on walden inversion in a previous communication levene and

ON WALDEN INVERSION

XV. THE INFLUENCE OF SUBSTITUTING GROUPS ON OPTICAL

ROTATION IN THE SERIES OF DISUBSTITUTED PROPI- ONIC ACIDS CONTAINING A METHYL GROUP

BY P. A. LEVENE AND R. E. MARKER

(From the Laboratories of The Rockefeller Institute for Medical Research,

New York)

(Received for publication, January 17, 1931)

In a previous communication Levene and Mikeskal reported on the changes in the rotations of the derivatives of a-substituted propionic acid (3) (disubstituted acetic) produced by changing the character of the functional groups. The primary aim of the inves- tigation was to trace the effect of the substitution of the hydroxyl by a halogen in the disubstituted ethanols. In earlier communica- tions, Levene and Mikeska2 arrived at the conclusion that in opti- cally active secondary carbinols, the substitution of the hydroxyl by a halogen results in a change of direction of rotation. This view has been recently criticized by Houssa, Kenyon, and Phillips.3 The conclusion of these authors is based on indirect evidence as was also the conclusion of Levene and Mikeska. The decision between the two views will depend upon further data. Some such data are contained in the present article. We must, however, state that the present work was undertaken not because of the criticism of the above writers but for the reason that the a-substituted propionic acids proved unsatisfactory material because of the racemization which occurred in the series of reactions that had been planned. The assumed mechanism of the racemization was

1 Levene, P. A., and Mikeska, L. A., J. Biol. Chem., 84, 571 (1929). 2 Levene, P. A., and Mikeska, L. A., J. Biol. Chem., 69, 473 (1924); 66,

507 (1925); 70, 355 (1926).

3 Houssa, A. J. H., Kenyon, J., and Phillips, H., J. Chem. Sot., 1700 (1929).

77

by guest on February 18, 2018http://w

ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

78 Walden Inversion. XV

discussed in the paper by Levene and Mikeska and if their reason- ing is correct, then the series of disubstituted propionic acids should not present the same difficulty. In reality, such was the case. This series, however, presented greater difficulty in the resolution of the higher members.

Comparing the effect of the substituents on rotation, it is noted from Tables I, II, and III that it is practically identical in the four

TABLE I

Molecular Rotations of Derivatives of Alkyl B-Substituted Butyric Acid in 260 * 30

Homogeneous State ( [M 1, 1

~___

CzHsCH-CHz-- +4.21 +4.69 I CHs ___~

n-CSHY-CH-CHs- +2.84 -to.55 I CH, (+3.28)* (0.66):

