• • •

• . . . - . . ' . . - . . , . . , [ . : : , . . . " ' . . . • • " . : ; p - - ° _

. . • . . 1 3 - - - : - °

. . - " - " i . : - , : " : . - . " .

" • " : C o m m u m . ~ c a t i o ! . " • = -

• I r

"'" V.M. Rodionov and .B. L Kurte~" - . . . . . - . "

" . . " . . : . - - . . - - - . . . . . - - . ~ . ' "

In previous Investigations in o u r laboratory it has been sheba that aromatic" and aliphatic aldehydes readily react with m alonic acid in presence of ammonia. Reaction proceeds mainly In two directions: a ~°amino acid is formed, and a . derivative of acrylic acid arises in a "side-reaction. These reactions are as "" follows: - " ; " • . " - : - : . . . . . . . . ""-;"

• • j

R(~)C~O + ~ + C~2(C00~)2 -* RCAr)C~(.~)-C~CO0~ + ~0 + CO~ (z)

R(Ar)C~O + c~(coo~)2 ~ a(,~)c~=c~coo~ ÷ ~ o + co=. " ( n )

The total yield of the two readily separable substances is about 80%~ 3~-5~ being ~-smino acid. The first attenpts to extend this reaction to e-napbthalde~ . hyde led to the conclusion that in this case naphthylacrylic acid is considerably more readily foraed, while the yield of ~-(~-naphthyl)-~-aminopropionic acid is: insignificant [1]. However, it ~as shown in further experiments that ~-naphthalJ dehyde gives the B-amino acid of this series ~ith a yield of about 60%, and recently Kravchenko [2], by changing to som~ extent the conditions for the con- densation of a-naphthaldehyde ~ith malonic acid, has obtained a record yield of- '~ ~-(~-naphthyl)-~-alanlne (more than 70~). " . • . . . . . . . . .

In order to prepare ~-(~-naphthyl)-~-aminopropionic acid, it ~as necessary" to ~ork out a method of preparing ~-naphthaldehyde. Thls compound.was first pro- .

pared by Battersc~all [3] in 1873 by dry distiS]ation of the Ca salts of ~-qaph- thoic end formlc acids. A better yield (~0%) was obtained by Chichibabin [~] by treating ~-naphthylmaguesium bromide with orthoformic ester. By replacing 1~romoS naphthalene by iodonaphthalene, Peter Sah increased the yield of ~-naphthaldehyde to 7o~L5 ]. There Is a certaln preparative significance in the method based on the ~-bromlnation of ~-methyLnaphthalene followed by treatment of the bromo-deriv- ative with hexamethylenetetramine [6].

Very good yields "(up to 90%) can be obtained also by the use of Stephen°s "" method - reduction of ~-naphthonitrile followed by hydrolysis [7]':" :'.-

SnC]e. " ' " - H , ? . O ~ : , : : . ' " . . . . " ;

C~o~CN ~ C~o~CCi=~ ~ C~oH.~C~O. " '" . . . . . /

• " . . • . . , . . - : ~ _ " • . . ~ ~ . ~,;

" t , t 'C 'Z

i I . ~ I • •

A fairly h~gh yield (about 70-80~)" is obtained also by the reductlon of ~-naphthoyl chloride, following Rosenmund [8]. All these methods, in spite of their high yields, are compo~ed of many stages and give ~ great deal of difficulty. For this reason, an attempt vas made to prepare ~-naphthaldehyde by oxidiz~n~ ~-methylnaph~halene ~ith selenium dioxide. The oxidation of methyl groups in aromatic compounds to aldehyde groups has been employed on a number of occasion'~ vlth great success ~9]e "" • . " ..

