR spectrum of the oil were exhibited for C=O (1800 -1 -1 -1 cm. ), P-,Q (1270 and 1244 cm. ), and P-0-C (1001 cm. ). A complex

NMR spectrum indicated 2 nonequivalent _g-propyl groups [triplets at

00.77 (J = 7 c.p.s.) and 00.98 (J = 7 c.p.s.) and multiplets at Ol.43,

Ol.71, 03.89, and 64.35].

Attempted vacuum distillation of the oil resulted in decomposition producing considerable tar, a low-boiling fraction, and a high-boiling component. The low~boi1ing fraction gave positive tests for both phosphorus and chlorine. As suspected~ the high-boiling component was characterized as phthalic anhydride. Plate I

WAVENUMBER CM ' 700 650 : ! l I :lj I l I !1 : ! I I 100 : : : : : : : : : . : : . : .. : . ~· .. : . : :·: . : : ·::.;--.K.·: .. : : : : . : . : : : : .. : : · ·; .. : . : 'I ·:: : : . : ·::: : ·:: : ·:: : : : , : : : : : : : : : I:: 100 Ift::: __:L:,,.;,...:: I l ·:·: t 1s._ I --.. ~I·.1:· . ·:1. .. : I__:__::: l :::: I...... ' I ··,.I -: I :-"': 1-~:I l -~:' I ...'. l _:::...... :...... :::l I :::: I :::: I :::: I :::'. I ::::l :::.:'I so f I · I L' I I I \I ,q I: I I '. ,.-, , r: ', I I I V V Ill I I I I ,r: I I: I I I .. : I : : I : . : : I : : : : I 90

BOl---'-'-'-l-'--'-'-~-'-CIL.-'-1-'-'---'-+-'--'--+~..;_-+---'--'-4-~-'-+-+--'-IHl-+-'-l'--l'+-'~'--+-~'-'-+--'-1--,-++-'-+-ll---'--~f---'-'-'-:-'--'----!~~-'-t-'-lr--+-'-~---!--'--~-+-'-'-+--+-'----'-+-'-'--f-c-Hf--'-:-+-'-,---'-+--'-f--+--,--,-;-; BO

70

70~m=tfflR~Btiin~~m60 60

sol----'-'-l-----'-~-'---'--'-l-'-'--·'-+-'-~-+--'----l-"-----'-41--+--'-+--+~-+-'--'--+-'-'-'--+-..;_'--+--'-+++--'-~l---'-~f--'--~-'---'---!..;_'-'--'-+-'--'-4+~--l--+-'--~-+~-'-\#--'--'\.C-+--+----'-+-'-+-+-+----~.f.....;_'-'-+-+-'-'-l 50

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,oi...:..'--....+'----'-:..l-'--'--+----..C..:j...:..'---J.'--~:..l-'--~+l,l--~l--4f.,--+~-,---t---'--'---r-----'-l--'---,-f-,---'--+~--'-f-'~'-'-t---i-,--'--f-,-~'--j--'---'-i-'1:1---'-j-----'----t-,---,-'-t--:-:--'--t-,~c'""t--"C;"--t-,-:-:-:-t":"'-J-:-:-'."Ti 30

20

w++ttt=t=ti±±n=fDRITI+~lli±ilirrrnmfurr10!-'----'-~-'---'--'-l~'-'-'-+-'-'-'--+-'-..;_-+-'--'---'-+---'---'-+---'----'-+-'-'-'--+-~-~+-..;_;....:..+-~-'-l----'-'-l-'----'-'-:-f----'--'-l-'---'--'-l..;_;....:..-+_;_-'--+-'---,---+-'-'--'--+-f---'---+-'-'--'-'-+-'f----'-+-'-'-'-'-+-..;_;....:..+-_;_-'-l---'-'---l-'--'-+-H 10

Ol-'--'-'-'-:--'---'--'-l..;_'-'--+-'---,--+--'..;_-+~-'--+-'---'---+-'--"--+-'-'-'-:-+-~'--+--'-~t--'--'-l--~~;.-..c...:.i-,-f-----,---!~'---'-1-'-'---+-'--,-'-+c--:-..;_-+'-:--'-'-+-'---'---+-'-----'-+-'--,-'-:-+-..;_'---+-'-:-f--t-'-:--'-l----'-'-l-'-+--H 0 I ' ; I i , i JI 10 11 12 13 14 15 16

· 'WAVELENGTH IN MICRONS

£-PhenylbenzQyl Chloride (I), Film on NaCl Plates

w N Plate II

WAVENUMBER CM I

sooo Aooo 3000 zsoo 2000 1soo 1400 1300 1200 1100 ;ooo 900 soo 100 &so

. ~ . : . . . w -- ~--,--j~+-;--.;-;-J-c-c--;---;--j-'--:-;--+

60 -

, , , , , , , , : , : : , : : ,1=- 20 TTn 'TT , , , , , , , , , , , , , ,-,'3 ,,,11- -:

10 nn H ,f ,,_ ) j '.: '.: \ ~~: :- ~- ,;,, ., " ii 1; i! Ji 1iJJ Jtii H?t~ =~:= ~: 0 :JI 1~ ,,, '::: ,_,,, :;1_; llil lili lJtJ.JI~~i~~}~_-- - 0 10 11 12 13 -14 15 16

WAV~LENGTH. IN· MICR.ONS

Dimethyl ~=Phenylbenzoylphosphonate (VI), Film. on NaCl Plates

w w Plate III

Wlt[N lfO.DEIING sncrFV OIAU NO_ 199'0 l[Cl

5000 .4000 3000 2500 2000 1500 1400 1300 1200 1100 1000 900 800 700 650

!'TT:li •. 'Tl'TPTIJ I II I I IT I II I I I I I " LI . 1QQ ±1-'-'',.~ · 1·. · 1· .. ·1111,,JI •.. 'I I TI "I'" uTI ! !j II I d •: I 1 ·r .... ···· :•·: .;.r:. 100 -.-,-. 1 J ii; ):If · J:'.. ,q•n:1\i\1111:1p·rrilr''.'lj , c, ,c1. ;.;.;,! 'ic\J:i H H Jci+ 1 i: 90~ . :J: I I~ ~=n :... ••1 •· • • • l1LMR •• 1 •. • ,~ln Tl: r• •ruru #1IIfffffin:: :1:;:: 1i ·u1:u1n1n1.:J.itni1:1x1JJl •0 80 i-. ,- . 70 so' tt1tIEJ£B=i=i~bt=Ht±H-fffi+i~~=tt~~EmffimEEfflW-L 70

i l 1-l- ::rs ; : ;; I 50

• 1 ! "' •VI•· •I··•• t • ·, 11 1, t ., • I JT: p~~ J :q;<, H·i :'ITcJ'J.cjfc;ci! l+'T, ,. -- .. 40 t1 • l ~··~ i. I .F l: I l l I ,. 1 30 . LI. I 30 : './ I' -T·\.j :----:-::: j_t.( __i _;::1 .. :.: ~ . i - 20 ::· I I ' •ti.' I: i 11 IT ' ! 1 . ! ! ! '.· '.: ••· . tit.. :. -f-'-+-1~.-+,I· · •~·-4 . • '-'--h 10 • >I J · · ~-1-"~I I. I I·±Ht llinl . J· l · 1,· , I ·:·.·,, · , ··J. .:ITT: :;.'.: ;;{;i.1cti~t}r~:.;:r 10 a J ...... 1~r·1'IH'Tf tr I• : :a:J):::i~, HFi 1d'h{il 10 11 12 13 " 15 16 WAVELENGTH IN MICRONS

Dimethyl O'=Naphthoylphosphonate (VII)~ Film on NaCl Plates

w +"' Plate IV

WHfN KOlDBING snan' Ctl'Aln NO. 11910 atCiw.AN INSTIUMfNTS. INC .• fUUH10t,1, C,.UfORNIA, u.s .... WAVENUMBER CM·1

5000 ,40·00 3000 2500 2000 1500 1400 1300 1200 1100 1000 900 800 700 650

100 :' 1••1: I' l'.'r'I 11 II ;'I' : 11 I , , , I ri:"'" • : 1 :I "l"'I ti I l'Y'' pn rr ;;r-1'. •: ! i -;: :': 'I: l ITT! II I~iJ-1i~S _nt~ trt 100

90 • • It" ... : I~f j~vj: I~/_/;-~- ;f ~~ t~~Jrt1\ ,J :-i~' mJ ('\'.[ ~ !11 !iitl!! !fil ~\j· ~

50 ,~-:-,-.-::7---~ ,~-- -c-,-7 --,----·--- :-~ • r : :i J • . • •, ~ :1-, ,·~~ :1L; +J:L;J.U-:t:.t~ -:~:;~_ 50 l ~i : 40 u TI "! :-::-i , • 1: ; j-j ~Ft it: ~I~~t ~:~~i:1: ~rrn I •0 ·:·1 ..~.l .:J ;-;fJ 30 30 Ll •i d I ! • _c_j_ ~ ~- : ; : 1 20 ·20

IOJ j.i i-,-.,....-+-1---'--'----'--'--l,.C-'----'--'-+--'--'---'--'-+'--'-- cj_} _~:lJJ. io ii ... -:({lt: O 10 11 12 13 .. 15 16 I WAVELENGTH IN Mt_CRONS Dimethyl Mesitqylphosphonate (VIII), Film on NaCl Plates

l,.) \JI Plate. V

WHEN ltfOlll(mNG 9£0fY OLdi "'10. IUiO af(ICM ... 111 1NSTIUM[NT5. INC., fUtlrRTON. C.\llfORNI .... US .... WAVENUMBER CM-1

5000 4000 3000 2500 2000 1500 1.400 1300 1200 1100 1000 900 BOO 700 650 n nnr 'lP r:Tn r: HTTJE1? I I: I, I I' I r:ii :fl:l:1JllTl"J'lT:'f=qTIJlffUTf1HF1' PTI In! I' T:-11, 11 i: I r·-1 •1: I 1,.:r1: ! . . . .. -- - ... - . -...... rcr. -. ; i <: I' ; : :: l <: i. <,-...-r> i ;:1:rT::CT:fli:Tlr.·Ll-"'ll ii i:.i -~_j-- --Ll~ i~- ~-i~T.~J~1 '00- _,. : p::;.., : : ~ .. J.. L tlli[_Q . ,\: tLU Jl:: · 80 Aft ttttI' 0J..1 i' .:~-7'-'-4 •.• l I ; ; : {t-,+-: : : i ;-:- !'-,-,-' l..illLJ'"' _ ~·-· nl 1 - 70 W-W. I , rJi -~ \ -=~# ij;ifl!!i]:ltR: ~ :f: t-l . LWlU ___:_··~··,··k··· . : : : i_ __.: ~-~- : :. :~ HI !''" l ! ! . . . . . : : ! IT J.1 -~·~· --Pr-f . ;; I • ,.;: • '"" 60 'J ti;, .· ,-,--, , , r; , . , . , ._ . · ,, ,, " ':';fr :m • 50~ · i, I ,. "' ' , • • • II, ~ · • '" · '" ·1" m 1 ,oH-Hl--y