____ n-CaH9--CH-CHF- +5.45 +2.61

I CH1

___~ n-C5H11-CH-CHZ- i-7.13 +3.74

I CH,

n-C,H,a-CH-CHt-- +0.75 I C&

-

1

*

-

$ * 2 F ‘; ~___-

+3.69 +8.95

___-____ +1.62 -16.81

(+1.91)* (-4.93p

+3.5!3 _______ -15.03

--- $5.39 -13.02

~~~ +0.67 -1.56

* This st-ies was duplicated starting from acids of different rotations.

higher members, being for the dextrorotatory series in the following descending order.

C=N > CHnBr


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

TABLE II

Molecular Rotations of Derivatives of Alkyl I-Substituted Butyric Acid in

Homogeneous State ( [M 1”: * “‘1

CAH,CH-CHz- I CH,

n-C&-CH-CH2- I CH,

n-C4Hg-CH-CHZ- I CH,

+4.21 +7.33

+2.84 -3.65

+5.45 -3.16

1-7.13 -2.40

j1

-.

I

-.

-

+2.32 +3.41 f4.31

+5.36 -3.64 $0.29

~~ +8.85 -5.41 f1.73

+10.49 -5.59 +3.17

1 I

* The rotations of the amides were taken in 75 per cent alcohol.

TABLE III

Molecular Rotations of Carbinols, Bromides, and Hydrocarbons*

8 4 8 7

CzH,CH-CHz-- +1.70 $5.21 I C&

n-C3H7-CH-CHZ- +1.40t -16.83 I CH, I I

n-CdHg-CH-CHz- 1+3.58+15.1E

~-CSHII--CH--CH~- I I I

+5.39t -13.0:

+2.25 $4.22 +1.67

+2.29 -5.57 -10.96

i

+7.75

* [Ml, was taken at an average temperature of 25”. t This carbinol and the derivatives given in this table were levorotatory

but were tabulated as dextrorotatory for convenience of discussion.

79


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


In the Z-propylbutyric acid (4) the COCl and C EN have practically the identical rotation and their order may be interchanged. In detail the order of change is different from that observed in the series described by Levene and Mikeska. In the two most significant derivatives, the carbinol and the halide, the directions of the rotations are different in the old and in the new series; whereas in the Z-substituted propionic acids, the dextro acids lead to a levo- carbinol and a dextro-halide, the dextro-Z-substituted butyric acids lead to a dextro-carbinol and to a levo-halide, except in the case of the 2-ethylbutric acid (4), which leads to a dextro-carbinol and to a dextro-halide. Furthermore, in this case the numerical value of the rotation of the halide is higher than that of the carbinol. Thus on passing from carbinol to halide in this case, the change in rotation is in a direction opposite to that of the change in the other corresponding members of this series. In a general way, then, with the exception of the one case, the configurationally related carbinols and halides rotate in opposite directions, this being the relationship which Levene and Mike&a have assumed for the set- ondary carbinols and for the corresponding halides.

Case of SEthylbutyric Acid (4) (S,S-Meth$ethylpropionic) Series-The exceptional position of the members of this series a priori seemed to be possible to explain on the assumption that they are configurationally enantiomorphous to the dextrorotatory higher members in the following manner.

CH, CHs

C&Ha-C-CHJ3OOH COOH-CHz--C-C&H,

A I

H

Dextro (levo) Levo (dextro)

If this were so, then the change to the right from the dextro-carbinol to the higher dextro-halide would be a change in the same direction as that of the levo-carbinols of the higher homologues to their dextro-halides. Because of these considerations, it was de- cided to correlate the configurations of dextro-Z-ethyl- and dextro- 2-propylbutyric acids (4).

It is evident that if the acids are of the same configuration, then by converting the -CHzCOOH of the first into GHr and that of


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

P. A. Levene and R. E. Marker 81

the second into CzHs two enantiomorphous hydrocarbons (methyl- ethylpropylmethanes) should result.

C& CHs CH8 CHa I

GHs-C-CHGOOH -+ CzHs-C-CaH, CxH,--C-&H, +- CaH,-C-CHGOOH

l!I I I H H H

I II III IV

On the other hand, if the acids are enantiomorphously related, both should lead to the identical hydrocarbon.

CH, CHa CHs

CzHe-C-CH&OOH -+ CzH5-C-C$HI +- HOOC-CHz-C-CzH, I

JI I

H H

It was found that both acids yielded a dextrorotatory hydrocarbon. Hence, the dextrorotatory 2-ethylbutyric acid (4) and the dextrorotatory 2-propylbutyric acid (4) are of opposite conjigurations. From this observation it also follows that the con$gurations of the 2-substituted butyric acids (4) and their derivatives can be correlated on the basis of the changes in the direction of the rotations in passing from the carbinols to the halides. The set of reactions which lead from Z-ethylbutyric acid (4) to the hydrocarbon is the following.

CHa CH, CH, \ \ \

CH CH,COOH + CHCH&HzOH --f CHCHXH2Br + / / /

Cd% GHs C&&

CH, CH, \ \

CHCHdZHzMgBr + HCHO -+ CHCH&HzCH20H --j / /

C&H6 C&Ha

CHs CHs \ \

CHCH&H2CH2Br + CHC,H, / /

CzHs Cd%


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

Walden Inversion. XV

In this place it must be recalled that the same dextrorotatory hydrocarbon which was obtained in our case from the 1-brom-3- methyl hexane had been obtained many years ago by Marckwald4 from dextro-2-ethylpropyl (active amyl) iodide (3) by conden- sation with ethyl iodide. The dextro-iodide employed by him is a derivative of the levo-amyl alcohol, which in its turn, can be converted into dextro-valeric acid. Thus, through the reactions reported by us and those of Marckwald, levo-amyl alcohol and the dextro-2-ethylbutanol (4) and dextro-2-ethyl pentanol (5) and the corresponding dextro-halides are all configurationally related. In addition through the work of Van R.omburgh5 and of Walden6 the dextro-2-ethylbutyric acid (4) and 2-ethylvaleric acid (5) are correlated with 2-ethylpropionic acid (3) (active valeric). These relationships are given in the following formulz

COOH CHzOH CHzBr I I I

H-C-C&H6 -+ H-C-CzHa --+ H-C-GHs I I CHs CHs CHa

Dextro + 18.21 Levo - 5.19 Dextro + 5.56

CHzCOOH CHzCHzOH CHzCHzBr C I I I I

H-C-CzHs + H-C-CzHs -+ H--C-&H6 --+ H-C-GH, I CHs &Ii, AH,

I CHs

Dextro + 10.35 Dextro + 9.08 Dextro + 19.23 Dextro + 9.5

T

CHzCHzCOOH CHzCHzCHzOH CHGH2CH2Br I I

H-C-CzHs - H-C--CsHa ’ --J - H--C-&H6 I I

CHs C& CHs

Dextro + 13.53 Dextro + 13.70 Dextro + 25.70

