UNCLASSI FIED

AD29 _6

ARMED SERVICES TECHNICAL iNFORMATION AGENCYARLINGTON HALL STATIONARLINGTON 12, VIRGINIA

UNCLASSIFIED

NOTICE: When government or other drawings, speci-fications or other data are used for any purposeother than in connection with a definitely relatedgovern-ent procurement operation the U. S.Govertment thereby incurs no responsibility nor anyobligation whatsoever; and the fact that the Govern-ment may have fomuated, furnished or in an y waysupplied the said drawings, specifications, or otherdata is not to be regarded by implication or other-wise as in any manner licensing the holder or anyother person or corporation, or conveying any rights,or permission to manufacture, use or sell anypatented invention that may in any way be relatedthereto.

NOT R ELEASABLE

T0 OISDepartmenit or chemistry

f Duke University

Cq Durham, North Carolina

c -in& R-port

CertAin Reactions of Organoietal1ic

C.) c:r: Compounds and Some Cy)clizat ions

Contract No. DA-36"O3d-O0D-2O11

forthepelod1 eptember I95 -31 ecember 1962

Submitted byCharles R. Haus erChief Investigator

NO OTS

The first Sectioft of this report lists the titles thereports issued during the period 1 JUl1Y 1955- i 311 Augut1959. The second section lists additional. repor-ts issuedduring the latter part of conitract along- with a dsuss3Inof work still ina progress.

xL443-C

1. Acylatious of Nitriles with Esters by Sod-ium Amide in Liquid AuMonisato, Form:0-etonitrilles6 Consideration of Amide Formtion, by CharlesJ6 Eby, and Cf.R. Haner, in .1 An Chm So 79 (1957), p 723-725.AD-13 00A&

2. Cycijation of O-Ktoitviles or p-Ketoamides Vith Ketones byPolyphospoic Acid to I irfu gubtituted 2-Pyridontes, by C .R. Hauser

d Charles j,. 9by, in 3 Am 2o Chm oc 79 (1951),p~7871 AD"

~. The Conversion of 0.-Ktonitri'ltes to P46~toamid8 by Boo Fluo ridein Aq:ueous Aetic Acid by Polyphosphoric Acid, by C.R. Hauser andCharmlea 3. Eby, in 3' Am ChniSo 79 (19-57)) p 79&-797- ibse-7 006

4i* Aminomethylation of Ferrocene to Form N,N-Dimethyla-minomethylfer-roceaind Itb Conversion to the orreSPonding Alcohol and Aldehbyde byJacque K.- L-ndsay and C.R. Banner, in J_ ~ hi 2 (1957), "55-358.AD-137 002

5.Certain Acylat±±ons of Ferrocene and Some Condenasations Invol1vingthe a-Hyd ogen of Acetylferrocene, by C .R * Hauser and Jacque KLindsay, -in J 9M Chm- 22 (1957), p I482" 8. AD-137 007

6. Some Typical Aldehyde Addition -and Condensation Reactiow~of Forinyl-ferrocene, by C.R. Bauser and Jacque K. Lindsay,. in J hm22(1957), p 906-90. AD-137 008

7. N=-nd C-3enzoylation of p-minoacetophenone with Mthyl Benxioateby Sodlum Aide. Synthegis of P Diketones Waving p"Aqyl*;ino and

plyzOxy oupo, by C.R. Bagger and Chwles 3'. Eby, in J jChaan22 (957, p909"912. AD-l37 Oil

81. ANovo! Ring inr net Involving the ortho $mbtitution Rearoangepnent by Means of So ium Amid. in Li-quAANZonia, by Daniel L4iceiAn4 P.R. hauser, 1.n J Am Ce 422c 79 (1957 ), P 199"4-51. AD-137 012

9. 0-om eActious of the Xottiodlide of NNi-Diinetylainuoueth+.-ylerroone,by 0.R. Rawer ad Athera. ()s sub to hi)

1443-C

10. Certain Alklations vith the Methiodide of Nj,N-Detbyiaminomethyi-.ferrocene. Synthesis of an *.*Amino Acid Awing the FerroceneGroup, by C. &,user and Iacoze K, -Lindsay, in 0 Ce 22 (1957),p 12-46-1247. AD-137 013

U, . Rearrangemfenlt of 2, 4 ,o6 rfriioprpy-benytrimthyla.-moni-um on b-ySodium Amide to ForM an Mo-Methy~enecycohexadieneamine and ItsReactions- by Donald X. VaEnam and C .A. Blauser, in, J A mgaoc 79 (195-7), p5 -50-5524. AD-15 014