LJ-fLJLl_ji U~f!:I:! iJ+n !T: , 10 11 12 13 .. 15 16 WAVRENGTH IN MJCRONS

Dimethyl .2,=Ani_soylphosphonate (IX)~ Film on. NaCl Plates

I.,..) ~ Plate YI

WAVENUMBER CM- 1

1500 1400 1300 1200 1100 1000 900 700 650 1 1 1 1 1 1 1 111 1 1 1ffl~-t~l1$$~ 100 ,,F1TrTrn·T'TTI TT" :STJT~Tf1J1' l. I j\ •'• :1•JI' 'j'J '•'J If: : !! ! I! 1° 1:';'I :''V 1' )I! !.1 1Ff': qI ~1:~+:l: ~1J';c!fj~~f~+:~~P:!fn11a¥lfflttt!lf=fil~a 100

90 90 ITTJJJ!tttt:~~m+w+t++P~~t+8+4f+~rr+t-~~~~---5Jffl

80 BO lliill:1c:t:t=1tJctD~RIP~ll-I+HH-+**h=4~~**-TIH-r+H-~mfrr~tfuTirum~~w11 70 I ;,,;, " I : .: I . . Ill . : : : I : I : . I : . : t I : I : I : : Y : I : . I : ! : : . : I I : : : I : : ~ : l . · : : I : · · : I : : : : I : : : : I :\: : : I : : : .: ! : · : : ! : I : : : : 1 : : : '. ! : : ' : !~ : .': I ~:. : I i' '. :TL:: ':/: J 70

60 I : .. : I : : : : I : : : '. I : . : • I : .. : I : . : : I . : : I I : I : I : : : : I : : 1:11 : . :~ I :i: . : ~ .•, : l I : I : \ I :·: : ~ I : : : I : : : j' I : I : : I : : : n: : : : I : : : II :\: :: I 1..: ; : I :: : : I :t. :·: LI: ; : v~ :·:: I ;·:·11~ 60

so so J.: __ 4_ • -l •· JtWL-WJ •• i •• • \I •t •• 1 • • •· •JJJJ!l J•: ~+H F~l~:IF i iU :;x •H •Y I·•· Jd :l; ~M1-WJJ'Ulf •Ji :•; TH iHilllF :+~ttil4lLJ~j1it!~ •01:::•1••:•1::•:1::::1::::J:::1::· LJ•:1:·:.. :.:I Jl:l __ ::J:LJU:11:::_L~:•l ;:IJ: f:1:1 · I :LIJ.:;1:: :1 :.:~1;;J;1::;:1:u:1'.::~·1~-:--:j_-J 40

30

20

10

0 I W-1 I i I l+t-H ~~J-J ~~J~(l-f(~ll2~ 10 11 12 13 14 15 16 WAVELENGTH IN MICRONS

Dimethyl 3-Chlorophthalidylphosphonate (X), KBr Pellet

I.,.) "'-I Plate VII

I 2.0 3.0 4.0 5.0 PPM(T} 6.0 7.0 8.0 9.0 1b

1000 I >-H~ i ADO 300 200 100 .o CPS 250 I 100 C(O)P(O)(OCH ) so·I 3 2

. .

.--'I-~' ·+. .

8.0 7.0 6.0 5:0-~M(6)- 4.0 3.0 2.0 1.0 0

Dimethyl ..2,-Phenylbenzoylphosphonate (VI)

Soilvent • . . . CC14 R.F. Field. . . • 0.05 mG. s.w ...... 500 cps S.A...... 2.5 w co F.B .. . . . 4.0 cps S.T...... • 250 sec s.o. ' . . . 000 cps I.A. . . . . • off Plate VIII

I 2.0 3.0 4.0 5.0 PPM(T) 6,0 7.0 8.0 9.0 tb

1000 I )-H~ 500 <100 300 200 100 O CPS I 250 I 100 I 50 C(O)P(O)(OCH3) 2

_/_F

I ··-~1~-4-----'"---

.8;0 7.0 6.0 s.o PPM{o) 4.0 3.0 . 2.0 1.0 0

Dimethyl G'-Naphthoylphosphonate (VII)

Solvent . . . . . CC1 4 R.F. Field. . . . 0,05 mG . S,W. . . , 1000 cps S.A . . . . . 2.0 I.,.) I.O F. B •• . . . . .4.0 cps S. T. • 0 0 . ' . . 250 sec s.o. . . . 000 cps I.A...... 80 Plate IX

I 2.0 3,0 4.0 5.0 PPM{TJ 6,0 7.0 8.0 9.0 tb

1000 I )-H~ 500 4'0.0 300 200 100 O CPS I 250 I 100 I 50 H3C C(O)P(O)(OCH3) 2

111 ,/11 ,) ~ ..._.-~ ~-----~--

8.0 7,0 6.0 5.0 PPM!(i,1) 4.iO 3.0 2.0 1.0 0 Dimethyl Mesitoylphosphonate (VIII)

Solvent ' . . CC14 R.F. Field . . 0.05 mG S .. W...... 500 cps S. A. . . 2.0 .p-. F.B., . . . . 4.0-cps S.T...... 250 sec s.o...... 000 cps I.A...... off 0 Plate X

2.0 3.0 4.0 s:o PPM(T) 6.0 7.0 -8.0 9.0 10

1000 I >-H~ 500 400_ 300 200 100. o CPS I 250 I 100 I ·5!1

~ C(O)P(O)(OCH:1) 2

OCH 3

I

'~·....__,,. -~

8.0 7.0 6.0 5.0 PPM(6) 4..0 . 3.0 2.0 1.0 0 Dimethyl _2-AIJ.isoylphosphonate (IX)

· Solvent • . . • • CC14 ~.F...... • 0 .: 04~: I.Jl(; .: s. w...... • 500 cps S.A...... 1. 0 ~ F. B •• . . . • 4.0 cps S.T...... • 250 sec s.o...... 000 cps I.A...... 80 ..... ~ Plate XI

2.0 3.0 4.0 s'.o PPM(T) 6.0 7.0 8.0 9.0 1to

HlOO I }-H~ 500 ,oo 300 200 100 O CPS I 250 I 100 soI 0

P(O) (OCH3 ) 2

, A . ~11 .__, ~---~-----'-"~-J l ~ \J -..,,.,.-,.,,,,.,.,__,_,~....,_.,,,.J

8.0 7.0 6.0 5.0 PPM ( o) 4.0 3.0 2.0 1.0 0

Dimethyl 3=Chlorophthalidylphosphonate (X)

Solvent . . CC1 4 R.F, . 0.05 mP s. w. ' . . 500 cps S. A. . . 20.0 ;p. N F,B,. ' 4,0 cps S,T. ' . . 250 sec s.o. 045 cps I.A. . . .off BIBLIOGRAPHY

·.1. · Anschutz, L., Klein, E., and Cermak,. G., Ber~., 77b, 726 (1944).

2. Arbuzov, A. E. ,. J ,· Rus~. Phys. Chem. Soc., 42,. 395 (1910); Chem. · Abstr., 1, 1397 (1911).

~. · Arbuzov, A. E. and Azanovskaya,. M. M., Izv. Akad. Nauk. SSSR, Otd, Khim,· Nauk, 473 (1949); Chem,· Ab:str., 44, 1905 (1950).

· 4, · Arbuzov, A,· E. andAzanovskaya, M. M., ibid., 544 _(1951); CheQl, Abstr.• , 47, 98 (1953).

5. · Arbuzov, A. E. and, Zoroastrova, v.. M., ibid., 770 (1952); CheI!l, . A.bstr., 47, 9900 (1953).

6. ·Arbuzov,,A.E.and,Zoro.astrova,.V. M., ibid., 779 (1952); CheQl., · Ab.str., fil.,. 9901 (1953).

7. Arbuzov,. A. E., Zoroastronova,. V. M., and Myasoedova,. T. :r;:r., ibid., 2127 (1960);. Cher;n, Abstt,,.21, 14305 (1961). ·

8.. Ar.buzov, B. A., Pure tppl. Chem., .2., 307 (1964).

9. · Arbuzov, B.· A., Shapshinskaya, L. A., and. Erokhina, V. ~-, Bull. Acad, Sci.. USSR, Div. CheI!J.. Sci., 1782. (1965).

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11. · :Serl in,. K. D. and Burpo,· D. H. , J. Org. CheI!l, , 1!., 1304 ( 1966).

12, ·Berlin,.K.·D., Burpo, D.·H., Pagilagan, R.U., and Bude, D.,Chem. · Commun., 1060 (1967).

,, 13. ·Berlin,. K, D. · and Hellwege, D,. M., to be published.

14. Berlin, E:,,· ]) •• ,. Hellwege,. D,· M., and Nagabhushanam,. M., J. Org.: Chem., 30, 1265 (1965).

15. · Berlin, K. D., Hellwege, D. M. ,. Nagabhushanam,. M., and Gaudy, E. T, ,· Tetrahedron,. 22, 2191 (1966).

16. · Berlin, K. D., .Hildebran<;}, c;;., South, A.,. Hellwege,. D.· M. ,. Peter­ .son,. M., Pier,. E. A., and. Verkade,, J. G. ,. ibid., ~. 323 (1964). . .

43 44

17. Berlin, K. D~, Hildebrand, G., Verkade, J. G., and Dermer, O. c., Chem. Ind, (London), 291 (1963).

18. · Berlin, K. D. and Taylor, H. A., J. Am. Chem. Soc., 86, 3862 (1964.).

19. Boros, E. J., Coskran,. K. J.,. King, R. W., and Verkade,. J. G., ibid.,88, 1140 (1966).

20. · Buckler,. S, A. and Epstein,. M., J. Org. Chem., y_,. 1090 (1962).

21. · Buckler, S.· A. and. Wystrach, V. P., J. Am. Chem, Soc., 83, 168 (1961).

22. Cadogan,, J. ·. t. G.,. J. Chem. Soc., 3067 (1961).

23. Caciogan, J. I. G., Mackie, R. K., and Maynard, J. A., ibid., 1356 (1967).

24. Callis, C. F., Van, Wazer, J. R., Shoolery, J. N., and Anderson, W, A.,. J. Am. Chem, Soc., 1.2., 2719 (1957).

25. Coskran, K. J. and Verkade, J. G., Inorg. Chem., !!:_, 1655 (1965).

26. Davie.a, J. H. ,· Downer, J. D., and Kirby, P,, J. CheQ1, Soc,, C, Org., 245 (1966).

27, , Denny, D. B. and Varga, S, L. ,· Tetrahedron Lett., 4935 (1966).

28. · Derkach, G. I. and Piven, Yu, V., J, Gen, Chem. USSR, 1§., 1101 (1966).

29. Doak, G. O. ,· Freedman, L. D., and Levy, J. B., J, Or$, Chem,, 29, . 2382 (1964.).

30. Edmundson, R. s' ' Chem, Ind. (London), 1770 (1962). 31. Edmundson, R. s. '' ibid. ' 1809 (1967). 32, Edmundson, R. s. and Mitchell,. E. w.' Chem. Commun., 482 (1966). 33. Finegold,ll.,Ann. N. Y.Acad. Sci.,.70,. 875 (1958).