4 Marckwald, W., Ber them. Ges., 37, 1046 (1904). 6 Van Romburgh, Rec. trav. chim. Pays-Bus, 6,219 (1886). 6 Walden, P., 2. physik. Chem., 16,638 (1894).


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

P. A. Levene and R. E. Marker

In all of these the allocation of the ethyl group is arbitrary. The significant features of this series are the following. 1. In the carbinols the direction of rotation is to the left in the

first member and to the right in the other. Whether this change is due principally to the increase in mass, or to the distance of the polar group, or to both, cannot as yet be stated.

2. In the acids and halides with a strong polar group, the effect of the polarity seems to overweigh the other factors and hence the direction of rotation remains unchanged from member to member.

3. On passing from the carbinols to the bromides, the direction of change of rotation is the same in all members, namely to the right, and furthermore, the numerical value of the change in every instance is of the same order of magnitude. Thus the change of rotation from carbinol to halide may serve to recognize the configuration of the members of this series.

The question now arises as to the configurations of the 2-substituted butyric acids (4) in which the substituting group is a higher homologue of the radical ethyl. In the series of dextro-2-substituted propionic acids (3), (2,2-disubstituted acetic) series, the changes of rotations from carbinols to halides were always to the right irrespective of the size of the substituting alkyl. On the other hand, in the series described in this paper, namely in the 2- substituted butyric acids (4), the dextro acids in which the substituting alkyl is propyl or a higher homologue lead to a dextro-carbinol and a levo-halide. It was shown above that these acids have a configuration enantiomorphous to dextro-2-ethylbutyric acid (4). Does this then mean that the dextro-2-substituted propionic acids (3) in which the substituting group is a propyl or a higher homologue are enantiomorphously related to the corresponding dextro- a-substituted butyric acids (4) ? This question is still in need of an experimental answer.

EXPERIMENTAL

Dextro-2-Ethylbutyric Acid (4) (Dextro-S-Methylethylpropionic Acid)-The inactive acid was prepared from 2-bromobutane and ethyl malonate.

580 gm. of inactive acid were added to 3 liters of acetone and this heated to boiling on a steam-heated water bath. 1875 gm. of quinine were added and the solution filtered while hot. It was


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


cooled in ice and crystallization hastened by stirring. The quinine salt was filtered immediately; otherwise, on standing overnight both forms would crystallize. The resolution proceeded very slowly and after 10 crystallizations, the quinine salt was decomposed with an excess of 10 per cent hydrochloric acid and the organic acid extracted with ether. The ether solution was dried with sodium sulfate and the acid distilled. 80 gm. of product were obtained which gave a rotation of

[a]; = + 3.35”

1 x 0.923 = + 3.63”. [Ml: = -I- 4.21” (homogeneous)

700 gm. of inactive 3-methylethylpropionic acid were added to 4 liters of 35 per cent alcohol. This was warmed on a steam bath and 2750 gm. of brucine were added. The solution was filtered hot, and the filtrate cooled in an ice-salt mixture, with stirring, until crystallization set in. It was necessary to filter the brucine salt at about 10” as the salt is very soluble at room temperature. After three crystallizations the brucine salt was decomposed with 10 per cent hydrochloric acid and the organic acid recovered as described

above. B.p. 105” at 30 mm.; yield 135 gm.; ny = 1.4152; D 7 =

0.923; CY;’ = - 4.67”. The filtrate from the first crystallization of the brucine salt was

evaporated to a heavy syrup, then decomposed with 10 per cent hydrochloric acid. This gave 102 gm. of acid.

[a]; = + 3.70°

1 x 0.923 = + 4.01” (homogeneous)

3.165 mg. substance: 7.245 mg. CO2 and 2.920 mg. HzO. C6H1202. Calculated. C 62.02, H 10.42

Found. “ 62.4, “ 10.3

Dextro-Ethyl Ester of %Ethylbutyric Acid (4) (Dextro-Ethyl Ester of S-Methylethylpropionic Acid)-160 cc. of absolute alcohol were added to 80 gm. of 2-ethylbutyric acid (4), [(Y]:~ = +3.63”. To this solution were added 6 cc. of concentrated sulfuric acid and the mixture refluxed l$ hours on a steam bath. Some of the excess alcohol was distilled off under reduced pressure and the ester was


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


extracted from the residue with ether. The ether solution was washed with dilute sodium carbonate solution, then dried with sodium sulfate, and distilled. B.p. 68” at 25 mm.; yield 77 gm.;

D f = 0.864; ni5 = 1.4062.

[(Yf = + 2.82”

1 X 0.864 = + 3.26”. [M]: = + 4.69” (homogeneous)

4.615 mg. substance: 11.295 mg. CO, and 4.735 mg. HzO. CsH1602. Calculated. C 66.55, H 11.17

Found. “ 66.7 , “ 11.4

Dextro&Ethylbutanol (1) (Dextro-S-Methyl-1-Pentanol)-35 gm. of the ethyl ester of 2-ethylbutyric acid (4), [ol]i5 = +3.26”, were dissolved in 350 cc. of dry ethyl alcohol. This solution was slowly dropped into a suspension of 180 gm. of finely divided sodium in 300 cc. of boiling benzene. This mixture was stirred mechanically and heated while the alcoholic solution of the ester was allowed to flow in at such a rate as to keep the benzene boiling. At the end of the operation, enough alcohol was added to dissolve the excess of sodium. Water was added, and the carbinol extracted with et,her. The ether solution was dried over sodium sulfate and then distilled.

The carbinol was purified through its phthalic ester. An equiv- alent weight of phthalic anhydride was added to the carbinol in 30 cc. of pyricline and the mixture allowed to stand overnight. It was heated an hour on a steam bath, cooled, and acidified with hydrochloric acid. The phthalic ester was extracted with chloroform and the solution dried with anhydrous sodium sulfate. After evaporation of the chloroform under reduced pressure, the residue was dissolved in an excess of sodium carbonate solution. The solution was extracted several times with ether, then acidified with hydrochloric acid, and the phthalic ester extracted with chloroform. This solution was dried with anhydrous sodium sulfate and the chloroform evaporated under reduced pressure. The carbinol was obtained on saponification of the residue with 10 per cent sodium