The first experiments on the preparation of ~-naphthaldahy~2 .by this metho~ have already been described [R]. The yield of aldehyde ~as only 34~ of theoret- ical, on the basis• of the ~-methylnaphthalene taken. ~e have succeeded in almost doubling the yield of ~-naphthaldehyde by using a mixture of naphthalene an~ methylnaphthalene (i.9:I) in the oxidative reaction. At first the reaction vas carried out ~ith mechanical stirring, but it ~as found later that the reaction could be carried out equally successfully by adding selenium dioxide to the ~ixe ture of naphthalene and P-methylnaphthalene heated to 2-20 G . This method of ob~ talnlng ~-naphthaldehyde, using the readily accessible ~-methylnaphtb~lene~ is the most suitable for preparative purposes. The product that ~e obtained melted at 60.5-61.5 ° and was used by us for the'synthesis of ~-(~-naphthyl)-~-aminopro- ionic acid, of N-(~°naphtha!)-methylamine, of ~-(~-naphthyl)-acryl~c acid and its ester, and of ~-naphthalma!onic acid (see Experimental section).. -~

~-(~-Naphthyl)-~-alanine,C1oHzCH(~-H2)CHeC00Hs-;as first prepared by Rodionov' s method. The yield (16.5%) vas not very high, and variations of the basic method vere therefore tried, vim. JohnsonVs method [lO] and the method of Rodionov and Kravchenko [2]. In Johnson's method, ammonium acetate is used instead of alco- hol.~c ammonia, and in Kravchenko's - a m~xture of ammonium acetate and glacial acetic acid is used. By the use of Johnson's method, the yield of ~-(~-naphthyl)- ~-alanine ~as raised to 6~, and when we used Kravchenko and Rodionov's modifica~ tion, which appears to be the most suitable for aldehydes of the naphthalene series, the yield rose to 69% of the theoretical.

~hen Johnson's method was used, the •residue remaining after separating the- amino acid was not investigated. In the remaining experiments, carried out by ~ Kravchenko's method, the residue appeared to be almost pure ~-(~-naphthyl)-acrylic acid. The Tormation of ~-naphthalmalonic acid could not be detected in this method. The results of the experiments are given in Table I.

• . • TABLE i . . . .

~- ( ~-Naphthyl ) - ~- ( ~ -N~phthyl ) - ~-Naphthalmalonic Method of preparation ~-alanine acrylic acid acid (~)

a) Basic method ~ 16 ~7 17 "

b). Johnson's method 65 The unsaturated acids vere not • .•= . investigated •

c) Rodionov and Krav- 6~ 19 Not detected chenko ~ -: r~odif : . c a ~ i o n - :- "

d) In a !'argo-amount of : ~8.~ " "" ~i Not de+Jected glacial acetic acid - - ~ • "

. . . . . . . - : - ; . : : -" .. " :-. : . ' " -- i ' - . ' - .--. -'... ~ : - . - : - .

For c acter ,:atio= of several deri t ves" ~ e r e p r e ~ e d ~ I ) t h e m e t h y l e s t e r , b y h e a t i n g t h e f r e e ~ - ~ - ~ i n o a c i d ~ i t h m e t h y l

alcohol i~ presence of sulfuric acid; 2) the amide, by alloying the methyl ester

.- : : : . . , : : . - . . . . : . . " . , .- . . . - ' - - .

J

#.

i -

irOrmu and name •

to stand ~ith ammonia at,r0om temperature for a monthi )) N'-benzoyl'-~-~(~" i .-'

n a p h t l k v l ) - ~ - a l a n t n e l ' 1~) N - a c e t y l - ~ - ( l L n a p h t h y l ) - ~ - a l a n l n e and its amide ang'Ji~ 1. ' anillde; and 5) N-methyl-~-(~-naphthyl)-~-alanine. The yields and melting . : : : •

~olnts of these substances are given.in Table ~ .,.

•

¢ . .

, . • " J'" . .: : • .. -. ' .. 7 ":..:'::. • . ~ , : . - . , . ~ . : , -

--_

Methy l ether of ~-(~-naphthyl)-~-alanine

-C o zC ( )c hcom 2 . . . .

Amide of ~-(~-naphthyl)-~'-alanine

Yiel~

6 .5

m

-C oHvCH( .C0.OeH )CH C00N N-Benzov "!-~ " ~ -~-alanlne ._L" -c o cH( -coc )c coo

N-Ace t~l - ~- ( ~-na~~ - ~-alan Ine -C o CH( HCOCH )C CO .

