8/3/2019 Solvent Catalyzed

1/4

4868 SHIMO, WAIL4MATSU, AND I N O U E VOL. 6

presence of meth anol). T he ketala 8-10 w ere prepa red fromthe corresponding alcohol anddimethoxydiphenylmethane.

Interac tion of d,bdim ethoxypr opane wit h ferric chloride andantimony pentaehloride. A solution of 10.4 g . (0.1 mole) of2,2-dimethoxypropane in 50 ml. of he xane wa s cooled to-40' an d 16.2 g. (0.1 mole) of sublimed ferric chloride wasadded. Anhydrous conditions were maintained throughoutthe experiment. T he mixturewm st i rred and the temperaturewas allowed to increase slowly. At -10' th e mix tureturned yellow and the black crystalsof suspended ferricchloride turned red-brown.@Above O ', an exothermic re-action started, and a black, viscous, oily layer separated.Th e hexane layer was decanted an d the oil was treated with100 ml. 0.1N hydrochloric acid. About80% of th e ironwas extracted as ferric chloride and ferrous chloride( 1 1) .The sa me experiment was repeated w ith 29.9 g.(0.1 mole)of antimony pentachloride. Th e oxonium compound whichformed initially was white, andit decomposed slowly a t 25"to a black tar. The antimony was not extensively reducedand the tarry polymer was similar to that obtained in theferric chloride exp eriment.

Interaction of dimethoxydiphenylmethane wit h ferric chlorideand antimony pentachloride. A solutio n of 22 .8 g.(0.1 mole)of dimethoxydiphenylmethane in 100 ml. of hexane wasmixed with 16.2 g. (0.1 mole)of anhydrous ferric chloride.Reddish needles, which decomposed slowly in contact withmoisture but remained unchanged in the hexane solution,were hydrolyzed quantitatively with 0.1N hydrochloric acid

(9 ) When this solid, believed to be a n oxonium com-pound of the ketal, was filtered in a separate experiment,it quickly decomposed to a tar ry material.

to benzophenone, methanol, and ferric chloride.A similarexperiment with antimony pentachloride yielded a white,crystalline oxonium compound which hydrolyzed easilyinthe same manner.

Preparation of 2,d-bis(6-di-n-6utylaminoethoxy)propane.A mi xtu re of 44 ml. (0.25 mole) of2,2-bis(p-chloroethoxy)-propane and 205 ml. (1.25 mole) of di-n-butylamine wasrefluxed for 12 hr. T he reaction mixture was extracted withether, leaving 78.1 g. (yield 94.5y0) butylamine hydrochlo-ride. The ether extract was fractionatedin vacuo and acolorless fraction, b.p . 123-128' ( 2 mm .), &-as collected. Ananalytical sample was obtained by redistilling this fraction,b.p. 125' (2 mm.), molar refraction 74.07 (calculated 74.02).

Prepa ration of d,&bis(@-aminoethoxy )propane. A mixtureof 25 ml. of (0.14 mo le) of 2,2-bis(~-chloroethoxy)propane,15 ml. (0 .71 mole) of liquid am mon ia, and 1 5 ml. of me th-anol was heated in a Carius tube a t 90' for3 hr. The pre-cipita ted 10.8 g. (yield 70%) of amm onium chloride was fil-tered out and th e filtrate waa fractionatedat 0.5 mm. Evolu-tion of gases an d discoloration indica ted dec ompositionabov e 100'. An acid hydrolysis of t he residue yielded aceto neand a mixture of ethanolamines.

Acknowledgment.The author is grateful to JudyB. Chapman, Elizabeth A. Greene, and George B.Clemans who synthesized some of t he kehl s, andto the National Science Foundation and theHollins College FacultJy Research Fund for financialsupport.

HOLLINS, A.

[CONTRIBUTIONFROM THE DEPARTMENTF CHEMISTRY, DEFENSEACADEMY]

Solvent-Catalyzed Alkylations of Active Methylene Groupsin Liquid Ammonia

KOTARO SHIMO, SHIGERU WAKAMATSU, AN D TAD.40 I NOUE

Received Ju ne 19, 1961

A new modification of th e alkylation reaction was investigated.It was foun d tha t some active m ethylene compounds,such as malononitrile, cyanoacetamide, and substituted cyanoacetamide, could be successfully alkylated with alkyl halideto form the corresponding C-alkylation products witho ut th e condensing agent in liquid ammonia. T he high yields weregenerally obtained with v ery reactive benzyl a nd allyl halides. Six new compounds were prepared in this investigation.