hydroxide. B.p. 72” at 25 mm.; yield 15 gm.; D F = 0.822; n2d =

1.4182


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


[a]“,: = + 2.98O

~ = + 3.62”. 1 X 0.822

[Ml: = -I- 3.69” (homogeneous)

4.000 mg. substance: 10.350 mg. COz and 5.060 mg. HzO. C6Hx40. Calculated. C 70.52, H 13.81

Found. “ 70.56, “ 13.87

Dextro-1-Chloro-g-Ethyl Butane (Dextro-1-Chloro-S-Methyl Pen- tune)-10 gm. of 3-methyl-1-pentanol, [ali = +3.62”, were cooled in ice and 30 gm. of thionyl chloride slowly added. The solution was refluxed 1 hour on a steam bath, cooled, and poured on to ice. The chloride was extracted with ether, dried with anhydrous

sodium sulfate, and distilled. B.p. 73” at 100 mm.; D s = 0.892;

25 n, = 1.4210.

[a]; = + 6.65”

1 x 0.892 = + 7.46”. [Ml: = -I- 8.95” (homogeneous)

0.2021 gm. substance: 0.2340 gm. silver chloride.

C6H&l. Calculated. Cl 29.43. Found. Cl 28.64

Dextro-%Ethylbutyric Chloride (4) (Dextro-S-Methylethylpro- pionyl Chloride)-60 gm. of 2-ethylbutyric acid (4), [a]:’ = +3.63”, were cooled in ice and 120 gm. of thionyl chloride added. The mixture was refluxed 1 hour on a steam bath and then fractionated.

B.p. 81” at 100 mm.; yield 53 gm.; D F = 0.957; ni5 = 1.4245.

I ],, = + 5.20” aD 1 x 0.957

= + 5.43”. [M]: = -I- 7.33” (homogeneous)

0.1330 gm. substance required 9.70 cc. 0.1 N silver nitrate.

C6HuOC1. Calculated. Cl 26.37. Found. Cl 25.9

Dextro-%Ethylbutyric Amide (Dextro-S-Methylethyl Propionic Amide)-300 cc. of aqueous ammonia were cooled in ice and 60 gm. of 2-ethylbutyric chloride, [cr]:’ = +5.43”, were allowed to flow in slowly from a dropping funnel. The solution was stirred during the operation. The amide was filtered, then recrystallized from watex. A second crop of crystals was obtained on evaporation of the filtrate to a small volume. The amide was dried overnight under reduced pressure at 65”. Yield 4.5 gm.


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


[al”; = + 0.24” x 100 1 X 20 X 0.600

= + 2.00”. [M]2,6 = + 2.32” (in 75 per cent alcohol)

Dextro-SEthylbutyric Nitrile (Dextro-3-Methylethylpropionitrile) -40 gm. of 2-ethylbutyric amide, [a]i5 = +2.00” (in 75 per cent alcohol), were mixed with 50 gm. of phosphorus pentoxide in a distilling flask. The mixture was heated in a metal bath at 150” under a pressure of 100 mm. until the nitrile discontinued distilling. The product was redistilled. B.p. 87” at 100 mm.; yield 25 gm.;

Dz = 0811 n25 - 14070 4 . ;n-- .

[a]; = f 3.02” 1 X 0.811

= + 3.72”. [M]‘: = + 3.41” (homogeneous)

4.200 mg. substance: 0.500 cc. N1 at 26” and 753 mm. CsHI~N. Calculated. N 14.4. Found. N 13.5

Dextro-i-Amino-3-Ethyl Butane (Dextro-l-Amino-S-Methyl Pen- tune)-22 gm. of 2-ethylbutyric nitrile, [(Y]:~ = +3.72”, were dissolved in 1 liter of absolute alcohol. 90 gm. of metallic sodium were added to this solution in small quantities with stirring. When the sodium had dissolved, the product was cooled and acidified with hydrochloric acid (concentrated). The sodium chloride was filtered, washed with hot aIcoho1, and the combined fihrates evaporated to dryness under reduced pressure. The residue was dissolved in a minimum amount of water and the amine liberated by adding solid potassium hydroxide. The amine was extracted with ether and the ether solution dried with powdered potassium hydroxide. It was then distilled over sodium. B.p. 67” at 100

mm.; yield 20 gm.; D y = 0.767; nz5 = 1.4196.

+ 3.27’ ralE = 1 X 0.767

- = + 4.27”. [Ml: = + 4.31” (homogeneous)

4.635 mg. substance: 12.080 mg. COz and 5.995 mg. HzO. C~HI~N. Calculated. C 71.22, H 14.93

Found. “ 71.07, “ 14.47

Levo-g-n-Propylbutyric Acid (4) (Levo-3-Methylpropylpropionic Acid)-The inactive acid was prepared from 2-bromopentane and


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


ethyl malonate. 224 gm. of the inactive acid were dissolved in 1300 cc. of 95 per cent alcohol and heated to boiling on a steam bath. 511 gm. of cinchonidine were added to the hot solution. It was then filtered and 550 cc. of water were added to the filtrate. The salt crystallized by cooling the alcoholic solution in ice. After six crystallizations from 60 per cent alcohol the rotation of the free acid seemed to remain constant. The cinchonidine salt was decomposed with 10 per cent hydrochloric acid and the organic acid extracted with ether. The ether solution was dried with anhydrous sodium sulfate and the acid distilled. B.p. 113” at 17 mm.;

D~=0911~n2”=14214 4 .‘D * *

[a]:: = - 2.30”

1 x 0.911 = - 2.52”. [M]: = - 3.28” (homogeneous)

[a]‘,” = - 0.37” x 100 1 X 20 X 0.5442

= - 3.4” (in chloroform)

[a]; = - 0.61” X 100

1 x 20 x 0.9752 = - 3.1” (in benzene)

2.875 mg. substance: 6.805 mg. CO, and 2.820 mg. HtO. CTHIa02. Calculated. C 64.62, H 10.84

Found. “ 64.54, “ 10.97

Levo-Ethyl Ester of W-n-Propylbutyric Acid (4) (Levo-Ethyl Ester of S-Methylpropylpropionic Acid)-100 cc. of absolute alcohol were added to 40 gm. of 2-n-propylbutyric acid (4), [(Y]:’ = - 2.52”. To this solution were added 4 cc. of concentrated sulfuric acid. The ester was obtained as described for ethyl ester of 2-ethylbutyric

acid (4). B.p. 60” at 10 mm.; yield 43 gm.; D T = 0.806; ni” =

1.4102.

Id = - 0.34O

1 x 0.806 = - 0.42”. [Ml: = - 0.66” (homogeneous)

[cd]“,” = - 0.30” x 100

1 X 20 X 0.8076 = - 1.86” (in benzene)

[a]; = - 0.38” X 100

1 x 20 x 0.9934 = - 1.91’ (in chloroform)


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


6.070 mg. substance: 15.115 mg. COZ and 6.260 mg. HzO. CoH1802. Calculated. C 68.31, H 11.47

Found. “ 67.90, “ 11.54

80 gm. of Z-n-propylbutyric acid (4), [a]E6 = - 2.19’, esterified as above gave 85 gm. of ester.

[a]; = - 0.30”

~ = - 0.35”. 1 X 0.862

[M]: = - 0.55” (homogeneous)