34. ·· Fitch, S. J. and Moedritzer,. I<., J. Arµ. Cherp.. Soc., 8H, 1876 (1962).

35. Gerrard, W. and Green, W. J., J. Chem. S0c ., , 2550 (1951).

36. .Ginsburg, V, A. ,. Vasi 1' eva, M. :W. , Dubov, S. · S. , and Yakubovich, . A. Ya., J. Gen, Chem. 'USSR, 30, 2834 (1960).

37. Green,. M. and Hudson,. R.· F,, J, Chem,· Soc., 1004 (1963). 45

38. Greene, F. D. ,. Van Norman, G. R., Cantrill, J. C., and Gilliom, R. D., J. Org. Chem., 25, 1790 (1960).

39. Gruttner, G. and Krause, E., Ber., 49, 437 (1916).

40. Gruttner, G., and Wiernik, M., ibid., 48, 1473 (1915).

41. Handbook of Chemistry and Physics, College Edition, 46th Ed., The Chemical Rubber Co., Cleveland, Ohio, 1965, pp. C-75 ff.

42. Harvey, R. G. and De Sombre, E. R., "Michaelis-Arbuzov and Related Reactions," in Grayson, M. and Griffith, E. J., Eds., Topics in Phosphorus Chemistry, Vol. I, New York, N. Y., 1964, Chapter 3.

43. Harwood, H. J. and Grisley, D. W., J. Am. Chem. Soc., 82, 423 (1960).

44. Hasserodt, U., Hunger, K., and Korte, F., Tetrahedron, 12,, 1563 (1963).

45. Helferich, B. and Aufderhaar, E., Ann., 658, 100 (1962).

46. Hellwege, D. M., "I. The Stereospecificity of the Michaelis­ Arbuzov Rearrangement in 4-!-Butylcyclohexyl Diphenylphos­ phinate. II. NMR Analysis of Substituted Phosphonates," Ph.D. dissertation, Oklahoma State University, 1966.

47. Henning, H. and Hilgetag, G., z. Chem., 2, 169 (1967).

48. Horner, L. and Winkler, H., Tetrahedron Lett., 3271 (1964).

49. Issleib, K., Z. Chem., 1, 163 (1962).

50. Issleib, K. and Hanser, S., Ber., 94, 113 (1961).

51. Issleib, K., Krech, K., and Gruber, K., ibid.,~, 2186 (1963).

52. Johnson, C. E., Jr. and Bovey, F. A., J. Chem. Phys., 12,, 1012 (1958).

53. Jones, R. A. Y, and Katritzky, A. R., Angew. Chem., Internat. Edit., .1:., 32 (1962).

54. Kosolapoff, G. M., "Organophosphorus Compounds," J. Wiley and Sons, New York, N. Y., 1950:

55. Kosolapoff, G. M., "The Synthesis of Phosphonic and Phosphinic Acids," in Adams, R. et al., Eds., Organic Reactions, Vol. VI, J. Wiley and Sons, New York, N. Y., 1951, Chapter 6.

56. Kukhtin, V. A. and Gozman, J. P., Proc. Acad. Sci. USSR, Chem. Sect., 158, 850 (1964). 46

57. Landauer, S. R. and Rydon, H. N., J. Chem. Soc., 2224 (1953).

58. Laube, B. L., Bertrand, R. D., Casedy, G. A., Compton, R. D., and Verkade, J. G., Inorg ... Chem.,.§., 173 (1967).

59. Laughlin, R. G., J. Org. Chem., ]:l_, 1005 (1962).

60. Leavitt, F. C.,.Manuel, T. A., and Johnson, F., J. Am. Chem. Soc., ..§!, 3163 (1959).

61. Maier, L., Helv. Chim. Acta., 48, 1034 (1965).

62. Mark, V., Amer. Chem. Soc., Abstr. 14.7th Meet., 1964, p. 291.

63. Markl, G., Angew. Chem., Internat. Edit.,~' 1023 (1965).

64. McCormack, W. B., U. S. Pat. 2,663,736 (1953); Chem. Abstr., 49, 7602 (1955).

65. McCormack, W. B., U. S, Pat. 2,663,737 (1953); Chem. Abstr., 49, 7601 (1955).

66. McCormack, W. B., U, S. Pat. 2,663,738-9 (1953); Chem. Abstr., 49, 7602 (1955).

67. Michaelis, A. and Kaehne, Ber,, 11',' 1048 (1898).

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70. Muller, N. Lauterbur, P. C., and Goldenson, J., J. Am. Chem. Soc., 78, 3557 (1956).

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72. Pagilagan, R. U., Unpublished results.

73. Pfundt, G. and Schenck, G. O., "Cycloadditions to ortho-Quinones, 1,2'-'Diketones, and Some of Their Derivatives," in Hamer, J., Ed., 1,4-Cycloaddition Reactions, Academic ~ress, New York, N. Y., 1967, Chapter 11,

74. Pilgram, K. and Korte, F,, Tetrahedron, 1.2., 137 (1963).

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78. Quin, L. D, and Barket, T. P., Chem. Commun., 914 (1967).

79. Quin, L. D. and Mathewes, D, A., J, Org, Chem.,~. 836 (1964).

80. Ramirez, F., Pure Appl, Chem., 2, 337 (1964).

81. Ramirez, F. and Desai, N. B., J. Am. Chem. Soc., 85, 3252 (1963),

82. Ramirez, F., Desai, N. B., and Mitra, R. B., ibid., 83, 492 (1961).

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84. Ramirez, F., Patwardhan, A. V., and Smith, C. P., J. Org. Chem., 30, 2575 (1965).

85. Ramirez, F. and Ramanathan, N., ibid., 1§., 3041 (1961).

86. Ramirez, F., Smith, C. P., Gulati, A. S., and Patwardhan, A. V., Tetrahedron Lett., 2151 (1966).

87. Ramirez, F., Yamanaka, H., and Basedow, 0, H., J. Am. Chem, Soc., 83, 173 (1961).

88, Razumov, A. I., J, Gen. Chem. USSR,~' 1609 (1959),

89. Razumov, A, I. and Bankovskaya, N. N., Dokl. Akad, Nauk SSSR, 116, 241 (1957); Chem. Abstr., 52, 6164 (1958).

90. Razumova, N, A, and Petrov, A, A., J. Gen. Chem. USSR, 33, 77,1 ( 1963).

91, Razumova, N, A. and Petrov, A, A., ibid., 33, 3796 (1963),

92. Siddall, T, H,, III and Prohaska, C. A., J, Am. Chem. Soc,, 84, 3467 (1962).

93. Smith, B. E. and Burger, A., ibid., J.2, 5891 (1953).

94, Speziale, A, J. and Freeman, R. C., J. Org. Chem., l},, 1883 (1958).

95. Taylor, H, A., "The Synthesis and Properties of Dialkyl Aroyl­ phosphonates," M,S, thesis, Oklahoma State University, 1964,

96. Van Wazer-, J, R., Callis, C, F,, Shoolery, J, N., and Jones, R, C,, J. Am. Chem. Soc,, 78, 5715 (1956). 48

97. Whitesides, G. M., Grocki, J. J.s Holtz, D., Steinbu~g, H., and Roberts, J, D,, ibid., 87, 1058 (1965),

98. Wittig, G. and Geissler, G., Ann., 580, 44 (1953). PART II

SOME SYNTHESES OF OPTICALLY ACTIVE

PHOSPHORUS COMPOUNDS

49 TABLE OF CONTENTS

Chapter Page

PART II

L HISTORICAL. . 53

IL DISCUSSION OF RESULTS AND CONCLUSIONS 63

III .. EXPERIMENTAL. 78

Preparation of Diphenylphosphinic Chloride (I) 78 Preparation of Optically Active N=Substituted Diphenylphosphinic Amides II-IV •.... , . . 79 Preparation of (- )-Menthyl Diphenylpho sphinate ('If) 80 Preparation of (-)-Bornyl Diphenylphosphinate (VI) 81 Preparation of (+)-2-Methyl-l-butyl Diphenylphosphinate (VII). . 81

BIBLIOGRAPHY 95

50 LIST OF TABLES

· Table Page

I. IR Absorption Maxima (cm, -l) of Optically Active Phosphorus Compounds II-VII , • , , • , 73

II. NMR Coupling Constants and Chemical Shifts of Products. 74

III, Synthesis and Properties of Optically Active Phosphorus Compounds II-VII ••• , •••• 77

51 LIST OF ILLUSTRATIONS

Plate Page

Infrared Spectra

I. (+)-N-(0:'-Methylbenzyl)diphenylphosphinic Amide (II), KBr Pellet. , , , , , . , . , . • . 83

II, (+)-N-(0:'-Methylphenethyl)diphenylphosphinic Amide (III), KBr Pellet • ...... , . 84

III. (- )-N-[a- ( 1-Naphthyl) ethyl]diphenylphosphinic .Amide(IV), KBrPellet ...... ,., .. 85

IV. (-)-Menthyl Diphenylphosphinate (V)j KBr Pellet 86

V, (-)~Bornyl Diphenylphosphinate (VI), KBr Pellet 87

VI. (+)-2-Methyl-l-'butyl Diphenylphosphinate (VII), KBr Pel let. . , . , , . . . , . . • . . . . . 88

Nuclear Magnetic Resonance Spectra

VIL (+)-N-(0:'-Methylbenzyl)diphenylphosphinic Amide (II) , . 89

VIII. (+)-N-(0:'-Methylphenethyl)diphenylphosphinic Amide (III) 90

IX. (- )-N-[a- ( 1-Naphthyl) ethyJ]dipl;i.enyJpl:iospl:iinic Amide (IV)...... , . . . 91

X. (-)-Menthyl Diphenylphosphinate (V) . 92

XI, (-)-Bornyl Diphenylphosphinate (VI) 93

XII. ( +)- 2-Methyl-1-butyl Diphenylpho sphinate (VII). 94

52 CHAPTER I

HISTORICAL

The synthesis, resolution 1 and reactions of optic.;:1lly active

organophosphorus compounds in which phosphorus.is the asymmetric center have been the subject of a considerable amount of recent interest. 13 •23 •

34.40,44 Optically active phosphoryl and thiophosphoryl compounds have

been prepared either by the resolution of suitable derivatives or by . 34 40 synthesis from resolved phosphonium salts. • In particular, the

method of resolution of alkyl alkylphosphonothioic acids developed by s t RP-OR 1 ! OH 1 Aaron and co-workers has made available intermediates from which a

number of optically active derivatives have been prepared by nucleo=

t" 1 f f p hL. 1ic. d'isp l acemen.t reac ions. 2,8· 18,45,46,48 · By ar t h e maJority. . o · . 2 8 18 34 40 45 46 48 .. the evidence 1 1 ' · 1 • 1 1 · indicates that such displacements

occur with inversion. of configuration at the phosphoryl and thiophos=

phoryl centers.

Seiber and Tolkmith55 reported the preparation and certain stereo-

specific transformations of (- )-1- [ (diethylamino) phenylpho sphinothioyl]-

2 1 3-dimethylimidazolium iodide. The imidazolium function was demon=

stratea55 to be a facile leaving group in nucleophilic displacements by

53 54

2-methylimidazo 1-1.. yl anion~ methoxide · ion~ and _g,- butylamine.