In our previous paper1** new modification ofthe Michael reaction was reported wherein thereactions between active methylene groups andacrylic acid derivatives proceeded without thecondensing agent in liquid ammonia to produce th ecorresponding addition products. The reaction wasprobably at tributed to the basic character of liquidammonia compared with the common organicsolvent usually employed, and it mas suggestedthat the base-catalyzed ionic organic reactions ingeneral would be promoted to a great extent b y theuse of liquid ammonia as solvent.

From th is viewpoint, in the present investigation

(1 ) S. Wakamatsu, Bullet in of the Chemical ResearchInst i tu te of Non-Aqueous Solutions Tohoku University,10,

111 (1961).(2 ) K. Shimo an d S. Wakamatsu, J . Org. C h m . , 26,'3788(1961).

we have attempted the reaction between the activemethylene group and the alkyl halide without thecondensing agent in liquid ammonia. We have nowfound tha t some active methylene compounds, suchas malononitrile, cyanoacetamide, and substitutedcyanoacetamide, which have the enhanced acidityresulting from the substitution of phenyl or acet-amido group on the a-carbon a tom are successfullyalkylated with the alkyl halide to give the cor-responding C-alkylation products in liquid am-monia. I n general, the high yields are obtained withvery reactive halogen compounds such as benzylhalide and allyl halide. Attempted alkylations ofless acidic monoalkyl cyanoacetamide, and phenyl-or acetamidomalonamide have been unsuccessfuleven with a halide of allyl type under th e samereaction conditions. The results of the alkylationreactions are shorn in Tables I and 11. Table I11

8/3/2019 Solvent Catalyzed

2/4

DECEMBER 1961 ALKYLATIONS IN LIQUID AMMONIA 4869

TAB LE I

ALKYLATIONF MALONONITRILESND CYANOACETAMIDESITH ALKYL ALIDESN LIQUIDAMMOKIA

Compound Yield,Alkylated Alkyl Halidea Meth odb Product %"

CHz(CN)z CH2=CH-CH2Br B (CB=C H--CHZ)~C ( CN)z 91C& ( CN ) CeHsCHzCl A (Ce.HsCHz)zC(CN)z 74CHe(CN12 C&CHzC1 B ( C K H ~ C H ~ ) ~ C (N)z 75CH*(CPi)z CzHsI A (CZHS)ZC(N)2 44CHz(CN)z CzHsI B (CzHs)zC(CN)2 72CHz( CN)COXHz CHs=CH-CH?Br B CH pCH -CH zCH ( C N )COSHz 21

(CH~=CH-CHZ)ZC(CN)CONHz 43CHz(CN ) CONHn CzHsI B CtHsCH( CN ) CONHz 24

a T w o molar equivalents were used per moleof malononitrile and cyanoacetamide. See Experimental. Based on the start-ing active methvlene compound.

TABLE I1

ALKYLATION O F PHESYL- ANI) A4CETAMIDOCYANOACETA\l IDES WITH ALKYL ALIDESS LIQUIDAMMONIA

RRiC( CN)CONHzYield,

ICH( CN) CONHz

R1 Alkvl Halidea Methodb R R1 %c

CHz=CH-CHzBrCoHsCHzCl

C2Hs ICzHj I

CzH5BrCzH6BrC8H7BrC3H7Br

i-C3H7 Bri-CaH7 BrC4H8 BrC ~ H Qr

~ - C P H QrCHZ=CH-CHzBr

CaHaCHzClCsHsCHzClC2H5 I

CzH5 ICzH5 BrCsH, Br

BBBAABABABABxBB

BABA

H -

91746945436

(79)424

(86)40

(94)33

(91)30917165 d7141d212 1 d

One molar equivalent per moleof RIC H(C N)C ON Hz was used unless otherwise specified.See Experimental. c YieldsTw oased on the starting cyanoacetamides. Parenthesized figures indicate recovered RICH(CN)COSHz unchanged.

molar equivalents per moleof R I C H (C N)C OYH%were used.

gives melting points and analyses of the reactionproduct,s.