7~m~de" o~ ~ ~ ) - ~ - a l a n ~ n e

cotH )c c0 .c Anil~ £e of N-acetyl-~- (~-naphthyl)-~-a!anlne

• .M,p,of ~ure " " sub~,t~.~ .~e ~'. :

.i

• " . . .

I13, , - "

"

2%/2n -CioHTCH( CH3)CH2COOE •

N-methyl- 6- (~-naphthyl) - Z-alan Ine ~91 ) ': :

• . • + ,

X ) Y i e l d from ~ - n a p h t ~ Z d e h y d e j malonlo a c i d 3 and potassium ace ta te in presence o f glacial acetic acid• . . " . .

2)Yield from N-(~-naphthal)-methylamlne and malonic acid (see Experimental ~ " section) " : "

• . , . . . • * ;

. . ° .

o _

~_~htha~de. A mix tu re o f 5 6 . 8 g o f ~ -methylnaphthalene ( b . p ; 2 3 5 - 2 3 6 ° ) " and ~0 6 ~ napntha--~ene ~as heated on an o i l - b a t h up to a temperature o f ~ 0 ~ , Freshly activated selenium dioxide (b4.~ g) was introduced into the mixture at'" - this temperature in small portions at a time over 30-40 mln. After each additionl the mixture ~as stirred with a glass rodj 8_nd vigorous ebullition occurred. Five minutes after adding the last portion of sele_~ium dioxide, the reaction mixture began to boil gently. Heating was di~contlnued, and the cooled mixture was dis- o solved in ether and fi!t~red from.the biack selenium powder. The residue ~as • carefu!ly washed with ether The main ~+~a e the . . . . . . . t_ and washings were mixed with 150 m! of a bisulflte solution and stirred mechanically for 3 hours. A v61umlnous precipitate of the bisulfite compound of ~-maphtha]dehyde began to ~p.~ecipitate . " rapidly. After a few hours the strongly colored ethereal solution above the pre- cipitate was carefully poured off; ether was again poured on to'the precipitate~ • and the mixture was stirred and allowed to stand until the ether had completely ~ separated. The latter was again poured • off, and the precipitate 3 mixed ~ith a~ fresh portion of ether, was transferred to a filter and wash'ed on the filter with ether until the washings became completely colorless "

k

" l P 5

I

The a~debyde-bisulfi%e compound obtalned in this May - it consisted of fine falntly pink scales - was introduced with stirring into a hot strong soda solu- tion. Napht,haldehyde 'separated as a dark..co]ored oil. ' The whole mass ~as dilu- ted with cold water and stirred. The naphthaldehyde, which rapidly crystallized, was filtered off, ~ash~d -~Ith water~ and JJ~medlately stesm-dlstilled.

The completely colorless crystalline ~-naphthaldehyde wa~ filtered off and ~rled at 50 ~. Yield 41.3 g, i.e., about 66~ of theoretlca!~ m°p. 60.5-61.~®o

N r ~L-Na~hthml)-meth~lam~ue. To ~ sclution of 15.6"g of ~-naphthaldehyde and ~.l g ~f ~ ~ n e h--~chloride in 50ml of alcohol a solution of 6.2 of caustic potash in ~0 ml of alcohol and 20 ml of water is added drop by drop with stlrriug and cooling. Crystalliz~tlon rapidly sets in. After 5~6 hours" the crystall~ne precipitate is filtered off and washed %~ith alcohol and water. Yield ii®~ g (about 67~ of theoretical)~ m-P. 81-82 ~. Fro~ the mother-llquor a , further 5.2 g of a strongly contaminated product, m.p. "66-74 ~, may be sepaz°ate~ • by adding ~ a t e r . . . -

N-(~-Naphtb~l)-znet~ylamfne crystallizes :~elf from gasoline .(b,p. I15-I~5~}. Glistening scales 3 m.p, 80.6-8!.6 °. -- •. -" " "" ":,

Cle~HI~N. C a l c u l a t e d ~: N 8 . ~ 8 . --. . : .