Optically active phosphonochloridothionates were.recently used to

stu d y t h e stereoc h emistry. at an asymmetric. p h osp h orus a t om. 45~47,49

Examples include the ethyl ethylphosphonochloridothionates, CH 3cH2P(S)­ (OCH2CH3) CL The readily avail ab le ethyl ethylpho sphonothioic acidR, s t CH 3CH 2fOCH 2CH3 Cl 1 resolved according. to Aaron and co-workers, were converted into opti=

cally active phosphonochloridothionates with phosphorus pentachloride.

The optically active phosphonochloridoj::hionatesreacted with a number of

nucleophilic reagents yielding optically active esters, amides, and

anhydddes. 45 Reaction of ethyl ethylphosphonothioic acids :with phos=

phorus pentachloride and the subsequent reaction of the chloride with

.. potas~ium hydroxide. both proceed with inversion of configuration49 at

the thiopbosphoryl center. Together these reactions lead to the acid

of the original configuration. s + CH3CH 2- 1-oc 2H5 OH (-) {-)

The present revival of interest.in phosphorus stereochemistry per­

haps began :with the re.solution of the phosphonium salts19 ' 22 shown

below. The fir.st. optically active quaternary phosphorus ,compound 55 obtained.in which the phosphorus atom was- not incorporated in a hetero=

e Br e ,I

cyclic ring was re~olved via its hydrogen dibenzoyltartrate salt. 37 A number of phasphonium salts have been resolved more recently by the 27 33 42 same method, ' ' 'l'he absolute configuration of one.of these salts, 52 .(+)-benzylmethylphenyl""',!!-propylphosphonium bromide, is now.known.

9 ,Br

Optically active phosphonium salts containing.a 2-cyanoethyl group undergo reaction with sodium etho:dde to give optically active phos= phines and 3-ethoxypropionitrile.42 Reduction.of _several phosphonium

salts has produced the following_orders of phosphorus=carbon bond · 25 26 strengths: ' 56

Optically active phosphonium salts are r~duced by lithium aluminum

hydride to give racemic phosphines, 42 Conversely, electrochemical re= 33 duction~ using a mercury cathode 9 forms optically active phosphines,

. That cathodic cleavage and quaternization both proceed with retention

0 f. ' 33 h as b een proven b y t h e f o 11. owing set o · reacti.ons:

0 e t ,, Br

{ +) ( =)

lL,02 L. ..,

(+) ( =)

The scheme depends on the known inversion of an optically active phos=

phonium salt when it reacts with alkali to give an optically active

phosphine.oxide. Methyl=_!!-propylphenylphosphine which was synthesized

from itsbenzyl bit'omide quaternary salt reformed the same optically

active.quaternary salt upon alkylation with benzyl bromide, Oxidation 57

.with hydrogen peroxide gave the mirror image.of the phosphine.oxide that

was. obtained by reaction.of the corresponding.ph~sphonium si:ilt with

alkali,

Heating< optically active phosphines at atmospheric pressure. re-

. . 0 33 su 1 ts in racemization, The kinetics of racemizi:ition of (+)-methyl-

phenyl-~-propylphosphine have been measured and the energy of ac.tivation · 31 for the process determined as being about 30 kcal./mole, 14 Campbell resolved a cyclic phosphine)) (+) and (-) 10=(.E,-

dimethylaminophenyl)-9 9 10-dihydro-9-aza-10-phosphaphenanthrene.

27 · Horner reported the isolation of the first optically active trii:lryl.;..

phosphine 9 phenyl-.E,=anisyl-a'-naph thylpho sphine, Another unsymmetric13 l

triarylpho sphine, . ..2,-biphenylyl .. a'-naphthylphenylpho.sphin,.e, was resolved

O 57 0 b y.W ittigo an d co-.wor. k ers,, · I nor d er to accomp 1°is h. t h e,reso 1u t ionll use

·was ITu!!de of the fact that phosphines in the presence of acid and par13-

forrm:ildehydereact to g;i.ve.a-hydroxymethylphosphqnium Si:ilts, 58

Oxidation of optically ac.tive. phosphines with hydroperoxides re-

o f fo o 16,33 b o h b 1 h hl o su l ts in retention. o con iguration 1 ut wit !- uty ypoc orite in methanolic methylene chloride,. inversion of· configuration is noted 16

In the absence of methanol, !,-butyl hypochloriteleads to almost com,., plete.racemizationo This was construed as supporting the following

O 16 mec h anism:

Reaction of methyl""',g-propylphenylphosphine :with benzenesulfi.nic acid giveso a part 1 y rac:emico p h osp ho.. ine o:xiO d e, 32 The amount of racemization increases when a more polar solvent is used, Reaction of .the same phos- phine with benzoyl peroxide also gives increasing racemization as the po 1.arity 0 . o £ t h e so 1vent . increases,0 32

Reaction of optically active phosphines with halogens, fol16wed.by

0 1 d O h h O O d 30 h y d ro 1ysis 1 .. ea s to rac:emic p osp ine oxi es, In aqueous acetoni¥

trile 1 this same reaction sequence produces phosphine oxides of inverted coi;i."f0 iguration, 0 30 These results are consistent with a mechanism in which an optically active phosphonium salt, formed initially, is in 59 equilibrium with a pentacovalent=phosphorus intermediate, The latter is initially in the form of a symmetric trigonal bipyramid. Subsequent to the formation of this trigonal-bipyrarnidal structure, flipping of 50 group positions could occur. This cone lusion ·appears to be strength= x x ' x i~ i )-3 ' '/ P,. 1 • ,X K1-·.·-p or

.X //~\ . ll'R R1 Rz R3 x: 2 ened by the observations that: (a) optically active phosphonium salts react with sodium hydroxide to form phosphine oxides of inverted con= figuration; 29138 and_ (b) optically active phosphine oxides racernize in

l~l'-."~ I op o o o X /\ K.,. R .:,, 2

the presence of anhydrous hydrochloric acid. 17 It is interesting to contrast the decomposition of optically active methylethylphenylbenzyl= 51 phosphonium E,=butoxide 1 which is reporte, d to pro d uce methy 1ethy 1.~ phenyl.phosphine oxide with over 90% racemization,

Optically active phosphines retain their configuration on sulfura= 33 t:ion, Either c.yclohexene episulfide 1 octatomic sulfur, or monat:omic sulfur reacts with optically active methyl-E;-butylbenzylphosphine to give the phosphine sulfide with retention of configuration, 28 •58

In the presence of phenyllithium1 optically active benzylethyl- methylphenylphosphonium iodide affords the corresponding phosphoranre with retention of configuration. 6 Reaction of this phosphorane with 60

benzaldehyde gives•phosphine o~ide-with. a h~Sh degree of retention of 6 configuration • This supports · t.he existence of a cyclic transition

. state for the Wittig reaction. · Similarly, reaction of the phosphorane

c6H5CH=CKC6H5 a·

+ . tp ,/'l~ . H5c2 C6H5 CH3

with benzonitrile affords an intermediate~. which upon treatment with

alkali yields a phosphine O}(:ide with 68% inversion of configuration.

This show.s that two paths are involved~ one proceeding with retention

and the other withinversion.of configuratien,

retention H06 ~ inversion

0

• RR I R'1p-i>Q . C H CH !IC H . + ""-PRR' R" + 6 5 2~.6 5 v-- 61

The same phosphorane was shown to react with styrene oxide to form a betaine, which upon pyrolysis at 190-200° yielded, among other prod- ucts, racemic phosphine and phosphine oxide of 50% net inverted config­ uration.41 Racemic phosphine presumably arose as a consequence of the thermal racemization of the optically active phosphine, A concerted, base-assisted decomposition of a pentacovalent-phosphorusintermediate has been suggested to lead to the inverted phosphine oxide,

Optically active phosphine oxides occupy a key position in the 36 stereochemical investigations of phosphorus compounds. Resolution of ethylmethylphenylpho sphine oxide provided the fir st example of an 43 optically active phosphorus compound. Phosphine oxides are precursors to optica. 11 y active" p h osp h ines.. b y re d uction" wit. h tric· 'h l orosi· l ane. 24

I;Korpiun and Mislow36 have developed a synthetic route to the prep- aration and configuration.al correlation of optically active phosphine oxides that does not require resolution of phosphine oxides or phos- phonium salts, Unsymmetrically substituted menthyl phosphinates were

readily separated into the diastereomeric forms. Reaction of hhe phos- phinates with alkyl o;r aryl Grignard reagents in benzene at 70° affo:r:qs phosphine oxides5 with a.high degree of stereospecificity, For ex:amt 36 ple~ methylmagnesium chloride and diastereomeric.ally pure (=)-menthyl phenyl':'!!,= propylpho sphinate give ( +)=methylphenyl'c' ,!!-propylpho sphine oxide, Since the absolute configuration of the above phosphinic ester 62

+· 0 .....

had been determined by X=ray analysis~ it was concluded that the Grig=

nard reaction proceeded with inversion of configuratiori.o The diastereo= 39 meric:ally pure menthyl pl;10sphinates are reported to give NMR and ORD

. spectra which are characteris.tic of their config1;1rations. Optic.13.l

rotations are known for both (=)=menthyl- and (=)=bornyl Lf'.00 diethy1

2~puosp ~ h onoprop1onate.. · 56 The latter two compounds were synthesized 0 t (CH 3 CH· 20) · 2 P~·CH(CH· 3 )=CO·. 2R

from triethyl phoisphite and the corresponding G'=bromopropiQJnic ester.