The new alkylation reaction in liquid ammoniawill include the following stages ( X is halogenatom, R1and RI are both electrophilic groups or one

of them hydrogen) which may be qu ite characteris-tic of the effective catalytic action of the solvent

R lR,-C-H + X H ~ R A ~ NHP

l i q . NH3 1C N

IC N

Ri R II +a -6

IC N

R2-Ce + Rx + 2-J-R + x aliq. NHa I

C N

to form th e enolate of the active methylene com-pound.

The reaction temperature had a serious effect onth e alkylation reaction in liquid ammonia. When thealkyl halide wscs relatively less reactive, the reac-

tion was best carried out at room temperatureunder pressure. On the other hand, in most cases,the desired reaction d d not proceed a t atmos-pheric pressure below the boiling point of liquidammonia (-50'). However, not only the enolate

of active methylene rompound but also the am-monia itself can react with the alkyl halide toform the alkylation product. I t was found tha t thisundesirable side reaction competed remarkablywith the normal alkylation when the reactiontemperature was increased. Actually, by t he use ofvery reactive allyl halide a t room temperature noneof the desired C-alkylated product could have beenobtained.

EXPERIMENTAL3

The reactions were carried outby two general methods;(A) the use of a pressure vessel a t room tem perature a nd(B)

(3 ) Melting points are uncorrected. Microanalyses wereperformed by T he Instit ute of Physical an d ChemicalResearch, Tokyo, Japan.

8/3/2019 Solvent Catalyzed

3/4

8/3/2019 Solvent Catalyzed

4/4

DECEMBER 1961 STOBBE CONDENSATION 4871

the reaction at atmospheric pressure below the boiling pointof liquid ammonia (-50'). These are illustrated by thefollowing instances.

Dibenzylmalononitrile (MethodA ) . To a mixture of 3.3 g.(0.05 mole) of m alono nitrile an d 12.7 g.(0.1 mole) of benzylchloride contained in a glass pressure vessel4 was adde d50c'c. of liquid ammonia. Ina mom ent th e exothermic reactionoccurred,& an d a gre at deal of cry stalline solids began toseparate. The reaction mixture was allowed to stand a t roomtemperature for abou t 24 hr .; then the amm onia was evapo-rated. The remaining solids were washed m-ith water andrecrystallixed from eth anol ; yield, 9.1g. (74%) of dibenzyl-malononitrile, m.p. 127.5-129'. An addi tiona l recrystalliza-tion from ethanol raised the m.p. t o 130-131'.

&Allyl- and b,%diallylcyanoacetamide (Method B ) . Allylbromide (36.3 g., 0. 3 mole) was added dropwise toa stirredsolu tion of 12.6 g. (0.15 mole) of cyanoacetam ide in 150 cc.of liquid amm onia contained ina three necked flask equippedwith a mechanical stirrer an da Dewar reflux condenser over

(4 ) K. Shimo and S. Wakamatsu, J . Orp. Chem., 24 , 19

( 5 ) External cooling with cold water was desired until(1959).

th e reaction waa completed (for abo ut0.5 hr.).

a period of 1 hr. while maintaining th e reaction te mperatureat -50'. After the add ition was completed, the mixture wasstirred for 3 hr , and then the ammonia was evaporated.The residue was washed with water. The remaining solidswere dissolved in boiling water, and the solution wasallowed to stand at room temperature. 2,2-Diallylcyaneacetamide was precipitated rapidly from the still warmsolution; yield, 10.5 g. (43% based on cyanoacetamide)which melted at 128-129'. 2-Allylcyanoac etamide was iso-lated thereafter as a crystalline produ ct from th e filtrate bycooling with ice water; i t m eltedat 101-104, 4.0 g. (21%based on cyanoacetamide).

I-Acetamide-Bethylcyanoacetamide (Mcthod B ) . T o astir red soluti on of 7.1 g. (0.05 mole) of %ace t am i decyanoacetam ide an d 150 cc. of liquid a mmo nia, 7.8g. (0.05 mole) of ethy l iodide was ad ded dropwise a t-50". Stirrin g was continued for2 hr.; then t he ammoniawas evaporated. The resulting mixture was washed withwa ter an d recrystallized from water. Th e yield of % aceta-mido-2-ethylcyanoacetamide, m.p. 20P205' dec., waa 6.0g. (71%). Upon repe ated recryetallization from wate ritmelted at 205' dec.