N-(~-Naphtha!)-m..thy-emlne is readily soluble i~ a]cohoi~ ether, benzene~ and COl4; it is insoluble in %-ater. It dissolves uncha~zed in hydrochloric acid ~n the cold, but is hydzolyzed on heating. .

The methyl ester of ~-(~-naphthyl)-ac~llc acid -ads prepared'by ~a~nlng naphthylacrylic acld (2 g) in methyl alcohol" (20 ml) in presence of sulfuric acid (3 g). Yield about ~ g, i.e. 9~ of theoretical~ m.p. 93-95.5" (after recrystF _- allization from methyl alcohol). It consists of glistening scales. -~"

F o u n d c 79.o .51 /- .

" -:" C14H1202. C a l c u l a t e d ~: C 79.29) H 5.70 " " : - " - " :

• . . . . : . : : . " 1 . " . . : . : - . ° . •

a) PFeparat/on b_zy Rodlonov ~ s basic method. A mixture of 7.8 g of ~-naphthal- dehyde, ~.72 g of malonic acid, and 13.4 ml of a 7~ solution of ammonia in abso- lute alcohol ~as heated in a flask, fitted with condenser for distillation, on the %rater bath for lO hours. The dry residue in the flask weighed about i~ g. ~alf of the residue ~as ground into a fine powder and was extracted for I~ hours ~Ith ~0 m! of hydrochloric acid (l~10) with mechanical stirring. The insoluble residue ~as ~_.te_ed .. and ~ashed with dilute hydrochloric acid. The acid fil- trate was evaporated clown somewhat on the water-hath, cooled, extracted ~ith ether s_v,_a~.~ ~ " t~mes~ and then neutralized with sedi,m~ acetate. After standing for 10-12 hours~ the precipitate that fo~e& was /lltered off, washed with water~ with a lcol~3i; and then with etherS, and f~_za~ dried at ".v0~89"~ -m.p. ~1~-2i6 ~

• -'~ l.e~ o-_Zi-z 16~ of theoretical. After recl~j~- with decom~o~!tlo:n~ ~ . , . . - d 0.85 g, tallizatfon from ~,eth~_v" a!co_~.ni~ the .melting point ~as raised to R20~221 ® (with ~ecom~ositlon , . . . • . . . . • _- • . - . . - ~.. - - . . . . ~ - . . . , , . - - . . . . . . . . . ~,. : .-.' -...

: - -: , ~ - " . ' . F o u n d ~ : C 7 ~ . i I ~ 7 - ~ . 0 8 ~ _ , "=_ 6 . 0 ~ ~ : ~ N 6 . 9 1 , 6 . 9 2

~lSHzsOaN. Ca!culated" ~C ~= =4- H 6.09 N 6.91 : |=-~ .? . . . - ° .

° . . . .

" T h e - r e s i d u e f o r m s c o l o r l e s s , t h i c k p l a ± e s ~ a l m o s t ~ n s o l u b l e i n t h e c o l d i n J

°

. : < : . . ' . . . - ~ . . . - . . - . " .

" "

water, methanol, and etha~ol. It doe~ not dissolve in acet ~enzene Or ~..... • ether, but dissolve~ yell in glacial acetic acid. It remains unchanged after." ~. long boiling with caustic soda (i0~) or with cone. ECl.. Investigation of the.: residu~ that is insoluble in hydrochlorfc acid showed that it consist~ essent-.~ ialiy qf ~naphthalmalonlc acid 41.02 g isolated) and ~-(~-naphthyl)~acryllc'aci~ "