Ano.ther example of an op.tic.ally active, organophosphosphorus compound is

· (=)-menthyl diphenylphosphinate. 39 CH,A.PIJC'ER ·. I I

:OISCUSSION OF RESULTS·AND CONCLUSIONS

Op.tic.ally ac.tive primary amines and optically active alcohols were

starting materialsin the synthesis of amides and esters of diphenyl=

phosphinic acid" The purpose of this work was to develop go0d methods

for the preparation,of some optically active.organophosphorus compounds

·which do not contain an asymmetric phosphorus atom" The products were

as follows~ (+)=N=(Cl'=methylbenzyl)diphenylphosphink amide {II) 9 (+)=

N=(Cl'=methylphenethyl)diphenylphosphinic amide (III) 9 (=)-N=[Cl'-(1=

naphfthyl)ethyl]diphenylphosphirlliie amide. {IV) 9 (=)-menthyl dipheny1,-

phospbinate {V) 9 (=)=bornyl diphenylphosphinate (VI) 9 and (+)=2=methyl=

l= butyl diphen.ylpho sphina te · (VII) s

H i O I t . H3C--~--NHP(C6H5) 2 I C6H5

(+)=N=(Cl'=rnethylbenzyl)diphenylphosphin.ic amide (U)

[Q/]~305 = +33.5°

63 64

CH2C6H5 ! 0 o:r. H__.b....,.NH:P(C6H5 ) 2 I I CH3

(+)-N-(0!-methylphenethyl)diphenylphosphinic amide (III)

or

( 6 )-N-[O!- (1-na.phthyl)ethyl] diphenylphosphinic amide (

),-menthyl diphenylphosphinate (V)

2~,5 0 '[O!JD = -73,0

(-)-bornyl diphenylpllllosphinate

' 25 0 5 - 14 30 [ O!D ] ,--· .. ·". 65

CiH3 0 I 1" H ...-?--cH20P(C6H5 ) 2 ! C2H5

( +)- 2-methyl- l;;,butyl diphenylphosphinate (VII)

The primary amines were (+)-Q'-methylbenzylamine:i (+)-QI-methyl-

phenethylamine~ and (+)-Q'-(1-naphthyl)ethylamineo The alcohols. were

(-)-menthol, (-)-borneol~ and (-)-2-methyl-l-butanoL Two equivalents

. of amine per one equivalent of diphenylphosphinic chloride (I) were

utilized in the preparation of the amideso The second equivalent of

amine was used to combine with the hydrochloric acido The sodium

alkoxides. of (-)-menthol and (-)-borneol were prepared in order to

promote formation of esters from Io Triethylamine was used as an acid

ROH + Na --iDJIID- RONa + \H 2

scavenger in. the ester synthesis from (-)-2-methyl-l-butanol and Io

NMR (Table II), IR (Table I), and elemental analyses (Table .. III)

for II-VII are in accord with the proposed structures, Physical prop-

erties such as melting point and specific rotation also are recorded in

Table IIIo 66

II

61.2\ r-63.39

H3CCHNHP(O)(C6H5) 2

,02._so----1> L2c~63.39

III

IV

:::r:._R spectra. of the amides II-IV <;lisp lay hydrogen-bonded N-H absorp­ tion maxima at 3090-3160 C!Jl.-l. The phosphoryl frequencies are ob= served at 1182-1197 cm. -l. These, values ~pproxima:te the'. N-H and ~O 67

ma:x.ima reported by Be,llamy.4 A bread multiplet at c~. S:,3.3_8=~.80 ap=.

pears_: in the -NMR spectra of rr_... ,rv fer. the NH proton, of the alllide link-

· age. Likewise:;, a multiplet at ca. 6~. 39-5, 14 is observed for the

single-methine.proton,intheamides, Eachaf theamides 1:11so gives

. ~foublets: in the,range. of. Sl.23=i.64 with coupling :constants: af ca, 5.2=

6,5 c.p.13. for the methyl graup. - The remaii;,-ing peaks .for II-IV appear

at 6 values accor<;ling to the ~lassical predictians,

0 t . P(C6H5)2

t A Sp, 88 -----1)111.a -- CB:3 CH3 •4---, 6p, 55

,V

Cf13 : . 6 0 , 7 3 ._ ....t-- ___ 64, 61 _60,82~

60,87

VI

VII 68

IR spectra of the esters V-VII display P"""O and P-0-C absorption maxima in the ranges of 1224"° 1230 cmo = 1 and 1014= 1023 cm.= 1 •. respective- ly. · The above values correlate well w.ith those for a series of alkyl diphenylphosphinates prepared by Austin. 3 Each of compounds V-VII produces a multiplet in the NMR spectrum at 67.2-8.1 for the aromatic protonso The OCH proton in V and VI gives a multiplet at 64.23 and

64.61, respectively. The OCH2 protons in VII produce a triplet at

63.84 (J = 5,9)a The three methyl groups in V [(a), (b'9 and (d) 9 respectively] give rise to doublets at 00.55 (J = 6.8), 50.88 (J = 7.0), and 00.83 (J = 5.0) while the three methyl groups in VI yield singlets

at 00.73 9 60.82, and 60.87. The two methyl groups [(b) and (c)] in VII overlap in the spectrum and appear at ca. Ol.00 and 60.90 (J = 3,0), respectively, As with the amides, the remaining peaks for the esters appear at 6 values c~nsistent with classical predictions,

Compound I was obtained by oxidative chlorination of diphenyl­ phosphinous chloride in the presence of phosphorus pentoxide, The reaction equation is given below. Vac.uum distillation was used to

obtain the pure product,

The reactions involving the optically active amines with I were only slightly exothermic.. During addition of I to the amine, the amide and the hydrochloride of the amine imm.ediately began to precip{= tate. In the workup of the reaction mixtures, the solid precipitate was washed with water to dis.solve the ionic salt. The residue was then recrystallized to give pure amide,

Formation of the sodium derivatives of (-)-menthol and (,,,)-borneol 69

required vigorous stirring and heating at 100-105° for 7. hours, · After

cooling. to room temperature, the excess .sodium was re.moved with forceps,

The subsequent reactien. between the alkoxide .·and· I was highly exethermic

but could be controlled by the use.of an extern?l ice-water bath, I

was removed by extraction with aqueous .sodium bicarbonate, Attempts to

remove unreacted (~)-menthel by vacuum distillation and (-)-borneol by

sublimation were unsuccessful, · However, steam distillation proved us.e-

· ful for this purpose, Stability ef the phosphinic esters,. V and VI,

·toward aqueous hydrolysis was evident in the fact that the unreacted

alcohols could be removed by steam distillation,

The reaction between (-)-2-methy1-l-butano·l~ I, and triethylamine I was only, slightly exothermic, · Excess.I and triethylamine hydrochloride

were removed by extrpct.ion with aqueous .sodium bicarbonate., Agai~

steam clistillation was used to remove the unreacted alcohol,

· The reactions involving I include the formation of P-N. and P-0

bonds in nucleophilic displacement on phosphorus by nitrogen and oxygen

a.toms,· respectively, The transition state probably ~n,volves a penta- . 34 40 substituted phosphorus atom, '

X - Nor O

Compounds very similar to V and VI have been prepared, They are . . 15 ( . ) menthyl and bornyl hydrogen ph~nylphosphonate see Chapter L, . Opti-

ca 1 rotation. has been.measured 56 for two organoph osphosp h orus compound s

which contain either a menthyl or bornyl group, The compounds• 1;1re (~,) ..

menthyl and (-)-bornyl l,.f.-diethyl 2-phosphonopropionate. (.see Chapter

·I), Respective specific· rotations :l:or these .compounds in ethano1 are: 70

-50,9 0 and -32,5 0 , Temperature was not reported,

Specific rotations. of chloroform solutions containing the starting

0 0 0 materials leading to compounds II-VII were.+35,6 ~ +36,2, +41,3,

-44,7°,. -20,8°, and -5,33°, respectively, Specific rotations for com- pounds II-VII in chloro.form were +33,5 0 , +19,6. 0 , -44,80 , -73,0 0 , -14,3· 0 , and +4,18°, respectively, Of course inherent asymmetry arising from

t h e asymmetri.c· con.f igur.ation· . · 9 - 11 in· t.h e amine· or a 1co· h o, 1 ic· portion. o.f

II-VII is a sufficient cause for producing optical activity, In addi-

tion,. asymmetric· conormationsf ... 12 o f t h e mo: l ecu l e cou ld contri"b ute to

the sign and magnitude of the specific rot.ation, Knowledge of "allowed" 9 12 9~12 conformations 9 and of the rotatory effects of dissymmetric mole-

cules and certain molecular conformations conceivably might be useful

in explaining the sign and magnitude of the specific rotation for II-

VII, 9 Brewster reported that the known configurations. in the "carbinyl"

series (HCXRR') ahd in the "methine" series (HCRR 1 R") made feasible an

attempt to relate sign of rotation to structure, absolute configuration,

and conform.ation, · This was done for a few compounds by use of two

general rules, a simple method of conformational analysis and a small

number of empirical rotation constants, It is interesting.to note

Brewster's rationalization9 that the result of opposed atomic and con-.

formational asymmetry effects could be a relatively small rotation of

unpredictable sign,

I n Brewster I s d'iscussion 0 9 •12 o f . open-c h ain• compoun d s, opticaO 1

rotatory. effects of asymmetric conformational units are said to be

observable only.when enantiomeric units exist in unequal amounts, .71

,A.' or A/- H ~. v! \.'.) Restraints on rotation about the central bond of the c:onformational unit

.·. is sufficient cause for the above situat.ior1, In 3-me'thylhexanel) which

contains three .such conformational unitsl) all combinations: of 11 .llllowed"

conformations are considered to contribute equally to the specific ro-

tat ion.

Empirical rotation constants for all the substituent groups bonded

to the asymmetric carbon atoms in compounds II-VII are not known,· Fur-

thermorel) a useful method for predicting the preferred conformations

-in such compounds has not yet. been developed, These limitations make

it impossible to explain fully the magnitude- or sign of the specific

rotation for II-VII, It should be noted that the sign of specific ro-

tation for the organophosphorus productl) IV or VIIl) is opposite to that

of the .corresponding amine or alcohol, l'he observed changes are from

+4L 3° to -44. 8° and from -5, 33° to +4, 18°, The reversals of sign

suggest that (in these compounds) .. some .P-Nl) N-Cl) P-Ol) and 0-C .conforma-

· tions may be preferred over the corresponding.enantiomeric conformations,

It appears reasonable that the change in conformational asymmetry effect

in going from (+)-0'-(l-naphthyl)ethylamine to IV (or from (-)-2-methyl-

1-butanol to VII) may account for the change in sign of the specific

rotation.

When m>n- in the series. of compounds belowl) it has been postulated

that: (1) a negative rotation'will be observed if A and'B hive similar

(CHz) CH 1· m 3 I B --· r-- (C.Hz)nCH3 ! A 72

. steric re,q1;1irements; and (2) a positive rotation, will be observed if A

has larger steric requirements than :a, Coj:nparison, of the above config=

uration·with those for (=)-2-methyl-l-butanol and VII produces interest=

ing, results, In the reaction which gave VII~ configuration of the asym=

CH I 3 I CH3CH2--~ __.fit i CH20P(O)(C6H5 ) 2 VII

metric carbon,was not changed 9 but the size of one, of the substituents

· [OH changed to OP(O) (C6H5 ) 2] was greatly increased, · All .substituents

remained unchanged except the, OH function which. was cenverted. to a

.OP(O)(C6H5) 2 group, Therefor.e 9 a change of sign from negative to posi=

tive appears to be logical,

. In summary 9 a series of amides and esters of diphenylphosphinic

acid were·f;!ynthesized, These.compounds are among.the few optically

ac.tive organophosphorus compounds which do not c:ontain an asymmetric

phosphorus a.to1p., · The methods of preparation are qiscussed and phyi:;ic1;1l

constants. of the compeunds are reporte~, IR and NMR spectra and specif-

ic rotations have.been used to characterize the optically.active pro9=

ucts 9 . II=VII, . TABLE I

IK ABSORPTION MAXI~ ( ci;n" - l) OF. OPTH',ALLY ACTIVE PHOSPHORUS COMPOUNDS II-VII

Cpd" Plate N-H P--0 P-0-C-

II I 3160 1182

III II 3090 1197

IV III 3150 1192

v . IV _ 1224 1014

VI v . 1230 1023

VII VI 1224 1016

...... w TABLE II

NMR COUPLING CONSTANTS AND CHEMICAL· SHIFTS OF PRODUCTS8

b Cpdo Plate o(popomo) J(coposo) Int ego Assignment

(b) .H (c) VII 1055 d 605 3 CH (a) I 3 I 4o32 m = = l CH (b) (a) . H39 ;_.. f--NHP(O)(C6H5)2 3038 m =· = l NH (c) I C6H5 7ol=8ol m = - 15 Ar-H