YOKOSUKA,APAN

[CONTRIBUTIONFRO M THE DEPARTXENTF ORGANIC CHEMISTRY, NATIONALESEARCHENTRE]

The Stobbe Condensation with 0 - and p-Chlorobenzaldehyde

A. M. EL-ABBADY, S. H. DOSS, (MISS) H. H. MOUSSA, AND (IN PART)M. NOSSEIR

Received M a y 26, 1961

0- an d pChlorob enzaldehy de condense with methyl succinate to give methyl hydrogencis- -o-chlorophenyl-, a nd m ethy lhydrogen cis-y-p-chlorophenylitaconate together with di-o-chlorobenzylidene-,and di-p-chlorobenzylidenesuccinic acid.

Th e itaconates ar e cyclized by acetic anhydride a nd sodium ac etate t o m ethyl Cacetoxy-%, and -6-chloro-2-naphthoatewhich are converted into 5 , nd 7-chlorc-l-naphthol, respectively. T he anh ydrid e of thedi-0-chlorobenzylidenesuccinicacid is cyclized by th e action of hea t to th e corresponding I-phenylnaphthalene derivative.

Continuation of th e investigation of the Stobbecondensation on substituted aromatic aldehydes,'cis-p-half esters, methyl hydrogen cis-yo-(Ia;Rr= CHI) and cis-7-p-chlorophenylitaconate (Ib ;RS = CH3) together with di-o-chlorobenzylidene-(VIa) and di-p-chlorobenzylidenesuccinic acid(VIb)2 were obtained in about 52% and 14% yieldrespectively by Stobbe condensation of 0- and p -chlorobenzaldehyde with dimethyl succinate andt-butyl alcohol potassium t -b ut ~x id e. ~ n the case ofp-chlorobenzaldehyde, a small amount of p-chlorobenzoic acid was also isolated. Repeating thereaction under nitrogen atmosphere gave no suchacid. The structure and the cis configuration of t hehalf esters (Ia and b) were confirmed by theircyclization with fused sodium acetate in aceticanhydride's4 to methyl 4-acetoxy-8-(IIa;Ra = CH3,R, = Ac) and -6-chloro-2-naphthoate (IIb;

(1) A. M . El-Abbady and Lanson S. El-Assal, J. Chem.Soc., 1024 (1959).

(2) F. G. Baddar, L. S. El-ks sal, N. A. DOSE, ndA. H.Shehah,J . Chem. SOC., 016 (1959).

(3) Cf. W. S. Johnson and G. H. Daub, Org. Reactions,VI , l (1951) .(4) W. Borsche, S. Kettner, M. Gillies, H. Kuhn, and R.Manteuffel, Bnn. 5 2 6 , I(1936).

R3 = CH3, R4 = Ac) in a good yield. Alkaline hy-drolysis of t he acetoxy esters gave 8-, and 6-chloro-Phydroxy-Znaphthoic acid (TIa and b; R3 = Rq =H), respectively.

These phenolic acids were converted by methylsulfate and potassium carbonate in acetone into thecorresponding methoxy esters (IIa and b; Ra = R,= CHa) which were hydrolyzed to the methoxyacids (IIa and b; R3 = H, R4 = CHa) and thendecarboxylated by quinoline and copper-bronzeto give 5- , and 7-chloro-l-methoxynaphthalene,respectively.

The structure of these naphthol ethers was con-firmed by their cleavage with hydriodic acid to t heknown 5-, and 7-chloro-l-naphth01.~

Hydrolysis of the cis-&half esters (Ia and b;Rt = CHa) with boiling barium hydroxide solu-tion gave the cis-itaconic acids (Ia and b; Rs = H).These were converted into their cis-anhydrides(IVa and b), which on boiling with methanolgave the cis-a-half esters (Va and b) which weredifferent from the cis-&half esters (Ia and b;Rs = CH J obtained by the Stobbe condensation.

The anhydride (VII) was cyclodehydrogenated(5) H. Erdmann and R. Kirchhoff, Ann..247,366 (1888).