ac.~ " (10.4 g), ammonlum ~ (-~ g~ and alcohol 429 ml) were h~ated for lO-ll hours on a boiling water bath. ~ At first the mixture dissolved rap!dly~ . and then a brisk evolution of gas set in and after 5-6 r a i n . a voluminous pre- cipitate was formed. Iu order to isolate the ~-(~-naphthyl)-~-alanine~ ~il~ ]]CA (60 ml, I~) was added, ~ith constant stirrlng~ to the reaction mixture. After .. heating for I0 min. at 70-80 m, the precipitate formed ~as filtered off, ~ashe~ ~ on the filter three times with ~ara hydrochloric acid (1:5)# and then washe~ " with water. The acid filtrate together with the .;ater ~ashings ~ere extracted " 5-6 times with ether and neutralized ~ith a solution of sodium acetate." Tn~ voi- u~mous precipitate that formed ~as a!le'~ed %o stan~ for some time and th~n f!it- ered off and ~ashed ~ith water. The crude product was boiled for t~o hours .~ith i00 m! of alcohol and then filtered hot. The residue on the filter ~as washe~ with alcohol smd ether and was dried at 70-80 ~ . Yield of ~-(~-naphthyl)-~- :" alanine lh g, i.e. about 6~ of theoretical. The residue that was insoluble i~ hydrochlorlc acid ~as heavily contaminated naphthylacryllc acid and ~as not investigated in greater deta~l... .: . .

• c. Preparation b X Rodlonov and Eravchenko's variant. ~-Naphthaldehyde "(6 g), malonic acid (9 g = 2~ excess), ammonium ace?ate (12 g = about 300~ excess), and glacial acetic acid 420 m!) were heated on a boiling water-bath for I0 hours. The mixture went into complete solution at 89 ~, with vigorous gas evolution. Already after bo~ling for l hour a voluminous crystalline precipitate started to separateo When reaction was complete, water (50 ml) was added •to the m~xture, and the reac- tion mass was carefully stirred. The well cooled precipitate was filtered off and repeatedly extracted with ~ater.. The united aqueous extracts were acidifiedwith hydrochloric acid to •Congo Red and ~ere evaporated down almost to dryness on the water bath. The • residue was treated in the way indicated above• and yielded 0.ge g of ~-(~-naphthy!)-~-a!~nlne.

The water-insoluble part of the solid reaction mass was extracted with warm h~drochloric acid; the hydrochloric acid filtrate was extracted several t~mes with ether and then evaporated to dryness" on the water bath. 6.81 g of the amino acid hydrochloride (m.p. 210-212 ~ with decomposition) was obtained. One third of the fresh hydrochloride (2.27 g) was converted into free ~-amino acid, For this purpose the hydrochloride was dissolved in dilute acid, filtered from small amount of insoluble precipitate, extracted with ether, and precipitated in the usual way with sodium acetate. After puri~ng by boiling with alcohol, 1.751 g of Very pure ~-(~-napht~vl)-~La]aniue, m.p. 217-218 ~, was ebta~_ned~ Thus~ the total yield of the latter was 9.71 g, i.e. 69~ of theoretical. The residue that remained after treating the reaction mass with hydrochloric acid was fairly pure ~-(~-naphthyl)-acrylic acid, m.p. ~06-207 .~. Yield 1.~6 g, i.e. about 19% of. theoretical. . : .. " . . - ~ ~, .

d. On Carrying out the experimgnt with somewhat different proportions of the components, namely with the mixture: 7.8 g Of ~-naph._m~d__y~_ (0.05 mole), 5.7~ g of malonic acid (O.095 mole), 9.78g of ammonium acetate (0.075 mole), and 20 ml of glacial acetic acid, and working up as in experiment c, ~.59 g of- •

~-(~-naphthyl)-~-alanine, i.e. 98.8~ of theoretical, and 3.~6 g Of ~-(~-naphthyl), acrylic acid, i.e. about • 31~ of theoretical, were obtained.

q

127

~- (~-~phthyl)-ILal~nlne I T h r : m e t h ~ _ ! e s t e ~ : ~ . p f ~ - ~ . r , ~ . p b ~ i ~ - a l a n ~ n e ' " "

(8 .6 a .d eeoc. for ourB on water bath~ methyl a~cohol (50 ml) ~as then driven off. On cooling s the resl- due ~as n~utral~zed ~ith a soda solution. The oil that separated rapidly crys- tallized. The crystals ~ere filtered off, vashed wlth water~ and then recrys- taillzed fro~ diluted methyl alcohol. Yield 7.39 g, i.e. 6bout 80% of theoret- ical. Me~tiug point of the ester after recrystalllzation from l~groln~ 9~-99®o

• . . . Found ~: C 7~,96j 73,19; H 6,66~ 6J79~ N 6~20% 6,16. CI~HxsO2N. Calcui~oted ~: C 73.7~ H 6.60 N 6,L~.