12.i Reaction, of 9-fromoethylofefluorenei with Potassium .Aside inivuid Ama-oni Z a O Dimeri ati--n- by- C.R. Hauser and Daniel Ledniaer,

in J 2M Chem 22 (1957),j p 12 .81Z50. AD -iS-3, 015

15. Conjuga&te Addition Condensations of Diphenylmethane Involving Mths-ylene Hydrogen, by Potassium Amide. Cyclizations of ProdUcts byPolyphospboric Acid, -by Ma.vin T. Tetenibaum and C.R, Hauser, inJ ~ hm2 158), p 229"255. AD.-137 067

14. Condesations of Benthy-dryl-Ithyl Ethe In volvinhg a-Hydrognb

Potassium Am-ide. CycJlizationi of Conjugate Addition Product byPolyphospboric Acid, by Cilt. ilauser and Ma-n .eebauam, inJ 2-: 2h~nj 23 (1958), P 253-235. AD-137 069

15. The ortho Substitution Rearrangemenlt and Certain Rel.ated Reactiornsin the Naplhthylene Series by Sodium Amide, by C.R. fauser,, Donald N.Van Eenam and PhiLlp L, Bayless, inJ9 Ciu 2 (1958), p 354w558. AD-137 070

16. Reaction of the Methiodide of NN-Dilethya noiethylfroane

with Potassium Cyande to Form Fer-rocylacetonitrile, by DanielLdicer, Jacque K. aids an C.R. BauseriJ Chm2(15)

p 653"655. __

17. Rearrangem~ent of the Methiodide of N.N-Diethyla noiethyferrocen,by Potassium Aznide in Liquid Ammonia, by C .R. Hauser Jacque K.Lindsa and Da)iel Lednacer., 1.n J Og C3rn 2(98,p 5-0.AM - 1 - 7 o-6 8_ __

18. Five-" vs. Six-Memnbered Ring Formaion in the Cyclization of 2,.,4-Triphen~1butyric Acid; the Relative Importance of Stereocemistry,by Daiel Ledncer and C.A. Hauser.. in J Am Ch Scem.198)p 34109"34l2. ,l) 401 e(9

19. a, O-DiPhentylbutyronitrile- (Eyh- Ioe), by C .R. Hauser ahd

20. ~,riphenyl rpontie, by C.R6 Hauser and W.R. DwmnaVaIt.(4s &Ub4 to gypSnthesis).

2-1. , -ihenylpropionic AcidI by C .R. Hauser and W.R. Dunnavant.(subto Synthess.

22. ac.gp-,Triphenylpropinic Acid, by C .R., Hauser and W .R * Dunnavant.(Ms sub to J Oraher)

25. Reductive Met-lation of Bentzophenione and Benztacetophfienonte byAlk&ai Met..ls in Liquid Atmonia and Somie Condenuations. of theResulting Dialkcali Salts, byPhllip J. H-anrick, r n ?R aasrin J AMCm So 81 (159), p 4934966

24. Alkylations of Certain Carbaniong with l-Chloro-l, 2-Dephenylethane6P-Eliminations with Other Bases, by C .R. iAusr Charles F. HUserand Phillip J. Hamrick, Jr., in J 23 Ce 2(1958), P 751I.jOi)/'

25. The Benzal Derivative of Fertocenylaetonitrile, by C.R. IH auser andCharles E. Cain, in .1 M Phe32 (1958), p 2006-2007.

26. The Methiodide of N-C if benzyloxy-2, 6-dimethylbenzy )-N, N-Dimethyl-amine. Attempted Rearrangement, by Daniel Lednicer and C .R. HAuser,in i 2M Chei 25 (1958), -p 2008-2009.

27. Rydroxymethyl- and FormyJ~ferrocene with OWcdizing AgentB. Bisfer-rocenyaxetby! Ether, by C . Hauser and Charles E. Cain, in jChem. 25 (1958), P 2007-20)8.

28. FTive- vs. Six-Memlbered Ring Formation in Acid Catayzed CyclIzations.n-. 5,J4-Diphelvalepric Acid and 2,5-Diphenyiglutaric Acid byD)aniel Leduicer and C.A. Hausr (n 958C1e.So6564".6367t- 19-) QiO 64 -, 80(158,

29. The Structure of the Product of the Aniomalou Leckart Reactionof 2-Ferrocylethyamno. A Boute to I,2D -sisiue ercnby Daniel Lednicer and C.R. Hauser, -in jg-rChern 21 (1959)1, p 4w6Al) /j/c5(/e?