II

VIII 2080 m = = 2 CH2 (a) (b) (d) 3o39 m = = l CH (b) R CCHNHP(O)(C H5) (c) 3 6 2 , L23 d 502 3 CH3 (c) I 3o39 m . = = .1 NH (d) (a) CH2c6H5 609-800 m = = 15 Ar-H III

-..J .i::- TABLE II (CONTINUED)

b Cpd. Plate o(p.p,m,) J(c.p.s.) Integ. Assignment

(b) (c) IX 1.64 d 6.5 3 CH3 (a)

(a) H3C~HNHI'(O)(C6H5) 2 5.14 m - - 1 CH (b)

3.80 m - - 1 NH (c) .,~ 7. 0-8. 1 m - - 17 Ar-H IV

x 0.55 d 6.8 3 CH3 (a) (d) CH . 3 0.88 d 7.0 3 CH3 (b)

pro)(C H) 4. 23 m - - 1 OCH (c) 1. ' 6 5 2 0.83 d 5,0 3 -cH 3 (d) I l1 (c) 7.2-8,1 m - - 10 Ar-H (b) (a) c03.J v

-...J Vt TABLE II (CONTINUED)

b Cpd. Plate 8(p.p.m.) J(c.p.s.) Integ Assignment

XI 0.73 s 3 CH3

0.82 s 3 CH3

o. 87 s 3 CH H (a) 3

OP(O) (Clls) 2 4.61 m 1 OCH (a)

7. 2-8.1 m 10 Ar-H VI

(b) CH3 (a) I XII 3.84· t 5.9 2 CH 2 (a) I H~C • CH 0P(O)(C H ) 2 6 5 2 ca. 1.00.d 3 CH3 (b) I I o. 90 t 3.0 3 CH3 (c) (c) H3CcH2 7.2-8.1 m 10 Ar-H VII

aThe solvent used was deuterochloroform.

bThe multiplicity of each signal is indicated as follows: singlet, s; doublet, d; triplet, t; multiplet, m. . -...J °' TABLE III

SYNTHESIS AND,PROPERTIES OF OPTICALLY ACTIVE PHOSPHORUS COMPOUNDS II-VII

Analysis,% [O! Jt') o· J.J. Cpd. Yield,a M.p., ,C .. :.: c .H N p (c, g./100 mlj % in chlorofor · Ca led. Found Ca led. Found Ca led. Found Ca led. Found

II 71. 7 192,-193 , +33.523 · 5 (6.160) 4.36 4.31 9.64 9.57

III 61. 3 121 . 5 ":' 12 2. 5 . __ · +19.624 , 0(5.467) 4.18 4.05 9.24 9.29

IV 60.8 163-164 -44.824 · 5 (3.261) · 3. 77 3.70 8.34 8.11

v '.51. 2 72-73 -73.025 · 5 (8.280) 74.13 74.17 8.20 8.15 8.69 8.69 VI 53.8 74-75 -14. i 5 · 5 (s. 892) 74.55 74.61 7.68 . 7 .66 8. 74 9.01 VII 43.1 42-43 +4.1824 · O(4. 658) 70.81 71.04 7.34 .7.41 10.74 10.89

aYields are based on optically active amine or alcohol as starting material.

-..J -..J CHAPTER III

EXPERIMENTALa-e

Preparation of Diphenyiphosphinic Chloride (I). This compound was 3 synthesized by modification of a known procedure. . A c,ylinder of chlor- ine was connected through a trap to a 3-1.1 3-necked flask equipped with a mechanical stirrer, a condenser with a drying tube, a thermometer, and a fritted glass delivery tube. To the flask was added 761.6 g.

(3.45 moles) of diphenylphosphinous chloride (neat). Phosphorus pent- oxide (155 g., 1.09 moles) was slowly added to the flask with gentle stirring, and a suspension of the solid in the acid chloride was ob- tained. With vigorous stirring, chlorine gas was passed into the flask

aAll melting points are corrected; all boiling points are uncor­ rected. The petroleum ether used boiled at 37.4-50.7°.

bThe infrared spectra were determined using a Beckman IR-SA spec­ trometer as films on sodium chloride plates or as potassium bromide pellets.

cThe microanalyseswere performed by Galbraith Laboratories, Knox­ ville, Tennessee.

dThe proton nuclear magnetic resonance spectra were determined on a Varian .A-60 high resolution spectrometer with a field-sensing stabil­ izer ("Super-Stabilizer"). Tetramethylsilane was used as an internal standard. The solvent employed was deuterochloroform.

eThe optical rotations were obtained using a Model 80 universal high precision polarimeter manufactured by O. C. Rudolph and Sons, Caldwell, New Jersey. The solvent used was Certified A.C.S. chloroform sold by Fisher Scientific Company.

78 through the fritted glass tube at such a rate that the exothermic reac-

tion produced a slow rise in temperature. When the temperature reached

70° (20 minutes), a water bath was applied and the temperature was held

between 70 and 80.0 Chlorination of the mixture was continued until a

greenish color developed in it (color change occurred abruptly). A

slow stream.of chlorine gas-was maintained while the mixture was heated

slowly to 110° at which point the chlorination was terminated. The

mixture was then boiled for L 5 hours (maximum temperature attained was

145°). Distillation of the phosphoryl chloride was accomplished at

reduced pressure using a potassium hydroxide-calcium oxide trap between

the apparatus and the water aspirator. The mixture was heated (71-76°)

until 150 ml. of phosphoryl chloride had been collected and the distil-

lation was terminated. Transfer of the reaction mixture to a 2-1.

distillation flask was accomplished under anhydrous conditions. Di-

phenylphosphinic chloride was distilled in vacuo [142-147°/0.0l mm.;

lit. 21 135-136°/0.07 mm.]; yield 518.1 g. (63.6%)[n~4 · 5 1,6076; lit. 21 20 nD 1.6068].

Preparation of Optically Active N-Substituted Diphenylphosphinic

Amides II-IV. The general method54 of preparation is illustrated in

detail for ( +) - N- (Q'=methylbenzyl )d ipllenylpho sphiriic. · amide (II). Sig-

nificant deviations from the general procedure are then stated for the

other amides III and IV. Elemental analyses (Table III) and spectral

data (Tables I-II) support the proposed structures for II-IV.

A 200-ml., 3-necked flask equipped with a magnetic stirring bar,

addition funnel, condenser, and thermometer was charged with a solution

·of 3.5 g. (0.0289 mole) of (+)-Q'-methylbenzylamine ([a]~3 = +35.6°)

in 160 ml. of anhydrous (dried over Linde 3A molecular sieve) ethyl. 80

ether. Diphenylphosphinic chloride (3,41 g. 1 0,0144 mole) in 15 ml. of anhydrous ethyl ether was added dropwise at such a rate as to cause gentle boiling of the solvenL The addition required 10 minutes, The reaction mixture was then boiled (34°) for 6 hours. The amide and the hydrochloride of the amine were removed from the ether by filtration,

This solid residue was washed with four 125-ml. portions of water.

Recrystallization of the remaining solid from ethanol00 water (2: 1) gave

3.3 g. (71,7%) of II, m.p. 192-193°.

A mechanical stirrer was used in the preparation of (+)-N-(a­ methylphen?thyl)diphenylphosphinic imide (III) and of (-)-N-[a-(1- naphthyl)ethyl]diphenylphosphinic amide (IV). Diphenylphosphinic chloride (17. 5 g.; O. 074 mole) in 50 ml. of anhydrous ethyl ether was added dropwise to 20,0 g. (0,148 mole) of (+)-a-methylphenethylamine

([a]~3 = +36.2°) in 250 ml. of anhydrous ethyl ether. Other reaction conditions and workup were essentially the same as those for II. Re- crystallization of the crude product from chloroform-heptane (1:3) gave

15.2 g. (61.3%) of III 1 m.p. 121.5-122.5°.

Diphenylphosphinic chloride (13.8 g.; 0.0585 mole) in 50 ma, of anhydrous ethyl ether was added dropwise to 20,0 g. (0.117 mole) of

( +)-a- (1-naphthyl)ethylamiri.e ([Cl!]~4 = +41. 3°) in 350 ml, of anhydrous ethyl ether. Again other reaction conditions and workup were essen­ tially the same as those for II. Recrystallization from benzene-heptane

gave 13.2 g. (60.8%) of IV 1 m.p. 163-164°.

Preparation of (-)-Menthyl Diphenylphosphinate (V). A 500-mw.

flask was equipped with an immersion thermometer, nitrogen inlet tube 1

mechanical stirrer, addition funnel 1 condenser 1 and calcium chloride drying tube. An oil bath was placed around the reaction flask. Sodium 81

(2.76 g.:; 0.12 Q1ole), 15.63 g. (0.10 mole) of (-)-menthol ([0!]~3 =

~44.7.0 ), and 50 ml. of toluene (dried over sodium) were stirred vigor- o 35 ously for 7 hours while the oil bath temperature was held at 100-105 .

After the mixture was allowed to cool to room temperature, the unreac- ted chunk of sodium was removed mechanically. Next 26.0 g. (0.11 mole) of diphenylphosphinic chloride in 50 ml. of toluene was added dropwise to the sodium alkoxide with external cooling. During addition (15 minutes), the temperature was kept below 40.0 The mixture was then boiled at 85° for 4 hours, cooled, extracted with 200 ml. of 5% sodium bicarbonate, and washed with water. Steam distillation of the organic layer was performed until about 1.5 1. of distillate had been collected in order to remove the unreacted menthol. The nonvolatile organic residue was extracted with ethyl ether. The ether solution was dried

(Mgso4 ) and then evaporated. After a small amount of n-hexane was added to the residual oil, cooli~g in dry ice-acetone bath caused solid- ification. Recrystallization from _g-hexane gave 18.25 g. (51,2%) of V, m.p. 72-73.0 Elemental analysis (Table III) and spectral data (Tables

I-II) support the proposed structure.

Preparation of (-)-Bornyl Diphenylphosphinate (VI). The reaction conditions and workup were essentially the same as those for V. Amounts of sodium, toluene, and diphenylphosphinic chloride were the same as above. The weight of (-)=borneol ([0!]~3 = -20,8°) used was 15.43 g.

(0.10 mole). Recrystallization from_!!=hexane gave 19.1 g. (53.8%) of

VI, m.p. 74-75 0 . Elemental analysis (Table III) and spectral data

(Tables I-II) support the proposed structure,

Preparation of (+)-2-Methyl-l-butyl Diphenylphosphinate (VII).