' The methyl"ester is formed as large glistening prisms from ligro~a~. It i8 readily'soluble in alcohol, ether, benzene, acetone, a~ud in dilute mineral aci~s~ in ligroin it is difficulty soluble in the cold, but fairly soluble on ~araing~ It is readily hydrolyzed on boiling with a lkal~ to a salt of the ~-smiuo acld. On st~uding for many d~ys in ammonlaca! alcoholic solution, it is converted into the amlde of ~(~°naphthyl)-~-alanlne. The alcoholic solution ~as filtered fro~ small amounts of contamination and gave, after driving off the alcohol, am ap- proximately 63~ yield of not altogether pure amide, m~p. I~2-1~3 ~ . Eecryst~l-. lizatlon from ~.,ater raised the m.p. to 143.~-14~.5 ~. Analysis for nitrogen showed that the compound obtained ~as not quite homogeneous.

F o ~ m a . ~ : ~ : ~ . 6 ~ l ~ . ~ l ' " -. "

Cxs~_ONa. Calculated ~: N 13.08 . , o

~~-naohthvl)-~,.alan~.e. ~-(~ihphthyl)-~-a!anlne (6.4~ g) was d~ssolved in l~0 ml of a 4~ solution of caustic soda, and benzoyl chloride (4.2 ml) was added 5radually from a dropping funnel to the ice-cooled s61ution. The solution obtained ~as left overnIzht, then filtered fro~ the small amount of sus- pended matter, extracted twice with ether, and acidified with hydrochloric acid. The precipitate that i~mediately formed ~.,as filtered off some hours later and was ~ashed with water. In order to remove benzoic acid, the p~-ecipitate ~,as boiled with ~ater, filtered off, washed with hot water on the filter, and then recrys- tall~zed from aqueous alcohol. Yield 8.6~ g, i.e. 90:3~ of theoretical° .

• N-Benzoyl-~-(~inaphthyl)-~-alanine crystallizes in fine glistenLng prlszs (from aqueous alcohol); m~p. 209-210 ~. It is insoluble in water, ether, benzene, and mineral acids. It readily dissolves in a~<alis, acetone, methanol, and ethanol, - . - ..

CmoHz~sN. Calculated ~: C 73.22; H ~.37 N 4.39

N_-Acetyl-~o~-na2hth.vl)-~-a!an~ne. Acetic anhydride (l~ ml)was added from a dropping funnel to an ice-cooled mechanically stirred solution of 10.?5 g of ~-(~-naphthyl)L~-alanlue in 160 ml of a lO~ solution of caustic soda. The reac- tion mixture was left overnight dud ~as then acidified with hydrochloric acid. The voluminous precipitate that ~mmediately formed was filtered off some hours later, washed ~ith water~ azi .~_~led to constant w_~ight. Yield 12.7o g; re.p° 164-!7~®. ~ A~ter recrystall~zlzg once from alcohol~ the acetyl derivative ap- peared to be quite pure and ~-elted s.~ply at 177.5-178.5 e. It crystallizes from alcohol i~ glistening ~.~"̂ -~--~..~ prisms. Xt dissolves readily in alkalis, ace- tone, metbzncl, and ethane':.; w~th difficulty in water, ether, and benzene. Yield of recrystai!ized product 10.16 g, i.e. 77~ of theoretical. •

.- " . . . . . - " - F b ~ a ~ : N 5 ; ~ . 6 ; ~ . ~ 5 , - ,

-'" " C z s ~ i s O ~ ' C a l c u l . a t e d - % ~ N 5 . Z ~ 5 " -- : . . . . :" ' ~ " ~" "

i~8

o~e,

J(nillde and"nmlde of N-scet l-y_~-naa _ht hhzll-~ . A mixture of 7.7~ S~' of N-acetyl-~-(~naphthyl~-~-a!anine, ~hich ~as finely sround and dried ins vac- uum desiccator, and 5 ml of thionyl chloride was heated on th~ ~ater~bath at ~ ~' ~0-50 ~ until gas evolution ceased. The excess of thionyl chl6ride was driven off in a vacuum at 40~50". The residue in the flask ~as a ~reds very viscous oi!s ~ ~ .~

difficultly soluble in absolute ether~ " -"