1443-C

30. Addition Adetions of the Methiodide of Benzo-phenoznethyli-mite WidItts 4.Methyl Anaogue, with Nucleophilic Reageifta, by C.RA. Hauserand Daniel Lednicer, in J Chm 214 (1959), p 46"1496

51. N-ercl~h1NNNTintyam~ Iulodide (Mthiodide of~ byc C.H. Hauser. (Ma sub to ggs

13yntei.

52. Two-Fol1d Alkylationa of Sodium Diphenylmethide with Mthy1--h, M -*Halides to Form bis-BenIzhydr-ylinethvlene Hydroarbafns. Alkcylationisot Sodium Tripheftyl-ethide, by C.R Ilusr Char-lea F., Hauser andP5hillip J1. Hamrick, Jr, in 1 h~~ (1959),. p 397"40

Final Report for Contract with Army Research Office (Durham) for

period September 1, 1959 to December 31, 1962

By Charles R. Hauser

Duke Univevzi-y, Durhamj N. C.

"Certain Reactions of Organometallic Compounds and Some Cyclizations

(A) Publications.- The eighteen original articles listed below

were published or were accepted for publication during the three

year and four month period, September 1, 1959 to December 31, 1962.

Fifteen of the eighteen articles are papers, one is a communication

and two are notes, the communication and notes being indicated.

Ten of the articles were supported wholly by the Army Research

Office (Durham)), and five in part by this Office. Also, five

Preparations were published in Organic syntheses; these are listed

under titles 19-23.

1. "Condensation of Phenylacetic Acid with Certain Ketones

to Form aipha-Phenyl-beta-hydroxy Acids by Alkali *miles. Equili-

brium Factors' P. J. Hamrick, Jr. and C. R. Hauser, J. Am. Chem,

Soc., 82, 1957"1959 (April, 1960).

2. "Synthesis of beta-Hydroxy Esters from Ethyl Acetate and

Ketones or Aldehydes by Means of Lithium Amide. Some Results with

other Esters," W. R. Dunnavant and C. R. Hauser, Je Org. Chem., 25,

501-507 (April, 1960),

3. "2-Acetyl-6-methoxycoumaran-3-one. Benzylation at the

Terminal Methyl Groups," W. I. O'Sullivan and C. R. Hauser, J.

Org. Chem., g, 839 40 (1960)(A Note).

-2-

4&. "Certain Condensations at the Terminal Methyl Group of

3 -Phenylpentane-b2,4k-dionte through Its Dipotassio Derivative Cycli-

zations.." W. 1. O'Sullivan and C. A~. Hauser, j. Org. Chem,25

11l0-4114, (July, 19,60).

5. "Factors in Aldol Conde nat ions of Alkyl Acetates with

benzophenone arid -Reversals by Sodium Amide Versus Lithium, Amide.C. R. Hauser and W. R. Dunnavant,

Metallic Cation Effet,"x:63 Org. Chew., 2,5, 1296"1302 (August, 1960

6. "Condensation of' Alkcyl Acetates with Benzophenone by Lithiui

Aside to ForM: beta-Hydroxy Esters. Relative Ease of self-dondensa"

tion of Esters," W6 R. Dunnavant and C. R. H1auser, .1. Org. Chem.,

gj, 169341699 (October, 1960).

7. "Alkali Catalyzed Aldol Condensation of Bisacetylferrocene

with Benzaldehy-de to Form Mono- and Dibenzaldehyde Derivatives,"

T. A. Mashburn, Jr., C. E. Cain, and C. R. Hauser, :. Org. Chem.,

110 1982-4986 (November, 1960).

8. "Acylations of' Bisacetylferrocene with Esters by Potassium

Amide to Form Bis..beta-diketones. Consideration of Mechanism,*"

C. - . Cain, T.- A . Mashburn, Jr. , and C. R . Hauser, J. Org. Chem. , 26,9

l03o-lo34& (April, 1961).

9. "Influence of the Matellc Cation of Certain Organometallic

Compounds on the Courses of' Some Organic Reactions," W. 1. O'Sulliva

F. W.Sae:W .Hmphlett, and C. R. Hauser, J. Org. Ce. 6

2306-2310 (July, 1961).

10. "some Condensations at the Methylene and Terminal Methyl

Groups of Benzene sulronylace tone Through its Mono- and Dipotassio

Salts.." W. I. O'Sullivan, D, F. Tavares and C. R. Hauser, J. Am.