The apparatus used was the same as that used for V. Diphenylphosphinic 82:. chloride (26. 0 g. ;, 0, 11 mole) in 50 ml. of anhydrous (Linde 3A molecul- ar sieve) ethyl ether was added dropwise to 12.15 g. (0.12 mole) of triethylamine and 8, 8 g. (0, 10 mole) of (-)-2-methyl-1-butanol ([Q']~3

-5. 33°) in 150 ml. of anhydrous ethyl ether. The temperature rose from

25 to 30° during the 10-minute addition, After the mixture was boiled

at 37° for 4 hours 9 it was stirred at room temperature for 1 hour. The mixture was then extracted with 400 ml. of 5% sodium bicarbonate and washed with water. Steam distillation of the organic layer was per- formed until 0,5 1. of distillate had been collected in order to remove the unreacted alcohol and amine. The nonvolatile organic residue was extracted with a1mixture of benzene and ethyl ether. After drying the organic layer (Mgso4) and evaporation of the solvent~ the crude ester VII was mixed with 250 ml. of warm hexane (50°). The resultingj warm mixture was filtered to remove 0.4 g. of diphenylphosphinic acid; then the solvent was evaporated from the filtrate. Cooling of the residual oil to -15° made it solidify. Recrystallization of the solid from n­ hexane-ethyl ether (20:1) gave 12.4 g. (43.1%) of VIIj m.p. 42-43°.

Elemental analysis (Table III) and spectral data (Tables I-II) are in accord with the proposed structure, Plate I

WAVENUMBER CM·'

5000 4000 1200 1100 1000 900 800 700 650 10°1·-·· 1::-::1:···:1::::1:· :1·::1·:· ·1 ::.1··:.:1:· :1:··:1:·::1 ::1. :1:· 1·.::1:· :1:··:1::::1 :::1:·::1::::1::::1::::1:.:::1.·1.::T:·r;·~:~::.;:r:::-;--:=;=t100 90[IIJ=:=[IIJJJ~II~J_---+~---+--~-+--~-+-----+-----i------l------i-~--+-~--+-~---f----~t---..:_...:t----:-...:_H---:--i--:---:--i-'--H--t~-:=;:t:T'-rtt~-rtttt~:-ttt~-:t:u:!i;:ttt!1::tt·t·I··1··@· 90 80 : : I ... : I : . : I : . .;..I..: it! /\r··v ,, II : I : I : : .• I ·. : 11 .,, : . I . . : I : : : : I : : : : I .. : : I : : : I,... \: I : . : ;' I : . : I ',; : : I : . : : I : : : : I : : : : I • : ! I : : : : J: :.1.11 80

10 1::~:1·~:·1 :: 1:· i.J'PI 1v:.1·:::1::•,11:1· IPlll\r \.IV! .. J:·::11 ·:u:::fl{\':I·' 1:~:·:1::::1::::f;:'.:1::::11:~:~.1 70 so I : : : : '.fi 1 1 . : : I /. . . I . I : : : I . I : I : \ I I : ' . I 1 ... . I. . 1 .· ...· · · I : · : I 1 . r ' II f .I ·. ·. l ·. . I : . 11 I: : : I : . . i : : I 111: . : : I~ .. : I : .. : I . : I : . : : I . • .I 60 sot;,....,. 11 ll I I I l I I \If I I I I Ii I !II JI' 111 I \IJ I I VII I', I :1·::L..;,"4: :1 so

40 I : : : : I : : : I I 11111 I . I I I I I 11 I : . I . I : I : I :/ I : . ·r: I J: I I I .' ; . I . I I : : I : . I I : : II : I : : JI : : I : :r : I ; : : : I : : I 40

3o I : L: I .\ T I . : I I I : : : : I : ·. : : I : : : . I . : : : I : . : : I l .'l :11 : :1: .: II :1: : ; i : ,: : .; fl : : : I ;-; :~·1 30

,o I:: : : 4: : : : I lJ : 1 : . : : I . . : • I . : I : I . I : . : • F : 1 : : : I I I : : ! 4 ; .. I .: Y : I : : I : : : I : . : : I : . : : I : .. : I : . : 1 :. : \ i' I : : 'i 11 , l : : 1 I; : : I: ! : :.1 ;.:;. J.:1.1 20

10 1-=::.-:·1:;:1·~· 1•••• 1.:·.1:.::1.:·:1:::.1 ·: I• ••I• •. 1:•••l••·'tll••?.W•••J• .1.::··1.:::j .•• 1•• :.1:;;1;: 1:.:·: 1::::L;;;T~t1 u;:-:11·4:1r::1 10 t·:w·~ :; 1, • •1 • • • • 1•- • • • 1·--=i-:-m-··--1= .• 1 • ·• .• - i.• •• • 1 • • •- • 1-•- • • 1 • •.. l-•. <·I ; • . • 1: • •-· • l •- rn:tttrwtrsrtIJ 1 HH ifrH iJt-iM~1~1t~acHffl o 10 11 12 13 14 15 16

WAVELENGTH IN MICRONS

(+)-N-(a-Methylbenzyl)diphenylphosphinic Amide (II), KBr Pellet

00 L,.J Plate II

WAVENUMBER CM·'

1500 1400 700

100 100

90 90

80 80

70 70

60 60

50 50

40 40

30 30

20 20

10 10

0 ij__:_c_d .. ,T' •, ,j'c O : 0 , Ji+• :q H i+j ,:,=1::r::1°fcEFEflJ=r=13±:icff.P=!-'.1T..fll:ff:l 10 11 12 13 14 15 16

WAVELENGTH IN MICRONS

(+)-N-(a-Methylphenethyl)diphenylphosphinic Amide (III), KBr Pellet

CXl -I> Plate III

WAVENUMBER CM 1

5000 4000 1400 1300 1200 1100 700 650 CT fl :-l, 1+111,IJ dl1L!:Jlf-:J 100 100

90 90

80 80

70 70

60 60

50 50

40 40

30 30

20 20

10 10

o I i

WAVELENGTH JN MICRONS

(-)-N-[a-(1-Naphthyl)ethyl]diphenylphosphinic Amide (IV), KBr Pellet

00 Ln Plate IV

WAVENUMBER CM '

5000 4000 3000 2500 1500 1100 900 800 700 650 ••

r':'="'-:--r-:c-~',--1~:---:--'--1----:-;-;--'--t-;-;--'-;-+-'----:--=-c'+-'----:-----:-'+.:..--;---'----'-t-:---:--'----:--t-;-;--;-;--+-;-;-.:..--;--+---'-.:..--;-+-'----:-:---:-+-:-...;_;-;-t-'--;-;--;-t-,--;--;----;-t-,--;-;-'-,f---,---'----:---;-,--;-.:..--;--;--,--'-;-;--'--l----:-:---:--'--t----:---;--'--t-;.c;'-i--;-++=fcf'!-++'f----:-'+~~S,:l',l'Cf',-3"l3'333 100 w w

w ro

ro ro

I . . : : : : : : : • • . t1 I • • • \; ; i ; i ; i ii :-: i'i jj. _ll i+:" 60 bU .. -· 'Ii' ···: •••• :••• •:•: ··1 <\r ·I In: :{ ·, : .• •• A~(,., :jV· T:· '''hi ,,, :;]·! :;-iL,

Or~~: .. ~::;: 0 - .:- ·-;- :...--: ::: j_-;_:.r_l .. 1:i JJJ-tI1J\f :Ef-~41*+=+:_1:_- tO 11 12 13 14 15 ·16

WAVELENGTH IN MICRONS

(-)-Menthyl Diphenylphosphinate (V), KBr Pellet

00 0\ 87

.µ Q) ...... Q) P-i 1-,f ~ ,...,. 1-1 .._,,:::>

Q) U1z .µ 0 ,.u'" r::Cl! •.-l ;!, ..c: j!: 0.. ..z 11.l ~ 0 > ..c: 0.. "~ ...... :>.. r:: Q) ..c: 0.. •.-l A ...... ~ 1-,f 0 ~ ,...,.I .._,,I Plate VI

WAVENUMBER CM 1

1300 1200 1000 900 800 700 650

100 100

~ ~

~ ~

ro ro

OU ; : ; ; ; : ; ; ; ; .

10

10 11 12 13 14 15 16

WAVELENGTH IN MICRONS

(+)-2-Methyl-l-butyl Diphenylphosphinate (VII), KBr Pellet

00 00 Plate VII

2.0 3.0 4.0 s'.o PPM (T) 6.0 7.0 8.0 9.0 i'o

1000 I )-H~ 500 400 300 200 100 CPS I 250 I H 100 I I l r I H3 c iillll NHP(O)(C6H5) 2 c•••- I I I C6H5

r . ~r \---~-~-~-=··h---·=-~=~--r-=,'~~"-~"-=JL _ _;

8.0 7,0 6.0 5.0 PPM( c\) 4.0 3.0 2.0 1.0 0

(+)=N=a=Methylpenzyldiphenylphosphinic Amide (II)

Solvent . . . . .CDC1 3 R.F...... 0,05 mG s. w...... 500 cps S.A...... 8.0 ', 00 F.B .• . . . . ~ l. Oc icps S.T...... 250 sec s.o...... • 004 cps I.A. . . . • off \Cl Plate VIII

2.0 3.0 4.0 s'.o PPM{T) 6.0 T.O 8.0 9.0 fo

1000 I )-H~ 500 400 300 200 100 O CPS 2lo I 100 I 50

H3CCHNHP(O)(C6H5) 2 I CH2C6H5

8.0 7.0 6.0 5.0--PPM(c5 ) 4.0 3.0 2.0 1.0 0

(+)=N=~=Methylphenethyldiphenylphosphinic Amide (III)

Solvent . • CDC1 0 . . . 3 R.F. . . . . ' . 0.05 mG s. w. . . . . 500 cps S.A. . . . ' . 4.0 I.Cl F .B .• . . . LO, cps S.T...... 250 sec s.o...... 000 cps I.A...... off 0 Plate IX

2.0 3.0 4.0 5'.0 PPM(T) 6.0 7.0 8.0 9.0 fo

1000· I >-H~ 500 400 300 200 100 O CPS 2lo I 100 I I H3C~HNHP(O)(C6H5) 2 '. l .. ··?J.····II~. .

. ·. . \. . . . A/\. • . . . • .·. ~ . ~-__...I'~·--- ...... , ~ - -~-.-----~ .