LevoS-Propyl-I-Butanol (Levo-S-Methyl-i-Hexanol)-28 gm. of ethyl ester of 2-n-propylbutyric acid (4), [ar]E7 = - O-42”, were mixed with 400 cc. of dry alcohol. This was then dropped into a suspension of 46 gm. of sodium in 400 cc. of benzene. The reduc- tion was carried out as described for 3-methyl-1-pentanol, B.p.

80” at 25 mm.; yield 13 gm.; D F = 0.8208; nt” = 1.4202.

[a]; = - 1.35”

1 X 0.8208 = - l&Y. [Ml: = - 1.91’ (homogeneous)

[a]; = - 0.20” x 100

1 X 20 X 0.7624 = - 1.3” (in benzene)

M:: = - 0.49” x 100

2 X 20 X 0.7616 = - 1.6’ (in chloroform)

3.315 mg. substance: 8.755 mg. CO, and 4.125 mg. HzO. C7HL60. Calculated. C 72.35, H 13.86

Found. “ 72.02, I’ 13.92

A second portion of ester, [cr]i5 = - 0.35’, was reduced as above. This gave a rotation of

[a]“,’ = - 1.16’

1 X 0.826 = - 1.40”. [Ml: = - 1.62’ (homogeneous)

cr-Naphthylurethane of Levo-S-Methyl-1-Hexanol-To 1 gm. of cr-naphthylisocyanate was added 0.6 gm. of 3-methyl-1-hexanol, [a]2,9 = - 1.65”. The mixture was heated on a steam bath for 10 minutes, then allowed to stand overnight. The urethane was


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


extracted with hot absolute alcohol, filtered, and placed in the coId room until crystallization. M.p. 73”.

3.990 mg. substance: 11.050 mg. CO* and 2.760 mg. HzO. C18H23N02. Calculated. C 75.74, H 8.12

Found. “ 75.52, “ 7.74

Dextro-1-Chloro-S-Methyl Hexane-12 gm. of 3-methyl-1-hexanol [oL]~’ = -1.65’, were treated with 50 gm. of thionyl chloride as described for 1-chloro3-methyl pentane. B.p. 66” at 25 mm.;

D ; = 0.854; n:’ = 1.4282.

[ ]” = + 3.14O ffD 1 x 0.854

= + 3.68”. [MJZ = + 4.93” (homogeneous)

[(Y]; = + 0.42’ x 100

1 x 20 x 0.6008 = + 3.5’ (in chloroform)

[a]“,” = + 0.94” x 100

1 x 20 x 0.8122 = + 5.78” (in benzene)

4.455 mg. substance: 10.295 mg. CO, and 4.515 mg. HzO. 0.1360 gm. “ : 0.1438 gm. AgCl.

C&H&l. Calculated. C 62.41, H 11.22, Cl 26.37 Found. “ 63.0 , “ 11.34, “ 26.15

Dextro-I-Bromo-S-n-Propyl Butane (Dextro-I-Bromo-S-Methyl Hexane)-30 gm. of 3-n-propyl-1-butanol, [crp = - 1.40”, were cooled in ice and 60 gm. of phosphorus tribromide slowly added with stirring. The mixture was refluxed 1 hour and then poured on ice. The halide was extracted with ether. The ether was evaporated and the residue shaken with cold concentrated sulfuric acid, separated, and washed with water, then dilute sodium carbonate solution. It was extracted with ether. The ether solution was dried with anhydrous sodium sulfate and the halide distilled.

B.p. 65” at 20 mm.; yield 39 gm.; D p = 1.141.

+ 10.72” [a]:: = ~

1 x 1.141 = + 9.39”. [Mf,’ = + 16.81” (homogeneous)

3.270 mg. substance: 5.675 mg. COZ and 3.455 mg. H1O. GH16Br. Calculated. C 46.90, H 7.99

Found. ” 47.32, “ 8.40


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


S-n-Propyl Butane-35 gm. of 1-bromo-3-n-propyl butane, [cy]:’ = +9.39”, were slowly added to a suspension of 4.5 gm. of finely divided magnesium in 50 cc. of anhydrous ether. The Grignard reagent was poured on ice, and the magnesium hydroxide dissolved in hydrochloric acid. The hydrocarbon was extracted with ether. The ether was distilled and the residue shaken with cold concentrated sulfuric acid. It was separated, washed with water, and extracted from the water solution with a small amount of ether. The ether solution was dried with anhydrous sodium sulfate. The ether was then removed and the residue was frac-

tionated. B.p. 92”; yield 8 gm.; D y = 0.687; ni5 = 1.3854.

[a]; = - 5.32O

~ = - 7.75”. 1 X 0.687

[M]; = - 7.75” (homogeneous)

3.080 mg. substance: 9460 mg. CO, and 1.430 mg. HzO. CJL. Calculated. C 83.90, H 16.10

Found. “ 83.75, “ 16.09

Dextro-d-n-Propylbutyric Chloride (4) (Dextro-S-Methyl-n-Propyl- propionyl Chloride)-80 gm. of 2-n-propylbutyric acid (4) [cr]? = - 2.19”, were treated with 150 gm. of thionyl chloride as described for 2-ethylbutyric chloride. B.p. 82’ at 50 mm.; yield 87 gm. ;

DF = 0.954;n”,” = 1.4293.

+ 2.36’ [a]‘,” = ~

1 x 0.954 = + 2.47”. [Ml: = + 3.65’ (homogeneous)

0.1300 gm. substance required 8.40 cc. 0.1 N AgNO,. CTH~PC~. Calculated. Cl 23.90. Found. Cl 22.94

Levo-2-n-Propylbutyric Amide (4) (Levo-S-Methylpropyl Propio- nit Amide)-80 gm. of 2-n-propylbutyric chloride (4), [o(]i6 = +2.47”, were converted into the amide by dropping into aqueous ammonia as described for 2-ethylbutyric amide (4). Yield 55 gm.

I&z = - 0.25’ X 100

1 x 20 x 0.300 = - 4.16”. [M]: = - 5.36” (in 75 per cent alcohol)

Dextro-%2-n-Propylbutyric Nitrile (4) (Dextro-S-Methyl-n-Propyl- propionitriZe)-55 gm. of 2-n-propylbutyric amide (4), [ali =


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

92 Vrlalden Inversion. XV

-5.36” (in 75 per cent alcohol), were mixed with 75 gm. of phosphorus pentoxide in a distilling flask. The mixture was heated in a metal bath at 170” under a pressure of 70 mm. until no more nitrile distilled. The nitrile was then redistilled. B.p. 95” at 70

mm.; yield 42 gm.; D y = 0.810; nt5 = 1.4137.

[a]‘,” = + 2.66”

~ = + 3.28”. 1 x 0.810

[Ml: = + 3.64” (homogeneous)

3.720 mg. substance: 0.397 cc. Nf at 23” and 755 mm. C7H13N. Calculated. N 12.60. Found. N 12.23

Levo-l-Amino&Methyl Hexane-35 gm. of 3-methylpropyl- propionitrile, [a]“,” = +3.28”, were reduced by sodium in absolute alcohol and the amine isolated as described for 1-amino-3-methyl

pentane. B.p. 67” at 45 mm.; yield 26 gm.; D 7 = 0.772; n:5 =

1.4249.

[a]; = - 0.190”

1 x 0.772 = - 0.25”. [Ml: = - 0.29” (homogeneous)

0.0906 gm. substance required 7.75 cc. 0.1 N HCl. CTHI~N. Calculated. N 12.16. Found. N 11.97

LevoQ-n-Butylbutyric Acid (4) (Levo-S-Methyl-n-Butylpropionic Acid)-The inactive acid was prepared from 2-bromohexane and ethyl malonate.

720 gm. of the inactive acid were dissolved in 5 liters of hot acetone. To this boiling solution 1900 gm. of quinine were added. The solution was filtered and the quinine salt of the acid crystallized by cooling in ice and salt. It was filtered in a cold room. After seven crystallizations from acetone, the quinine salt was decomposed by shaking with 10 per cent hydrochloric acid. The organic acid was extracted with ether, dried with sodium sulfate, and then distilled. This was not resolved to its maximum rotation. B.p.