Chew. Soc., 9-I 3453"3457 (August, 1961).

-3-

11. "Reactions of Alkali Diphenylmethides with Certain Poly-

halides. Displacement on, Halogen or Hydrogen"' C. R. Hauser, W. 0.

Kofron,. W. ft. funnavant, and W. F. 0Owenz, J. Org. Chem., 293 2627-

2629 (August, !961).

12. "2 -w 3-, and 4-ithiobenzyldimethylamines. Grignard

!Reagent of -rmbnydmtyann, P6 N. Jones and C. R. Hauser

J. Org. Chem., 2 -7, 701 (October, 1961) (A Communic-ation) .

1.3. "Acetylation of Benzenesulfonylacetone with Acetic- An-

hydride by Means or Boron Fluoride to Form the Terminal Methyl

Derivative,"e D6 P. Tavares, W. I. O'Sullivan, and C. Ri Hauser,,

Jo Org. Chem., 27, 12,51-1254 (April, 1962).

14. "Ortho-Substitution Rearrangement vs. Elimination Reactic

of Certain Benzyl-Type quaternary Ammonium Ions with Sodium Amide,"

F. N. Jones and C. ft. Hauser, J. Org. Chem., 27, 1542-1547 (May,1962).

15. "Synthesis of 3-Substituted 3-Phenylphthalides," F. N.

Jones and C. R. Hauser, Jr. Org. Chew., 27, 3364 (April, 1962)

(A Note).

16 "rto ubsttto Reragement vs. Elimination Reactior

or Ring-osubstituted Benzyldimethylethylammonium, Ions," F. N. Jones,

and C. R. Hauser, j. Org. Chem., ~,k2O~I Nvme,16)

17. "Halogen-metal Interchan e of 2-, 3-", and 4-Bromobenzyl-w

dimethylamlnes with n-B$utyllithiumq Orignard Reagent of 2.-Bromo-s

benzyldimethylamine," F. N. Jones and C. R. Hauser, j. Org. Chem.,

(in Press).

i."Metalations of' Be nzyldimnethy lamne and Related Amines

with no-Butyllithium In Ether. Deuteration to Form, Ring and Side".

chain Derivatives,." P'. N. Jones,, M. P. Zinn, and C. R. Hauser,

J. Org. Chem., (In Press).

19. a, a ,0-TR IPHE NYLPR OPIONIMUMILEj C. R. Hauser and W. R.Dunnavant, Organic Syntheses, 39-, 73-7 15)

20. NNDMTftAMNEhLEROEEMBTHIODDE, D. Lednicer

and C. R. Hauser, Organic Synthetss 4f 0, 3-1--3- (-196)

21. aI$ DIPHENYLPROP IONT C ACID, C. R, Hauser and W. R,

Dunnavant,, Organic Syntheses, 4Q, 38-40 (1960).

22. FERROCENYLACETONITRILE, D. Lednicer and C. R. Hauser,

Organic Syntheses, 402 45-k6 (l960).

23. HYROXY14ETHYLFERROMEE, L. Lednicer, T. A. Mashburn.. Jr.,.

and C. H. Hauser, Organic Syntheses, 40, 52-53 (1960).

(B Work in Progress.- This work Is considered below under

appropriate titles (i-4). The completeness of' each of the problems

is indicated in the outline. We anticipate that these problems

will be completed under the new grant.

1. "Condensation of Aldehydes, Ketones and Other Compounds

at the Ortho Position of Benzyldimethylamine and Related Amines by

Means of' n-Butyllithbium."

BenzyldImethylamine was converted by n-butyllithium In ether

to the ortho lithio intermediate I, which was condensed with

benzaldehyde and certain substituted benzaldehydes to form II and

with benzophenone and acetone to give IMI The yields were good.

-5

CH~C~ CH2 N(C HS) MN s

O1H

Also, I was condensed with benzonitri-le to af'ford IV (%)and

with cyclohexene oxide to give the ortho derivative V (36%).

KNCH2N(CHC)2 cN(CH3) 9

TV V

Simiarl dibnzymetylamine was metalated with n-butyllithium

to form the ortho lithio intermediate VI, which was condensed with

benzaldehyde to give the Qrtho derivative VII (56%).

CH2 CH2CSHS CHSC

Li CH I

VI VII

jLikewise c,a-dimethylbenzyldimethylamine was metalated with

n-butyliithium to form3 the ortho lithio intermediate VIII" which

was condensed with benzophenone to give IX (57%).