Anillde| A small quantity of the prepared acid chloride ~as tres~te~ ~ith a .

smallexcess of aniline in ethereal solution at roo~ temperature. The. powder- " .', like precipitate formed Mas filtered off and extracted successively Mith dilute HCI~ caustlc soda, and finally water. After one reer~stallization from alcohol~" ? 0.14 g of a substance of m.p. 236-237 ~ ~as obtained. After a further recrystal~ o~ lization the product melted at 237-238 ~. The anilide crystallizes from alcohol ~ ' in colorless pris~s. It is insoluble in water, acids, alka!is~ ether~ and ben- ~' ~ zene} rather difficultly soluble in •cold methano!~ ethanol~ and acetone~ but /~ d i s s o l v e s more r e a d i l y on h e a t i n s ~ ". . . . - . "- - , , . . ::

Found 8.60; ? " . .

02:tl~2oO2N2. Calculated ~: N 8.1~.. . " : . . . . . . . - Amid__~e. Strong aqueous ammonia (I~0 pl) was added to the main mass of the -

acid chloride. The mixture was shaken vigorously for 30 rain. and then left to ~ stand for several hours~ the precipitate that had formed was then filtered off and yell ~ashed with alkali and ~ater. The dried precipitate was ground and re~ crystallized from dilute alcohol• ~.66 gel amide, m.p. 2~.~-227.~ e, was ob~ tained. By repeated recrysta!llzation from a mixture of Mater and alcohol (~:I)~ . constant m.p.; 230~2~1 ~, Mas attained. The amide of N-acetyl-~-(~-naphthyl)-~ alanine crystallizes from aqueous a~cohol in glistening long plates. It does not dissolve in ether or benzene; it is of rather poor solubility.in methanoI~ '~ et.hanol, and acetone in the cold, but dissolves readily on Marming, it is almost insoluble in cold water~ but dissolves in hot ~ater . . . . . -. : •-

From the mother liquor, after evaporation and acidification, 0.76 g of the original 2-(~-naohthyl)-~-alanine ~.as isolated. Thus, the yield of amide calc- ulated on the amount of ~-(~°naphthyl)-~-alanine that reacted (7.7~-0.76) Ss ~.56 g~ i.e. about 80-81~. of theoretical (not taking into account the amount of acid chloride taken for preparing the anilide,) -. ~

N-Meth I-~- ~-na-hth i -~-alanine . . • - ..

a) ~-Naphthaldehyde (1.56 g), malonic acid (1.30 g), methy!amine hydrochlo- • ride (I.01 g), anhydrdus potassium acetate (l.50'g), and glacial ac4tic acid (5 ml) were heated on a boiling water bath for 8-9 hours. The originally homogene- ous mixture evolved gas with formation of a crystalline prec~pi±ate. The thick crystalline mass obtained after cooiin& was extrac%ed wi~h dil. HC1 (see synthesis of ~-(~naphthyl)-~-alanlne). The hydrochloric acid fil+.rate was first concen tra' ted on the water-bath and then extracted h-5 times with ether and neutralized with . a concentrated soZutlon of sodium acetate. • After a few hours~ +_he preclpitate that separated was filtered off~ ~ashed with water# and d~ed at 70-80~. i.fi0 g of a substanhe of m.p. 187-188 ~ (with deccm~ositlon) was obta~n::d. After purl-" "

lying for a-~alysis by repeated crystalllzation, the substance mel~ed at 19~-19~.~ ® (with d~composlt~on). " : ""- " " ......... " ' .... . --

N-Met~!.-b-([~-~aphthyl)~alan'ine • crysta~..l~ze's Inprt_-~nsI" it is ea'si"~y sol- "~ in .water" and in acet-'- uble in mineral acids and in alkalis, and al~o~ oh boil~ng, ~... :..- ~-

$ CI4HIsO2N. •Calculated ~:

• : #

• "'i" ' .... ?"•" "'i • . o . . . . . . .