131’ at 19 mm.; yield 140 gm.; D y = 0.909; ni5 = 1.4259.

[a]; = - 3.45”

1 x 0.909 = - 3.79”. [Ml: = - 5.45’ (homogeneous)


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


5.375 mg. substance: 13.225 mg. CO, and 5.235 mg. Hz0 CsHIc02. Calculated. C 66.62, H 11.17

Found. “ 67.09, “ 10.89

Levo-Ethyl Ester of Z-n-Butylbutyric Acid (4) (Levo-Ethyl Ester of 3-Methyl-n-Butylpropionic Acid)-50 gm. of 2-n-butylbutyric acid (4), [LY]~~ = - 3.79”, were mixed with 120 cc. of absolute alcohol and 5 cc. of concentrated sulfuric acid. Esterification was carried out as described for ethyl ester of 2-ethylbutyric acid (4).

B.p. 104” at 35 mm.; yield 54 gm.; D 7 = 0.862, nE5 = 1.4162.

[& = - 1.33O

1 X 0.862 = - 1.54”. [M]: = - 2.61’ (homogeneous)

3.765 mg. substance: 9.665 mg. COZ and 4.000 mg. HzO. CloHzoOz. Calculated. C 69.71, H 11.63

Found. “ 70.03, “ 11.89

Levo-S-Methyl-1-Heptanol-50 gm. of ethyl ester of 2-n-butylbutyric acid (4), [(Y]:~ = -1.54”, were added to 250 cc. of dry alcohol. This was dropped into a suspension of 80 gm. of sodium in 375 cc. of boiling toluene with rapid stirring. The carbinol was isolated from this as described for 3-methyl-1-pentanol. B.p. 99”

at 25 mm.; yield 31 gm.; D F = 0.824; n2d = 1.4295.

[a]; = - 2.27” ____ = _ 2750

1 X 0.824 ’ . [Ml: = - 3.58” (homogeneous)

4.190 mg. substance: 11.275 mg. CO, and 5.155 mg. HZO. CSHISO. Calculated. C 73.78, H 13.95

Found. “ 73.37, ” 13.76

This carbinol was purified through its half phthalic ester but the rotation did not change.

Dextro-1-Bromo-3-n-Butyl Butane (Dextro-1-Bromo-S-Methyl Heptane)-20 gm. of 3-n-butyl-1-butanol, [a]z4 = - 2.75”, were cooled in ice and 35 gm. of phosphorus tribromide slowly added. The halide was worked up as described for 1-bromo-3-propyl

butane. B.p. 85” at 21 mm.; yield 24 gm.; D 7 = 1.106; ni5 =

1.4512.


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


+ 8.62’ kd = 1 X 1.106

= + 7.79”. [Mfl = + 15.03” (homogeneous)

4.705 mg. substance: 8.610 mg. COZ and 3.810 mg. HzO. 0.1226 gm. “ : 0.1199 gm. AgBr.

CsH1?Br. Calculated. C 49.72, H 8.86, Br 41.43 E’ound. “ 49.90, “ 9.06, “ 41.62

Dextro-9-n-Butylbutyric Chloride (4) (Dextro-S-Methyl-n-Butyl- propionyl Chloride)-40 gm. of 2-n- butylbutyric acid (4), [OL]~~ = -3.79”, were treated with 120 gm. of thionyl chloride as described for 3-methylethylpropionyl chloride. B.p. 88” at 30 mm.; yield 43

gm.;DF = 0.944;ni5 = 1.4331.

14: = + 1.84”

1 X 0.944 = + 1.95O. [Mfl = f 3.16’ (homogeneous)

3.495 mg. substance: 7.595 mg. COz and 2.905 mg. H20. 0.1438 gm. “ : 0.1274 gm. silver chloride.

CsHIsOC1. Calculated. C 59.22, H 9.29, Cl 21.83 Found. “ 59.26, “ 9.30, “ 21.93

Levo-Z-n-Butylbutyric Amide (4) (Levo-S-Methyl-n-B&y1 Pro- pionic Amide)-40 gm. of 2-n-butylbutyric chloride (4), [ar]t4 = + 1.95”, were slowly added to 150 cc. of cold aqueous ammonia. The amide was filtered, recrystallized from water, and dried overnight in a vacuum oven at 70”. Yield 30 gm.

[(Y]Z = - 0.55” x loo = _ 6 lgo

1X20X0.4440 . * [M]: = - 8.85” (in 75 per cent alcohol)

DextroQ-n-Butylbutyric Nitrile (4) (Dextro-?l-Methyl-n-Butyl- PropionitriZe)-30 gm. of 2-n-butylbutyric amide (4), [cy]i4 = - 6.19” (in 75 per cent alcohol), were mixed with 50 gm. of phosphorus pentoxide in a distilling flask. The flask was heated at 160” in a metal bath at 85 mm. until no more nitrile came over. The

nitrile was redistilled. B.p. 120’ at 85 mm.; yield 22 gm.; D $ =

0.811;n;5 = 1.4196.

bl: = + 3.51”

1 X 0.811 = + 4.33”. [Ml: = -I- 5.41” (homogeneous)


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


3.425 mg. substance: 9.786 mg. CO2 and 3.780 mg. H10. 6.730 “ “ : 0.617 cc. Nz at 23” and 757 mm.

C,H15N. Calculated. C 76.74, H 12.68, N 11.18 Found. “ 77.40, “ 12.34, “ 10.53

Levo-1-Amino-n-Butyl Butane (Levo-l-Amino-S-Methyl Heptane) -20 gm. of 2-n-butylbutyric nitrile (4) were reduced by 80 gm. of sodium in 1 liter of absolute alcohol as described for 1-amino-3-

ethyl butane. 24

B.p. 87” at 47 mm.; yield 17 gm.; D --4- = 0.782;

25 n, = 1.4288.

[(Y]; = - 1.05”

1 X 0.782 = - 1.34O. [M]: = - 1.73” (homogeneous)

3.905 mg. substance: 10.650 mg. COz and 5.155 mg. HzO. 0.1090 gm. “ : required 8.54 cc. 0.1 N HCl.

CSHIQN. Calculated. C 74.33, H 14.81, N 10.84 Found. “ 74.37, “ 14.77, “ 10.71

Levod-n-Amylbufyric Acid (4) (Levo-S-Methyl-n-Amybpropionic Acid)-The inactive acid was prepared from 3-bromoheptane and ethyl malonate.

475 gm. of inactive acid were dissolved in 3 liters of hot acetone. 1125 gm. of quinine were added and the solution filtered while hot. The quinine salt was crystallized by cooling the solution in ice and salt. It was filtered in the cold room as it is very soluble in acetone at room temperature. After eight recrystallizations from acetone, the quinine salt was decomposed by shaking with 10 per cent hydrochloric acid. The organic acid was extracted with ether

and then distilled, B.p. 135” at 16 mm.; yield 110 gm.; D F =I

0.899; nt5 = 1.4298.

[CY]‘,” = - 4.11°

1 x 0.899 = - 4.57”. [Ml; = - 7.13” (homogeneous)

3.840 mg. substance: 9.685 mg. COZ and 3.990 mg. HzO. CsHIs02. Calculated. C 68.31, H 11.48

Found. Lc 68.77, “ 11.62

Levo-Ethyl Ester of W-n-Amylbutyric Acid (4) (Levo-Ethyl Ester of S-Methyl-n-Amylpropionic Acid)-50 gm. of 2-n-amylbutyric acid


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


(4), [&It3 = - 4.57’, were mixed with 120 cc. of absolute alcohol and 6 cc. of sulfuric acid. The esterification was carried out as described for the ethyl ester of 2-ethylbutyric acid (4). B.p. 117’

at 35 mm.; yield 55 gm.; D 7 = 0.860; ni5 = 1.4200.

[a]“,” = - 1.74”

~ = _ 2030 1 X 0.860 ’ .

[M]: = - 3.74” (homogeneous)

2.685 mg. substance: 6.955 mg. COz and 2.870 mg. HzO. C,HS20~. Calculated. C 70.89, H 11.93

Found. “ 70.63, “ 11.96

Levo-3-n-Amyl-I-Butanol (Levo-S-Methyl-I-Octanol)-50 gm. of ethyl ester of 2-n-amylbutyric acid (4), [cx]~~ = - 2.03”, were added to 250 cc. of dry alcohol. This was dropped into a suspension of 80 gm. of sodium in 375 cc. of boiling toluene. The reduc- tion was carried out as described for 3-n-butyl-1-butanol. B.p.