"6

~~~C (ci3)2 g~H)N~H, L!

OH

ViII Ix

Certain other metalations and condensations have been effected

but the structures of the produets have not yet been established.

Some related reactions are contemplated,

2. "Condensations of Aldehydes and Ketohes at the Side-chain

of 2-Methylbenzyldimethylamine and Related Amines by Means of n-

Butyllithium."

2-Methylbenzyidimethylamine was metalated at the methyl side-

chain with n-butyllithium in ether to form the lithio intermediate

I, which was condensed with benzaldehyde, acetone and benzophenone

to give, fcr example, II. Mixtures of products were obtained with

the first two compounds but benzophenone afforded ii in 82% yield,

though the structure of this product has not yet been definitely

established.

-Hg OH

CHgC'(C8H8)2

CH2 1 OCHN(CHs) 2

Similarly 2,3-dimethylbenzyldimethylamine was metalated with

n-butyllithium to form III, which was condensed with benzophenone

and acetone to give IV where R 1s phenyl and methyl, respectively.

The yields were good.

-7-

CH3 H CH-3 OH.. ' w NG Z ,H 2COR2

-9(,C'CH(0 A3) 9H9

Also tertiary aMine V was Metalated with n-butyllithium: to

form apparently V! which reacted with benzophenone to give VII (35%)

though the structure of this produot has not yet been established.

Li

C'B5CHCH2CH9(C-3)9 C&H5CHCHtiC-H2N'(CHS5 CHCC 20H9N(HO

V VI VII

Purther studies are being made on such sideo-chain metalations

and condensations.

3. "Carbonyl Versus Conjugate Addition of Dipotassio-O-Di-

ketones with Cinnamic Esters."

It has recently been shown that dipotassiobenzoylacetone under-

goes carbonyI addition with chalcone but conjugate addition with

2,'&,6-trimethylehalcone (Re J. Light, T. MI Harris and C. R. Hauser,

J. Org. Chem., 26, 1344~ (1961)).

It has now been found that dipotassiqbenzoylacetone can be

made to undergo either carbonyl or conjugate addition with cinnamic

esters, the course of reaction depending on the R group in the

alkoxy or aryloxy portion of the ester I. Thus carbonyl addition

occurs with phenyl cinnamate to form II (550), whereas conjugate

addition takes place with t-butyl cinnamate to give III (70%).

Both courses of reaction occur with methyl cirmnamate.

CeH9CHCHCOOR CaHsCH&CHCO7CH2 C!OCH9COC6 HS CesSK-CH20C( CHs)sCH2 COCH2COC.5H6

The structures of the products are being established, and

certain related reactions are being studied.

4. "Reactions oD l,l-&Dichloro-2,2-diphenylethylene with

Nucleophilic Reagents. "

ljl-Dichloro-2,2 -diphentylethyleneiL (1) has been found to react

with potassium amnide in liquid a-mmicania to form diphenylacetonitrile

(1!, 90%) but with phanyllithiumn in ether to give tolante (i,67%)

and chlorobenzente (?1%).

(C.H5 )2C4Ccl2 (Can 5)gCHCN CeH 5C IS

The Dormer reaction appears to involve substitution at the

vinylic carbon to Dorm IV, which undergoes B-elimination to give V

and subsequently the anion or II. The reaction with phenyllithium

evidently involves displacement on halogen to Dorm chlorobenzene

and carbanion VI, which undergoes rearrangement to afford tolane.

(ces) 2C=c-Cl (cSH4I) 2C=C9NH (cOnS)2c=Z-ClNH2

IV V VI

The reactions of I with certain other nucleophilic reagents

are being studied. Also certain related reactions are contemplated,

(C.)Resah- Persone Iand, Dere wared The f ollowing

graduate s tudents were supported on the cont-r'2ct for a few months

to a year:e W. R. Dunnavant, F. N. Jones, T. A. Mashburn, and

Re. Li Vaulx. The first three of these men c~ompleted the research

for the Ph.D. thesis while on the contract. The last man is pre-

sently a third year graduate stude-it who has been on the contract

since last September.

The followirZ t c.: fc;.Jows were supported on the

contract for a y'~each: W. ii o~Fsullivan, D. F. Tavares,

P. N. Jones "crd F~. B. Kirby. DC. -i the acadernic year,

Drs. O'Sullivan and Jones were supported partly by Duke University,

since they were part-time instructors of chemistry. This made

contract funds available for securing Dr. Kirby, who started work

last January (1962).