. . . 6.0 ------8,0 7.0 5.0 PPM( o j 4.0 3.0 2.0 1.0 0 (=)=N-[Ol=(l.,;,Naphthyl)ethyl]diphenylphosphinic Amide (IV)

Solvent " 0 ' ' ,CDC1 3 R,F, ' ' ' 0 . " " 0, 05 mG SoW. ' . 0 . . " 500 cps S.A" . 0 . 0 • 603 \0

F, Bo, 0 0 0 0 0 0 0 0 0 0 I-' , :1,0 cps SOTO . . • 250 ·Sec SoQo . . . • 001 cps Io A, ' . . . off Plate X

2.0 3.0 4.0 s'.o PPM ('T) 6.0 7.0 8.0 9.0 ltO

1()00 I }-H~ 500 400 300 200 100 O CPS I 250 oO. 8:3 ~ CH I ·~ 100 I 50 .,...._..,,0P(O) (C6H5) 6' ' 2 I' ' H '1r-~ so. 88 • .. A 64Jl ,.Ii 60,55 t13C GH 3

)

.· ~"'f"...f~\ ~-"!;;o,.~,w,,o;.,.· ...... ,;,~\4~-··=~".,,;;;·~4a;,,.,4;i,#¥'-'f,.,;.,;i

8.0 7.0 6.0 5.0 PPM( o) 4.0 3.0 2.0 1.0 0

(-)-Menthyl Diphenylphosphinate (V)

Solvent ,CDC1 3 R.F., 0 0.05 mG S. W, 500 cps S.A. ,10.0

N F. B .• 0 .2.0 cps S.T~ 0 0 0 0 250 sec s. o: . 000 cps I.A. . off '° Plate XI

2.0 3.0 4.0 s'.o PPM ('T) 6.0 7.0 8.0 9.0 1•0

1000 I >-H~ 500 400 300 200 100 O CPS I 250 I 'f° 50 H

OP(O)(C6H5)2 ~ \

8.0 7.0 6.0 5.0 PPM( o) 4.0 3.0 2.0 1.0 0

( = )~Bornyl Diphenylphosphinatie (VI)

, lvent , ' ' ' ,CDC1 3 R,L ' ' 0,05 mG S,W, ,500 cps S,A. . . 4.0 F, B,, ,LO cps 250 sec ~LO, ,000 icps I, A, ' ' ' So To ' ' ' . ' ' . off w'° Plate XII

2.0 3.0 4.0 s'.o PPM (7') 6.0 7.0 8.0 9.0 l'o

1000 I r-H:;)> 500 400 300 200 100 O CPS I CH 250 I I 3 100 i i 50 I HIP C !lllJCH20P(O)(C6H5 ) 2 I I ! C2H5

~l'

.) ,, ''rn.~r~~~~Zz.?~~.. ~~_:m"-~~ .. -~~ .r,:n;...... ~· =wk.t~

8.0 7.0 6.0 5.0 PPM ( o) 4.0 3.0 2.0 1.0 0

(+)=2=Methyl=l=butyl Diphenylphosphinate (VII)

R ,, .i,"'

1. Aaron, H. s.,. Shryne, T. ij09 and Miller, J, I,, J, Am. Chem, Soc, 9 80, 107 (1958) .•

2. Aaron 9 H. S., Uyeda, R. T., Frack 9 H.F., and Miller, J, I, 9 ibid,, 84, 617 (1962).

3. · Austin 9 T. H,, "I. A Study of the Nucleophilic .Displacement Reac= .tion on Trimethyl Phosphite by Phenyl Grignard Reagen:t, II, The Pyrolytic Decomposition of Alkyl Diphenylphosphinates== An Olefin=Forming. Elimination· Reaction," Ph, n: dissertation, Oklahoma State University 9 1965,

11 4, Bellamy 9 L. J., "The Infra=red Spectra of Complex Molecules 9 J, . Wiley and Sons, New York, N. Y,, 1956,

5, Berlin, K, D, and Pagilagan9 R. U, 9 J. Org. Chem. 9 32, 129 (1967),

6. Blade-Font, A, 9 VanderWeff, C. A., and McEwen, W. E., J,Am. Chem.

Soc, 9 ~. 2396 (1960),

7. Blade~Font, A., Vanderwerf, C, A, 9 and McEwen 9 W. E., ibid,,~.

26"-6 (1960) 0

8.' Boter 9 H. L. 9 .Oooms 9 A. J, JO 9 Van den Berg 9 G, R. 9 and Van Dijk, c. 9 Rec, Trav. Chem. 9 ...§2.9 147 (1966).

9. Brewster 9 J. H. 9 J. Am, Chem, Soc, 9 .§.b 5475 (1959).

10. · Brewster, ,JO H. 9 ibid o 9 fil,9 .5483 (1.959) •

11. Brewster, J, H., ibid, 9 81 9 5493· (19.59),

12. Brewster, J. H. 9 • Tetrahedron 9 Jd9 106 (1961).

13. ·Cammarata 9 A., J ..Chem. Ed, 9 43 9 64 (1966).

14 .. Campbell 9 J. G. M. and Way 9 . J, K, 9 J. Chem. Soc,, 5034 (1960),

15. Cherbuliez, E. and Rabinowitz, J. 9 .U. S. 3 9 268,629 (1966); Chem.

· Abstr. 9 . 65 9 17003 (1966),

16, Penney, D, B. and Hanifin 9 J, W. 9 Jr., Tetrahedron Lett., 2177 (1963).

95 96

17. Denney, D. B, 9 Tsolis 9 A. K. 9 and Mislow, K, 9 J. Am. Chem. Soc.SI ~' 4486 (1964).

18. Gerrard, A. F. and Hamer 9 N. K. 9 Chem. Commun.SI 475 (1966).

19. Hart 9 F. A. and Mann. 9 F. G. 9 J, Chem, Soc, 9 4107 (1955).

20. Hellwinke1 9 D. 9 Chem, Ber, 9 22, 9 3642 (1966).

21. Higgens, W. A. 9 Vogel 9 P. W., and Craig, W. G., J, Am. Chem. Soc. 9 ll, 1864 (1955).

22. Holliman 9 F. G. and Mann 9 F. G, 9 J, Chem. Soc.SI 1634 (1947).

23. Horner 9 L. H. 9 Pure Appl. Chem, 9 2, 9 225 (1964).

24. HornerSI L. H. and Balzer 9 W. D, 9 Tetrahedron Lett., 1157 (1965).

25, Horner 9 L. H. and Mentrupp 9 A.SI An.n, 9 646 9 65 (1961).

26. Hornerll L. H.SI RottgerSI F. 9 and FuchsSI H. 9 Chem, Ber., 96, 3141

(1963) 0

27. Horner SI L. H. SI Schedlbauer 9 F. SI an.d Beck:1 p •• Tetrahedron Lett., 1421 (1964).

28. Horner 9 L. H. and Winkler 9 H. • ibid o SI 2177 (1963).

29. Horner. L. H. and Winkler, H. SI ibid9, 175 (1964}.

30. Horner SI L. H. and Winkler 9 H. SI ibid., 455 (1964).

31. Horner, L. H. and Winkler, H. • ibid, SI 461 (1964).

32. Horner, L. H. and Winkler, H.» ibid., 3275 (1964).

33. Horner. L. H. » Winkler SI H. ll Rapp, A, 9 Mentrupp, A.SI Hoffmann 9 H.,

and Beck, p O • ibid .• 161 (1961) 0

34. Hudson 9 R. F. and Green 9 M. SI Angew. Chem. In.ternat. Edit,, 1 9 11 (1963).

35, Ingersol 9 A, W,SI "Preparation of (-)-Menthoxyacetic Acid," in

AdamsSI R. et al, 9 Eds.SI Organic Reactions 9 Vol. II, J. Wiley and Sons. New York. N. Y., 1944ll p. 398.

36. K.orpiunll 0, and Mislow 9 K.• J, Am. Chem. Soc.SI 89, 4784 (1967).

37. Kumli 9 K. F., McEwen, W. E, 9 and Vander Werf 9 C, A., ibid.,~.

248 (1959) 0

38. Kumli 9 K, F. 9 Vander Werf 9 C. A, 9 and McEwen 9 W. E .• ibid., 81, 3805 (1959). 97

39. Lewis 9 R, A. 9 Korpiun, O., and Mislow, K, 9 ibid., 89, 4786 (1967).

40, McEwen, W. E., "Stereochemistry of Reactions of Organophosphorus Compounds," in Grayson, ,M., and Griffithll E. J., Eds., Topics

in Phosphorus Chemistry, Vol. II, New York 9 N. Y., 1965, Chap­ ter l,

41. McEwen 9 W. E., Blade-Fontll A., and Vander Werf, C. A., J. Am. Chem, Soc., 84. 677 (1962).

42. McEwen 9 W. E., Vanderwerf, C. A., Blade-Font, A., Parisek, C. B.,

Keldsen 9 G., Velez, D. C., Young, D. P. 9 Kumli, K.• and Axelrad, G., Abstracts of Papers, 140th ACS Meeting, Chicagoll Septemberll 1961, p. 96Q.

43. Meisenheimer,, J. and Lichtenstadt, L., Bet), 44,j 3'.56 :(19.11),

44. Michalski, J., Bull. Soc. Chim. France, 1109 (1967).

45. Michalski, J, and Mikolajczyk, M., Chem, Ind. (London), 661 (1964),

46. Michalski, J. and Mikolajczyk, M., Chem, Commun., 35 (1965).

47. Michalski, J. and Mikolajczyk, M., Tetrahedron,~' 3055 (1966).

48. Michalski, J. 9 Mikolajczyk, M., and Omelanczuk, J., Tetrahedron Lett., 1779 (1965).

49. Mikolajczyk, M,, Tetrahedron. 23, /.543 (1967).

SO. Muetterties, E. L., Mahler, W. 9 and Schmutzler. R., Inorg. Chem., l, 613 (1963).

51. Parisekll C. B. 9 McEwen, W. E~, and Vanderwerf, C. A., J. Am. Chem.

Soc., 82 9 5503 (1960).

52. Peerdeman, A. F., Holst, J. P. c .• Horner, L. H., and Winkler 9 H., Tetrahedron Lett.~ 811 (1965),

53. Petrov, K. A, 9 Baksova, R. A. 9 Korkhoyanu, L. V. ll Sinogeikina, L,

P, 9 and Skudina 9 T. V., J, Gen, Chem, USSR, 35, 723 (1965).

54. Pivonka, W. C., Unpublished results,

55. Seiber, J. N. and Tolkmith, H'.,_ Tetrahedr:0n:Le,tt.,:'~33):3 ,(/f%7).

56. Tomoskozi, I .• Tetrahedron, 22, 179 (1966).

57. Wittig, G, 9 Cristau, H. J. 9 and Braun, H. 9 Angew, Chem, Internat. Edit.,&,, 700 (1967).

58. Young, D, P., McEwen 9 W. E., Velez, D. C, 9 Johnson, J. W,, and Vanderwerf, C. A,, Tetrahedron Lett., 359 (1964). VITA

Donald Howard.Burpo

Candidate for the Degree of

Doctor of Philosophy

Thesis: I. REACTIONS OF ORTHO-SUBSTITUTED AROYL CHLORIDES WITH TRIALKYL PHOSPHITES II. SOME SYNTHESES OF OPTICALLY ACTIVE PHOSPHORUS COMPOUNDS

Major Field: Organic Chemistry

Biographical:

Personal Data: The author was born. in Cushing, Oklahoma, on December 17, 1941, the son of Loyd V. and Ruby Burpo.

Education: The author attended the Ponca City Public School Sys­ tem and graduated from Ponca Senior High School in Ponca City, Oklahoma, in 1959. He received the Bachelor of Science degree from Bethany Nazarene College, Bethany, Oklahoma, in 1963. He received a Master of Science degree from Oklahoma State University, Stillwater, Oklahoma, in 1965. At Oklahoma State University he completed the requirements for the Doctor of Philosophy degree in May, 1968.

Professional Experience: The author worked in the chemical divi­ sons of Continental Oil Compapy and of Halliburton Company during the summers of 1963 and. 1964, respectively. He served as a graduate teaching assistant during 1963-1964 and during 1967-1968, He also served as a graduate research assistant from September, 1964, to May, 1967.

Membership in Professional Societies: The author is a member of Phi Lambda Upsilon.