110” at 25 mm. ; yield 41 gm. ; D T = 0.827; nE5 = 1.4328.

[a]; = - 3.09”

1 X 0.827 = - 3.74’. [Ml; = - 5.39” (homogeneous)

4.365 mg. substance: 12.065 mg. CO* and 5.545 mg. HXO. CsHzaO. Calculated. C 74.92, H 13.90

Found. “ 75.37, “ 14.21

Dextro-I-Bromo-S-Amy1 Butane (Dextro-I-Bromo-S-Methyl Oc- tune)-30 gm. of 3-methyl-1-octanol, [ali = -2.03’, were cooled in ice and 50 gm. of phosphorus tribromide were slowly added. The halide was prepared and purified as described for 1-bromo-3-

24 methyl heptane. B.p. 104’ at 25 mm.; yield 35 gm.; D 4 =

1085. nz5 = 14536 ’ >D . .

I ]24 = + 6.65” “D 1 X 1.085

= + 6.13”. [Ml: = -I- 13.02” (homogeneous)

3.725 mg. substance: 7.105 mg. CO2 and 2.990 mg. HSO. 0.1479 gm. “ : 0.1346 gm. AgBr.

COHIBBr. Calculated. C 52.10, H 9.26, Br 38.63 Found. “ 52.01, “ 8.98, “ 38.73


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

P. A. Levene and R. E. Marker

Dextro-2-n-Amylbutyric Chloride (4) (Dextro-S-Methyl-n-Amyl- propionyl Chloride)-40 gm. of Z-n-amylbutyric acid (4), [ar]E3 = - 4.57”, were cooled in ice and 100 gm. of thionyl chloride were then added. The product was refluxed 1 hour, then fractionated.

B.p. 95” at 20 mm.; yield 45 gm.; D s = 0.935; nt5 = 1.4362.

[cy]; = + 1.27” 1 X 0.935

= + 1.36’. [Ml: = + 2.40” (homogeneous)

3.045 mg. substance: 6.845 mg. CO2 and 2.600 mg. HzO. CsHITOC1. Calculated. C 61.15, H 9.70, Cl 20.10

Found. “ 61.28, “ 9.99, “ 19.93

Levod-n-Amylbutyric Amide (4) (Levo-S-Methyl-n-Amy1 Pro- pionic Amide)-The amide was prepared by dropping 40 gm. of 2-n-amylbutyric chloride (4), [oL]:* = + 1.36”, into 150 cc. of cold aqueous ammonia. Yield 31 gm.

[a]:: = - 0.65” x 100

0.4858 x 1 x 20 = - 6.68”. [M]: = - 10.49” (in 75 per cent alcohol)

Dextro-W-n-Amylbutyric Nitrile (4) (Dextro-S-Methyl-n-Amyl- propionitriZe)-30 gm. of 2-n-amylbutyric amide (4), [cr]t* = -6.68” (in 75 per cent alcohol), were mixed with 50 gm. of phosphorus pentoxide. The mixture was heated in a distilling flask at 160” and 85 mm. pressure until the nitrile ceased distilling. It was

redistilled. B.p. 135” at 85 mm.; yield 21 gm.; D F = 0.813; nE5

= 1.4239.

[a]; = + 3.27’ 1 X 0.813

= + 4.02”. [M]: = + 5.59’ (homogeneous)

3.265 mg. substance: 9.265 mg. CO2 and 3.495 mg. HzO. 0.4360 gm. “ : 4.10 cc. NS at 25” and 757 mm.

C8H17N. Calculated. C 77.64, H 12.30, N 10.07 Found. “ 77.39, ‘I 11.97, “ 10.36

Levo-l-Amino-S-Amy1 Butane (Levo-l-Amino-S-Methyl Octane)- 20 gm. of 2-n-amylbutyric nitrile (4) were reduced by 80 gm. of


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


sodium in 1 liter of absolute alcohol as described for 1-amino-3- 24

methyl pentane. B.p. 87” at 19 mm.; yield 16 gm.; D -4- = 0.788;

nz5 = 1.4326.

[a]; = - 1.75O

1 X 0.788 = - 2.22’. [M]; = - 3.17“ (homogeneous)

3.760 mg. substance: 10.375 mg. CO* and 4.685 mg. HnO. C9Hz1N. Calculated. C 75.41, H 14.79

Found. “ 75.24, “ 13.94

Dextro-Ethyl Ester of 2-n-Hexylbutyric Acid (Dextro-Ethyl Ester of S-Methyl-n-Hexylpropionic Acid)-60 gm. of 2-n-hexylbutyric acid, [a]z6 = + 0.78”, were mixed with 120 cc. of absolute alcohol and 5 cc. of concentrated sulfuric acid. The esterification was carried out as described for ethyl ester of 2-ethylbutyric acid (4).

B.p. 135’ at 36 mm.; yield 65 gm.; D f = 0.862;nf,5 = 1.4232.

[a]‘,” = + 0.33”

1 X 0.862 = + 0.38”. [M]: = + 0.75” (homogeneous)

3.330 mg. substance: 8.850 mg. CO* and 3.655 mg. HtO. C12Hz402. Calculated. C 71.93, H 12.09

Found. “ 72.47, “ 12.28

Dextro-S-Methyl-I-Nonanol-50 gm. of ethyl ester of 2-n-hexylbutyric acid (4), [cz]z5 = + 0.38”, were reduced by dissolving in 300 cc. of absolute alcohol and dropping this solution into a suspension of 80 gm. of sodium in boiling toluene. B.p. 122” at 24

mm.; yield 35 gm.; D 7 = 0.837; nE5 = 1.4348.

[ I%* = + 0.36” LyD 1 X 0.837

= + 0.43”. [M]: = + 0.67” (homogeneous)

3.185 mg. substance: 8.810 mg. COP and 3.945 mg. HzO. CloH2z0. Calculated. C 75.85, H 14.03

Found. (‘ 75.43, ‘I 13.86

Dextro-W-n-Hexylbutyric Acid (4) (S-Methyl-n-Hexylpropionic Acid)-The inactive acid was prepared from 2-bromooctane and ethyl malonate.


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


516 gm. of the inactive acid were dissolved in 2 liters of hot acetone. 1134 gm. of quinine were added and the solution filtered. It was very difficult to get the alkaloid salt to crystallize. It was recrystallized by stirring in ice and salt and filtered at 0”. After eight crystallizations the salt was decomposed and the acid recovered as described for 2-n-amylbutyric acid (4). B.p. 133” at 8 mm. ;

D Z = 0 899 nz5 = 14339 4 * ;Il * *

[ ]2, = + 0.71° ffD ~ = + 0.78”. [Ml”,” = f 1.32’ (homogeneous)

1 X 0.899

2.565 mg. substance: 6.595 mg. CO* and 2.700 mg. HzO. CdLoO2. Calculated. C 69.70, H 11.70

Found. “ 70.11, (‘ 11.78

Levo-1-Bromo-Z-n-Hexyl Butane (Levo-1-BromoS-Methyl No- nane)-20 gm. of 3-n-hexyl-1-butanol were cooled in ice and 30 gm. of phosphorus tribromide added. The bromination was carried out as described for 1-bromo3-methyl heptane. B.p. 116” at 21

mm.;yieldlSgm.;D~ = 1.063;nz5 = 1.4556.

- 0.73O [a]; = ___

1 x 1.063 = - 0.69”. [Ml: = - 1.56’ (homogeneous)

5.085 mg. substance: 10.250 mg. CO* and 4.480 mg. HzO. ClaHzlBr. Calculated. C 54.24, H 9.60

Found. “ 54.96, “ 9.85

Dextro-1-Bromo-Z-n-Ethyl Butane (Dextro-1-Bromo-Z-Methyl Pentune)- gm. of phosphorus tribromide were added to 180 gm. of cold 3-methyl-1-pentanol, [ar];’ = + 1.67”. The bromination was carried out as described for 1-bromo3-methyl heptane.

B.p. 80” at 85 mm.; yield 200 gm.; D 7 = 1.171; ni5 = 1.4415.

rff1; = + 3.70°

~ = + 3.16’. [MT; = + 5.21” (homogeneous) 1 x 1.171

4.810 mg. substance: 7.680 mg. CO, and 3.255 mg. HSO. 0.1464 gm. “ : 0.1674 gm. silver bromide.

CQ&Br. Calculated. C 43.60, H 7.93, Br 48.45 Found. “ 43.54, “ 7.57, “ 48.68


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


Dextro-.&Methyl-1-Hexanol-200 gm. of 1-bromo-3-ethyl butane, [aIt = + 3.16”, were slowly added to 28 gm. of magnesium in 300 cc. of ether. To this was added 60 gm. of paraformaldehyde. The Grignard reagent was poured on to a mixture of ice and hydrochloric acid and the carbinol ext,racted with ether. It was purified through its half phthalic ester. B.p. 77” at 20 mm.; yield 56 gm. ;