• : 0 T .

129

13o

The c r y ~ t a ~ i n e reatdue that remainB ou the f i l t e r ~ f ter extract ing the re - actiou m.~×ture with hydrochloric acid was found to be pure ~ - (~ ,naphthy l ) -acry l i c actd~ m,p, 207-208 *. Y i e l d 0 .78 g (about 39% o# t h e o r e t i c a l ) ,

b. Preparation from N-(~-naphthal)-methylamine. Dry N-~hnaphth~l)-methyl-~. "amine (1.69 g), malonlc acid (1.04 g), and ethyl alcohol (5 ml) ~ere boiled om "the rater-bath for I0 hours. Full dissolution occurred Inthe first I0 min. s and a large amount of gas ~as evolved. After 30 min.~ a precipitate started to appear. After cooling, the reaction mass was treated in the way indicated above. Yield of crude N-methyl-~-(~,naphthyl)-~-alanine (m.p. 189-190~) 0.68 g, i~e. 29.9% of theoretical. Yield of crude ~-(~-naphthyl)-acrylic acid, 1.14 g~ i.e. about 57.5~ of theoretical. • ~

• _ : " • °,

I. The method of preparing ~-'naphthaldehyde proposed by'Sultanov, Rodlonov s and Shemyakin, based on the oxidation of P-methylnaphthaleue with seleni~u diox~ Ide, has been improved by the use of naphthalene as solvent. The yield of alde- hyde rose from 34 to 66~67% of theoretlcal.

2. N-(~-Naphthal)~methylam~ne and methyl ~-(~-naphthyl)-acry!ate are de-

scribed for the first time.. - .-

3. The following have been synthesized: ~-(~zaphthyl)-~°amineproplonic" acid, its methyl ester~ its amide, and Its benzoy] and acetyl derlvatlves 3 the amlde and auillde of N-acetyl-O-(~-naphthyl)-~-aminoproplonlc acid; and N-methyl- - (~-naphthyl) -~ ~amlnopro~ ion ic acld.

~-(~-Naphthyl)-~-amlnoproplonic acid has been prepared by the basic reaction of Rodlonov and also by three variants of this method.

4. N-~'ethy!-~-(~-naphthyl)-~-amlnoproplonic acid has been prepared by two methods; one o f them i s new. . ~ ' i L . . . : "

D.I~Mendeleev Chemico-Technologlcal Institute. " '~ Received August 31~ 19~I

- LITERATURE ~ CITED . . - ~

[I] I.S. Belonosov. Degree thesi%-Noscow~ 1939." -

[2] N.A. Kravchenko. Degree thesis, Moscow, 1950. " . . . . . . . i , t . '

. [ ) ] J. Batterschall. Ann., 168, ii~ (187~). " - . . - . ; : -

[ ~ ] A.E.Ohlchibabln. Ber., ~ , 447 ( i 9 n ) . - - - : .

[5] Peter Bah. Rec. tray. chlm., 59, I021 (1940). " " :

[61 r. Meyer A. Sti .gntz. 18 7 . [7] g. Fulton and R.RobCnson. g.Chem.Soe., 1939, 200; g.Williams. Org.

Synth., 23, 63 (1943). . , • "

" [8] E.Hershberg and J.Casou. Org. Synth., ~I, 84 (19~i). " " .

[9] V.M.Rod!onov, and M.A.Berkengeym. J.Gen.Chem., I~, ~30 (19~)} A.S.. Suitanov, V.M.RodionoV, and M.M.Shemyakin. J.Gen.Chem., i6, e072 (1948). See also the monograph by N.I.Meln~kov "Selenlous Anhydride as an Oxidizing Agent in Organic Chemistry '~ in the CollectiOn of"~Reactions of Organic Compounds'~ vol. I. Moscow, State Chemistry Press~ lY3i, pp. 99-178.

[i0] T.Johnson and g.Evans. J.Am.Chem.So=., 52, ~995 (1936)} T.Johnson, Rec. tray. chtm., ~8, 87e (Iy29).

, ~.