D T = 1.809; ni5 = 1.4233.

[c?]%” = + 1.57”

1 x 0.809 = + 1.94”. [M]; = $ 2.25’ (homogeneous)

3.510 mg. substance: 9.270 mg. COz and 4.365 mg. HzO. C,H160. Calculated. C 72.5, H 13.8

Found. “ 72, “ 13.9

Dextro-1-Bromo+Ethyl Pentane (Dextro-I-Bromo-&Methyl Hex- ane)-This halide was prepared from 57 gm. of 4-methyl-1-hexanol, [a]i3 = + 1.94” and 95 gm. of phosphorus tribromide as described for 1-bromo-3-methyl pentane. B.p. 78” at 44 mm.; yield 58 gm. ;

DF = 1.070.

I& = + 2.52”

___ = + 2.36”. 1 x 1.070

[Ml: = + 4.22” (homogeneous)

4.850 mg, substance: 8.445 mg. CO2 and 3.625 mg. H20. 0.1482 gm. “ : 0.1563 gm. silver bromide.

C,H1bBr. Calculated. C 46.90, H 8.43, Br 44.67 Found. “ 47.48, ” 8.36, ‘I 44.88

Dextro-S-Methyl Hexane-52 gm. of 1-bromo-4-methyl hexane, [OL]~~ = + 2.36”, were slowly dropped into 7.2 gm. of magnesium in 75 cc. of dry ether. The solution was poured on to a mixture of ice and hydrochloric acid and the hydrocarbon worked up as

described for levo-&methyl hexane. B.p. 92”; yield 21 gm.; D 7

= 0.684;nE5 = 1.3854.

bl:: = + 1.14”

1 x 0.684 = + 1.67”. [M]: = + 1.67” (homogeneous)


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


3.185 mg. substance: 9.775 mg. COz and 4.510 mg. H,O.

G&. Calculated. C 83.90, H 16.10 Found. “ 83.69, ‘I 15.84

Levo-&Butyl-1-Pentanol (Levo-4-Methyl-1-Octanol)-A Grignard reagent was prepared from 11 gm. of magnesium in ether and 80 gm. of 1-bromo-3-methyl heptane, [oL]~~ = + 7.79”. To this was added 20 gm. of paraformaldehyde and the carbinol isolated as described for 3-methyl-1-pentanol. B.p. 106” at 17 mm.; yield

33 gm.; D ‘T = 0.820; nf = 1.4335.

[&8 = - 0.37” ~ = - 0 45”. [M];.’ = - 1 x 0.820 .

0.65” (homogeneous)

2.710 mg. substance: 7.480 mg. COz and 3.375 mg. HQO.

CsHzOO. Calculated. C 74.92, H 13.9 Found. “ 75.26, “ 13.93

Dextro-I-Bromo+Octyl Pentane (Dextro-1-Bromo+Methyl OC- tune)-This was prepared from 33 gm. of 4-methyl-1-octanol, [a]“,‘.” = - 0.45”, and 50 gm. of phosphorus tribromide as described for 1-bromo-3-methyl pentane. B.p. 95” at 17 mm.; yield 37 gm.;

D ‘T = 1.089;ni5 = 1.4540.

[&1 _ + 3.95” 1 X 1.089

= + 3.63”. [Ml”,.’ = + 7.51” (homogeneous)

4.955 mg. substance: 9.500 mg. CO2 and 4.220 mg. HzO. CsHxgBr. Calculated. C 52.10, H 9.26

Found. “ 52.28, “ 9.53

Levo+Butyl Pentane (Levo+Methyl Octane)-17 gm. of l-bromo- 4-methyl octane, [cx]~‘.~ = + 3.63”, were reduced by forming a Griqnard reagent and pouring into water as described for 3-methyl

hexane. B.p. 141’ at 760 mm.; yield 7 gm.; D y = 0.717.

[cl$ = - 0.76”

1 x 0.717 = - 1.06”. [Ml; = - 1.36” (homogeneous)

2.915 mg. substance: 9.000 mg. COz and 4.105 mg. HZO. C&Lo. Calculated. C 84.28, H 15.72

Found. “ 84.19, “ 15.75


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


Levo+Amyl-i-Pentanol (Levo-.&Methyl-i-Nonanol)-This carbinol was prepared by the action of 12 gm. of paraformaldehyde on a Grignard reagent formed from 60 gm. of 1-bromo-S-methyl octane, [a]E4 = f-6.13”, as described for 3-methyl-1-pentanol.

B.p. 120” at 17 mm.; yield 27 gm.; D F = 0.826; ni5 = 1.4364.

- 1.20” [a]“, = ~

1 X 0.826 = - 1.45’. [Ml; = - 2.29” (homogeneous)

3.230 mg. substance: 9.030 mg, COZ and 4.045 mg. HsO. CloHzzO. Calculated. C 75.85, H 14.03

Found. “ 76.23, “ 14.01

Dextro-1-Bromo+Amyl Pentane (Dextro-i-Bromo+Methyl No- nane)-20 gm. of 4-methyl-1-nonanol, [or];’ = - 1.45”, were cooled in ice and 30 gm. of phosphorus tribromide added. The halide was isolated and purified as described for 1-bromo-3-methyl

heptane. B.p. 115” at 17 mm.; yield 22 gm.; D ‘y = 1.081:

[a]? = -I- 2.72” 1 X 1.081

= $ 2.52’. [Ml:“ = -I- 5.57” (homogeneous)

Levo-S-Amy1 Butane (Levo-S-Methyl Octane)-A Grignard reagent was formed from 6 gm. of magnesium in ether and 50 gm. of 1-bromo-3-methyl octane, [cr]i4 = + 6.23”. The Grignard reagent was divided into two parts. To the first part was added bromine in ether. This was to form the original bromide in order to test whether racemization took place during the formation of the Grig- nard reagent. The halide had a rotation of

[cc]; = + 6.71’ 1 x 1.085

= + 6.17” (homogeneous)

4.415 mg. substance: 8.465 mg. CO2 and 3.700 mg. HzO. CsHlsBr. Calculated. C 52.10, H 9.26

Found. I‘ 52.28, *’ 9.37

The second portion of the Grignard reagent was poured on to ice and the hydrocarbon extracted and purified as described for 3-


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/


methyl hexane. B.p. 143”; yield 19 gm.; D T = 0.714; ni5 =

1.4052.

[Lx]; = - 6.10”

~ = - 8.5” (homogeneous) 1 x 0.714

2.525 mg. substance: 7.810 mg. CO2 and 3.560 mg. HZO. CJLo. Calculated. C 84.27, H 15.73

Found. “ 84.34, “ 15.77


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/

P. A. Levene and R. E. MarkerMETHYL GROUP

PROPIONIC ACIDS CONTAINING ATHE SERIES OF DISUBSTITUTED

GROUPS ON OPTICAL ROTATION ININFLUENCE OF SUBSTITUTING

ON WALDEN INVERSION: XV. THE

1931, 91:77-103.J. Biol. Chem.

http://www.jbc.org/content/91/1/77.citation

Access the most updated version of this article at

Alerts:

When a correction for this article is posted•

When this article is cited•

alerts to choose from all of JBC's e-mailClick here

#ref-list-1

http://www.jbc.org/content/91/1/77.citation.full.htmlaccessed free atThis article cites 0 references, 0 of which can be


ww

.jbc.org/D

ownloaded from

http://www.jbc.org/content/91/1/77.citation

http://www.jbc.org/cgi/alerts?alertType=citedby&addAlert=cited_by&cited_by_criteria_resid=jbc;91/1/77&saveAlert=no&return-type=article&return_url=http://www.jbc.org/content/91/1/77.citation

http://www.jbc.org/cgi/alerts?alertType=correction&addAlert=correction&correction_criteria_value=91/1/77&saveAlert=no&return-type=article&return_url=http://www.jbc.org/content/91/1/77.citation

http://www.jbc.org/cgi/alerts/etoc

http://www.jbc.org/content/91/1/77.citation.full.html#ref-list-1

http://www.jbc.org/content/91/1/77.citation.full.html#ref-list-1

http://www.jbc.org/

on walden inversion in a previous communication levene and

Documents